Experimental neurology
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Experimental neurology · May 2008
Intraspinal microinjection of chondroitinase ABC following injury promotes axonal regeneration out of a peripheral nerve graft bridge.
Chondroitin sulfate proteoglycans (CSPG) within the glial scar formed after central nervous system (CNS) injury are thought to play a crucial role in regenerative failure. We previously showed that delivery of the CSPG-digesting enzyme chondroitinase ABC (ChABC) via an osmotic minipump allowed axonal regeneration and functional recovery in a peripheral nerve graft (PNG)-bridging model. In this study, we sought to overcome the technical limitations associated with minipumps by microinjecting ChABC directly into the distal lesion site in the PN bridging model. ⋯ We also demonstrate that this delivery technique is relatively atraumatic and does not result in a noticeable inflammatory response. Importantly, microinjections of ChABC into the lesion site permitted more regenerating axons to exit a PNG and reenter spinal cord tissue than saline injections. These results are similar to our previous findings when ChABC was delivered via a minipump and suggest that microinjecting ChABC is an effective method of delivering the potentially therapeutic enzyme directly to an injury site.
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Experimental neurology · May 2008
Manually-stimulated recovery of motor function after facial nerve injury requires intact sensory input.
We have recently shown in rat that daily manual stimulation (MS) of vibrissal muscles promotes recovery of whisking and reduces polyinnervation of muscle fibers following repair of the facial nerve (facial-facial anastomosis, FFA). Here, we examined whether these positive effects were: (1) correlated with alterations of the afferent connections of regenerated facial motoneurons, and (2) whether they were achieved by enhanced sensory input through the intact trigeminal nerve. First, we quantified the extent of total synaptic input to motoneurons in the facial nucleus using synaptophysin immunocytochemistry following FFA with and without subsequent MS. ⋯ Thus, when the sensory system is intact, MS restores normal vibrissal function and reduces the degree of polyinnervation. When afferent inputs are abolished, these effects are eliminated or even reversed. We conclude that rehabilitation strategies must be carefully designed to take into account the extent of motor and/or sensory damage.
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Experimental neurology · May 2008
Systemic inflammation exacerbates behavioral and histopathological consequences of isolated traumatic brain injury in rats.
The proinflammatory cytokine interleukin-1beta (IL-1beta) is induced rapidly after traumatic brain injury (TBI) and contributes to the inflammatory events that lead to neuronal loss. Although an important source of IL-1beta is from the injured brain itself, in patients with multiple organ trauma (polytrauma) IL-1beta is also released into the bloodstream which may potentially influence brain vulnerability. The purpose of this study was to determine the effects of systemic inflammation induced by peripheral administration of IL-1beta on histopathological and behavioral outcome after moderate fluid percussion (FP) brain injury in rats. ⋯ These data show that the posttraumatic administration of IL-1beta significantly aggravates behavioral outcome and increases overall contusion volume after TBI. Increased systemic inflammatory processes, including extravasation of activated leukocytes and proinflammatory cytokines could participate in this detrimental outcome. Because peripherally circulating cytokines and other neurotoxic factors may be increased following multi-organ trauma, these findings may be important in targeting therapeutic interventions in this patient population.
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Experimental neurology · May 2008
Delayed treatment of spinal cord injury with erythropoietin or darbepoetin--a lack of neuroprotective efficacy in a contusion model of cord injury.
A number of drugs commonly used for a variety of clinical indications have been found recently to have substantial neuroprotective properties, raising the potential for rapid translation into human clinical trials of spinal cord injury (SCI). In this study we compared the neuroprotective efficacy of erythropoietin and a derivative of it, darbepoetin, in an acute model of thoracic SCI. Sprague-Dawley rats were randomized to receive erythropoietin (5000 IU/kg), darbepoetin (10 mug/kg), or saline, as a single intravenous injection 1 h after a thoracic contusion SCI. ⋯ Furthermore, no differences were observed in grey or white matter sparing between the three experimental groups. Using doses of erythropoietin and darbepoetin that other investigators have reported to be beneficial in SCI and stroke models, we were unable to demonstrate a neuroprotective effect when administered 1 h after injury. Further preclinical investigation is necessary to refine the treatment strategy of using erythropoietin or darbepoetin in acute spinal cord injury.
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Experimental neurology · Apr 2008
Serotonergic activation potentiates light resetting of the main circadian clock and alters clock gene expression in a diurnal rodent.
The main circadian clock, localized in the suprachiasmatic nuclei (SCN) in mammals, can be synchronized by light and non-photic factors such as serotonergic cues. In nocturnal rodents, injections during the subjective day of the 5-HT1A/7 receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) or its positive enantiomer, induce behavioral phase-advances in correlation with decreased expression of two clock genes, Per1/2. In addition, 8-OH-DPAT and the selective serotonin reuptake inhibitor fluoxetine reduce light-induced phase-shifts during the subjective night. ⋯ Light responses of Per1 and Rorbeta expression at CT0 and those of Per2 and Rev-erbalpha at CT12 were markedly altered by serotonergic activation. The present findings demonstrate that the serotonergic modulation of the SCN clock appears to differ between nocturnal species and the diurnal Arvicanthis. The potentiating effects of fluoxetine on light resetting in a diurnal rodent may be clinically relevant.