BACKGROUND It is well documented that the Blood-Brain barrier (BBB) can be damaged by matrix
metalloproteases (
MMPs) after
intracerebral hemorrhage (ICH), but little is known about the mechanism of this effect. MATERIAL AND METHODS We established an ICH model in rats by injecting
collagenase VII into the striatum. Afterwards,
intraperitoneal injection of these rats with 40 mg/kg
GM6001 (a
MMPs inhibitor). The effects of
GM6001 on ICH were investigated by neurological severity score, brain water content,
Evans blue staining,
hematoxylin-
eosin staining, immunohistochemical staining, and Western blot assays. RESULTS We demonstrated that the neurological damage caused by ICH was relieved at 5 and 7 days following administration of
GM6001. The impaired BBB induced by ICH was improved in response to
GM6001 treatment at around 3 days, as evidenced by alleviated
cerebral edema, decreased
Evans blue extravasation, and a reduction in inflammatory cellular infiltration. Mechanism analysis revealed that ICH induced the generation of β-
dystroglycan cleavage, which could be suppressed by
GM6001 treatment. Furthermore, we found that recombinant MMP2 and MMP9 triggered the cleavage of β-
dystroglycan in vitro, and this action could be inhibited by
GM6001 administration. CONCLUSIONS Taken together, our results suggest that
MMPs-mediated cleavage on β-
dystroglycan may play an important role in BBB after ICH.