All three Top1 inhibitors were found to suppress phenotypes in these mutants. In particular, for drug treatments, the recovery time from seizure and paralysis is greatly reduced compared with untreated animals. Intriguingly selleck kinase inhibitor we find that chronic drug treatments result in a small reduction
in seizure sensitivity. Taken together, the results suggest that Top1 inhibitors may have the potential to be developed into effective anti-epileptic drugs, especially for brain tumor patients presenting with epilepsy. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Objective: Thoracic and thoracoabdominal aortic surgery is sometimes complicated by subacute or delayed paraplegia. Pro-inflammatory cytokine interleukin-1 (IL-1) beta has been implicated in extensive inflammation and progressive neurodegeneration after ischemia. Using a rabbit model, we investigated the neuroprotective effects of IL-1 receptor antagonist (IL-1ra) in a temporal fashion.
Methods: Spinal cord ischemia was induced by aortic cross-clamping in New Zealand White rabbits. The animals were assigned to three groups. Group C (n = 20) received saline (0.2-mL) and Group I (n = 20) received IL-1ra (200-mu g/0.2-mL) intrathecally just after reperfusion. Group S (11
= 3) underwent sham operation without aortic occlusion. We assessed the neuroprotective effects of IL-1ra by evaluating neurological function, histopathological changes, and in-situ terminal BMS-754807 order deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL staining). We also measured the levels
of Nitric Oxide (NO) and S100 beta in cerebrospinal fluid (CSF). Each evaluation was performed sequentially within 120 hours after reperfusion.
Results: Group C showed progressive deterioration of motor function which became statistically significant from 48 hours after the onset of reperfusion (P < .05, P < .01, P < .001, P < .001 at 48, 72, 96, and 120 hours, respectively). Selleck BIBW2992 Compared to Group C, a higher number of viable neurons was observed with less severe spinal cord injury in Group I (P < .01,.05 and .05 at 24, 72, and 120 hours, respectively). TUNEL-positive neurons were also significantly reduced by the administration of IL-1ra (P < .01 and .05 at 24, and 120 hours, respectively). The difference between Group C and Group I with regard to NO was significant at 72 and 120 hours (P < .05), while that in terms of S100P was significant only at 24 hours (P < .05).
Conclusions: Administration of IL-1ra attenuates spinal cord ischemic-reperfusion injury as evidenced by reducing both neuronal necrosis and apoptosis.”
“Introduction: Classic studies of limb ischemia-reperfusion injury have been performed using young healthy mice.