28 January 2019 : Animal Research
Matrix Metalloproteases-Mediated Cleavage on β-Dystroglycan May Play a Key Role in the Blood–Brain Barrier After Intracerebral Hemorrhage in Rats
Xin Zhang1BEG, Yunhe Gu2BG, Peitong Li1C, Anqi Jiang1D, Xiaomeng Sheng3F, Xin Jin4F, Yue Shi1C, Guozhong Li1A*DOI: 10.12659/MSM.908500
Med Sci Monit 2019; 25:794-800
Abstract
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.
Keywords: Blood-Brain Barrier, Cerebral Hemorrhage, Dystroglycans, Matrix Metalloproteinases, Brain Edema, Collagenases, Dipeptides, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9
Editorial
01 February 2025 : Editorial
Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-SmokersDOI: 10.12659/MSM.948255
Med Sci Monit 2025; 31:e948255
In Press
Review article
Hydrogels in Oral Disease Management: A Review of Innovations in Drug Delivery and Tissue RegenerationMed Sci Monit In Press; DOI: 10.12659/MSM.946122
Clinical Research
Procedure Dynamics in Transfemoral vs Transradial Cerebral Angiography: A Retrospective StudyMed Sci Monit In Press; DOI: 10.12659/MSM.947603
Clinical Research
Predicting Cerebral Small Vessel Disease Burden Based on Thromboelastography in Patients with Acute Ischemi...Med Sci Monit In Press; DOI: 10.12659/MSM.946303
Clinical Research
Long-Term Outcomes of Implanon in Managing Adenomyosis: A 3-Year Prospective StudyMed Sci Monit In Press; DOI: 10.12659/MSM.945972
Most Viewed Current Articles
17 Jan 2024 : Review article 6,969,459
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research 701,879
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Mar 2024 : Editorial 25,628
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...DOI :10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
28 Jan 2024 : Review article 20,173
A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and FutureDOI :10.12659/MSM.943912
Med Sci Monit 2024; 30:e943912