Traumatic brain injury-induced acute gene expression changes in rat cerebral cortex identified by GeneChip analysis.
Proper CNS function depends on concerted expression of thousands of genes in a controlled and timely manner. Traumatic brain injury (TBI) in mammals results in neuronal death and neurological dysfunction, which might be mediated by altered expression of several genes. By employing a CNS-specific GeneChip and real-time polymerase chain reaction (PCR), the present study analyzed the gene expression changes in adult rat cerebral cortex in the first 24 hr after a controlled cortical impact injury. Many functional families of genes not previously implicated in TBI-induced brain damage are altered in the injured cortex. These include up-regulated transcription factors (SOCS-3, JAK-2, STAT-3, CREM, IRF-1, SMN, silencer factor-B, ANIA-3, ANIA-4, and HES-1) and signal transduction pathways (cpg21, Narp, and CRBP) and down-regulated transmitter release mechanisms (CITRON, synaptojanin II, ras-related rab3, neurexin-1beta, and SNAP25A and -B), kinases (IP-3-kinase, Pak1, Ca(2+)/CaM-dependent protein kinases), and ion channels (K(+) channels TWIK, RK5, X62839, and Na(+) channel I). In addition, several genes previously shown to play a role in TBI pathophysiology, including proinflammatory genes, proapoptotic genes, heat shock proteins, immediate early genes, neuropeptides, and glutamate receptor subunits, were also observed to be altered in the injured cortex. Real-time PCR analysis confirmed the GeneChip data for many of these transcripts. The novel physiologically relevant gene expression changes observed here might explain some of the molecular mechanisms of TBI-induced neuronal damage.
Raghavendra Rao
Vemuganti L
VL
Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin 53792, USA. vemugant@neurosurg.wisc.edu
Dhodda
Vinay K
VK
Song
Guoqing
G
Bowen
Kellie K
KK
Dempsey
Robert J
RJ
D000818:Animals; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D016000:Cluster Analysis; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation
D012333:RNA, Messenger