Carbon monoxide-from toxicity to therapeutic potential:Carbon monoxide(CO)has long been known as a toxic gas,primarily associated with environmental pollution and poisoning.Its strong affinity for hemoglobin causes th...Carbon monoxide-from toxicity to therapeutic potential:Carbon monoxide(CO)has long been known as a toxic gas,primarily associated with environmental pollution and poisoning.Its strong affinity for hemoglobin causes the formation of carboxyhemoglobin,which reduces oxygen delivery to the tissues and organs and leads to hypoxia.Despite its well-documented toxicity,previous studies have confirmed that CO also acts as a signaling molecule in the body and plays important physiological roles(Motterlini and Otterbein,2010).展开更多
A 60-year-old female with post-concussion syndrome (PCS) presented with persistent cognitive deficits and functional limitations following a slip and fall. She underwent a multimodal therapeutic protocol including hyp...A 60-year-old female with post-concussion syndrome (PCS) presented with persistent cognitive deficits and functional limitations following a slip and fall. She underwent a multimodal therapeutic protocol including hyperbaric therapy (HBT), photobiomodulation (PBM), and molecular hydrogen (MH) therapy over 10 sessions. Pre- and post-treatment assessments demonstrated significant improvements in cognitive function and neurophysiological markers, as evidenced by WAVi EEG and Trail Making Test (TMT) results. This case highlights the potential of a non-invasive, multimodal therapeutic approach to address persistent post-concussion symptoms, an area with limited effective interventions. Findings suggest that integrating these therapies into standard rehabilitation protocols may enhance recovery trajectories, particularly for patients with persistent cognitive symptoms. This case report explores the clinical course, treatment efficacy, and the potential for combining these therapies in addressing complex neurological recovery.展开更多
The blood-brain barrier(BBB)is a highly selective permeability barrier that safeguards the central nervous system(CNS)from potentially harmful substances while regulating the transport of essential molecules.Its dysfu...The blood-brain barrier(BBB)is a highly selective permeability barrier that safeguards the central nervous system(CNS)from potentially harmful substances while regulating the transport of essential molecules.Its dysfunction is increasingly recognized as a pivotal factor in the pathogenesis of Alzheimer's disease(AD),contributing to the accumulation of amyloid-β(Aβ)plaques.We present a novel therapeutic strategy that targets low-density lipoprotein receptor-related protein 1(LRP1)on the BBB.Our design leverages the multivalent nature and precise size of LRP1-targeted polymersomes to modulate receptor-mediated transport,biasing LRP1 trafficking toward transcytosis and thereby upregulating its expression to promote efficient Aβremoval.In AD model mice,this intervention significantly reduced brain Aβlevels by nearly 45%and increased plasma Aβlevels by 8-fold within 2 h,as measured by ELISA.Multiple imaging techniques confirmed the reduction in brain Aβsignals after treatment.Cognitive assessments revealed that treated AD mice exhibited significant improvements in spatial learning and memory,with performance levels comparable to those of wild-type mice.These cognitive benefits persisted for up to 6 months post-treatment.This work pioneers a new paradigm in drug design,where function arises from the supramolecular nature of the nanomedicine,harnessing multivalency to elicit biological action at the membrane trafficking level.Our findings also reaffirm the critical role of the BBB in AD pathogenesis and demonstrate that targeting the BBB can make therapeutic interventions significantly more effective.We establish a compelling case for BBB modulation and LRP1-mediated Aβclearance as a transformative foundation for future AD therapies.展开更多
This case report examines the impact of mild hyperbaric oxygen therapy (mHBOT) on cognitive function and symptom relief in a 35-year-old male presenting with concussive symptoms (CS) following a motor vehicle accident...This case report examines the impact of mild hyperbaric oxygen therapy (mHBOT) on cognitive function and symptom relief in a 35-year-old male presenting with concussive symptoms (CS) following a motor vehicle accident (MVA). The patient underwent 10 mHBOT sessions over five weeks (40 minutes per session at 1.5 ATA with 32% oxygen). Post-treatment assessments revealed significant improvements, including an increase in P300 voltage from 4.2 µV to 9.2 µV, aligning with the normative range of 8 - 21 µV. Electroencephalogram (EEG) analysis demonstrated enhanced alpha and theta band activity, reflecting improved cognitive processing and attentional regulation. Clinically, the patient reported reduced headache severity, improved sleep quality, and decreased pain intensity. These findings suggest that mHBOT may support neuroplasticity, mitigate inflammation, and restore cognitive function in patients with CS. Further research, including randomized controlled trials (RCTs), is warranted to validate mHBOT’s efficacy and explore its long-term benefits in traumatic brain injury (TBI) rehabilitation.展开更多
Deep cervical lymph-venous anastomosis(LVA)is a surgical procedure initially developed to treat cervical lymphatic obstruction,such as lymphedema,a condition caused by the accumulation of lymphatic fluid due to blocke...Deep cervical lymph-venous anastomosis(LVA)is a surgical procedure initially developed to treat cervical lymphatic obstruction,such as lymphedema,a condition caused by the accumulation of lymphatic fluid due to blocked or damaged lymphatic vessels.In early 2024,Dr.Qingping Xie from Hangzhou Qiushi Hospital,China,and Dr.Wei F.Chen from the Cleveland Clinic,USA,adapted LVA for the treatment of patients with Alzheimer’s disease(AD).As a VIEWPOINT,they presented a video showcasing the post-surgery cognitive recovery of an 84-year-old AD patient(Xie et al.,2024).展开更多
Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes af...Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.展开更多
Stem cell therapy shows promise for treating brain injuries;neural stem cells in particular are capable of repairing damage by forming new nerve cells and supporting recovery.However,optimizing the implantation and fu...Stem cell therapy shows promise for treating brain injuries;neural stem cells in particular are capable of repairing damage by forming new nerve cells and supporting recovery.However,optimizing the implantation and functionality of these cells in damaged brain regions remains challenging.Silk fibroin,a natural protein derived from silkworm silk,is a biocompatible material with exceptional properties that are useful for tissue engineering.Its biodegradability,mechanical robustness,and ability to promote cell growth make it particularly valuable for biomedical applications.Silk fibroin nanomaterials,which comprise silk fibroin processed into nanostructures,offer enhanced surface area,improved loading capacity for bioactive molecules,and superior nanoscale interactions with cells compared with bulk silk fibroin materials.In this study,we first extracted human-derived neural stem cells from a 14-week-old human fetus.Then,neural stem cells were loaded with 1%silk fibroin nanomaterials,which was identified as the optimal concentration to support human-derived neural stem cell growth and release of neurotrophic factors.Finally,1%silk fibroin nanomaterials were implanted into a rat model of hypoxic-ischemic brain injury.The results showed that,compared with the treatment with human-derived neural stem cells alone,silk fibroin hydrogel carrying human-derived neural stem cells was significantly more effective at alleviating brain tissue damage,increasing neurotrophic factor secretion in the brain microenvironment,and promoting motor and cognitive function recovery.These findings suggest that silk fibroin nanomaterials loaded with human-derived neural stem cells could be used to treat hypoxic-ischemic encephalopathy.However,the mechanisms and related signaling pathways by which hydrogels combined with cells exert their reparative effects still require further in-depth investigation.展开更多
基金supported in part by the NIH(R01NS113556,to KA).
文摘Carbon monoxide-from toxicity to therapeutic potential:Carbon monoxide(CO)has long been known as a toxic gas,primarily associated with environmental pollution and poisoning.Its strong affinity for hemoglobin causes the formation of carboxyhemoglobin,which reduces oxygen delivery to the tissues and organs and leads to hypoxia.Despite its well-documented toxicity,previous studies have confirmed that CO also acts as a signaling molecule in the body and plays important physiological roles(Motterlini and Otterbein,2010).
文摘A 60-year-old female with post-concussion syndrome (PCS) presented with persistent cognitive deficits and functional limitations following a slip and fall. She underwent a multimodal therapeutic protocol including hyperbaric therapy (HBT), photobiomodulation (PBM), and molecular hydrogen (MH) therapy over 10 sessions. Pre- and post-treatment assessments demonstrated significant improvements in cognitive function and neurophysiological markers, as evidenced by WAVi EEG and Trail Making Test (TMT) results. This case highlights the potential of a non-invasive, multimodal therapeutic approach to address persistent post-concussion symptoms, an area with limited effective interventions. Findings suggest that integrating these therapies into standard rehabilitation protocols may enhance recovery trajectories, particularly for patients with persistent cognitive symptoms. This case report explores the clinical course, treatment efficacy, and the potential for combining these therapies in addressing complex neurological recovery.
基金supported by the National Key R&D Program of China(2022YFC2009900)the Alzheimer’s Association New to the Field award,ERC Consolidator grant H2020-ERC-2018-CoG(769798 CheSSTag)+1 种基金the Plan de Recuperacion Nacional Biotech for Health Project(ADNano),Activitat científica dels grups de recerca de Catalunya(SGR-Cat 2021)the Spanish Research Agency Proyectos I+D+I PID2020-119914RB-I00。
文摘The blood-brain barrier(BBB)is a highly selective permeability barrier that safeguards the central nervous system(CNS)from potentially harmful substances while regulating the transport of essential molecules.Its dysfunction is increasingly recognized as a pivotal factor in the pathogenesis of Alzheimer's disease(AD),contributing to the accumulation of amyloid-β(Aβ)plaques.We present a novel therapeutic strategy that targets low-density lipoprotein receptor-related protein 1(LRP1)on the BBB.Our design leverages the multivalent nature and precise size of LRP1-targeted polymersomes to modulate receptor-mediated transport,biasing LRP1 trafficking toward transcytosis and thereby upregulating its expression to promote efficient Aβremoval.In AD model mice,this intervention significantly reduced brain Aβlevels by nearly 45%and increased plasma Aβlevels by 8-fold within 2 h,as measured by ELISA.Multiple imaging techniques confirmed the reduction in brain Aβsignals after treatment.Cognitive assessments revealed that treated AD mice exhibited significant improvements in spatial learning and memory,with performance levels comparable to those of wild-type mice.These cognitive benefits persisted for up to 6 months post-treatment.This work pioneers a new paradigm in drug design,where function arises from the supramolecular nature of the nanomedicine,harnessing multivalency to elicit biological action at the membrane trafficking level.Our findings also reaffirm the critical role of the BBB in AD pathogenesis and demonstrate that targeting the BBB can make therapeutic interventions significantly more effective.We establish a compelling case for BBB modulation and LRP1-mediated Aβclearance as a transformative foundation for future AD therapies.
文摘This case report examines the impact of mild hyperbaric oxygen therapy (mHBOT) on cognitive function and symptom relief in a 35-year-old male presenting with concussive symptoms (CS) following a motor vehicle accident (MVA). The patient underwent 10 mHBOT sessions over five weeks (40 minutes per session at 1.5 ATA with 32% oxygen). Post-treatment assessments revealed significant improvements, including an increase in P300 voltage from 4.2 µV to 9.2 µV, aligning with the normative range of 8 - 21 µV. Electroencephalogram (EEG) analysis demonstrated enhanced alpha and theta band activity, reflecting improved cognitive processing and attentional regulation. Clinically, the patient reported reduced headache severity, improved sleep quality, and decreased pain intensity. These findings suggest that mHBOT may support neuroplasticity, mitigate inflammation, and restore cognitive function in patients with CS. Further research, including randomized controlled trials (RCTs), is warranted to validate mHBOT’s efficacy and explore its long-term benefits in traumatic brain injury (TBI) rehabilitation.
基金supported by AG057842 from the National Institutes of Health,TRIBA/Physiology Faculty Startup Fund from Augusta University (to FF)the National Natural Science Foundation of China (82173384)(to MG)
文摘Deep cervical lymph-venous anastomosis(LVA)is a surgical procedure initially developed to treat cervical lymphatic obstruction,such as lymphedema,a condition caused by the accumulation of lymphatic fluid due to blocked or damaged lymphatic vessels.In early 2024,Dr.Qingping Xie from Hangzhou Qiushi Hospital,China,and Dr.Wei F.Chen from the Cleveland Clinic,USA,adapted LVA for the treatment of patients with Alzheimer’s disease(AD).As a VIEWPOINT,they presented a video showcasing the post-surgery cognitive recovery of an 84-year-old AD patient(Xie et al.,2024).
基金supported by NIH grants RF1 AG069466(to JL and LDM),R01 NS099628(to JL),and AG069466(to JL and LDM)the American Heart Association award 20POST35180172(to FB)。
文摘Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.
基金Dalian Science and Technology Talent Innovation Support Policy Implementation Plan High-Level Talent Team,No.2022RG18(to JL)the Science and Technology Plan Orientation of Liaoning Province,No.[2021]49(to JL)+1 种基金Dalian High-Level Talent Innovation Support Plan,No.2021RQ028(to CH)Natural Science Foundation of Liaoning Province,No.2022-BS-238(to CH).
文摘Stem cell therapy shows promise for treating brain injuries;neural stem cells in particular are capable of repairing damage by forming new nerve cells and supporting recovery.However,optimizing the implantation and functionality of these cells in damaged brain regions remains challenging.Silk fibroin,a natural protein derived from silkworm silk,is a biocompatible material with exceptional properties that are useful for tissue engineering.Its biodegradability,mechanical robustness,and ability to promote cell growth make it particularly valuable for biomedical applications.Silk fibroin nanomaterials,which comprise silk fibroin processed into nanostructures,offer enhanced surface area,improved loading capacity for bioactive molecules,and superior nanoscale interactions with cells compared with bulk silk fibroin materials.In this study,we first extracted human-derived neural stem cells from a 14-week-old human fetus.Then,neural stem cells were loaded with 1%silk fibroin nanomaterials,which was identified as the optimal concentration to support human-derived neural stem cell growth and release of neurotrophic factors.Finally,1%silk fibroin nanomaterials were implanted into a rat model of hypoxic-ischemic brain injury.The results showed that,compared with the treatment with human-derived neural stem cells alone,silk fibroin hydrogel carrying human-derived neural stem cells was significantly more effective at alleviating brain tissue damage,increasing neurotrophic factor secretion in the brain microenvironment,and promoting motor and cognitive function recovery.These findings suggest that silk fibroin nanomaterials loaded with human-derived neural stem cells could be used to treat hypoxic-ischemic encephalopathy.However,the mechanisms and related signaling pathways by which hydrogels combined with cells exert their reparative effects still require further in-depth investigation.
