Post-ischemic therapy with CGS-19755 (alone or in combination with hypothermia) in gerbils.
Hypothermia or a glutamate receptor antagonist may offer protection when used before or within seconds of an ischemic insult. In this experiment, we tested the efficacy of hypothermia (34 degrees C) versus CGS-19755 (a potent competitive N-methyl-D-aspartate (NMDA) receptor blocker) and their combination which was administered 0.5 h after a 5-min forebrain ischemic insult in gerbils. Morphological assessments were done in Group A at the end of 7 days while Group B was evaluated at 29 days. Each group had four sets of animals: saline treated controls; hypothermia treated; CGS-19755 treated; and a combination of CGS-19755 + hypothermia treated animals. Group A showed significant 'protection', i.e. minimal neuronal damage in the animals treated with hypothermia alone. Protection was evident in the cerebral cortex (P < 0.001), hippocampus CA1 (P < 0.01), and in the striatum (P < 0.05). There was no evidence of neuronal protection in the animals that had received either CGS-19755 alone or a combination of hypothermia and CGS-19755. In Group B (29 day assessment) the neuroprotective effects were not evident in any of the animals when compared to the controls. Behavioral testing with Morris water-maze testing showed no significant differences between the control and any of the treated animals. Our data suggests that 'post-ischemic' therapy with hypothermia may delay the effects of ischemia but does not offer significant long-term neuronal protection. Protection seen at 7 days is not evident at 29 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Shuaib
A
A
Saskatchewan Stroke Research Centre, Saskatoon, Canada.
Waqar
T
T
Wishart
T
T
Kanthan
R
R
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005849:Gerbillinae; D007036:Hypothermia, Induced; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D016548:Prosencephalon / Q000098:blood supply / Q000473:pathology
D010875:Pipecolic Acids; C053672:selfotel; D016202:N-Methylaspartate