Activation of Rho after traumatic brain injury and seizure in rats.
Traumatic brain injury (TBI) is characterized by a progressive cell loss and a lack of axonal regeneration. In the central nervous system (CNS), the Rho signaling pathway regulates the neuronal response to growth inhibitory proteins and regeneration of damaged axons, and Rho activation is also correlated with an increased susceptibility to apoptosis. To evaluate whether traumatic brain injury (TBI) results in changes in Rho activation in vulnerable regions of the brain, GTP-RhoA pull down assays were performed on rat cortical and hippocampal tissue homogenates obtained from 24 h to 3 days following lateral fluid percussion brain injury (FPI). Following FPI, a significantly increased RhoA activation was observed from 24 h to 3 days post-injury in the cortex and by 3 days in the hippocampus ipsilateral to the injury. We also detected activated RhoA in the cortex and hippocampus contralateral to the injury, without concomitant changes in total RhoA levels. To determine if immediate post-traumatic events such as seizures may activate Rho, we examined RhoA activation in the brains of rats with kainic acid-induced seizures. Severe seizures resulted in bilateral RhoA activation in the cortex and hippocampus. Together, these results indicate that RhoA is activated in vulnerable brain regions following traumatic and epileptic insults to the CNS.
Dubreuil
Catherine I
CI
Université de Montréal, 2900 Edouard-Montpetit, Faculté de médecine, Département de Pathologie et Biologie cellulaire, Montréal, QC, Canada H3T 1J4.
Marklund
Niklas
N
Deschamps
Kathleen
K
McIntosh
Tracy K
TK
McKerracher
Lisa
L
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004789:Enzyme Activation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000927:Anticonvulsants; D020741:rho GTP-Binding Proteins; D003975:Diazepam; D007608:Kainic Acid