Effect of local mild hypothermia on expression of matrix metalloproteinase-9 following intracerebral hemorrhage in rats

Objective To explore the effect of local mild hypothermia on the expression of matrix metalloproteinase-9(MMP-9)following intracerebral hemorrhage in rats.Methods 240 male Wistar rats were randomly divided into two groups:the intracerebral hemorrhage(ICH) group,in which autologous arterial blood were stereotaxically injected into right caudate nucleus;the local mild hypothermia(ICH +H) group,in which the rats were given 4h local mild hypothermia right after the injection of blood.Each group was divided into 6 subgroups:control,6h,24h,72h,5d and 7d after operation;Brain water content(BWC) was determined by dry-wet weight method and the permeability of BBB was measured by Evans-Blue extravasation.RT-PCR and Western blot were respectively used to evaluate MMP-9 mRNA and protein expression.Results In ICH group,compared with control,autologous arterial blood injection significantly increased BWC(P0.01) and the permeability of BBB(P0.05),both began at 6h and peaked at 72h,and thereafter decreased.Both the mRNA and the protein expression of MMP-9 were positively correlated with both the permeability of BBB(r=0.96 and r=0.85 respectively) and BWC(r=0.88 and r=0.78 respectively).In ICH +H group,compared with ICH group,the elevation of BWC and BBB permeability and MMP-9 protein expression were strongly attenuated at all time points by hypothermia treatment(P0.01),while MMP-9 mRNA levels demonstrated a modest attenuation.Conclusions These findings suggest that MMP-9 should be positively correlated with both the permeability of BBB and brain edema formation,and local mild hypothermia can reduce the brain edema formation following ICH by suppressing the elevation of MMP-9 protein expression.