Brain research
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Deep brain stimulation in the midbrain׳s central gray can relieve neuropathic pain in man, but for unclear reasons sometimes fails intraoperatively or in early weeks. Here we describe continuous bilateral stimulation in the central gray of two subjects with longstanding, severe neuropathic pain from spinal cord injury. Stimulation parameters were recursively adjusted over many weeks to optimize analgesia while minimizing adverse effects. ⋯ Oscillopsia, the only observed complication of stimulation, disappeared at low mean pulse rates (≤ 3/s). These subjects׳ responses are not likely to be unique even if they are uncommon. Thus daily or more frequent pain assessment, combined with slower periodic adjustment of stimulation parameters that incorporate mean pulse rates about one per second, will likely improve success with this treatment.
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Previous studies have shown that inhibition of prolyl hydroxylase(PHD) stabilizes Hypoxia-inducible factor 1, alpha subunit(HIF-1α), increases tolerance to hypoxia, and improves the prognosis of many diseases. However, the role of PHD inhibitor (PHDI) in the recovery of spinal cord injury remains controversial. In this study, we investigated the protective role of a novel PHDI FG-4592 both in vivo and in vitro. ⋯ Combination therapy including the specific HIF-1α blocker YC-1 down-regulated the HIF-1α expression and partially abolished the protective effect of FG-4592. Taken together, our results revealed that the role of FG-4592 in SCI recovery is related to the stabilization of HIF-1α and inhibition of apoptosis. Overall, our study suggests that PHDIs may be feasible candidates for therapeutic intervention after SCI and central nervous system disorders in humans.
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This study investigates the effect of beta-hydroxybutyrate (BHB) on blood-brain barrier (BBB) integrity during traumatic brain injury (TBI) in rats. Evans blue (EB) and horseradish peroxidase (HRP) were used as determinants of BBB permeability. Glutathione (GSH) and malondialdehyde (MDA) levels were estimated in the right (injury side) cerebral cortex of animals. ⋯ In animals exposed to TBI, EB extravasation was observed in the ipsilateral cortex regardless of BHB treatment. Ultrastructurally, BHB attenuated but did not prevent the presence of HRP in brain capillary endothelial cells of animals with TBI; moreover, the drug also led to the observation of the tracer when used in intact rats (P<0.01). Altogether, these results showed that BHB not only failed to provide overall protective effects on BBB in TBI but also led to BBB disruption in healthy animals.
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Mitochondria dysfunction, an enormous potential crisis, has attracted increasing attention. Disturbed regulation of mitochondrial dynamics, the balance of mitochondrial fusion and fission, has been implicated in neurodegenerative diseases, such as Parkinson׳s disease and cerebral ischemia/reperfusion. However the role of mitochondrial dynamics in traumatic brain injury (TBI) has not been illuminated. ⋯ Our findings showed that up-regulation of Drp1 expression started at 1h post-TBI and peaked at 24 h, but inhibition of Drp1 by Mdivi-1 significantly alleviated TBI-induced behavioral deficits and brain edema, reduced morphological change of mitochondria, and decreased TBI-induced cell death together with lesion volume. Moreover, treatment with Mdivi-1 remarkably inhibited TBI-induced the release of cyt-c from mitochondria to cytoplasm, and activation of caspase-3 at 24 h after TBI. Taken together, these data imply that inhibition of Drp1 may help attenuate TBI-induced functional outcome and cell death through maintaining normal mitochondrial morphology and inhibiting activation of apoptosis.
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Volatile anesthetic postconditioning has been documented to provide neuroprotection in adult animals. Our aim was to investigate whether sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage (HIBD) rats, and whether the PI3K/Akt pathway and mitochondrial permeability transition pore (mPTP) opening participate in the effect. ⋯ Sevoflurane postconditioning exerts a neuroprotective effect against HIBD in neonatal rats via PI3K/Akt/eNOS and PI3K/Akt/GSK-3β pathways, and blockage of mPTP opening may be involved in attenuation of histomorphological injury.