BackgroundThe prognosis of spinal cord injury (SCI) is closely related to secondary injury, which is dominated by neuroinflammation. There is evidence that α-synuclein aggregates after SCI and that inhibition of α-synuclein aggregation can improve the survival of neurons after SCI, but the mechanism is still unclear. This study was designed to investigate the effects of α-synuclein on neuroinflammation after SCI and to determine the underlying mechanisms.MethodA T3 spinal cord contusion model was established in adult male Sprague-Dawley rats. An SNCA-shRNA-carrying lentivirus (LV-SNCA-shRNA) was injected into the injury site to block the expression of α-synuclein (forming the SCI+KD group), and the SCI and sham groups were injected with an empty vector. Basso-Beattie-Bresnahan (BBB) behavioural scores and footprint analysis were used to detect motor function. Inflammatory infiltration and myelin loss were measured in the spinal cord tissues of each group by haematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining, respectively. Immunohistochemistry, Western blot analysis, and RT-qPCR were used to analyse protein expression and transcription levels in the tissues. Immunofluorescence was used to determine the morphology and function of glial cells and the expression of matrix metalloproteinase-9 in the central canal of the spinal cord. Finally, peripheral serum cytokine levels were determined by enzyme-linked immunosorbent assay.ResultsCompared with the SCI group, the SCI+KD group exhibited reduced inflammatory infiltration, preserved myelin, and functional recovery. Specifically, the early arrest of α-synuclein inhibited the pro-inflammatory factors IL-1β, TNF-α, and IL-2 and increased the expression of the anti-inflammatory factors IL-10, TGF-β, and IL-4. The neuroinflammatory response was regulated by reduced proliferation of Iba1+ microglia/macrophages and promotion of the shift of M1-polarized Iba1+/iNOS+ microglia/macrophages to M2-polarized Iba1+/Arg1+ microglia/macrophages after injury. In addition, compared with the SCI group, the SCI+KD group also exhibited a smaller microglia/astrocyte (Iba1/GFAP) immunostaining area in the central canal, lower MMP-9 expression, and improved cerebrospinal barrier function.ConclusionLentivirus-mediated downregulation of α-synuclein reduces neuroinflammation, improves blood-cerebrospinal barrier function, promotes functional recovery, reduces microglial activation, and promotes the polarization of M1 microglia/macrophages to an M2 phenotype to confer a neuroprotective immune microenvironment in rats with SCI.
Increased satellite cell differentiation is correlated with preserved muscle function in response to electrical stimulation after nerve injury.
Spinal cord injury (SCI) in humans is a common central nervous system trauma. Pathophysiologically, SCI involves both primary and secondary damages. Therapeutically, targeting secondary damage including inflammation, neuropathic pain, apoptosis, demyelination, and glial reaction to promote functional benefits for SCI patients has long been considered a potential treatment strategy by neuroscientists and clinicians. As a type of small non-coding RNA, microRNAs (miRNAs) have been shown to play essential roles in the regulation of pathophysiologic processes of SCI and are considered to be an effective treatment method for SCI. Dysregulated expression of miRNAs is observed in SCI patients and animal models of SCI. Furthermore, miRNAs might also be used as biomarkers for diagnostic and prognostic purposes in SCI. Given contusion injury is the most clinically relevant type of SCI, this review mainly focuses on the role of miRNAs in the pathophysiology of contusion SCI and the putative utilization of miRNAs as diagnostic biomarkers and therapeutic targets for contusion SCI.
Study design: This is a systematic review. Objective: The objective of this study was to review the literature on iatrogenic urological triggers of autonomic dysreflexia (AD). Setting: This study was conducted in an international setting. Methods: A systematic review was conducted from PubMed search using AD/ autonomic hyperreflexia and spinal cord injury (SCI). Studies selected for review involved iatrogenic urological triggers of AD in individuals with SCI, including original articles, previous practice guidelines, case reports and literature reviews. Studies that did not report AD or blood pressure (BP) assessments during urological procedures were excluded. Results: Forty studies were included for analysis and categorized into four groups: (1) urodynamics and cystometry; (2) cystoscopy and transurethral litholapaxy; (3) extracorporeal shock-wave lithotripsy (ESWL); and (4) other procedures. During urodynamics, the incidence of AD ranged from 36.7% to 77.8%. The symptomatic rate ranged from 50% to 65%, with AD symptoms seen predominantly in cervical SCI patients. The studies imply no consensus regarding the relationship between AD, neurogenic detrusor overactivity and detrusor sphincter dyssynergia. Without anesthesia, the majority of individuals develop AD during cystoscopy, transurethral litholapaxy and ESWL. The effectiveness of different anesthesia methods relies on blocking the nociceptive signals from the lower urinary tract (LUT) below the level of the neurological lesion. Other iatrogenic urological triggers were commonly associated with bladder filling. Conclusion: The LUT triggers of episodes of AD are often associated with iatrogenic urological procedures. AD was more prevalent in cervical SCI than in thoracic SCI. To detect this potential life-threatening complication following cervical and high thoracic SCI, routine BP monitoring during urological procedures is highly recommended.
Departmental sources Background: This study aimed to develop a risk prediction model for prolonged length of stay (LOS) in stroke patients in 50 inpatient rehabilitation centers in 20 provinces across mainland China based on the International Classification of Functioning, Disability, and Health (ICF) Generic Set case mix on admission. Material/Methods: In this cohort study, 383 stroke patients were included from inpatient rehabilitation settings of 50 hospitals across mainland China. Independent predictors of prolonged LOS were identified using multivariate logistic regression analysis. A prediction model was established and then evaluated by receiver operating characteristic (ROC) curve analysis and the Hosmer-Lemeshow test. Results: Multivariate logistic regression analysis showed that the type of medical insurance and the performance of daily activities (ICF, d230) were associated with prolonged LOS (P<0.05). Age and mobility level measured by the ICF Generic Set demonstrated no significant predictive value. The prediction model showed acceptable discrimination shown by an area under the curve (AUC) of 0.699 (95% CI, 0.646-0.752) and calibration (c 2 =11.66; P=0.308). Conclusions: The risk prediction model for prolonged LOS in stroke patients in 50 rehabilitation centers in China, based on the ICF Generic Set, showed that the scores for the type of medical insurance and the performance of daily activities (ICF, d230) on admission were independent predictors of prolonged LOS. This prediction model may allow stakeholders to estimate the risk of prolonged LOS on admission quantitatively, facilitate the financial planning, treatment regimens during hospitalization, referral after discharge, and reimbursement.
It is known that selective sacral roots rhizotomy is effective for relieving the neurogenic bladder associated with spinal cord injury. The goal of this study is to review the surgical anatomy of the lumbosacral nerve rootlets and to provide some morphological bases for highly selective sacral roots rhizotomy. Spinal cord dissections were performed on five cadavers under surgical microscope. At each spinal cord segment, we recorded the number, diameter and length of the rootlets, subbundles and bundles from the L1 to S2 spinal segments, and the length of the dorsal/ventral root entry zone. Peripheral nervous system myelin was examined by immunohistochemistry. We found: (1) the ventral or the dorsal root of the lumbosacral segment of the spinal cord was divided into one to three nerve bundles and each bundle was subdivided into one to three subbundles. Each subbundle further gave out two to three rootlets connected with the spinal cord; (2) there were no significant differences in the number of rootlets within the L1 to S2 segments, but the size of rootlets and the length of nerve roots varied (P < 0.05); and (3) the more myelinated fibers a rootlet contained, the larger transection area it had. The area of peripheral nervous system myelin positive cells and the total area of rootlets were correlated (P < 0.001). Thus, during highly selective sacral roots rhizotomy, the ventral and dorsal roots can be divided into several bundles of rootlets, and we could initially distinct the rootlets by their diameters. Anat Rec, 293:2123Rec, 293: -2128Rec, 293: , 2010. V V C 2010 Wiley-Liss, Inc.Key words: microsurgical anatomy; lumbosacral nerve rootlet; highly selective sacral rootlets rhizotomy; spinal cord injuryInjuries to the central nervous system in humans are associated with a low degree of neurological recovery and, in most cases, lifelong debilitation. Spinal cord injury (SCI) can result not only in paraplegia or quadriplegia but also in loss of urinary and defecatory control as well as alteration of sexual function (Pedersen, 1983;
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