Neuroprotective Effects of Fasudil, a Rho-Kinase Inhibitor, After Spinal Cord Ischemia and Reperfusion in Rats

BACKGROUND: Excessive Rho/Rho-kinase pathway activation occurs subsequent to stroke. We examined the neuroprotective effects of pre- and posttreatment with fasudil (a Rho-kinase inhibitor) in a rat transient spinal cord ischemia-reperfusion model under normothermic conditions. METHODS: After approval by our animal research committee, male Sprague-Dawley rats were assigned to 1 of 6 groups: pre- and postcontrol (C); pre- and postfasudil (F); and pre- and postsham (S). Fasudil (10 mg/kg) or normal saline was administered intravenously over 30 minutes before ischemia in the pre-F or pre-C groups, and over 30 minutes after reperfusion in the post-F or post-C groups. Sham groups were not subjected to ischemia. Ischemia was induced by aortic occlusion using a balloon catheter combined with hypotension for 10 minutes. Neurologic deficit scores (NDS; 0–8 points) were assessed 1, 7, and 14 days after ischemia, and then histopathologic outcomes were assessed. RESULTS: NDS 7 and 14 days after ischemia in the pre-F group (median [range]; 3.5 [2–6] and 2.5 [0–6]) were lower than those in the pre-C group (5.5 [4–7] and 4.5 [4–6]; P = .046 and P = .049), whereas NDS in the post-F group and in the post-C group were not different. The numbers of intact neurons in the gray matter in the pre- and post-F groups (mean ± standard deviation [95% confidence interval]: 25 ± 7 [20–30] and 16 ± 5 [12–19]) were greater than those in the pre- and post-C groups (11 ± 5 [7–14] and 9 ± 3 [7–11]; P

http://ift.tt/2zbPDQI