Matrix Metalloproteases-Mediated Cleavage on β-Dystroglycan May Play a Key Role in the Blood–Brain Barrier After Intracerebral Hemorrhage in Rats

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/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.