Effect of FK-506 on inflammation and behavioral outcome following intracerebral hemorrhage in rat.
Beginning 15 min after induction of intracerebral hemorrhage (ICH) by intrastriatal administration of collagenase, rats were treated intramuscularly with FK-506 (3 mg/kg) or with vehicle. Treatment was repeated daily for 7 days. MR imaging 1, 7, and 28 days post-ICH showed that treatment did not affect hematoma size or its subsequent resolution. Two days post-ICH, neutrophil infiltration around the hematoma was decreased in the FK-506-treated rats, as was the number of TUNEL-positive cells at the edge of the hematoma and in the peripheral region. The decreased inflammatory response was accompanied by functional improvement in the treated rats. The neurological deficit induced by the ICH (beam walking ability, postural reflex, spontaneous circling) was significantly decreased from 3 to 21 days post-ICH by treatment with FK-506. Skilled use of the forelimb ipsilateral to the ICH was improved and sensory neglect of the same limb was decreased 8-9 weeks post-ICH in rats treated with FK-506. However, neuronal loss assessed 9 weeks post-ICH was not different in the treated and untreated rats.
Peeling
J
J
Department of Chemistry, The University of Manitoba, Winnipeg, Manitoba, R3E 0W3, Canada.
Yan
H J
HJ
Corbett
D
D
Xue
M
M
Del Bigio
M R
MR
D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight; D001921:Brain / Q000187:drug effects / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D016559:Tacrolimus