The International journal of neuroscience
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The limited regenerative capability of central neurons and inhibitory factors are the main causes of axonal regeneration failure after spinal cord injury (SCI). Nogo receptors (NgR) are a family of receptors shared by three factors that inhibit axon outgrowth. In a previous study, siNgR199, an effective lentiviral siRNA vector of NgR1, was constructed and transfected into cortical neurons in vitro, and it effectively promoted axon outgrowth. The present study focused on the therapeutic effect of delivery of a recombinant lentivirus containing siNgR199 in vivo in rats. ⋯ Injection with lentivirus carrying siNgR199 into the sensorimotor cortex improved axonal regeneration and functional recovery of hindlimb after SCI in rats.
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Tissue-type plasminogen activator (t-PA) increases the risk of intracranial hemorrhage by gelatinase B (matrix metalloprotease-9; MMP-9) production in brain endothelial cells. It was recently reported that the free-radical scavenger edaravone significantly decreases t-PA-mediated MMP-9 production. Therefore, by using cultured brain endothelial cells (b. ⋯ Moreover, the combination of t-PA and ROS significantly increased I-κB degradation as well as NF-κB expression. Edaravone completely decreased the ROS plus t-PA-mediated MMP-9 enhancement. In conclusion, ROS enhanced t-PA-mediated MMP-9 production in brain endothelial cells; this MMP-9 production was decreased by the addition of edaravone, which inhibited the NF-κB pathway, specifically by enhancing I-κB degradation.
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Randomized Controlled Trial
A comparative study of the effects of low-dose topiramate versus sodium valproate in migraine prophylaxis.
The present study was performed to evaluate the efficacy of low-dose topiramate and compare it with sodium valproate that is prevalently prescribed as a migraine prophylaxis. This was a randomized, double-blind, parallel-group clinical trial on 56 patients who completed the course of study. Topiramate and valproate were administered at 50 mg/day and 400 mg/day, respectively, during the follow-up period. ⋯ The reduction of headache severity in the topiramate group was significantly more than that in the valproate group (p = .027). During the study, no statistically significant reduction in associated symptoms with migraine were observed in both the groups. Topiramate dose of 50 mg/day with fewer side effects in comparison with its higher doses may be an appropriate substitution for first-line migraine prophylaxis such as valproate.
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Melanocortin 4 receptor (MC4R) is implicated in the initiation and maintenance of neuropathic pain. Although the effect of MC4R on neuropathic pain is known, it remains unclear how MC4R mediates neuropathic pain. In vitro MC4R activates mitogen-activated kinase (MAPK). ⋯ Both MC4R and phosphorylated p38 localized in DRG neurons. These data suggest a sequential role for MC4R and p38 in the induction and maintenance of neuropathic pain. MC4R plays an important role in the establishment of neuropathic pain following CCI, seemingly dependent on p38 activation.
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Cervical artery dissection (CAD) is a common cause of stroke in young individuals. Risk factors, treatment, and outcome of CAD are not well established. Our aim is to identify risk factors, outcome, and discuss treatment of CAD. ⋯ Hypertension and hypercholesterolemia were risk factors in spontaneous dissections, speaking for vascular wall abnormalities as potential contributors to pathophysiology of CAD. There was no evidence supporting one type of treatment over the other. A large ongoing prospective study should quell this controversy.