Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority ...Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority of non-traumatic SAH occurring due to intracranial aneurysm rupture(Rutledge et al., 2014).展开更多
Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological da...Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury(TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood–brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.展开更多
OBJECTIVE:Chemotherapeutic agents such as docetaxel(DTX)can trigger chemotherapy-induced peripheral neuropathy(CIPN),which is characterized by unbearable pain.This study was designed to investigate the analgesic effec...OBJECTIVE:Chemotherapeutic agents such as docetaxel(DTX)can trigger chemotherapy-induced peripheral neuropathy(CIPN),which is characterized by unbearable pain.This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation(LFMNS)on DTX-induced tactile hypersensitivity in mice.METHODS:To produce CIPN,DTX was administered intraperitoneally 4 times,once every 2 d,to male ICR mice.LFMNS was performed on the wrist area,and the pain response was measured using von Frey filaments on both hind paws.Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brainderived neurotrophic factor(BDNF).RESULTS:Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area.CONCLUSIONS:LFMNS might be an effective nonpharmaceutical option for treating patients suffering from CIPN via regulating the expression of peripheral and central BDNF.展开更多
In this clinical practice review, the controversies and difficulties managing post concussion symptoms following mild traumatic brain injury are discussed. Based on considerable clinical experience in a designated Con...In this clinical practice review, the controversies and difficulties managing post concussion symptoms following mild traumatic brain injury are discussed. Based on considerable clinical experience in a designated Concussion Clinic, the authors (a neuropsychologist, a psychiatrist, and a neurologist) review relevant literature and issues for clinical practice, particularly with respect to understanding risk factors for and vulnerability to, development of chronic post-concussion symptoms. We contend it is not just the kind of head that matters but also the kind of complications, the kind of outcomes and the kind of management that can influence injury recovery. Given these complexities, a bio-psychosocial conceptualization of chronic post-concussion syndrome is appropriate. Though understanding is still elusive, management should not be biased by physiogenic or psychogenic aetiological theories for management needs to address patient reported outcomes regardless of underpinning aetiology.展开更多
Brain decoding based on functional magnetic resonance imaging has recently enabled the identification of visual perception and mental states.However,due to the limitations of sample size and the lack of an effective r...Brain decoding based on functional magnetic resonance imaging has recently enabled the identification of visual perception and mental states.However,due to the limitations of sample size and the lack of an effective reconstruction model,accurate reconstruction of natural images is still a major challenge.The current,rapid development of deep learning models provides the possibility of overcoming these obstacles.Here,we propose a deep learning-based framework that includes a latent feature extractor,a latent feature decoder,and a natural image generator,to achieve the accurate reconstruction of natural images from brain activity.The latent feature extractor is used to extract the latent features of natural images.The latent feature decoder predicts the latent features of natural images based on the response signals from the higher visual cortex.The natural image generatoris applied to generate reconstructed images from the predicted latent features of natural images and the response signals from the visual cortex.Quantitative and qualitative evaluations were conducted with test images.The results showed that the reconstructed image achieved comparable,accurate reproduction of the presented image in both highlevel semantic category information and low-level pixel information.The framework we propose shows promise for decoding the brain activity.展开更多
Acute stress disorder(ASD)is a transient psychiatric disorder that may arise subsequent to abrupt,extreme trauma exposure,and serves as a reliable indicator for the subsequent development of posttraumatic stress disor...Acute stress disorder(ASD)is a transient psychiatric disorder that may arise subsequent to abrupt,extreme trauma exposure,and serves as a reliable indicator for the subsequent development of posttraumatic stress disorder(PTSD)(Bryant,2011;Battle,2013).It exhibits rapid progression in the aftermath of trauma and persists for a duration of days or weeks(not exceeding one month),manifesting symptoms of dissociation,re-experiencing,avoidance,and hyperarousal(Bielas et al.,2018).In the absence of efficacious and prompt intervention,ASD is linked to substantial morbidity and functional impairment(McLean et al.,2022).展开更多
A growing interest in the comprehensive pathogenic mechanisms of psychiatric disorders from the perspective of the microbiome has been witnessed in recent decades;the intrinsic link between microbiota and brain functi...A growing interest in the comprehensive pathogenic mechanisms of psychiatric disorders from the perspective of the microbiome has been witnessed in recent decades;the intrinsic link between microbiota and brain function through the microbiota-gut-brain axis or other pathways has gradually been realized.However,little research has focused on viruses–entities characterized by smaller dimensions,simpler structures,greater diversity,and more intricate interactions with their surrounding milieu compared to bacteria.To date,alterations in several populations of bacteriophages and viruses have been documented in both mouse models and patients with psychiatric disorders,including schizophrenia,major depressive disorder,autism spectrum disorder,and Alzheimer’s disease,accompanied by metabolic disruptions that may directly or indirectly impact brain function.In addition,eukaryotic virus infection-mediated brain dysfunction provides insights into the psychiatric pathology involving viruses.Efforts towards virus-based diagnostic and therapeutic approaches have primarily been documented.However,limitations due to the lack of large-scale cohort studies,reliability,clinical applicability,and the unclear role of viruses in microbiota interactions pose a challenge for future studies.Nevertheless,it is conceivable that investigations into viruses herald a new era in the field of precise psychiatry.展开更多
Reward or stress,which exists extensively,causes resilient emotional fluctuations under common situations.However,reward or stress is a typical trigger for manic or depressive episodes of bipolar disorder(BD),which is...Reward or stress,which exists extensively,causes resilient emotional fluctuations under common situations.However,reward or stress is a typical trigger for manic or depressive episodes of bipolar disorder(BD),which is corroborated by psychological theory,biological findings,and psychosocial treatment approaches[1,2].During an episode of BD,the affective aberration can be persistent and switchable,accompanied by opposite constellations of cognitive and psychomotor symptoms.Characterized by uncontrollable mood ranging in severity,duration,and polarity,to disentangle the pathophysiology mechanism of BD is to delineate the mystery of affective fluctuations driven by reward or stress.展开更多
Background Postoperative delirium is one of the most common complications in the older surgical population,but its pathogenesis and biomarkers are largely undetermined.Retinal layer thickness has been demonstrated to ...Background Postoperative delirium is one of the most common complications in the older surgical population,but its pathogenesis and biomarkers are largely undetermined.Retinal layer thickness has been demonstrated to be associated with cognitive function in mild cognitive impairment and patients with Alzheimer’s disease.However,relatively little is known about possible retinal layer thickness among patients with postoperative delirium.Aims We aimed to investigate the relationship between retinal layer thickness and postoperative delirium in this cross-sectional study.Methods The participants(≥65 years old)having elective surgery under general anaesthesia were screened via medical records from Shanghai 10th People’s Hospital.Preoperative macular thickness and peripapillary retinal nerve fibre layer(RNFL)thickness were measured using optical coherence tomography(OCT).The Confusion Assessment Method(CAM)algorithm and CAM-Severity(CAM-S)were used to assess the incidence and severity of postoperative delirium on the first,second and third days after surgery.Results Among 169 participants(mean(standard deviation(SD)71.15(4.36)years),40(24%)developed postoperative delirium.Notably,individuals who developed postoperative delirium exhibited thicker preoperative macular thickness in the right eye compared with those who did not(mean(SD)283.35(27.97)µm vs 273.84(20.14)µm,p=0.013).Furthermore,the thicker preoperative macular thickness of the right eye was associated with a higher incidence of postoperative delirium(adjusted odds ratio 1.593,95%confidence interval(CI)1.093 to 2.322,p=0.015)and greater severity(adjusted mean difference(β)=0.256,95%CI 0.037 to 0.476,p=0.022)after adjustment for age,sex and Mini-Mental State Examination(MMSE)scores.However,such a difference or association did not appear in the left macular or bilateral peripapillary RNFL thicknesses.Conclusions Current findings demonstrated that preoperative macular thickness might serve as a potential non-invasive marker for the vulnerability of developing postoperative delirium in older surgical patients.Further large-scale validation studies should be performed to confirm these results.展开更多
Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression....Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.Methods:Patients with bipolarⅡdepression were enrolled in this prospective,two-center,randomized,12-week pilot trial.The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale(MADRS)of≥50%.All eligible patients initially received four weeks of lurasidone monotherapy.Patients who responded well continued to receive this kind of monotherapy.However,no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks.By comprehensively comparing the results of MADRS over a period of 4-12 weeks,a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.Results:Thirty-seven patients responded to lurasidone monotherapy,and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks.After two weeks of combined valproate or vortioxetine treatment,the MADRS score in the vortioxetine group was significantly lower than that in the valproate group.There was no difference in the MADRS scores between the two groups at 8 and 12 weeks.The incidence of side effects did not significantly differ between the valproate and vortioxetine groups.Importantly,three patients in the vortioxetine group appeared to switch to mania or hypomania.Conclusions:This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage,while disease progression should be monitored closely for the risk of switching to mania.展开更多
Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises...Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke.Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit.In this mini-review,we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia.Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery.Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery.First,new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling.Second,blood vessels are thought to enhance neurogenesis in three stages:1)Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals,2)microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen,nutrients,and soluble factors as well as serving as a scaffold for migration,and 3)oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons.Thus,the regions of angiogenesis and surrounding tissue may be coupled,representing novel treatment targets.展开更多
Axonal regeneration and ifber regrowth is limited in the adult central nervous system, but re-search over the last decades has revealed a high intrinsic capacity of brain and spinal cord circuits to adapt and reorgani...Axonal regeneration and ifber regrowth is limited in the adult central nervous system, but re-search over the last decades has revealed a high intrinsic capacity of brain and spinal cord circuits to adapt and reorganize after smaller injuries or denervation. Short-distance ifber growth and synaptic rewiring was found in cortex, brain stem and spinal cord and could be associated with restoration of sensorimotor functions that were impaired by the injury. Such processes of struc-tural plasticity were initially observed in the corticospinal system following spinal cord injury or stroke, but recent studies showed an equally high potential for structural and functional reorganization in reticulospinal, rubrospinal or propriospinal projections. Here we review the lesion-induced plastic changes in the propriospinal pathways, and we argue that they represent a key mechanism triggering sensorimotor recovery upon incomplete spinal cord injury. The for-mation or strengthening of spinal detour pathways bypassing supraspinal commands around the lesion site to the denervated spinal cord were identiifed as prominent neural substrate inducing substantial motor recovery in different species from mice to primates. Indications for the exis-tence of propriospinal bypasses were also found in humans after cortical stroke. It is mandatory for current research to dissect the biological mechanisms underlying spinal circuit remodeling and to investigate how these processes can be stimulated in an optimal way by therapeutic inter-ventions （e.g., ifber-growth enhancing interventions, rehabilitation）. This knowledge will clear the way for the development of novel strategies targeting the remarkable plastic potential of pro-priospinal circuits to maximize functional recovery after spinal cord injury.展开更多
Reactive oxygen species have been implicated in conditions ranging from cardiovascular dysfunc- tion, arthritis, cancer, to aging and age-related disorders. The organism developed several path- ways to counteract thes...Reactive oxygen species have been implicated in conditions ranging from cardiovascular dysfunc- tion, arthritis, cancer, to aging and age-related disorders. The organism developed several path- ways to counteract these effects, with base excision repair being responsible for repairing one of the major base lesions （8-oxoG） in all organisms. Epidemiological evidence suggests that cognitive stimulation makes the brain more resilient to damage or degeneration. Recent studies have linked enriched environment to reduction of oxidative stressin neurons of mice with Alzheimer＇s dis- ease-like disease, but given its complexity it is not clear what specific aspect of enriched environ- ment has therapeutic effects. Studies from molecular biology have shown that the protein p300, which is a transcription co-activator required for consolidation of memories during specific learning tasks, is at the same time involved in DNA replication and repair, playing a central role in the long-patch pathway of base excision repair. Based on the evidence, we propose that learning tasks such as novel object recognition could be tested as possible methods of base excision repair fa- cilitation, hence inducing DNA repair in the hippocampal neurons. If this method proves to be effec- tive, it could be the start for designing similar tasks for humans, as a behavioral therapeutic com- plement to the classical drug-based therapy in treating neurodegenerative disorders.展开更多
Over the last decade virtual reality （VR） setups for rodents have been developed and utilized to in-vestigate the neural foundations of behavior. Such VR systems became very popular since theyallow the use of state-...Over the last decade virtual reality （VR） setups for rodents have been developed and utilized to in-vestigate the neural foundations of behavior. Such VR systems became very popular since theyallow the use of state-of-the-art techniques to measure neural activity in behaving rodents that can-not be easily used with classical behavior setups. Here, we provide an overview of rodent VR tech-nologies and review recent results from related research. We discuss commonalities and differ-ences as well as merits and issues of different approaches. A special focus is given to experimental（behavioral） paradigms in use. Finally we comment on possible use cases that may further exploitthe potential of VR in rodent research and hence inspire future studies.展开更多
It is difficult to control the degree of ischemic postconditioning in the brain and other isch- emia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on ...It is difficult to control the degree of ischemic postconditioning in the brain and other isch- emia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on terminal organs. In this study, a focal cerebral ischemia-reperftlsion injury model was established using three cycles of remote ischernic postconditioning, each cycle consisted of 10-minute occlusion of the femoral artery and 10-minute opening. The results showed that, remote ischemic postconditioning significantly decreased the percentage of the in- farct area and attenuated brain edema. In addition, inflammatory nuclear factor-KB expression was significantly lower, while anti-apoptotic Bcl-2 expression was significantly elevated in the ce- rebral cortex on the ischemic side. Our findings indicate that remote ischemic postconditioning attenuates focal cerebral ischemia/reperfusion injury, and that the neuroprotective mechanism is mediated by an anti-apoptotic effect and reduction of the inflammatory response.展开更多
Objective To explore predictors of the 6-month clinical outcome ofthalamic hemorrhage, and evaluate if minimally invasive thalamic hematoma drainage （THD） could improve its prognosis. Methods A total of 54 patients ...Objective To explore predictors of the 6-month clinical outcome ofthalamic hemorrhage, and evaluate if minimally invasive thalamic hematoma drainage （THD） could improve its prognosis. Methods A total of 54 patients with spontaneous thalamic hemorrhage were evaluated retrospectively. Clinical data, including demographics, stroke risk factors, neuroimaging variables, Glasgow Coma Score （GCS） on admission, surgical strategy, and outcome, were collected. Clinical outcome was assessed using a modified Rankin Scale, six months after onset. Univariate analysis and multivariate logistic regression analysis were performed to determine predictors of a poor outcome. Results Conservative treatnaent was performed for five patients （9.3%）, external ventricular drainage （EVD） for 20 patients （37.0%）, THD for four patients （7.4%）, and EVD combined with THD for 25 patients （46.3%）. At six months after onset, 21 （38.9%） patients achieved a favorable outcome, while 33 （61.1%） had a poor outcome. In the univariate analysis, predictors of poor 6-month outcome were lower GCS on admis- sion （P = 0.001）, larger hematoma volume （P 〈 0.001）, midline shift （P = 0.035）, acute hydrocephalus （P = 0.039）, and no THD （P = 0.037）. The independent predictors of poor outcome, according to the multivariate logistic regression analysis, were no THD and larger hematoma volume. Conclusions Minimally invasive THD, which removes most of the hematoma within a few days, with limited damage to perihematomal brain tissue, improved the 6-month outcome of thalamic hemorrhage. Thus, THD can be widely applied to treat patients with thalamic hemorrhage.展开更多
The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneratio...The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor （NGF） al- terations in sporadic Alzheimer＇s disease （AD）, an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons （BFCN）, is one of the first homeostatic systems affected in prodromal AD. NGF signaling dysfunctions have been thought for decades to occur in AD late stages, as a mere consequence of amyloid-driven disruption of the retrograde axonal transport of neuro- trophins to BFCN. Nowadays, a wealth of knowledge is potentially opening a new scenario： NGF signaling impairment occurs at the onset of AD and correlates better than amyloid load with cognitive decline. The recent acceleration in the characterization of anatomical, functional and molecular profiles of early AD is aimed at maximizing the efficacy of existing treatments and setting novel therapies. Accordingly, the elucidation of the molecular events underlying APP metabolism regulation by the NGF pathway in the sep- to-hippocampal system is crucial for the identification of new target molecules to slow and eventually halt mild cognitive impairment （MCI） and its progression toward AD.展开更多
Compared with other stem cells,human induced pluripotent stem cells-derived neural progenitor cells(iPSC-NPCs)are more similar to cortical neurons in morphology and immunohistochemistry.Thus,they have greater potentia...Compared with other stem cells,human induced pluripotent stem cells-derived neural progenitor cells(iPSC-NPCs)are more similar to cortical neurons in morphology and immunohistochemistry.Thus,they have greater potential for promoting the survival and growth of neurons and alleviating the proliferation of astrocytes.Transplantation of stem cell exosomes and stem cells themselves have both been shown to effectively repair nerve injury.However,there is no study on the protective effects of exosomes derived from iPSC-NPCs on oxygen and glucose deprived neurons.In this study,we established an oxygen-glucose deprivation model in embryonic cortical neurons of the rat by culturing the neurons in an atmosphere of 95%N2 and 5%CO2 for 1 hour and then treated them with iPSC-NPC-derived exosomes for 30 minutes.Our results showed that iPSC-NPC-derived exosomes increased the survival of oxygen-and glucose-deprived neurons and the level of brain-derived neurotrophic factor in the culture medium.Additionally,it attenuated oxygen and glucose deprivation-induced changes in the expression of the PTEN/AKT signaling pathway as well as synaptic plasticity-related proteins in the neurons.Further,it increased the length of the longest neurite in the oxygen-and glucose-deprived neurons.These findings validate the hypothesis that exosomes from iPSCNPCs exhibit a neuroprotective effect on oxygen-and glucose-deprived neurons by regulating the PTEN/AKT signaling pathway and neurite outgrowth.This study was approved by the Animal Ethics Committee of Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,China(approval No.SRRSH20191010)on October 10,2019.展开更多
Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation. In this study, 10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation...Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation. In this study, 10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation and were used for the repair of left sciatic nerve defects through allograft bridging. Three days later, 1 mL ganglioside solution （1 g/L） was sub- cutaneously iniected into the right hind leg of rabbits. Compared with non-injected rats, muscle wet weight ratio was increased at 2-12 weeks after modeling. The quantity of myelinated fibers in regenerated sciatic nerve, myelin thickness and fiber diameter were elevated at 4-12 weeks after modeling. Sciatic nerve potential amplitude and conduction velocity were raised at 8 and 12 weeks, while conduction latencies were decreased at 12 weeks. Experimental findings indicate that ganglioside can promote the regeneration of sciatic nerve defects after repair with cryopre- served peripheral nerve allografts.展开更多
Autonomic disturbances often occur in patients with acute cerebrovascular disease due to damage of the central autonomic network. We summarize the structures of the central autonomic network and the clinical tests use...Autonomic disturbances often occur in patients with acute cerebrovascular disease due to damage of the central autonomic network. We summarize the structures of the central autonomic network and the clinical tests used to evaluate the functions of the autonomic nervous system.We review the clinical and experimental findings as well as management strategies of post-stroke autonomic disturbances including electrocardiographic changes, cardiac arrhythmias, myocardial damage, thermoregulatory dysfunction, gastrointestinal dysfunction, urinary incontinence, sexual disorders, and hyperglycemia. The occurrence of autonomic disturbances has been associated with poor outcomes in stroke patients. Autonomic nervous system modulation appears to be an emerging therapeutic strategy for stroke management in addition to treatments for sensorimotor dysfunction.展开更多
文摘Subarachnoid hemorrhage(SAH) is a devastating condition that affects a total of 8 million people worldwide each year(Lauzier and Athiraman, 2024). Etiologies of SAH can be traumatic or nontraumatic, with the majority of non-traumatic SAH occurring due to intracranial aneurysm rupture(Rutledge et al., 2014).
基金supported by the Zhejiang Provincial Key Research and Development Program (2021C03107)。
文摘Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury(TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood–brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.
基金“Korea Health Technology R&D Project through the Korea Health Industry Development Institute,funded by the Ministry of Health and Welfare,Republic of Korea(HI15C0007)”“Chungnam National University,and Basic Science Research Program through the National Research Foundation of Korea(2021R1F1A1062509)+1 种基金Study on the Angiotensin Converting Enzyme Inhibitor(ACEi)-related Pain Mechanism by Mediating Substance P,Bradykinin and AngiotensinⅡActivities,(2021R1A6A3A01086598)Study on the Role and Interaction Mechanisms of BDNF and APE1/Ref-1 in Animal Models of Chronic Pain Accompanied with Depression。
文摘OBJECTIVE:Chemotherapeutic agents such as docetaxel(DTX)can trigger chemotherapy-induced peripheral neuropathy(CIPN),which is characterized by unbearable pain.This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation(LFMNS)on DTX-induced tactile hypersensitivity in mice.METHODS:To produce CIPN,DTX was administered intraperitoneally 4 times,once every 2 d,to male ICR mice.LFMNS was performed on the wrist area,and the pain response was measured using von Frey filaments on both hind paws.Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brainderived neurotrophic factor(BDNF).RESULTS:Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area.CONCLUSIONS:LFMNS might be an effective nonpharmaceutical option for treating patients suffering from CIPN via regulating the expression of peripheral and central BDNF.
文摘In this clinical practice review, the controversies and difficulties managing post concussion symptoms following mild traumatic brain injury are discussed. Based on considerable clinical experience in a designated Concussion Clinic, the authors (a neuropsychologist, a psychiatrist, and a neurologist) review relevant literature and issues for clinical practice, particularly with respect to understanding risk factors for and vulnerability to, development of chronic post-concussion symptoms. We contend it is not just the kind of head that matters but also the kind of complications, the kind of outcomes and the kind of management that can influence injury recovery. Given these complexities, a bio-psychosocial conceptualization of chronic post-concussion syndrome is appropriate. Though understanding is still elusive, management should not be biased by physiogenic or psychogenic aetiological theories for management needs to address patient reported outcomes regardless of underpinning aetiology.
基金supported by the National Natural Science Foundation of China(61773094,61533006,U1808204,31730039,31671133,and 61876114)the Ministry of Science and Technology of China(2015CB351701)+1 种基金the National Major Scientific Instruments and Equipment Development Project(ZDYZ2015-2)a Chinese Academy of Sciences Strategic Priority Research Program B grant(XDB32010300)。
文摘Brain decoding based on functional magnetic resonance imaging has recently enabled the identification of visual perception and mental states.However,due to the limitations of sample size and the lack of an effective reconstruction model,accurate reconstruction of natural images is still a major challenge.The current,rapid development of deep learning models provides the possibility of overcoming these obstacles.Here,we propose a deep learning-based framework that includes a latent feature extractor,a latent feature decoder,and a natural image generator,to achieve the accurate reconstruction of natural images from brain activity.The latent feature extractor is used to extract the latent features of natural images.The latent feature decoder predicts the latent features of natural images based on the response signals from the higher visual cortex.The natural image generatoris applied to generate reconstructed images from the predicted latent features of natural images and the response signals from the visual cortex.Quantitative and qualitative evaluations were conducted with test images.The results showed that the reconstructed image achieved comparable,accurate reproduction of the presented image in both highlevel semantic category information and low-level pixel information.The framework we propose shows promise for decoding the brain activity.
基金supported by the National Natural Science Foundation of China(No.82271562)the Key Research and Development Program of Zhejiang Province of China(No.2023C03077).
文摘Acute stress disorder(ASD)is a transient psychiatric disorder that may arise subsequent to abrupt,extreme trauma exposure,and serves as a reliable indicator for the subsequent development of posttraumatic stress disorder(PTSD)(Bryant,2011;Battle,2013).It exhibits rapid progression in the aftermath of trauma and persists for a duration of days or weeks(not exceeding one month),manifesting symptoms of dissociation,re-experiencing,avoidance,and hyperarousal(Bielas et al.,2018).In the absence of efficacious and prompt intervention,ASD is linked to substantial morbidity and functional impairment(McLean et al.,2022).
基金supported by The Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2023001B)The National Key Research and Development Program of China(2023YFC2506200)+2 种基金The Zhejiang Provincial Key Research and Development Program(2021C03107)The Leading Talent of Scientific and Technological Innovation-“Ten Thousand Talents Program”of Zhejiang Province(2021R52016)The Fundamental Research Funds for the Central Universities(226-2022-00193,226-2022-00002,2023ZFJH01-01,and 2024ZFJH01-01).
文摘A growing interest in the comprehensive pathogenic mechanisms of psychiatric disorders from the perspective of the microbiome has been witnessed in recent decades;the intrinsic link between microbiota and brain function through the microbiota-gut-brain axis or other pathways has gradually been realized.However,little research has focused on viruses–entities characterized by smaller dimensions,simpler structures,greater diversity,and more intricate interactions with their surrounding milieu compared to bacteria.To date,alterations in several populations of bacteriophages and viruses have been documented in both mouse models and patients with psychiatric disorders,including schizophrenia,major depressive disorder,autism spectrum disorder,and Alzheimer’s disease,accompanied by metabolic disruptions that may directly or indirectly impact brain function.In addition,eukaryotic virus infection-mediated brain dysfunction provides insights into the psychiatric pathology involving viruses.Efforts towards virus-based diagnostic and therapeutic approaches have primarily been documented.However,limitations due to the lack of large-scale cohort studies,reliability,clinical applicability,and the unclear role of viruses in microbiota interactions pose a challenge for future studies.Nevertheless,it is conceivable that investigations into viruses herald a new era in the field of precise psychiatry.
基金supported by the National Key Research and Development Program of China(2023YFC2506200)the Leading Talent of Scientific and Technological Innovation-"Ten Thousand Talents Program"of Zhejiang Province(2021R52016).
文摘Reward or stress,which exists extensively,causes resilient emotional fluctuations under common situations.However,reward or stress is a typical trigger for manic or depressive episodes of bipolar disorder(BD),which is corroborated by psychological theory,biological findings,and psychosocial treatment approaches[1,2].During an episode of BD,the affective aberration can be persistent and switchable,accompanied by opposite constellations of cognitive and psychomotor symptoms.Characterized by uncontrollable mood ranging in severity,duration,and polarity,to disentangle the pathophysiology mechanism of BD is to delineate the mystery of affective fluctuations driven by reward or stress.
基金supported by grants from National Natural Science Foundation of China(81720108012,82001118)Ministry of Science and Technology of China(2021ZD0202003)+1 种基金Shanghai‘Rising Stars of Medical Talents’Youth Development Program(SHWSRS(2023)-62)Henry K.Beecher Professorship from Harvard University。
文摘Background Postoperative delirium is one of the most common complications in the older surgical population,but its pathogenesis and biomarkers are largely undetermined.Retinal layer thickness has been demonstrated to be associated with cognitive function in mild cognitive impairment and patients with Alzheimer’s disease.However,relatively little is known about possible retinal layer thickness among patients with postoperative delirium.Aims We aimed to investigate the relationship between retinal layer thickness and postoperative delirium in this cross-sectional study.Methods The participants(≥65 years old)having elective surgery under general anaesthesia were screened via medical records from Shanghai 10th People’s Hospital.Preoperative macular thickness and peripapillary retinal nerve fibre layer(RNFL)thickness were measured using optical coherence tomography(OCT).The Confusion Assessment Method(CAM)algorithm and CAM-Severity(CAM-S)were used to assess the incidence and severity of postoperative delirium on the first,second and third days after surgery.Results Among 169 participants(mean(standard deviation(SD)71.15(4.36)years),40(24%)developed postoperative delirium.Notably,individuals who developed postoperative delirium exhibited thicker preoperative macular thickness in the right eye compared with those who did not(mean(SD)283.35(27.97)µm vs 273.84(20.14)µm,p=0.013).Furthermore,the thicker preoperative macular thickness of the right eye was associated with a higher incidence of postoperative delirium(adjusted odds ratio 1.593,95%confidence interval(CI)1.093 to 2.322,p=0.015)and greater severity(adjusted mean difference(β)=0.256,95%CI 0.037 to 0.476,p=0.022)after adjustment for age,sex and Mini-Mental State Examination(MMSE)scores.However,such a difference or association did not appear in the left macular or bilateral peripapillary RNFL thicknesses.Conclusions Current findings demonstrated that preoperative macular thickness might serve as a potential non-invasive marker for the vulnerability of developing postoperative delirium in older surgical patients.Further large-scale validation studies should be performed to confirm these results.
基金partially supported by the Construction Fund of Key Medical Disciplines of Hangzhou(No.OO2020491)the National Key Research and Development Program of China(No.2023YFC2506200)+4 种基金the Zhejiang Provincial Key Research and Development Program(No.2021C03107)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2023001B)the Leading Talent of Scientific and Technological Innovation-“Ten Thousand Talents Program”of Zhejiang Province(No.2021R52016)the Innovation Team for Precision Diagnosis and Treatment of Major Brain Diseases(No.2020R01001)the Chinese Medical Education Association(No.2022KTZ004).
文摘Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.Methods:Patients with bipolarⅡdepression were enrolled in this prospective,two-center,randomized,12-week pilot trial.The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale(MADRS)of≥50%.All eligible patients initially received four weeks of lurasidone monotherapy.Patients who responded well continued to receive this kind of monotherapy.However,no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks.By comprehensively comparing the results of MADRS over a period of 4-12 weeks,a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.Results:Thirty-seven patients responded to lurasidone monotherapy,and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks.After two weeks of combined valproate or vortioxetine treatment,the MADRS score in the vortioxetine group was significantly lower than that in the valproate group.There was no difference in the MADRS scores between the two groups at 8 and 12 weeks.The incidence of side effects did not significantly differ between the valproate and vortioxetine groups.Importantly,three patients in the vortioxetine group appeared to switch to mania or hypomania.Conclusions:This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage,while disease progression should be monitored closely for the risk of switching to mania.
基金supported by a Grant-in-Aid for Scientific Research(Research Project No.15K19478 and 18K07493,both to MK)Japan Science and Technology Agency(JST),the Translational Research program+7 种基金Strategic Promotion for practical application of Innovative medical Technology(TR-SPRINT)supported by Japan Agency for Medical Research and Development(AMED)under Grant No.JP19lm0203023a grant from Takeda Science Foundationthe Bayer Scholarship for Cardiovascular ResearchJapan Cardiovascular Research FoundationAstellas Foundation for Research on Metabolic DisordersYoung Investigator Okamoto AwardMedical Research Encouragement Prize of the Japan Medical Association(to MK)supported by a grant from Tsubaki Memorial Foundation(to MH and IN)
文摘Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke.Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit.In this mini-review,we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia.Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery.Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery.First,new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling.Second,blood vessels are thought to enhance neurogenesis in three stages:1)Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals,2)microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen,nutrients,and soluble factors as well as serving as a scaffold for migration,and 3)oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons.Thus,the regions of angiogenesis and surrounding tissue may be coupled,representing novel treatment targets.
文摘Axonal regeneration and ifber regrowth is limited in the adult central nervous system, but re-search over the last decades has revealed a high intrinsic capacity of brain and spinal cord circuits to adapt and reorganize after smaller injuries or denervation. Short-distance ifber growth and synaptic rewiring was found in cortex, brain stem and spinal cord and could be associated with restoration of sensorimotor functions that were impaired by the injury. Such processes of struc-tural plasticity were initially observed in the corticospinal system following spinal cord injury or stroke, but recent studies showed an equally high potential for structural and functional reorganization in reticulospinal, rubrospinal or propriospinal projections. Here we review the lesion-induced plastic changes in the propriospinal pathways, and we argue that they represent a key mechanism triggering sensorimotor recovery upon incomplete spinal cord injury. The for-mation or strengthening of spinal detour pathways bypassing supraspinal commands around the lesion site to the denervated spinal cord were identiifed as prominent neural substrate inducing substantial motor recovery in different species from mice to primates. Indications for the exis-tence of propriospinal bypasses were also found in humans after cortical stroke. It is mandatory for current research to dissect the biological mechanisms underlying spinal circuit remodeling and to investigate how these processes can be stimulated in an optimal way by therapeutic inter-ventions （e.g., ifber-growth enhancing interventions, rehabilitation）. This knowledge will clear the way for the development of novel strategies targeting the remarkable plastic potential of pro-priospinal circuits to maximize functional recovery after spinal cord injury.
基金supported by a grant from Synergon Consulting Companya grant from Romanian Ministry for Education and Research,No.PCCE 140/2008
文摘Reactive oxygen species have been implicated in conditions ranging from cardiovascular dysfunc- tion, arthritis, cancer, to aging and age-related disorders. The organism developed several path- ways to counteract these effects, with base excision repair being responsible for repairing one of the major base lesions （8-oxoG） in all organisms. Epidemiological evidence suggests that cognitive stimulation makes the brain more resilient to damage or degeneration. Recent studies have linked enriched environment to reduction of oxidative stressin neurons of mice with Alzheimer＇s dis- ease-like disease, but given its complexity it is not clear what specific aspect of enriched environ- ment has therapeutic effects. Studies from molecular biology have shown that the protein p300, which is a transcription co-activator required for consolidation of memories during specific learning tasks, is at the same time involved in DNA replication and repair, playing a central role in the long-patch pathway of base excision repair. Based on the evidence, we propose that learning tasks such as novel object recognition could be tested as possible methods of base excision repair fa- cilitation, hence inducing DNA repair in the hippocampal neurons. If this method proves to be effec- tive, it could be the start for designing similar tasks for humans, as a behavioral therapeutic com- plement to the classical drug-based therapy in treating neurodegenerative disorders.
文摘Over the last decade virtual reality （VR） setups for rodents have been developed and utilized to in-vestigate the neural foundations of behavior. Such VR systems became very popular since theyallow the use of state-of-the-art techniques to measure neural activity in behaving rodents that can-not be easily used with classical behavior setups. Here, we provide an overview of rodent VR tech-nologies and review recent results from related research. We discuss commonalities and differ-ences as well as merits and issues of different approaches. A special focus is given to experimental（behavioral） paradigms in use. Finally we comment on possible use cases that may further exploitthe potential of VR in rodent research and hence inspire future studies.
基金supported by the Natural Science Foundation(Joint Fund)of Liaoning Provincial Science and Technology Department,No.2013022021
文摘It is difficult to control the degree of ischemic postconditioning in the brain and other isch- emia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on terminal organs. In this study, a focal cerebral ischemia-reperftlsion injury model was established using three cycles of remote ischernic postconditioning, each cycle consisted of 10-minute occlusion of the femoral artery and 10-minute opening. The results showed that, remote ischemic postconditioning significantly decreased the percentage of the in- farct area and attenuated brain edema. In addition, inflammatory nuclear factor-KB expression was significantly lower, while anti-apoptotic Bcl-2 expression was significantly elevated in the ce- rebral cortex on the ischemic side. Our findings indicate that remote ischemic postconditioning attenuates focal cerebral ischemia/reperfusion injury, and that the neuroprotective mechanism is mediated by an anti-apoptotic effect and reduction of the inflammatory response.
基金This study was supported by National Natural Science Foundation of China （81501054）, and Kejihuimin Project of Shandong Province （2014kjhm0101）.
文摘Objective To explore predictors of the 6-month clinical outcome ofthalamic hemorrhage, and evaluate if minimally invasive thalamic hematoma drainage （THD） could improve its prognosis. Methods A total of 54 patients with spontaneous thalamic hemorrhage were evaluated retrospectively. Clinical data, including demographics, stroke risk factors, neuroimaging variables, Glasgow Coma Score （GCS） on admission, surgical strategy, and outcome, were collected. Clinical outcome was assessed using a modified Rankin Scale, six months after onset. Univariate analysis and multivariate logistic regression analysis were performed to determine predictors of a poor outcome. Results Conservative treatnaent was performed for five patients （9.3%）, external ventricular drainage （EVD） for 20 patients （37.0%）, THD for four patients （7.4%）, and EVD combined with THD for 25 patients （46.3%）. At six months after onset, 21 （38.9%） patients achieved a favorable outcome, while 33 （61.1%） had a poor outcome. In the univariate analysis, predictors of poor 6-month outcome were lower GCS on admis- sion （P = 0.001）, larger hematoma volume （P 〈 0.001）, midline shift （P = 0.035）, acute hydrocephalus （P = 0.039）, and no THD （P = 0.037）. The independent predictors of poor outcome, according to the multivariate logistic regression analysis, were no THD and larger hematoma volume. Conclusions Minimally invasive THD, which removes most of the hematoma within a few days, with limited damage to perihematomal brain tissue, improved the 6-month outcome of thalamic hemorrhage. Thus, THD can be widely applied to treat patients with thalamic hemorrhage.
基金supported by Ministry of Education,Universities and Research(MIUR/FIRB)funding to PC
文摘The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor （NGF） al- terations in sporadic Alzheimer＇s disease （AD）, an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons （BFCN）, is one of the first homeostatic systems affected in prodromal AD. NGF signaling dysfunctions have been thought for decades to occur in AD late stages, as a mere consequence of amyloid-driven disruption of the retrograde axonal transport of neuro- trophins to BFCN. Nowadays, a wealth of knowledge is potentially opening a new scenario： NGF signaling impairment occurs at the onset of AD and correlates better than amyloid load with cognitive decline. The recent acceleration in the characterization of anatomical, functional and molecular profiles of early AD is aimed at maximizing the efficacy of existing treatments and setting novel therapies. Accordingly, the elucidation of the molecular events underlying APP metabolism regulation by the NGF pathway in the sep- to-hippocampal system is crucial for the identification of new target molecules to slow and eventually halt mild cognitive impairment （MCI） and its progression toward AD.
基金This work was supported by the Foundation of Zhejiang Provincial Basic Public Welfare Research Program of China,No.LGF19H090024(to XYX)the Natural Science Foundation of Zhejiang Province of China,No.LY17H090006(to WYL)National Natural Science foundation of China,No.81901073(to QBZ).
文摘Compared with other stem cells,human induced pluripotent stem cells-derived neural progenitor cells(iPSC-NPCs)are more similar to cortical neurons in morphology and immunohistochemistry.Thus,they have greater potential for promoting the survival and growth of neurons and alleviating the proliferation of astrocytes.Transplantation of stem cell exosomes and stem cells themselves have both been shown to effectively repair nerve injury.However,there is no study on the protective effects of exosomes derived from iPSC-NPCs on oxygen and glucose deprived neurons.In this study,we established an oxygen-glucose deprivation model in embryonic cortical neurons of the rat by culturing the neurons in an atmosphere of 95%N2 and 5%CO2 for 1 hour and then treated them with iPSC-NPC-derived exosomes for 30 minutes.Our results showed that iPSC-NPC-derived exosomes increased the survival of oxygen-and glucose-deprived neurons and the level of brain-derived neurotrophic factor in the culture medium.Additionally,it attenuated oxygen and glucose deprivation-induced changes in the expression of the PTEN/AKT signaling pathway as well as synaptic plasticity-related proteins in the neurons.Further,it increased the length of the longest neurite in the oxygen-and glucose-deprived neurons.These findings validate the hypothesis that exosomes from iPSCNPCs exhibit a neuroprotective effect on oxygen-and glucose-deprived neurons by regulating the PTEN/AKT signaling pathway and neurite outgrowth.This study was approved by the Animal Ethics Committee of Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,China(approval No.SRRSH20191010)on October 10,2019.
文摘Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation. In this study, 10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation and were used for the repair of left sciatic nerve defects through allograft bridging. Three days later, 1 mL ganglioside solution （1 g/L） was sub- cutaneously iniected into the right hind leg of rabbits. Compared with non-injected rats, muscle wet weight ratio was increased at 2-12 weeks after modeling. The quantity of myelinated fibers in regenerated sciatic nerve, myelin thickness and fiber diameter were elevated at 4-12 weeks after modeling. Sciatic nerve potential amplitude and conduction velocity were raised at 8 and 12 weeks, while conduction latencies were decreased at 12 weeks. Experimental findings indicate that ganglioside can promote the regeneration of sciatic nerve defects after repair with cryopre- served peripheral nerve allografts.
基金supported partly by grants from the National Institutes of Health,USA(NS081740 and NS082184)
文摘Autonomic disturbances often occur in patients with acute cerebrovascular disease due to damage of the central autonomic network. We summarize the structures of the central autonomic network and the clinical tests used to evaluate the functions of the autonomic nervous system.We review the clinical and experimental findings as well as management strategies of post-stroke autonomic disturbances including electrocardiographic changes, cardiac arrhythmias, myocardial damage, thermoregulatory dysfunction, gastrointestinal dysfunction, urinary incontinence, sexual disorders, and hyperglycemia. The occurrence of autonomic disturbances has been associated with poor outcomes in stroke patients. Autonomic nervous system modulation appears to be an emerging therapeutic strategy for stroke management in addition to treatments for sensorimotor dysfunction.
