Objective: To determine the effects of albumin administration on lung injury and apoptosis in traumatic/hemorrhagic shock (T/HS) rats. Methods: Studies were performed on an in vivo model of spontaneously breathing rat...Objective: To determine the effects of albumin administration on lung injury and apoptosis in traumatic/hemorrhagic shock (T/HS) rats. Methods: Studies were performed on an in vivo model of spontaneously breathing rats with induced T/HS; the rats were subjected to femur fracture, ischemia for 30 min, and reperfusion for 20 min with Ringer's lactate solution (RS) or 5% (w/v) albumin (ALB), and the left lower lobes of the lungs were resected. Results: Albumin administered during reperfusion markedly attenuated injury of the lung and decreased the concentration of lactic acid and the number of in situ TdT-mediated dUTP nick-end labelling (TUNEL)-positive cells. Moreover, immunohistochemistry performed 24 h after reperfusion revealed increases in the level of nuclear factor κB (NF-κB), and phosphorylated p38 mitogen-activated protein kinase (MAPK) in the albumin-untreated group was down-regulated by albumin treatment when compared with the sham rats. Conclusion: Resuscitation with albumin attenuates tissue injury and inhibits T/HS-induced apoptosis in the lung via the p38 MAPK signal transduction pathway that functions to stimulate the activation of NF-κB.展开更多
BACKGROUND:Patients suffering from hemorrhagic shock(HS)complicated by severe trauma are at high risk of developing acute lung injury(ALI)and acute respiratory distress syndrome(ARDS).The underlying pathophysiology is...BACKGROUND:Patients suffering from hemorrhagic shock(HS)complicated by severe trauma are at high risk of developing acute lung injury(ALI)and acute respiratory distress syndrome(ARDS).The underlying pathophysiology is complex,and the lack of targeted therapeutic strategies remains a major clinical challenge.METHODS:In this narrative review,a literature search was conducted in the PubMed to identify articles published from 2006 to August 2025 concerning trauma,HS,traumatic HS(THS),biomarkers related to ALI,ARDS and HS,as well as their treatment.Through its multifactorial pathogenesis,we discuss the diagnostic and prognostic values of biomarkers,their potential role in treatment,and therapeutic advancements and perspectives.RESULTS:ALI and ARDS are serious complications in severe trauma patients with HS.Hypoperfusion,hypoxia,endothelial cell activation,inflammation,ischemia/reperfusion injury and the intestinal response,as well as chest trauma and transfusion-related events are potential causes of lung injury.The pulmonary epithelial biomarkers soluble receptor for advanced glycation end products(sRAGE)and surfactant protein-D provide indicators for evaluating the severity of lung contusion and injury,whereas Clara cell protein 16 may have clinical value for trauma patients with ALI complicated by pneumonia.Elevated endothelial biomarkers angiopoietin-2 and syndecan-1 are correlated with injury severity,transfusion,coagulopathy,the onset of ARDS,and patient outcomes.The role of biomarkers in therapeutic benefit is reviewed.CONCLUSIONS:Preventive and therapeutic strategies for THS-induced ALI/ARDS rely on the implementation of multi-target,multi-mechanism interventions that address the complex pathophysiology.Targeted phenotypic therapy guided by biomarkers would be of interest for future research aimed at improving clinical outcomes.展开更多
Objective. To determine the effect of albumin administration on lung injury in traumatic/hemorrhagic shock （T/HS） rats. Methods： Forty-eight adult Sprague-Dawley rats were divided into three groups randomly （ n =...Objective. To determine the effect of albumin administration on lung injury in traumatic/hemorrhagic shock （T/HS） rats. Methods： Forty-eight adult Sprague-Dawley rats were divided into three groups randomly （ n = 16 in each group） ： Group A, Group B, Group C. In Group A, rats underwent laparotomy without shock. In Group B, rats undergoing T/HS were resuscitated with their blood plus lactated Ringer＇s （twice the volume of shed blood ）. In Group C, rats undergoing T/HS were resuscitated with their shed blood plus additional 3 ml of 5% human albumin. The expression of polymorphonuclear neutrophils CD18/CD11b in jugular vein blood was evaluated. The main lung injury indexes （the activity of myeloperoxidase and lung injury score） were measured. Results： Significant differences of the expression of CD18/11b and the severity degree of lung injury were found between the three groups. （P〈0.05）. The expression of CD18/CD11b and the main lung injury indexes in Group B and Goup C incresed significantly compared with those in Group A （P 〈0.05）. At the same time, the expression of CD18/CD11b and the main lung injury indexes in Group C decreased dramatically, compared with those in Group B （ P 〈0.05 ）. Conclusions ： The infusion of albumin during resuscitation period can protect lungs from injury and decrease the expression of CD18/CD11b in T/HS rats.展开更多
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the curr...Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
Traumatic brain injury(TBI)is a significant public health issue,affecting approximately 1.7 million people annually in the United States alone,with over 5 million experiencing long-term disabilities(Roozenbeek et al.,...Traumatic brain injury(TBI)is a significant public health issue,affecting approximately 1.7 million people annually in the United States alone,with over 5 million experiencing long-term disabilities(Roozenbeek et al.,2013).A major sequela of TBI is long-lasting white matter injury(WMI)which includes traumatic axonal injury and loss of myelination,resulting in cognitive,behavioral,and psychiatric deficits in survivors.展开更多
The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cel...The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cellular interactions and circuitry.Therapeutic interventions seek to modify some aspects of the injury course to enable the re-establishment of functional circuitry.Interventions often target one cell type(e.g.,promoting neuroprotection or neural regeneration)or one process(e.g.,modulating inflammation,affecting astrocytic,microglial,or macrophage responses.)Many axons in the spinal cord are myelinated,and after injury oligodendrocyte death causes demyelination.Promoting remyelination of spared or new axons to re-establish conduction seems a logical choice as a therapeutic target.展开更多
BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in m...BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in many biological processes that supports cellular homeostasis,including the inhibition of apoptosis by preventing mitochondrial BAX localization(Lin et al.,2022)and the promotion of the degradation of hyperphosphorylated tau aggregates by its interactions with SQSTM1(p62)(Hamano and Mutoh,2022).展开更多
AIM:To evaluate the clinical features,diagnosis,treatment,and outcome of peripheral exudative hemorrhagic chorioretinopathy(PEHCR),a variant of polypoidal choroidal vasculopathy(PCV),in a case series of Chinese patien...AIM:To evaluate the clinical features,diagnosis,treatment,and outcome of peripheral exudative hemorrhagic chorioretinopathy(PEHCR),a variant of polypoidal choroidal vasculopathy(PCV),in a case series of Chinese patients.METHODS:This study was retrospectively conducted from September 2018 to March 2025.Clinical examinations included color fundus photography,B-scan ultrasonography,fluorescein angiography(FA),indocyanine green angiography(ICGA),swept-source optical coherence tomography(SS-OCT),and optical coherence tomography angiography(OCTA),and two active or inactive subgroups and misdiagnosed cases were analyzed.RESULTS:Totally 19 patients(21 eyes)with a mean age of 54.3±9.4(range,36–68)y were included,with a majority of women(n=13,68.4%).The mean follow-up period was 13±1.4(range:1–57)mo.Decreased visual acuity was the most frequent initial manifestation(17 eyes,84.2%),and lesions were mainly distributed in the inferotemporal or temporal quadrant(14 eyes,66.7%),with choroidal polyps and branching neovascular networks revealed by OCTA and ICGA.Nine patients had been previously misdiagnosed with choroidal melanoma,and 6 of them had massive vitreous hemorrhage(VH).PEHCR manifested along a spectrum ranging from active or inactive subretinal hemorrhagic forms to chronic fibrotic or atrophic forms.One patient experienced natural regression.Ten eyes received a mean of 4.7±1.1(range:3–7)intravitreal anti-vascular endothelial growth factor(VEGF)injections,two eyes underwent vitrectomy,and six eyes were treated with vitrectomy combined with anti-VEGF therapy.Best-corrected visual acuity(logMAR)in treated eyes(18 eyes)improved to 0.31±0.25 from the baseline of 1.50±0.75(P<0.001).CONCLUSION:PEHCR is a variant of PCV.Chinese patients with PEHCR have a relatively younger age of onset.Anti-VEGF injections and/or vitrectomy are treatment options for lesion regression or dense VH to gain better visual outcomes.展开更多
The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiqui...The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.展开更多
Dear Editor,Acute subhyaloid hemorrhage causes sudden profound vision loss in the macular region.This is a term that designates ocular hemorrhages lying between the posterior hyaloid membrane and the retina,often pres...Dear Editor,Acute subhyaloid hemorrhage causes sudden profound vision loss in the macular region.This is a term that designates ocular hemorrhages lying between the posterior hyaloid membrane and the retina,often presented as a‘boat’or‘D’shaped hemorrhage[1].The development of optical coherence tomography(OCT)had enabled detailed differentiation of subhyaloid hemorrhage,allowing the term sub-internal limiting membrane(ILM)hemorrhage to be applied in selected cases where the blood is located beneath the ILM[1-2].However,it is not always possible to distinguish the location of the hemorrhage due to the attenuation of the retinal structures on OCT.Accordingly,subhyaloid hemorrhage remains a widely used term,implying both subhyaloid and sub-ILM hemorrhage[1].展开更多
AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trau...AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trauma patients.METHODS:A retrospective,multicenter interventional case series involving 7 eyes of 7 patients who underwent PPV with subretinal tPA administration for SMH secondary to closed-globe injury were conducted.The primary outcome measure was the change in Snellen visual acuity.RESULTS:The mean age of patients was 32y(range:21-51y),with a mean follow-up duration of 4.6mo(range:1.1-14.9mo).The average best-corrected visual acuity(BCVA)was 20/1020 at baseline and 20/114 at the final visit,respectively(P=0.025).Preoperative BCVA was not a significant predictor of final BCVA(r=0.102,P=0.827).Final BCVA did not differ significantly between patients who underwent PPV within 14d of symptom onset and those who underwent surgery after 14d(P=0.57).All eyes received SF6 or C3F8 gas tamponade.CONCLUSION:Surgical intervention involving tPAmediated clot lysis and pneumatic displacement may yield visual benefits in trauma-induced SMH without underlying retinal vascular disease;however,larger prospective studies are warranted to confirm these findings.展开更多
Objective: to explore the effect of emergency nursing on patients with severe traumatic hemorrhagic shock. Methods: 100 patients with severe traumatic hemorrhagic shock were selected for group nursing, the control gro...Objective: to explore the effect of emergency nursing on patients with severe traumatic hemorrhagic shock. Methods: 100 patients with severe traumatic hemorrhagic shock were selected for group nursing, the control group for routine nursing, and the experimental group for emergency nursing. The clinical data of the two groups were observed. Results: the rescue success rate and nursing satisfaction of the experimental group were higher than those of the control group (P < 0.05), and the incidence of complications, the whole operation time and the stay time in the emergency department were lower than those of the control group (P < 0.05).Conclusion: emergency nursing for patients with severe traumatic shock can effectively improve the success rate of rescue and reduce the incidence of complications.展开更多
Objective:To analyze the value of emergency rescue nursing intervention in the care of patients with traumatic hemorrhagic shock and its impact on the success rate of rescue efforts.Methods:A total of 80 patients with...Objective:To analyze the value of emergency rescue nursing intervention in the care of patients with traumatic hemorrhagic shock and its impact on the success rate of rescue efforts.Methods:A total of 80 patients with traumatic hemorrhagic shock were selected as samples,with the timeframe from July 2022 to July 2023.The patients were randomly divided into two groups using a random number table method.Group A received emergency rescue nursing,while Group B received routine nursing care.The success rate of rescue,rescue indicators,complication rates,and family satisfaction with nursing care were compared between the two groups.Results:The rescue success rate in Group A was higher than in Group B(P<0.05);the total blood loss in Group A was less,and the rescue time,full transportation time,and hospitalization time were shorter than in Group B(P<0.05);the complication rate of patients with traumatic hemorrhagic shock in Group A was lower than in Group B(P<0.05);the family satisfaction with emergency nursing care in Group A was higher than in Group B(P<0.05).Conclusion:Emergency rescue interventions for patients with traumatic hemorrhagic shock can reduce blood loss,shorten rescue times,and improve the success rate of shock rescue,providing a safe and effective approach.展开更多
Objective: to explore the clinical value of emergency nursing intervention in patients with severe traumatic hemorrhagic shock, and then to understand the treatment of various complications of patients. Methods: the o...Objective: to explore the clinical value of emergency nursing intervention in patients with severe traumatic hemorrhagic shock, and then to understand the treatment of various complications of patients. Methods: the objective of the study was to select 80 patients with traumatic hemorrhagic shock and divide them into groups. Results: after receiving different nursing, the shock improvement and complications of the observation group were better than the control group, P < 0.05. Conclusion: using emergency nursing intervention for patients with shock and strengthening the prevention of complications can significantly improve the success rate of rescue, reduce the occurrence of various complications, and effectively improve the prognosis of patients, which has a good application value.展开更多
Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela ...Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.展开更多
Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary injury.Withi...Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary injury.Within minutes of TBI,a neuroinflammatory response is triggered,driven by intricate molecular and cellular inflammatory processes.展开更多
Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for pati...Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”展开更多
Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In ...Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.展开更多
基金Project supported by the National Natural Science Foundation of China (No. 30672071) the Traditional Chinese Medicine Foun- dation of Zhejiang Province, China (No. 2004C071)
文摘Objective: To determine the effects of albumin administration on lung injury and apoptosis in traumatic/hemorrhagic shock (T/HS) rats. Methods: Studies were performed on an in vivo model of spontaneously breathing rats with induced T/HS; the rats were subjected to femur fracture, ischemia for 30 min, and reperfusion for 20 min with Ringer's lactate solution (RS) or 5% (w/v) albumin (ALB), and the left lower lobes of the lungs were resected. Results: Albumin administered during reperfusion markedly attenuated injury of the lung and decreased the concentration of lactic acid and the number of in situ TdT-mediated dUTP nick-end labelling (TUNEL)-positive cells. Moreover, immunohistochemistry performed 24 h after reperfusion revealed increases in the level of nuclear factor κB (NF-κB), and phosphorylated p38 mitogen-activated protein kinase (MAPK) in the albumin-untreated group was down-regulated by albumin treatment when compared with the sham rats. Conclusion: Resuscitation with albumin attenuates tissue injury and inhibits T/HS-induced apoptosis in the lung via the p38 MAPK signal transduction pathway that functions to stimulate the activation of NF-κB.
基金supported by grants from the Zhejiang Provincial Key Research and Development Program of China(2023C03085).
文摘BACKGROUND:Patients suffering from hemorrhagic shock(HS)complicated by severe trauma are at high risk of developing acute lung injury(ALI)and acute respiratory distress syndrome(ARDS).The underlying pathophysiology is complex,and the lack of targeted therapeutic strategies remains a major clinical challenge.METHODS:In this narrative review,a literature search was conducted in the PubMed to identify articles published from 2006 to August 2025 concerning trauma,HS,traumatic HS(THS),biomarkers related to ALI,ARDS and HS,as well as their treatment.Through its multifactorial pathogenesis,we discuss the diagnostic and prognostic values of biomarkers,their potential role in treatment,and therapeutic advancements and perspectives.RESULTS:ALI and ARDS are serious complications in severe trauma patients with HS.Hypoperfusion,hypoxia,endothelial cell activation,inflammation,ischemia/reperfusion injury and the intestinal response,as well as chest trauma and transfusion-related events are potential causes of lung injury.The pulmonary epithelial biomarkers soluble receptor for advanced glycation end products(sRAGE)and surfactant protein-D provide indicators for evaluating the severity of lung contusion and injury,whereas Clara cell protein 16 may have clinical value for trauma patients with ALI complicated by pneumonia.Elevated endothelial biomarkers angiopoietin-2 and syndecan-1 are correlated with injury severity,transfusion,coagulopathy,the onset of ARDS,and patient outcomes.The role of biomarkers in therapeutic benefit is reviewed.CONCLUSIONS:Preventive and therapeutic strategies for THS-induced ALI/ARDS rely on the implementation of multi-target,multi-mechanism interventions that address the complex pathophysiology.Targeted phenotypic therapy guided by biomarkers would be of interest for future research aimed at improving clinical outcomes.
文摘Objective. To determine the effect of albumin administration on lung injury in traumatic/hemorrhagic shock （T/HS） rats. Methods： Forty-eight adult Sprague-Dawley rats were divided into three groups randomly （ n = 16 in each group） ： Group A, Group B, Group C. In Group A, rats underwent laparotomy without shock. In Group B, rats undergoing T/HS were resuscitated with their blood plus lactated Ringer＇s （twice the volume of shed blood ）. In Group C, rats undergoing T/HS were resuscitated with their shed blood plus additional 3 ml of 5% human albumin. The expression of polymorphonuclear neutrophils CD18/CD11b in jugular vein blood was evaluated. The main lung injury indexes （the activity of myeloperoxidase and lung injury score） were measured. Results： Significant differences of the expression of CD18/11b and the severity degree of lung injury were found between the three groups. （P〈0.05）. The expression of CD18/CD11b and the main lung injury indexes in Group B and Goup C incresed significantly compared with those in Group A （P 〈0.05）. At the same time, the expression of CD18/CD11b and the main lung injury indexes in Group C decreased dramatically, compared with those in Group B （ P 〈0.05 ）. Conclusions ： The infusion of albumin during resuscitation period can protect lungs from injury and decrease the expression of CD18/CD11b in T/HS rats.
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
基金supported by Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZhao).
文摘Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
文摘Traumatic brain injury(TBI)is a significant public health issue,affecting approximately 1.7 million people annually in the United States alone,with over 5 million experiencing long-term disabilities(Roozenbeek et al.,2013).A major sequela of TBI is long-lasting white matter injury(WMI)which includes traumatic axonal injury and loss of myelination,resulting in cognitive,behavioral,and psychiatric deficits in survivors.
基金supported by Grant 3195 from Paralyzed Veterans of America Research Foundation(to BRK).WT holds the Edie Ehlers Chair in spinal cord injury.
文摘The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cellular interactions and circuitry.Therapeutic interventions seek to modify some aspects of the injury course to enable the re-establishment of functional circuitry.Interventions often target one cell type(e.g.,promoting neuroprotection or neural regeneration)or one process(e.g.,modulating inflammation,affecting astrocytic,microglial,or macrophage responses.)Many axons in the spinal cord are myelinated,and after injury oligodendrocyte death causes demyelination.Promoting remyelination of spared or new axons to re-establish conduction seems a logical choice as a therapeutic target.
基金supported by the awardW81XWH1910309(to HF)from the Department ofDefense,the award R01-AG075092-01(to HF)the award RF1AG063521 from the National Instituteof Aging at the National Institutes of Health,theNeurological Research Institute Seed grant(to HF)from The Ohio State University,and the SummerUndergraduate Research Fellowship(to NS)from TheOhio State University Chronic Brain Injury DiscoveryTheme.
文摘BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in many biological processes that supports cellular homeostasis,including the inhibition of apoptosis by preventing mitochondrial BAX localization(Lin et al.,2022)and the promotion of the degradation of hyperphosphorylated tau aggregates by its interactions with SQSTM1(p62)(Hamano and Mutoh,2022).
基金Supported by the National Natural Science Foundation of China(No.82220108017,No.82141128)The Capital Health Research and Development of Special(No.2024-1-2052)+1 种基金Science&Technology Project of Beijing Municipal Science&Technology Commission(No.Z201100005520045)Sanming Project of Medicine in Shenzhen(No.SZSM202311018)。
文摘AIM:To evaluate the clinical features,diagnosis,treatment,and outcome of peripheral exudative hemorrhagic chorioretinopathy(PEHCR),a variant of polypoidal choroidal vasculopathy(PCV),in a case series of Chinese patients.METHODS:This study was retrospectively conducted from September 2018 to March 2025.Clinical examinations included color fundus photography,B-scan ultrasonography,fluorescein angiography(FA),indocyanine green angiography(ICGA),swept-source optical coherence tomography(SS-OCT),and optical coherence tomography angiography(OCTA),and two active or inactive subgroups and misdiagnosed cases were analyzed.RESULTS:Totally 19 patients(21 eyes)with a mean age of 54.3±9.4(range,36–68)y were included,with a majority of women(n=13,68.4%).The mean follow-up period was 13±1.4(range:1–57)mo.Decreased visual acuity was the most frequent initial manifestation(17 eyes,84.2%),and lesions were mainly distributed in the inferotemporal or temporal quadrant(14 eyes,66.7%),with choroidal polyps and branching neovascular networks revealed by OCTA and ICGA.Nine patients had been previously misdiagnosed with choroidal melanoma,and 6 of them had massive vitreous hemorrhage(VH).PEHCR manifested along a spectrum ranging from active or inactive subretinal hemorrhagic forms to chronic fibrotic or atrophic forms.One patient experienced natural regression.Ten eyes received a mean of 4.7±1.1(range:3–7)intravitreal anti-vascular endothelial growth factor(VEGF)injections,two eyes underwent vitrectomy,and six eyes were treated with vitrectomy combined with anti-VEGF therapy.Best-corrected visual acuity(logMAR)in treated eyes(18 eyes)improved to 0.31±0.25 from the baseline of 1.50±0.75(P<0.001).CONCLUSION:PEHCR is a variant of PCV.Chinese patients with PEHCR have a relatively younger age of onset.Anti-VEGF injections and/or vitrectomy are treatment options for lesion regression or dense VH to gain better visual outcomes.
基金supported by grants from the Major Projects of Health Science Research Foundation for Middle-Aged and Young Scientist of Fujian Province,China,No.2022ZQNZD01010010the National Natural Science Foundation of China,No.82371390Fujian Province Scientific Foundation,No.2023J01725(all to XC).
文摘The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury.The post-transcriptional modification of N^(6)-methyladenosine is ubiquitous in the immune response of the central nervous system.The fat mass and obesity-related protein catalyzes the demethylation of N^(6)-methyladenosine modifications on mRNA and is widely expressed in various tissues,participating in the regulation of multiple diseases’biological processes.However,the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear.In this study,we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model.After fat mass and obesity interference,BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b^(+)/CD86^(+)cells and the secretion of pro-inflammatory cytokines.Fat mass and obesity-mediated N^(6)-methyladenosine demethylation accelerated the degradation of ADAM17 mRNA,while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA.Therefore,down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia.These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N^(6)-methyladenosine modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.
文摘Dear Editor,Acute subhyaloid hemorrhage causes sudden profound vision loss in the macular region.This is a term that designates ocular hemorrhages lying between the posterior hyaloid membrane and the retina,often presented as a‘boat’or‘D’shaped hemorrhage[1].The development of optical coherence tomography(OCT)had enabled detailed differentiation of subhyaloid hemorrhage,allowing the term sub-internal limiting membrane(ILM)hemorrhage to be applied in selected cases where the blood is located beneath the ILM[1-2].However,it is not always possible to distinguish the location of the hemorrhage due to the attenuation of the retinal structures on OCT.Accordingly,subhyaloid hemorrhage remains a widely used term,implying both subhyaloid and sub-ILM hemorrhage[1].
基金Supportea by DeNardo Education and Research Foundation GrantJeffrey T.Fort Innovation Fund+3 种基金Siteman Retina Research FundResearch to Prevent Blindness IncGetahun H is supported by Washington University in St.Louis School of Medicine Dean’s Medical Student Research Fellowship for the MD5 Yearlong Research ProgramGetahun H is also a recipient of a Research to Prevent Blindness Medical Student Eye Research Fellowship.
文摘AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trauma patients.METHODS:A retrospective,multicenter interventional case series involving 7 eyes of 7 patients who underwent PPV with subretinal tPA administration for SMH secondary to closed-globe injury were conducted.The primary outcome measure was the change in Snellen visual acuity.RESULTS:The mean age of patients was 32y(range:21-51y),with a mean follow-up duration of 4.6mo(range:1.1-14.9mo).The average best-corrected visual acuity(BCVA)was 20/1020 at baseline and 20/114 at the final visit,respectively(P=0.025).Preoperative BCVA was not a significant predictor of final BCVA(r=0.102,P=0.827).Final BCVA did not differ significantly between patients who underwent PPV within 14d of symptom onset and those who underwent surgery after 14d(P=0.57).All eyes received SF6 or C3F8 gas tamponade.CONCLUSION:Surgical intervention involving tPAmediated clot lysis and pneumatic displacement may yield visual benefits in trauma-induced SMH without underlying retinal vascular disease;however,larger prospective studies are warranted to confirm these findings.
文摘Objective: to explore the effect of emergency nursing on patients with severe traumatic hemorrhagic shock. Methods: 100 patients with severe traumatic hemorrhagic shock were selected for group nursing, the control group for routine nursing, and the experimental group for emergency nursing. The clinical data of the two groups were observed. Results: the rescue success rate and nursing satisfaction of the experimental group were higher than those of the control group (P < 0.05), and the incidence of complications, the whole operation time and the stay time in the emergency department were lower than those of the control group (P < 0.05).Conclusion: emergency nursing for patients with severe traumatic shock can effectively improve the success rate of rescue and reduce the incidence of complications.
文摘Objective:To analyze the value of emergency rescue nursing intervention in the care of patients with traumatic hemorrhagic shock and its impact on the success rate of rescue efforts.Methods:A total of 80 patients with traumatic hemorrhagic shock were selected as samples,with the timeframe from July 2022 to July 2023.The patients were randomly divided into two groups using a random number table method.Group A received emergency rescue nursing,while Group B received routine nursing care.The success rate of rescue,rescue indicators,complication rates,and family satisfaction with nursing care were compared between the two groups.Results:The rescue success rate in Group A was higher than in Group B(P<0.05);the total blood loss in Group A was less,and the rescue time,full transportation time,and hospitalization time were shorter than in Group B(P<0.05);the complication rate of patients with traumatic hemorrhagic shock in Group A was lower than in Group B(P<0.05);the family satisfaction with emergency nursing care in Group A was higher than in Group B(P<0.05).Conclusion:Emergency rescue interventions for patients with traumatic hemorrhagic shock can reduce blood loss,shorten rescue times,and improve the success rate of shock rescue,providing a safe and effective approach.
文摘Objective: to explore the clinical value of emergency nursing intervention in patients with severe traumatic hemorrhagic shock, and then to understand the treatment of various complications of patients. Methods: the objective of the study was to select 80 patients with traumatic hemorrhagic shock and divide them into groups. Results: after receiving different nursing, the shock improvement and complications of the observation group were better than the control group, P < 0.05. Conclusion: using emergency nursing intervention for patients with shock and strengthening the prevention of complications can significantly improve the success rate of rescue, reduce the occurrence of various complications, and effectively improve the prognosis of patients, which has a good application value.
文摘Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.
基金FEDER Prostem Research Project,No.1510614(Wallonia DG06)the F.R.S.-FNRS Epiforce Project,No.T.0092.21+4 种基金the F.R.S.-FNRS Cell Squeezer Project,No.J.0061.23the F.R.S.-FNRS Optopattern Project,No.U.NO26.22the Interreg MAT(T)ISSE Project,which is financially supported by Interreg France-Wallonie-Vlaanderen(Fonds Européen de Développement Régional,FEDER-ERDF)Programme Wallon d’Investissement Région Wallone pour les instruments d’imagerie(INSTIMAG UMONS#1910169)support from the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation programme(AdG grant agreement no.834317,Fueling Transport,PI Frédéric Saudou)。
文摘Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary injury.Within minutes of TBI,a neuroinflammatory response is triggered,driven by intricate molecular and cellular inflammatory processes.
基金supported by the National Natural Science Foundation of China,No.82174112(to PZ)Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,No.22HHZYSS00015(to PZ)State-Sponsored Postdoctoral Researcher Program,No.GZC20231925(to LN)。
文摘Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”
基金supported by the Fundamental Research Program of Shanxi Province of China,No.20210302124277the Science Foundation of Shanxi Bethune Hospital,No.2021YJ13(both to JW)。
文摘Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.
