Research on the Pathogenesis and Drug Intervention of Cerebrovascular Disease

Cerebrovascular disease, due to brain microvascular lesions, can lead to ischemic or hemorrhagic brain conditions. Clinically, these cause transient or permanent functional impairment, making stroke and vascular dementia serious threats to elderly health. Current interventions include risk factor control, antiplatelet or anticoagulant drugs, and surgical embolectomy. Our laboratory combines neurobiology, vascular pharmacology, physiology, and anatomy, utilizing two-photon and optogenetic techniques to investigate neuron-blood vessel communication and cerebrovascular disease mechanisms. Drug intervention research has led to scientific innovations. We focus on integrating neurovascular biology and cerebrovascular studies of the nervous system. We found that activating nitrative stress-related signaling in cerebral microvessels damages organelles and causes autophagy or apoptosis. We identified signaling patterns associated with cerebral microvessel pathology and demonstrated the potential of calmodulin inhibitors and ONOO— scavengers for cerebrovascular disease. Our team also revealed the communication rules between vascular endothelial and other brain cells under inflammation, using two-photon imaging. We found inflammation-induced BBB damage occurs through P2RX7-mediated activation of the NLRP3 inflammasome, sensitizing Mac-1/ICAM-1 signaling. Recently, our team has focused on intercellular communication, discovering new methods and clues from associated drug targets under pathological conditions.