Behavioral recovery patterns in rats receiving the NMDA receptor antagonist MDL 100,453 immediately post-stroke.
Rats were given MDL 100,453 ((R)-4-Oxo-5-phosphononorvaline) in a pre-determined neuroprotective dose consisting of a bolus of 24.8 mg/kg followed by an infusion of 1.05 mg/kg*h for 24 h (MDL group; n = 8) or saline of the same volume (SALINE group; n = 8) 30 min. after the onset of a 90 min. period of middle cerebral artery occlusion. Eight animals underwent SHAM surgery. Rats were evaluated post-operatively for 14 days using seven neurological tests, including water maze. SALINE animals exhibited a pattern of neurological impairment compared to SHAMs (poor performance in five of the six motor/reflex tests) peaking five days post-injury. Relative to the SALINE group, the MDL group exhibited significantly improved outcome on two of the tests and a pattern of improved behavior on the remainder of the battery. By day 14 post-ischemia, all groups exhibited recovery on the motor/reflex tests. Learning ability was disrupted in the SALINE group on days 17 and 18, whereas the MDL group's performance was not distinguishable from the SHAM group in the water maze. Thus, a neuroprotective dose of MDL 100,453 produced a pattern of behavioral sparing in the immediate post-ischemic days that was uniquely different than saline. The addition of behavioral outcome measures to histological neuroprotection data adds significantly to the ability to better evaluate a putative neuroprotective compound.
Markgraf
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CG
Hoechst Marion Roussel Inc., Cincinnati, OH 45215-6300, USA.
Johnson
M P
MP
Braun
D L
DL
Bickers
M V
MV
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects*; D002536:Cerebral Arteries / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006120:Grooming / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C066280:4-oxo-5-phosphononorvaline; D014633:Valine