Extradural compression of sensorimotor cortex: a useful model for studies on ischemic brain damage and neuroprotection.
Behavioral and morphological changes were examined for up to 9 days after moderate cerebral ischemia caused by slow compression of a specific brain area in the sensorimotor cortex of Sprague-Dawley rats. Functional deficits after the cerebral ischemia were assessed by daily beam-walking tests, whereas morphological changes were verified using Nissl staining on day 1, 2, 3, 5, and 9, respectively. Rats exposed to cerebral ischemia displayed impaired beam walking performance. Mild hypothermia prevented both the compression-produced functional deficits and the brain damage. Younger (5 weeks) animals showed less neurological deficits than older (9 weeks) animals. Histological examination revealed a pronounced increase in the number of injured pyramidal neurons from day 1 to day 3 in the primarily damaged brain region. Between day 3 and day 5, the number of injured cells remained constant, whereafter there was a slow decline of thionin-positive neurons as examined on day 9. The noncompetitive NMDA receptor antagonist, dizocilpine (MK-801; 3 mg/kg, i.p.), did not alter the neurological impairment on day 1, but improved thereafter the rate of functional recovery and reduced the number of damaged cells. The AMPA receptor antagonist, LY326325 (15 or 30 mg/kg; i.p.), dose-dependently diminished the neurological deficits on day 1, enhanced the rate of recovery, and reduced the number of injured neurons over time. Our data suggest that short-lasting extradural compression of a well-defined brain area in the sensorimotor cortex is a highly reproducible model with a high success rate for the study of functional and morphological consequences after cerebral ischemia as well as for the evaluation of the therapeutic potential of novel, neuroprotective pharmacological agents.
Kundrotiené
Jurgita
J
Department of Clinical Neuroscience, Karolinska Hopsital, Stockholm, Sweden.
Wägner
Anna
A
Liljequist
Sture
S
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004388:Dura Mater; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007036:Hypothermia, Induced; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009044:Motor Cortex / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013003:Somatosensory Cortex / Q000503:physiopathology*; D013777:Tetrazoles / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D018696:Neuroprotective Agents; D017470:Receptors, Glutamate; D013777:Tetrazoles; D016291:Dizocilpine Maleate; C082309:tezampanel