Curcumin ameliorates ischemic stroke injury in rats by protecting the integrity of the blood‑brain barrier

Abstract

The blood-brain barrier (BBB) is critical for proper cerebral homeostasis and its dysfunction during ischemic stroke can result in significant neurological injury. The major goal of the present study was to identify whether curcumin pretreatment possessed protective effects on BBB integrity during the 24 h of acute ischemic brain injury. To investigate the protective effects of curcumin, male Sprague-Dawley rats were divided into multiple groups, including sham, middle cerebral artery occlusion/reperfusion (MCAO/R) vehicle and curcumin pretreated MCAO/R groups. The effects of curcumin were measured by analyzing neurological deficits, infarct size, BBB permeability and expression levels of permeability-related proteins in the brain. It was found that curcumin pretreatment significantly improved neurological scores, decreased infarct size, and protected synaptic remodeling of hippocampal neurons and upregulated the protein expression level of tight junction proteins, ZO-1, occludin and claudin-5 in ischemic rat brains. Furthermore, curcumin pretreatment before stroke was shown to downregulate the phosphorylation of NF-κB and MMP-9, which are central mediators of inflammation. The results from the present study indicated that curcumin pretreatment ameliorated ischemic stroke injury by protecting BBB integrity and synaptic remodeling, as well as inhibiting inflammatory responses.

Hypoxia- and Inflammation-Related Transcription Factor SP3 May Be Involved in Platelet Activation and Inflammation in Intracranial Hemorrhage

“…TIMP1 and PLAUR have been identified in the previous studies as involved in the progression of ICH. Matrix metalloproteinases (MMPs) are the most important degrading enzymes in the pathogenesis of ICH ( 49 ), during extracellular matrix reconstruction and blood–brain barrier disruption ( 50 ). TIMP1 is a major endogenous inhibitor of MMP-9 and was found to be significantly more expressed in the serum of patients with ICH than in normal controls in a study of the Chinese Han patients with ICH ( 51 ).…”

Potential Role of Curcumin for the Treatment of Major Depressive Disorder

“…Perturbations in BBB regulation may contribute to the development of psychiatric disorders, including depression [ 119 – 121 ]. In vitro and animal studies have demonstrated that curcumin can protect the integrity of the BBB after ischemic stroke injury [ 122 ], cerebral ischemia-reperfusion injury [ 123 ], subarachnoid haemorrhage [ 124 ], and hypoxia [ 125 ].…”

Mechanisms Underlying Curcumin-Induced Neuroprotection in Cerebral Ischemia

“…Numerous studies have explored the protective role and mechanism of action of curcumin on BBB after ischemic stroke. Curcumin can protect the integrity of BBB and reduce brain edema by the upregulation of aquaporin 4 and tight junction proteins such as zonula occluden 1 (ZO-1), occludin, and claudin-5, and the downregulation of matrix metalloproteinase 9 (MMP-9), intercellular adhesion molecule-l (ICAM-1), and vascular cell adhesion molecule-l (VCAM-1) ( Li et al, 2017 ; Wang et al, 2019a ; Wicha et al, 2020 ; Wu et al, 2021 ). Furthermore, curcumin attenuates cerebral capillary endothelial cell damage by inhibiting the expression of inducible nitric oxide synthase (iNOS) and the generation of NO(x) (nitrites/nitrates contents), thereby preventing BBB damage ( Jiang et al, 2007 ).…”