Cognitive and histopathological outcome after weight-drop brain injury in the rat: influence of systemic administration of monoclonal antibodies to ICAM-1.
The aim of this study was to evaluate whether treatment with the anti-ICAM-1 antibody 1A29 influences functional or histopathological outcome following severe controlled cortical contusion in rats. The spatial learning deficits were studied using Morris water maze (MWM) paradigm in which the animals were given four daily acquisition trials for four consecutive days, starting on day 10 post-injury. Both 1A29-treated (n=8) and vehicle-treated (n=8) traumatized animals needed longer time than sham-operated rats (n=8) to find the hidden escape platform on days 11, 12 and 13. Compared to shams, significantly increased escape latency was noted on day 12 in vehicle-treated group and on days 12 and 13 in 1A29-treated animals. MWM performance did not differ significantly between the two trauma groups. Histopathological evaluation of the injured brains 15 days after trauma revealed ipsilateral cortical cavitation as well as ipsilateral hippocampal and thalamic lesions. MAP2 immunostaining showed a nonsignificant tendency towards more pronounced hippocampal injury in the 1A29-treated animals. Image analysis of glial fibrillary acidic protein- and ionized calcium binding adapter molecule 1-immunostained sections revealed astrocytic activation in the ipsilateral thalamus and microglial activation in both ipsilateral thalamus and hippocampus of traumatized animals, but no significant differences between the trauma groups. In summary, this study shows that spatial memory deficits occur following a weight-drop injury to the rat brain. Treatment with the anti-ICAM-1 antibody 1A29 did not significantly change the recorded functional or histopathological measures of outcome.
Isaksson
J
J
Department of Genetics and Pathology, Uppsala University Hospital, Sweden. jonasisak@hotmail.com
Hillered
L
L
Olsson
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D018799:Intercellular Adhesion Molecule-1 / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008568:Memory / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1