The effect of local mild hypothermia on MMP-2/9 expression and brain edema in experimental intracerebral hemorrhage in rats

Objective To study the effect of local mild hypothermia on the expression of matrix metallopro- teinases-2/9 (MMP-2/9) and brain edema in experimental intracerebral hemorrhage (ICH) in rat. Methods One hundred and forty-five Wistar rats were randomly divided into a normothermia sham-operation (NSO) group ( n = 15 ), a normothermia intracerebral hemorrhage (NICH) group (n = 75 ) and a mild hypotbermia intracerebral hemor- rhage (MHICH) group (n = 75). Autologous arterial blood was stereotaxically injected into the right caudate nucleus of the rats of the NICH and MHICH groups to make intracerebral hemorrhage model. The rats in the MHICH group were then subjected to 4 hours of local mild hypothermia, while those in the NICH group were under the room temper- ature. The brain water content, permeability of brain-blood barrier (BBB) and expressions of MMP-2/9 were meas- ured by immunohistochemistry method at 6 h, 24 h, 72 h, 5 d and 7 d after operation. Results In NICH group, the brain water content, permeability of BBB and expression of MMP-9 all began to increase at 6 h and peaked at 3 d after injection of blood and still higher than the NSO group at 7 d. The expression of MMP-2 only began to increase little at 24 h and peaked at 5 d after operation and remained highly expressed at 7 d. In the MHICH group, the chan- ges of brain water content, permeability of BBB and expression of MMP-9 were similar to those of the NICH group, but the extent of changes was significantly lower at the every time point. In NICH group and MHICH group, MMP-9 expression was positively correlated with both the brain water content and the permeability of BBB, but MMP-2 ex- pression was not correlated with them. Conclusion Mild hypothermia might protect BBB against injury caused by ICH and relieve brain edema and inflammation reaction through inhibiting the expression of MMP-2/9.