COG133 Attenuates the Early Brain Injury Induced by Blood-Brain Barrier Disruption in Experimental Subarachnoid Hemorrhage

Author:

Zhang Yongfa1ORCID,Gao Baocheng1,Ouyang Jingsong1,Tai Bai1,Zhou Shuai2ORCID

Affiliation:

1. Department of Neurosurgery, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China

2. Department of Neurosurgery, The Affiliated Hospital of Kunming University of Science and Technology, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China

Abstract

Subarachnoid hemorrhage (SAH) is a kind of severe hemorrhagic stroke, and early brain injury acted as one of the main causes of death and delayed neurological deficit in patients with subarachnoid hemorrhage. In this process, the function and structural integrity of the blood-brain barrier play an important role. In this study, we have observed whether the apolipoprotein E (apoE) mimetic peptide, COG133, can alleviate early brain injury after subarachnoid hemorrhage. For this purpose, an experimental subarachnoid hemorrhage model was constructed in mice and treated by intravenous injection of COG133 at a dosage of 1 mg/kg. Then, the function and integrity of the blood-brain barrier were detected, and the pyroptosis level of the neuron was determined. The results showed that COG133 could protect blood-brain barrier function and structure integrity, reduce early brain injury, and ameliorate neurological function after subarachnoid hemorrhage. In terms of molecular mechanism, COG133 inhibits blood-brain barrier destruction through the proinflammatory CypA-NF-κB-MMP9 pathway and reduces neuronal pyroptosis by inhibiting NLRP3 inflammasome activation. In conclusion, this study demonstrated that apoE-mimetic peptide, COG133, can play a neuroprotective role by protecting blood-brain barrier function and inhibiting brain cell pyroptosis to reduce early brain injury after subarachnoid hemorrhage.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Health Informatics,Biomedical Engineering,Surgery,Biotechnology

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