Cerebralcare Granule® combined with nimodipine improves cognitive impairment in bilateral carotid artery occlusion rats by reducing lipocalin-2

Abstract

Aims: Clinically, Cerebralcare Granule® (CG) has been widely utilized to treat various types of headache, chronic cerebral insufficiency and other diseases, and the effect is significant. Clinical studies have shown that CG can significantly relieve vascular dementia (VaD), however, the molecular mechanisms haven't been established. To clear the therapeutic mechanisms of CG against VaD, a hypothesis was proposed that CG could treat neurovascular injury by inhibiting the production of lipocalin-2 (LCN 2).

Main methods: 90 dementia rats were selected by water maze test and randomly divided into 6 groups, including nimodipine (NM), CG L (low dose) (0.314 g kg^-1), CG H (high dose) (0.628 g kg^-1), and combined group (CG + NM). And in vitro neuronal cell OGD modeling to evaluate the effect of CG on JAK2/STAT3.

Key findings: CG could significantly shorten the escape latency of two-vessel occlusion (2-VO) rats, increase their exploratory behavior, alleviate the symptoms of VaD and improve the ultrastructural pathological damage of neurovascular unit and accelerate the recovery of cerebral blood perfusion. CG combined with NM is better than NM alone. It was further showed that CG could inhibit the pathogenicity of LCN 2 through JAK2/STAT3 pathway and suppress the production of inflammatory cytokines. It plays a role in the protection of cerebral microvasculature and BBB in 2-VO rats.

Significance: Taken together, there data has supported notion that CG can protect the integrity of cerebral blood vessels and BBB and improve cognitive impairment through mainly inhibiting LCN 2, which provides scientific evidence for clinical application.

Keywords: Cerebralcare Granule®; Cognitive impairment; JAK2/STAT3; Lipocalin-2; Neurovascular unit; Vascular dementia.