Genomic responses in rat cerebral cortex after traumatic brain injury.
BACKGROUND
Traumatic brain injury (TBI) initiates a complex sequence of destructive and neuroprotective cellular responses. The initial mechanical injury is followed by an extended time period of secondary brain damage. Due to the complicated pathological picture a better understanding of the molecular events occurring during this secondary phase of injury is needed. This study was aimed at analysing gene expression patterns following cerebral cortical contusion in rat using high throughput microarray technology with the goal of identifying genes involved in an early and in a more delayed phase of trauma, as genomic responses behind secondary mechanisms likely are time-dependent.


RESULTS
Among the upregulated genes 1 day post injury, were transcription factors and genes involved in metabolism, e.g. STAT-3, C/EBP-delta and cytochrome p450. At 4 days post injury we observed increased gene expression of inflammatory factors, proteases and their inhibitors, like cathepsins, alpha-2-macroglobulin and C1q. Notably, genes with biological function clustered to immune response were significantly upregulated 4 days after injury, which was not found following 1 day. Osteopontin and one of its receptors, CD-44, were both upregulated showing a local mRNA- and immunoreactivity pattern in and around the injury site. Fewer genes had decreased expression both 1 and 4 days post injury and included genes implicated in transport, metabolism, signalling, and extra cellular matrix formation, e.g. vitronectin, neuroserpin and angiotensinogen.


CONCLUSIONS
The different patterns of gene expression, with little overlap in genes, 1 and 4 days post injury showed time dependence in genomic responses to trauma. An early induction of factors involved in transcription could lead to the later inflammatory response with strongly upregulated CD-44 and osteopontin expression. An increased knowledge of genes regulating the pathological mechanisms in trauma will help to find future treatment targets. Since trauma is a risk factor for development of neurodegenerative disease, this knowledge may also reduce late negative effects.
von Gertten
Christina
C
Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Christina.von.Gertten@cns.ki.se
Flores Morales
Amilcar
A
Holmin
Staffan
S
Mathiesen
Tiit
T
Nordqvist
Ann-Christin Sandberg
AC
D000818:Animals; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley