TFP5 IS COMPARABLE TO MILD HYPOTHERMIA IN IMPROVING NEUROLOGICAL OUTCOMES IN EARLY-STAGE ISCHEMIC STROKE OF ADULT RATS

Aim: We compared the efficacy of a modified truncated 24-aa peptide (TFP5), derived from the cyclin-dependent kinase 5 (CDK5)-activating cofactor p35, with mild hypothermia (MH), and determined whether the efficacy of TFP5 is affected by MH. Methods: Ischemic stroke was induced in adult male Sprague Dawley rats for 2 h. Immediately after initiating reperfusion, TFP5, MH, or the combination of the two were administrated. 48 h after reperfusion, neurological outcomes were evaluated. Results: Rats that received either MH, TFP5, or the combined treatment showed smaller brain infarct size than normothermia control (NT), and there was no apparent difference among these three treatment groups. The neurological deficit was significantly improved only by the combined treatment. MH or TFP5 ameliorated the blood brain barrier (BBB) disruption in ischemic regions with similar efficacy, whereas the combination of them had a trend toward better effect. Besides, the cleavage of p35 into p25 and apoptosis in ischemic regions was inhibited by TFP5 or the combination, but not by MH alone. Conclusions: TFP5 is comparable to MH in improving neurological outcomes in early-stage adult ischemic stroke. When TFP5 is given along with MH, less neurological deficit tends to be achieved. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.