Behavioral pre-conditioning enhances angiogenesis and cognitive outcome after brain trauma.
OBJECTIVE
In this study, we used Marmarou's model of traumatic brain injury (TBI) and sought to determine: (1) the effect of TBI on cognitive outcome measured on a radial arm maze; (2) the effect of behavioral conditioning before TBI, i.e. pre-conditioning, on cognitive outcome; (3) the effect of pre-conditioning on angiogenesis.


METHODS
Cognitive outcome was measured by performance on an eight-arm radial maze. Behavioral conditioning consisted of daily exposure of animals to the radial arm maze. Latency and number of errors were recorded as an index of overall performance and acquisition of the test. Extent of angiogenesis was measured by vascular endothelial growth factor receptor 2 (VEGFR2) immunofluorescence and by determining capillary density.


RESULTS
Our results indicated that trauma alone causes significant cognitive impairments. Pre-conditioning caused a marked improvement in radial arm maze performance following injury. These results coincide with both a significant increase in VEGFR2 expression and increased capillary density within the cortex and hippocampus.


CONCLUSIONS
TBI causes significant impairments in cognition. These deficits can be ameliorated using a pre-conditioning paradigm. While the precise mechanism has yet to be elucidated, our results indicate that angiogenesis may underlie the cognitive sparing seen in pre-conditioned animals.
Kreipke
Christian W
CW
Department of Anatomy and Cell Biology, Scott Hall, Room No. 9312, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA.
Morgan
Randy
R
Kallakuri
Srinivas
S
Rafols
José A
JA
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001930:Brain Injuries / Q000150:complications*; D003072:Cognition Disorders / Q000209:etiology* / Q000628:therapy*; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D040301:Vascular Endothelial Growth Factor Receptor-2