Experimental neurology
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Experimental neurology · Nov 2008
Surgical implantation of avulsed lumbosacral ventral roots promotes restoration of bladder morphology in rats.
Injuries to the cauda equina and conus medullaris of the spinal cord commonly result in paraplegia, sensory deficits, neuropathic pain, as well as bladder, bowel, and reproductive dysfunctions. In a recently developed lower motoneuron model for cauda equina injury and repair, we have demonstrated that an acute surgical implantation of avulsed lumbosacral ventral roots into the conus medullaris is neuroprotective, promotes regeneration of efferent spinal cord axons into the implanted roots, and may result in functional reinnervation of the lower urinary tract. Here, we investigated the effects of a bilateral lumbosacral ventral root avulsion (VRA) injury and re-implantation on the morphology of the rat bladder at twelve weeks post-operatively. ⋯ Interestingly, the injury-induced changes in bladder wall morphology were ameliorated by an acute implantation of the lesioned roots into the conus medullaris. Specifically, bladders of the implanted group showed a partial restoration of the thickness of the lamina propria and epithelium as well as a return of CGRP immunoreactivity to baseline levels in the lamina propria. Our results support the notion that surgical implantation of severed ventral roots into the spinal cord may promote the recovery of a normal morphological phenotype in peripheral end organs.
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Experimental neurology · Nov 2008
Blockade of microglial glutamate release protects against ischemic brain injury.
Glutamate released by activated microglia induces excito-neurotoxicity and may contribute to neurodegeneration in numerous neurological diseases including ischemia, inflammation, epilepsy, and neurodegenerative diseases. We observed that the gap junction blocker carbenoxolone (CBX) or the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine (DON) decreased glutamate release from activated microglia and rescued neuronal death in a dose-dependent manner in vitro. In gerbils, treatment with CBX or DON also prevented the delayed death of hippocampal neurons following transient global ischemia. Thus, blockade of microglial glutamate release may be an effective therapeutic strategy against neurodegeneration after ischemic injury.
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Experimental neurology · Nov 2008
The role of p53 in brain edema after 24 h of experimental subarachnoid hemorrhage in a rat model.
Our previous study demonstrated that p53 plays an orchestrating role in the vasospasm and apoptotic cell death after subarachnoid hemorrhage (SAH). We now hypothesize that p53 also plays an important role in brain edema by up-regulating the expression of MMP-9 via the NF-kappaB molecular signaling pathway. Adult male rats (300-350 g) were divided into five groups (n=20 each): Sham, SAH treatment with DMSO or PFT-alpha (0.2 mg/kg and 2.0 mg/kg), intraperitoneally. ⋯ Treble labeling showed p53 colocalized with NF-kappaB and MMP-9 in cerebral endothelia cells. We thus conclude that the level of p53 in cerebral microvasculature significantly affects the BBB permeability and brain edema after 24 h of SAH in rats. This can be at least partially ascribed to p53 inducing a significant up-regulation of MMP-9 via NF-kappaB in the endothelium, which in turn opened the tight junction by degrading Occludin and disrupting the basal lamina by degrading collagen IV.
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Experimental neurology · Nov 2008
Effects of local release of hepatocyte growth factor on peripheral nerve regeneration in acellular nerve grafts.
Options for reconstructing peripheral nerve gaps after trauma are limited. The acellular nerve is a new kind of biomaterial used to reconstruct the peripheral nerve defect, but its use could be improved upon. We aimed to investigate the effect of adenoviral transfection with hepatocyte growth factor (HGF) on the functional recovery of transected sciatic nerves repaired by acellular nerve grafting. 30 Rats were divided into three groups (10/group) for autografting and acellular grafting, as well as acellular grafting with adenovirus transfection of HGF (1 x 10(8) pfu) injected in muscles around the proximal and distal allograft coapation. ⋯ Neovascularization was greater with HGF-treated acellular grafting than with autografting and acellular grafting alone. Axonal regeneration distance of autografting on the 20th postoperative day was the longest in the three groups,while that of acellular grafting alone was the smallest. Acellular nerve grafting may be useful for functional peripheral nerve regeneration, and with human HGF gene transfection may improve on acellular grafting alone in functional recovery.
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Experimental neurology · Nov 2008
CommentGliopathy ensures persistent inflammation and chronic pain after spinal cord injury.
Research focused on improving recovery of function, including the reduction of central neuropathic pain (CNP) after spinal cord injury (SCI) is essential. After SCI, regional neuropathic pain syndromes above, at and below the level or spinal injury develop and are thought to have different mechanisms, but may share common dysfunctional glial mechanisms. Detloff et al., [Detloff, M. ⋯ The term "gliopathy" is proposed to describe the dysfunctional and maladaptive response of glial cells, specifically astrocytes and microglia, to neural injury that is initiated by the sudden injury induced increase in extracellular concentrations of glutamate and concomitant production of several proinflammatory molecules. It is important to understand the roles that different glia play in "gliopathy", a condition that appears to persist after SCI. Furthermore, targeted treatment of gliopathy will attenuate mechanical allodynia in both central and peripheral neuropathic pain syndromes.