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Cyclophilin D-induced mitochondrial impairment confers axonal injury after intracerebral hemorrhage in mice

Neural Regeneration Research 2023年第4期18卷 849-855页

作者： Yang Yang Kai-Yuan Zhang Xue-Zhu Chen Chuan-Yan Yang Ju Wang Xue-Jiao Lei Yu-Lian Quan Wei-Xiang Chen Heng-Li Zhao Li-Kun Yang Yu-Hai Wang Yu-Jie Chen Hua Feng Department of Neurosurgery The 904th Hospital of PLAAnhui Medical UniversityWuxiJiangsu ProvinceChina Department of Neurosurgery and State Key Laboratory of Trauma Burn and Combined InjurySouthwest HospitalThird Military Medical University(Army Medical University)ChongqingChina Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration Third Military Medical University(Army Medical University)ChongqingChina Wuxi Translational Medicine Center WuxiJiangsu ProvinceChina Department of Neurosurgery General Hospital of Xinjiang Military Command of PLAUrumqiXinjiang Uygur Autonomous RegionChina Department of Neurology The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijingChina

The mitochondrial permeability transition pore is a nonspecific transmembrane *** of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling,calcium overload,and axonal *** D is an important component of the mitochondrial permeability transition *** cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not *** this study,we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice,in which pyramidal neurons and axons express yellow fluorescent *** also simulated intracerebral hemorrhage in vitro in PC12 cells using *** found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore *** further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral *** found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial *** addition,inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral *** findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage;inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral *** findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.

关键词： axonal injury corticospinal tract cyclophilin D cyclosporin A intracerebral hemorrhage mitochondrial impairment mitochondrial permeability transition pore motor dysfunction retraction bulb white matter

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Diffusion tensor tractography characteristics of axonal injury in concussion/mild traumatic brain injury

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Neural Regeneration Research 2022年第5期17卷 978-982页

作者： Sung Ho Jang You Sung Seo Department of Physical Medicine and Rehabilitation College of MedicineYeungnam UniversityDaeguRepublic of Korea

The main advantage of diffusion tensor tractography is that it allows the entire neural tract to be *** addition,configurational analysis of reconstructed neural tracts can indicate abnormalities such as tearing,narrowing,or discontinuations,which have been used to identify axonal injury of neural tracts in concussion *** review focuses on the characteristic features of axonal injury in concussion or mild traumatic brain injury(m TBI)patients through the use of diffusion tensor *** injury in concussion(m TBI)patients is characterized by their occurrence in long neural tracts and multiple injuries,and these characteristics are common in patients with diffuse axonal injury and in concussion(m TBI)patients with axonal ***,the discontinuation of the corticospinal tract is mostly observed in diffuse axonal injury,and partial tearing and narrowing in the subcortical white matter are frequently observed in concussion(m TBI)patients with axonal *** difference appears to be attributed to the observation that axonal injury in concussion(m TBI)patients is the result of weaker forces than those producing diffuse axonal *** addition,regarding the fornix,in diffuse axonal injury,discontinuation of the fornical crus has been frequently reported,but in concussion(m TBI)patients,many collateral branches form in the fornix in addition to these findings in many case *** is presumed that the impact on the brain in TBI is relatively weaker than that in diffuse axonal injury,and that the formation of collateral branches occurs during the fornix recovery *** the occurrence of axonal injury in multiple areas of the brain is an important feature of diffuse axonal injury,case studies in concussion(m TBI)have shown that axonal injury occurs in multiple neural *** axonal injury lesions in m TBI patients may persist for approximately 10 years after injury onset,the characteristics of axonal injury in co

关键词： axonal injury brain injury concussion diffusion tensor imaging diffusion tensor tractography mild traumatic brain injury neural tract

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PTEN and AKT/GSK-3β/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in rats

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Genes & Diseases 2022年第1期9卷 252-267页

作者： Hong Chen Chao Zhou Jianfeng Zheng Zhaosi Zhang Yongbing Deng Chongjie Cheng Zongduo Guo Gang Huo Cheng Yin Xiaochuan Sun Department of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University Chongqing 400016PR China Department of Neurosurgery of the Chongqing Emergency Medical Center Chongqing 400014PR China Department of Neurosurgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072PR China

In early brain injury(EBI)after subarachnoid hemorrhage(SAH),white matter(WM)axonal injury plays a key role in the prognosis of the *** purpose of this study was to investigate the effects of phosphatase and tensin homolog deleted on chromosome ten(PTEN)on axonal injury and neuronal apoptosis post-SAH in rats and to find its underlying ***-associated virus was injected into the lateral ventricle to suppress or promote *** function post-SAH in animals was determined by the modified Garcia score,beam balance,and Rotarod test,and the blood–brain barrier disruption was assessed by the brain water *** injury post-SAH was observed by TEM and determined by IF,and neuron apoptosis was measured by TUNEL *** mechanism was analyzed by Western blot to detect p-PTEN/PTEN,p-AKT/AKT,p-GSK-3β/GSK-3β,p-CRMP-2/CRMP-2,axonal injury markerβ-APP and pro-and anti-apoptosis proteins,including Bax and Bcl-2,*** found *** knocking down PTEN,neuronal apoptosis and axonal injury were alleviated,and nerve function and blood–brain barrier were protected;accordingly,after overexpression of PTEN,neuronal apoptosis and axon damage were aggravated,and nerve function damage and blood–brain barrier damage were *** and AKT/GSK-3β/CRMP-2 pathway were jointly involved in regulating neuronal apoptosis and WM axon injury after *** to our research,PTEN was a negative factor of EBI,and together with the AKT/GSK-3β/CRMP-2 signaling pathway aggravates neuronal apoptosis and WM axon damage after *** of PTEN expression may become a new target for SAH treatment.

关键词： AKT/GSK-3β/CRMP-2 pathway axonal injury Early brain injury Neuronal apoptosis PTEN Subarachnoid hemorrhage

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Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

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Neural Regeneration Research 2024年第10期19卷 2119-2131页

作者： Nikita Ollen-Bittle Austyn D.Roseborough Wenxuan Wang Jeng-liang D.Wu Shawn N.Whitehead Department of Anatomy and Cell Biology Western UniversityLondonONCanada Schulich School of Medicine and Dentistry Western UniversityLondonONCanada Deparment of Clinical Neurological Sciences Western UniversityLondonONCanada

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

关键词： axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation neuroinflammation traumatic brain injury

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Promoting axonal regeneration following nerve surgery： a perspective on ultrasound treatment for nerve injuries

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Neural Regeneration Research 2018年第9期13卷 1530-1533页

作者： Konstantin D. Bergmeister Simeon C. Daeschler Patrick Rhodius Philipp Schoenle Arne Bocker Ulrich Kneser Leila Harhaus Department of Hand Plastic and Reconstructive Surgery Burn Center Department of Plastic and Hand Surgery University of Heidelberg BG Trauma Hospital Ludwigshafen Ludwigshafen Germany

Nerve injury is often associated with limited axonal regeneration and thus leads to delayed or incomplete axonal *** a consequence of slow nerve regeneration,target muscle function is often insufficient and leads to a lifelong ***,the diagnosis of nerve injuries has been improved and likewise surgical reconstruction has undergone significant ***,the problem of slow nerve regeneration has not been *** a recent meta-analysis,we have shown that the application of low-intensity ultrasound promotes nerve regeneration experimentally and thereby can improve functional *** we want to demonstrate the experimental effect of low intensity ultrasound on nerve regeneration,the current state of investigations and its possible future clinical applications.

关键词： peripheral nerve injuries nerve regeneration reinnervation experimental studies low-intensityultrasound adjunct treatment nerve reconstruction nerve surgery axonal injury

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Optic nerve crush as a model of retinal ganglion cell degeneration

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Annals of Eye Science 2022年第2期7卷 27-32页

作者： Maurizio Cammalleri Department of Biology University of PisaPisaItaly

Background:axonal degeneration caused by damage to the optic nerve can result in a gradual death of retinal ganglion cells(RGC),leading to irreversible vision *** example of such diseases in humans includes optic nerve degeneration in *** is characterized by the progressive degeneration of the optic nerve and the loss of RGCs that can lead to loss of *** different animal models developed to mimic glaucomatous neurodegeneration,all result in RGC loss consequent optic nerve ***:The present article summarizes experimental procedures and analytical methodologies related to one experimental model of glaucoma induced by optic nerve crush(ONC).Point-by-point protocol is reported with a particular focus on the critical point for the realization of the ***,information on the electroretinogram procedure and the immunohistochemical detection of RGCs are described to evaluate the morpho-functional consequences of ***:Although the model of ONC is improperly assimilated to glaucoma,then the ONC model simulates most of the signaling responses consequent to RGC apoptosis as observed in models of experimental *** this respect,the ONC model may be essential to elucidate the cellular and molecular mechanisms of glaucomatous diseases and may help to develop novel neuroprotective therapies.

关键词： axonal injury retrograde degeneration cell death

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A novel transgenic mouse model of Chinese CharcotMarie-Tooth disease type 2L

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Neural Regeneration Research 2014年第4期9卷 413-419页

作者： Ruxu Zhang Fufeng Zhang Xiaobo Li Shunxiang Huang Xiaohong Zi Ting Liu Sanmei Liu Xuning Li Kun Xia Qian Pan Beisha Tang Department of Neurology Third Xiangya HospitalCentral South University Department of Neurology Xiangya HospitalCentral South University National Key Laboratory of Medical Genetics Central South University

We previously found that the K141N mutation in heat shock protein B8 （HSPB8） was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this K141NHSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. Transgenic mice overexpressing K141N HSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. PCR and western blot analysis confirmed integration of the KI41NHSPB8 gene and widespread expression in tissues of the transgenic mice. The K141N HSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assessment. Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was significantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated fiber density, notable axonal edema and vacuolar degeneration in K141N HSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These findings indicate that the KI4mHSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease.

关键词： nerve regeneration peripheral nerve injury axonal injury animal models Charcot-Ma-rie-Tooth disease type 2L gene mutation pronuclear injection transgenic model small heat shockprotein B8 NSFC grant neural regeneration

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An improved fiber tracking algorithm based on fiber assignment using the continuous tracking algorithm and two-tensor model

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Neural Regeneration Research 2012年第21期7卷 1667-1674页

作者： Liuhong Zhu Gang Guo Department of Radiology Xiamen Second Hospital Teaching Hospital of Fujian Medical University Xiamen 361021 Fujian Province China

This study tested an improved fiber tracking algorithm, which was based on fiber assignment using a continuous tracking algorithm and a two-tensor model. Different models and tracking decisions were used by judging the type of estimation of each voxel. Thismethod should solve the cross-track problem. This study included eight healthy subjects, two axonal injury patients and seven demyelinating disease patients. This new algorithm clearly exhibited a difference in nerve fiber direction between axonal injury and demyelinating disease patients and healthy control subjects. Compared with fiber assignment with a continuous tracking algorithm, our novel method can track more and longer nerve fibers, and also can solve the fiber crossing problem.

关键词： two-tensor model fiber assignment by continuous tracking fiber tracking axonal injury demyelinating disease diffusion tensor imaging neural regeneration

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Diagnostic Prospectives with Tau Protein and Imaging Techniques to Detect Development of Chronic Traumatic Encephalopathy

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Journal of Behavioral and Brain Science 2023年第4期13卷 55-65页

作者： Amit Naskar Danielle Jayanty Kimberly Head Gulshan L. Khanna Vatsalya Vatsalya Arpan Banerjee Cognitive Brain Dynamics Lab National Brain Research Centre Manesar India Department of Medicine University of Louisville Louisville KY USA Professor and Pro Vice Chancellor Manav Rachna International Institute of Research and Studies Faridabad India Robley Rex VA Medical Center Louisville KY USA National Institute on Alcohol Abuse and Alcoholism NIH Bethesda MD USA

Brain damage sustained from repeated blows in boxing, wrestling, and other combat sports has serious physical and mental health consequences. The degenerative brain disease, chronic traumatic encephalopathy (CTE), presents clinically with memory loss, aggression, difficulty in rational thinking and other cognitive problems. This spectrum, which mimics Alzheimer’s disease, is diagnosed post-mortem through a brain biopsy in many professional athletes. However, little is known about the process of development and how to identify vulnerable individuals who may be on course for developing CTE. Boxing is a sport that has a severe toll on athletes’ health, primarily on their brain health and function. This review addresses the concerns of brain injury, describes the pathologies that manifest in multiple scales, e.g., molecular and cognitive, and also proposes possible diagnostic and prognostic markers to characterize the early onset of CTE along with the aim to identify a starting point for future precautions and interventions.

关键词： Athletes axonal injury Tau Protein Chronic Traumatic Encephalopathy Traumatic Brain injury Boxing Wrestling

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Neuroprotective effect of heat shock protein 70 Inhibition of Tau protein expression

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Neural Regeneration Research 2009年第12期4卷 1104-1109页

作者： Zhaohui He Xiaochuan Sun Feng Li Yong Jiang Haitao Wu Luping Zheng Department of Neurosurgery First Affiliated Hospital of Chongqing Medical University Chongqing 400016 China Department of Neurosurgery Second People's Hospital of Jining City Jining 272049 Shandong Province China Department of Neurosurgery Affiliated Hospital of Luzhou Medical College Luzhou 646000 Sichuan Province China

BACKGROUND： Previous studies have shown that heat shock protein 70 （HSP70） has neuroprotective effects by decreasing phosphorylation of Tau protein, thereby reducing the expression of Tau protein and proper aggregation. OBJECTIVE： To observe and verify expressional changes of HSP70 and Tau in retinal ganglion cells following stretch injury to the right optic nerve in rats, and to determine the effect of heat stress pretreatment on HSP70 and Tau protein expressions. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Neurology Research Institute of the First Affiliated Hospital of Chongqing Medical University from March to June 2006. MATERIALS： Instant SABC immunohistochemistry kit, as well as mouse anti-HSP70 and rabbit anti-Tau polyclonal antibodies, were purchased from Wuhan Boster Bioengineering Limited, China. METHODS： A total of 57 male, Wistar rats were randomly assigned to 4 groups： control （n = 3）; 150-180 g stretch force was induced in the right optic nerves in stretch-only group （n = 18） to establish optic nerve stretch injury model; heat stress was applied to 18 animals in heat-stress treatment group; 18 rats in the heat-stress pretreatment plus stretch group were subjected to identical stretch injury as stretch-only group after 24-hour heat-stress pretreatment. According to sacrifice time, the groups were assigned to 6 subgroups at different time points of 4, 8, and 16 hours, and 1,3, and 5 days, with 3 rats in each subgroup. No treatment was performed in the control group except anesthesia. MAIN OUTCOME MEASURES： Morphological changes of optic nerves and retinal ganglion cells following stretch injury were observed by light microscopy following hematoxylin-eosin staining. HSP70 and Tau protein expression levels were observed in retinal ganglial cells from each group using im munohistochemistry. RESULTS：（1） Compared with the control group, morphological axonal and retinal ganglial cell changes, as wel

关键词： heat stress heat shock protein 70 Tau axonal injury

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