Experimental neurology
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Experimental neurology · Apr 2006
Comparative StudyActivation of Rho after traumatic brain injury and seizure in rats.
Traumatic brain injury (TBI) is characterized by a progressive cell loss and a lack of axonal regeneration. In the central nervous system (CNS), the Rho signaling pathway regulates the neuronal response to growth inhibitory proteins and regeneration of damaged axons, and Rho activation is also correlated with an increased susceptibility to apoptosis. To evaluate whether traumatic brain injury (TBI) results in changes in Rho activation in vulnerable regions of the brain, GTP-RhoA pull down assays were performed on rat cortical and hippocampal tissue homogenates obtained from 24 h to 3 days following lateral fluid percussion brain injury (FPI). ⋯ To determine if immediate post-traumatic events such as seizures may activate Rho, we examined RhoA activation in the brains of rats with kainic acid-induced seizures. Severe seizures resulted in bilateral RhoA activation in the cortex and hippocampus. Together, these results indicate that RhoA is activated in vulnerable brain regions following traumatic and epileptic insults to the CNS.
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Experimental neurology · Apr 2006
Comparative StudyBDNF/TrkB signaling regulates HNK-1 carbohydrate expression in regenerating motor nerves and promotes functional recovery after peripheral nerve repair.
Functional recovery after peripheral nerve injury is often poor despite high regenerative capacity of peripheral neurons. In search for novel treatments, brief electrical stimulation of the acutely lesioned nerve has recently been identified as a clinically feasible approach increasing precision of axonal regrowth. The effects of this stimulation appear to be mediated by BDNF and its receptor, TrkB, but the down-stream effectors are unknown. ⋯ Accordingly, the degree of proper reinnervation of the quadriceps muscle, as indicated by retrograde labeling of motoneurons, was reduced in TrkB+/- mice compared to wild-type littermates. Also, recovery of quadriceps muscle function, evaluated by a novel single-frame motion analysis approach, and axonal regrowth into the distal nerve stump, assessed morphologically, were considerably delayed in TrkB+/- mice. These findings indicate that BDNF/TrkB signaling is important for functional recovery after nerve repair and suggest that up-regulation of the HNK-1 glycan is linked to this phenomenon.
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Experimental neurology · Apr 2006
Comparative StudyTraumatic axonal injury in the perisomatic domain triggers ultrarapid secondary axotomy and Wallerian degeneration.
Traumatic axonal injury (TAI) arising from diffuse brain injury (DBI) results in focally impaired axonal transport with progressive swelling and delayed disconnection over several hours within brainstem axons. Neocortical DBI-mediated perisomatic axotomy does not result in neuronal death, suggesting that a comparably delayed axotomy progression was responsible for this unanticipated response. To evaluate delayed perisomatic axotomy, the current study was initiated. ⋯ Distal axonal segment ultrastructure now revealed the initial stages of Wallerian degeneration. The site of perisomatic axotomy did not internalize dextran, suggesting that its pathogenesis occurred independent of altered axolemmal permeability. Collectively, this DBI-mediated ultrarapid perisomatic axotomy and its sequelae further illustrate the varied axonal responses to trauma.
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Experimental neurology · Apr 2006
Comparative StudyProgesterone administration modulates AQP4 expression and edema after traumatic brain injury in male rats.
This study investigates whether progesterone administration regulates AQP4 and GFAP expression in rats with bilateral contusion injuries of the medial frontal cortex. Male rats were given 0 or 16 mg/kg injections of progesterone at 1, 6, 24, and 48 h post-injury. Brains were extracted at 24 h or 72 h post-injury and assayed for cerebral edema and AQP4 and GFAP expression using Western blot analysis. ⋯ However, progesterone significantly reduced AQP4 expression at 72 h post-injury in the tissue bounded by the lateral ventricles and the peri-contusion areas compared to lesion+ vehicle rats, but increased AQP4 expression in the tissue surrounding the third ventricle. Also progesterone effects on GFAP expression varied according to brain region. Our results can be taken to show that the expression of AQP4 protein after TBI is time-dependent, region-specific, and possibly implicated in the formation and resolution of TBI-induced cerebral edema.
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Experimental neurology · Apr 2006
Comparative StudyDisruption of glial function enhances electroacupuncture analgesia in arthritic rats.
Activated glia play a major role in mediating behavioral hypersensitive state following peripheral inflammation. Electroacupuncture is well known to relieve persistent inflammatory pain. The present study was undertaken to examine whether fluorocitrate, a glial metabolic inhibitor, could synergize electroacupuncture antagonizing thermal hyperalgesia and mechanical allodynia evoked by ankle joint inflammation. ⋯ Unilateral electroacupuncture stimulation of "Huantiao" (GB30) and "Yanglingquan" (GB34) acupuncture points (100/2 Hz alternation, 1-2-3 mA) significantly elevated the PWLs and PWTs for 45 min after cessation of electroacupuncture in monoarthritic rats. Co-application of 0.1 or 1 nmol fluorocitrate with electroacupuncture significantly potentiated electroacupuncture analgesia, although 0.1 nmol fluorocitrate alone had no effect on PWLs and PWTs in monoarthritic rats. These results suggested that electroacupuncture and disrupting glial function could synergistically antagonize inflammatory pain, which might provide a potential strategy for the treatment of arthritic pain.