Increases in matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 mRNA after cerebral contusion and depolarisation.
Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play major roles in physiological extracellular matrix turnover during normal development and in pathological processes. In brain, increases in MMP activity occur, for example, in multiple sclerosis, Alzheimer's disease, and after head trauma. We examined MMP-9 and TIMP-1, -2, and -3 in events after head trauma. A time-course study was carried out using two different rat injury models, cerebral contusion and depolarisation. Brains were analysed by RT-PCR and in situ hybridisation. We observed a distinct and time-dependent upregulation of MMP-9 and TIMP-1 mRNA in ipsilateral cortical areas. MMP-9 mRNA levels were upregulated 1 day after cerebral contusion with a peak at Day 4. Depolarisation per se, which also occurs after traumatic brain injury, lead to delayed increase of MMP-9 mRNA, 4 days post application. At Day 14, MMP-9 mRNA levels were indistinguishable from controls in both models. TIMP-1 mRNA increases were observed in both models 4 hr after injury, and increased further at Days 1 and 4. At Day 14, mRNA levels declined and were no higher than control levels. No alterations in mRNA levels were noted for TIMP-2 or -3. Our results support earlier reports on MMP-9 involvement in brain injury. It also shows a role for TIMP-1 in the mechanisms of trauma, where depolarisation could be the mechanism responsible for this upregulation.
von Gertten
Christina
C
Department of Clinical Neuroscience, Karolinska Institutet, Section of Neurosurgery, Karolinska Hospital, Stockholm, Sweden.
Holmin
Staffan
S
Mathiesen
Tiit
T
Nordqvist
Ann-Christin Sandberg
AC
D000818:Animals; D006259:Craniocerebral Trauma / Q000378:metabolism* / Q000503:physiopathology; D017931:DNA Primers / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D017931:DNA Primers; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D020780:Matrix Metalloproteinase 9