spinal cord injury

摘要： Based on the Wallerian degeneration in the spinal cord pathways,the changes in synaptic connections,and the spinal cord-related cellular responses that alter the cellular structure of the brain,we presumed that brain diffusion tensor imaging(DTI)parameters may change after spinal cord injury.However,the dynamic changes in DTI parameters remain unclear.We established a Beagle dog model of T10 spinal cord contusion and performed DTI of the injured spinal cord.We found dynamic changes in DTI parameters in the cerebral peduncle,posterior limb of the internal capsule,pre-and postcentral gyri of the brain within 12 weeks after spinal cord injury.We then performed immunohistochemistry to detect the expression of neurofilament heavy polypeptide(axonal marker),glial fibrillary acidic protein(glial cell marker),and NeuN(neuronal marker).We found that these pathological changes were consistent with DTI parameter changes.These findings suggest that DTI can display brain structure changes after spinal cord injury.

摘要： Injuries to the spinal cord result in permanent disabilities that limit daily life activities.The main reasons for these poor outcomes are the limited regenerative capacity of central neurons and the inhibitory milieu that is established upon traumatic injuries.Despite decades of research,there is still no efficient treatment for spinal cord injury.Many strategies are tested in preclinical studies that focus on ameliorating the functional outcomes after spinal cord injury.Among these,molecular compounds are currently being used for neurological recovery,with promising results.These molecules target the axon collapsed growth cone,the inhibitory microenvironment,the survival of neurons and glial cells,and the re-establishment of lost connections.In this review we focused on molecules that are being used,either in preclinical or clinical studies,to treat spinal cord injuries,such as drugs,growth and neurotrophic factors,enzymes,and purines.The mechanisms of action of these molecules are discussed,considering traumatic spinal cord injury in rodents and humans.

摘要： The spinal cord is at risk of injury during spinal surgery.If intraoperative spinal co rd injury is identified early,irreve rsible impairment or loss of neurological function can be prevented.Different types of spinal cord injury result in damage to diffe rent spinal cord regions,which may cause diffe rent somatosensory and motor evoked potential signal res ponses.In this study,we examined electrophysiological and histopathological changes between contusion,distra ction,and dislocation spinal cord injuries in a rat model.We found that contusion led to the most severe dorsal white matter injury and caused considerable attenuation of both somatosensory and motor evoked potentials.Dislocation resulted in loss of myelinated axons in the lateral region of the injured spinal cord along the rostrocaudal axis.The amplitude of attenuation in motor evoked potential responses caused by dislocation was greater than that caused by contusion.After distraction injury,extracellular spaces were slightly but not significantly enlarged;somatosensory evoked potential res ponses slightly decreased and motor evoked potential responses were lost.Correlation analysis showed that histological and electrophysiological findings we re significantly correlated and related to injury type.Intraope rative monitoring of both somatosensory and motor evoked potentials has the potential to identify iatrogenic spinal cord injury type during surgery.

摘要： Central nervous system(CNS)trauma,including traumatic brain injury and spinal cord injury,has a high rate of disability and mortality,and effective treatment is currently lacking.Previous studies have revealed that neural inflammation plays a vital role in CNS trauma.As the initial enzyme in neuroinflammation,cytosolic phospholipase A_(2)(cPLA2)can hydrolyze membranous phosphatides at the sn-2 position in a preferential way to release lysophospholipids andω3-polyunsaturated fatty acid dominated by arachidonic acid,thereby inducing secondary injuries.Although there is substantial fresh knowledge pertaining to cPLA2,in-depth comprehension of how cPLA2 participates in CNS trauma and the potential methods to amelio rate the clinical res ults after CNS trauma are still insufficient.The present review summarizes the latest understanding of how cPLA2 participates in CNS trauma,highlighting novel findings pertaining to how cPLA2 activation initiates the potential mechanisms specifically,neuroinflammation,lysosome membrane functions,and autophagy activity,that damage the CNS after trauma.Moreover,we focused on testing a variety of drugs capable of inhibiting cPLA2 or the upstream pathway,and we explored how those agents might be utilized as treatments to improve the results following CNS trauma.This review aimed to effectively understand the mechanism of cPLA2 activation and its role in the pathophysiological processes of CNS trauma and provide clarification and a new referential framework for future research.

摘要： Ferroptosis plays a key role in aggravating the progression of spinal cord injury(SCI),but the specific mechanism remains unknown.In this study,we constructed a rat model of T10 SCI using a modified Allen method.We identified 48,44,and 27 ferroptosis genes that were differentially expressed at 1,3,and 7 days after SCI induction.Compared with the sham group and other SCI subgroups,the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was lower.These findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis progression.Bioinformatics analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI:STAT3,JUN,TLR4,ATF3,HMOX1,MAPK1,MAPK9,PTGS2,VEGFA,and RELA.Real-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3,JUN,TLR4,ATF3,HMOX1,PTGS2,and RELA mRNA levels were up-regulated and VEGFA,MAPK1 and MAPK9 mRNA levels were down-regulated.Ten potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair SCI.We also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs,10 miRNAs,and 12 genes.Our results help further the understanding of the mechanism underlying ferroptosis in SCI.

摘要： Spinal cord injury is a severe and devastating disease,and spasticity is a common and severe complication that is notoriously refractory to treatment.However,the pathophysiological mechanisms underlying spasticity and its development remain largely unknown.The goal of the present study was to find differences,if any,in metabolites of the left precentral gyrus and basal ganglia of patients who have spinal cord injury with or without spasticity,and to explore the relationship between the brain metabolite concentrations and clinical status.Thirty-six participants were recruited for magnetic resonance spectroscopic examination:23 with spinal cord injury(12 with spasticity and 11 without spasticity)and 13 healthy controls.We acquired localized proton spectra from the precentral gyrus and basal ganglia via 10 mm^(3) voxels.Notably,univariate linear regression analysis demonstrated that the lower that the N-acetylaspartate concentration(a marker for neuronal loss)was in the precentral gyrus of the patients,the lower their ASIA(American Spinal Injury Association)light-touch scores,pinprick scores,and motor scores.Additionally,longer durations of injury were associated with higher N-acetylaspartate levels in the precentral gyrus.Compared with the healthy participants and patients without spasticity,N-acetylaspartate levels in the patients with spasticity were significantly lower in both the precentral gyrus and basal ganglia.Lower N-acetylaspartate levels also correlated with greater sensory and motor dysfunction in the patients who had spinal cord injury with spasticity.

摘要： Spinal cord injury is one of the leading causes of morbidity and mortality among young adults in many countries including the United States.Difficulty in the regeneration of neurons is one of the main obstacles that leave spinal cord injury patients with permanent paralysis in most instances.Recent research has found that preventing acute and subacute secondary cellular damages to the neurons and supporting glial cells can help slow the progression of spinal cord injury pathogenesis,in part by reactivating endogenous regenerative proteins including Noggin that are normally present during spinal cord development.Noggin is a complex protein and natural inhibitor of the multifunctional bone morphogenetic proteins,and its expression is high during spinal cord development and after induction of spinal cord injury.In this review article,we first discuss the change in expression of Noggin during pathogenesis in spinal cord injury.Second,we discuss the current research knowledge about the neuroprotective role of Noggin in preclinical models of spinal cord injury.Lastly,we explain the gap in the knowledge for the use of Noggin in the treatment of spinal cord injury.The results from extensive in vitro and in vivo research have revealed that the therapeutic efficacy of Noggin treatment remains debatable due to its neuroprotective effects observed only in early phases of spinal cord injury but little to no effect on altering pathogenesis and functional recovery observed in the chronic phase of spinal cord injury.Furthermore,clinical information regarding the role of Noggin in the alleviation of progression of pathogenesis,its therapeutic efficacy,bioavailability,and safety in human spinal cord injury is still lacking and therefore needs further investigation.

摘要： Ferroptosis,a new non-necrotizing programmed cell death(PCD),is driven by iron-dependent phospholipid peroxidation.Ferroptosis plays a key role in secondary traumatic brain injury and secondary spinal cord injury and is closely related to inflammation,immunity,and chronic injuries.The inhibitors against ferroptosis effectively improve iron homeostasis,lipid metabolism,redox stabilization,neuronal remodeling,and functional recovery after trauma.In this review,we elaborate on the latest molecular mechanisms of ferroptosis,emphasize its role in secondary central nervous trauma,and update the medicines used to suppress ferroptosis following injuries.

摘要： Axon regeneration of central neurons is a complex process that is tightly regulated by multiple extrinsic and intrinsic factors.The expression levels of distinct genes are changed after central neural system(CNS)injury and affect axon regeneration.A previous study identified dusp2 as an upregulated gene in zebrafish with spinal cord injury.Here,we found that dual specificity phosphatase 2(DUSP2)is a negative regulator of axon regeneration of the Mauthner cell(M-cell).DUSP2 is a phosphatase that mediates the dephosphorylation of JNK.In this study,we knocked out dusp2 by CRISPR/Cas9 and found that M-cell axons of dusp2(-/-)zebrafish had a better regeneration at the early stage after birth(within 8 days after birth),while those of dusp2^(+/-)zebrafish did not.Overexpression of DUSP2 in Tg(Tol 056)zebrafish by single-cell electroporation retarded the regeneration of M-cell axons.Western blotting results showed that DUSP2 knockout slightly increased the levels of phosphorylated JNK.These findings suggest that knocking out DUSP2 promoted the regeneration of zebrafish M-cell axons,possibly through enhancing JNK phosphorylation.

摘要： Although little attention has been paid to cognitive and emotional dysfunctions observed in patients after spinal co rd injury,several reports have described impairments in cognitive abilities.Our group also has contributed significantly to the study of cognitive impairments in a rat model of spinal co rd injury.These findings are very significant because they demonstrate that cognitive and mood deficits are not induced by lifestyle changes,drugs of abuse,and combined medication.They are related to changes in brain structures involved in cognition and emotion,such as the hippocampus.Chronic spinal cord injury decreases neurogenesis,enhances glial reactivity leading to hippocampal neuroinflammation,and trigge rs cognitive deficits.These brain distal abnormalities are recently called te rtiary damage.Given that there is no treatment for Tertiary Damage,insulin growth factor 1 gene therapy emerges as a good candidate.Insulin growth factor 1 gene thera py recove rs neurogenesis and induces the polarization from pro-inflammato ry towards anti-inflammatory microglial phenotypes,which represents a potential strategy to treat the neuroinflammation that supports te rtiary damage.Insulin growth factor 1 gene therapy can be extended to other central nervous system pathologies such as traumatic brain injury where the neuroinflammatory component is crucial.Insulin growth factor 1 gene therapy could emerge as a new therapeutic strategy for treating traumatic brain injury and spinal cord injury.