TFP5 is comparable to mild hypothermia in improving neurological outcomes in early-stage ischemic stroke of adult rats

Neuroscience. 2017 Feb 20;343:337-345. doi: 10.1016/j.neuroscience.2016.12.009. Epub 2016 Dec 18.

Abstract

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 2h. Immediately after initiating reperfusion, TFP5, MH, or the combination of the two were administrated. 48h 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.

Keywords: CDK5/p25; CDK5/p35; hypothermia; ischemia; stroke.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy*
  • Combined Modality Therapy
  • Cyclin-Dependent Kinase 5 / metabolism
  • Disease Models, Animal
  • Hypothermia, Induced*
  • Immunoglobulin G / metabolism
  • Male
  • Matrix Metalloproteinase 9 / blood
  • Neuroprotective Agents / pharmacology*
  • Peptides / pharmacology*
  • Random Allocation
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Stroke / metabolism
  • Stroke / pathology
  • Stroke / therapy*

Substances

  • Immunoglobulin G
  • Neuroprotective Agents
  • Peptides
  • TFP5 peptide
  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat