YiQiFuMai powder injection ameliorates blood–brain barrier dysfunction and brain edema after focal cerebral ischemia–reperfusion injury in mice

Abstract

YiQiFuMai powder injection (YQFM) is a modern preparation derived from the traditional Chinese medicine Sheng-Mai-San. YQFM is widely used in clinical practice in the People’s Republic of China, mainly for the treatment of microcirculatory disturbance-related diseases. However, little is known about its role in animals with ischemic stroke. The aim of this study was to examine the effect of YQFM on brain edema and blood–brain barrier (BBB) dysfunction induced by cerebral ischemia–reperfusion (I/R) injury. Male C57BL/6J mice underwent right middle cerebral artery occlusion for 1 hour with a subsequent 24-hour reperfusion to produce I/R injury. YQFM (three doses: 0.336, 0.671, and 1.342 g/kg) was then given intraperitoneally (IP). The results demonstrated that YQFM significantly decreased infarct size, improved neurological deficits, reduced brain water content, and increased cerebral blood flow after I/R injury. 18F-fluorodeoxyglucose micro-positron emission tomography imaging and hematoxylin and eosin staining results indicated that YQFM is able to ameliorate brain metabolism and histopathological damage after I/R. Moreover, YQFM administration reduced BBB leakage and upregulated the expression of zona occludens-1 (ZO-1) and occludin, which was confirmed by Evans Blue extravasation, Western blotting, and immunofluorescence assay. Our findings suggest that YQFM provides protection against focal cerebral I/R injury in mice, possibly by improving BBB dysfunction via upregulation of the expression of tight junction proteins.

YiQiFuMai Powder Injection Protects against Ischemic Stroke via Inhibiting Neuronal Apoptosis and PKCδ/Drp1‐Mediated Excessive Mitochondrial Fission

“…We first investigated the effects of YQFM on rat cerebral I/R injury. We selected the dose (0.957 g/kg) from previous studies performed in mice but adjusted to rats [ 38 ]. According to the body surface area conversion, the dose of mice is about 1.4 times to rats; thus, 0.957 g/kg of YQFM was used in rats in our study.…”

“…Recent studies have also indicated that YQFM protects against ischemic injury through regulating endoplasmic reticulum stress-mediated neuronal damage [ 36 ]. YQFM also ameliorates blood-brain barrier (BBB) dysfunction through NF- κ B and ROCK1/MLC signaling pathways [ 37 , 38 ]. More importantly, YQFM is effective in mitigating myocardial ischemia/reperfusion injury by modulating AMPK activation-mediated mitochondrial fission [ 39 ].…”

<p>The Traditional Chinese Medicine Compound, GRS, Alleviates Blood–Brain Barrier Dysfunction</p>

“…Several reports have demonstrated that Shengmai preparation, administered via injection or orally, and its active ingredients, Rb1 and ruscogenin, exert obvious protective effects against inflammation and BBB damage induced by ischemic brain injury. 16,19,49 However, the beneficial activity of GRS against ischemic stroke and associated mechanisms have not been established until now.…”

“…MCAO was induced in C57BL/6J mice, followed by reperfusion, as reported previously ( Figure 1B). 19 Mice were anesthetized with 4% chloral hydrate (0.1 mL per 10 g body weight, i.p.). Neck vessels were exposed by a midline incision, and the branches of the right external carotid artery carefully isolated and cauterized.…”

Total Glycosides of Cistanche deserticola Promote Neurological Function Recovery by Inducing Neurovascular Regeneration via Nrf-2/Keap-1 Pathway in MCAO/R Rats

“…Reperfusion after cerebral ischemia increases the risk of brain hemorrhage, while leading to neurovascular injury and producing excessive reactive oxygen species (ROS) which damage the blood-brain barrier (Alluri et al, 2015). A number of studies have confirmed that the disruption of the BBB is a major cause of the pathogenesis of ischemic stroke (Cao et al, 2016b).…”