Abstract
BackgroundUncaria sinensis (US) has long been used in traditional Korean medicine to relieve various nervous-related symptoms and cardiovascular disease. We recently showed the neuroprotective and cerebrovascular protective effects of US on cerebral ischemia; however, its effects on the blood–brain barrier (BBB) are poorly understood. In this study, the effects of partially purified components of US (PPUS) on BBB disruption were investigated in mice subjected to ischemic brain injury.MethodsFocal cerebral ischemia was induced in C57BL/6J mice by photothrombotic cortical ischemia. PPUS was injected intraperitoneally 30 min before ischemic insults. Infarct volume, neurological score, wire-grip test, Evans blue leakage and brain water content were then examined 24 h after ischemic brain injury.ResultsInfarct volume was significantly reduced and neurological deficit and motor deficit were greatly improved in PPUS-pretreated mice relative to those treated with vehicle following photothrombotic cortical ischemia. Brain edema-induced change of Evans blue extravasation and water content in the ipsilateral hemisphere were alleviated by treatment with PPUS. In addition, PPUS significantly reduced ischemic brain injury-induced degradation of tight junction proteins and elevation of matrix metalloproteinase-9 (MMP-9).ConclusionsPPUS prevents cerebral ischemic damage by BBB protection, and these effects were associated with inhibition of tight junction degradation and MMP-9 induction.
Highlights
Uncaria sinensis (US) has long been used in traditional Korean medicine to relieve various nervous-related symptoms and cardiovascular disease
We examined whether preischemic purified components of US (PPUS) treatment ameliorates photothrombotic cortical ischemia-induced blood–brain barrier (BBB) disruption and brain edema and, if so, whether these protective effects are associated with inhibition of tight junction protein degradation and matrix metalloproteinase-9 (MMP-9) elevation in the brain
PPUS attenuated brain infarction and improved functional outcome As shown in Fig. 1a, triphenyltetrazolium chloride (TTC) staining revealed that infarct volume was significantly decreased at 24 h after ischemic brain injury in the 3 mg/kg PPUS-treated mice relative to the vehicle treated mice (38.6 ± 3.8 mm3 vs 53.4 ± 4.1 mm3, respectively, P < 0.05; Fig. 1b)
Summary
Uncaria sinensis (US) has long been used in traditional Korean medicine to relieve various nervous-related symptoms and cardiovascular disease. We recently showed the neuroprotective and cerebrovascular protective effects of US on cerebral ischemia; its effects on the blood–brain barrier (BBB) are poorly understood. The effects of partially purified components of US (PPUS) on BBB disruption were investigated in mice subjected to ischemic brain injury. Limited advances have been made in developing therapies to reduce the deleterious effects of ischemic stroke, whereas efforts in prevention have reduced stroke incidence and mortality [3]. During the acute phase of ischemic stroke, the BBB is the first structure to be injured, and stroke-induced BBB disruption can lead to further progression of brain damage [5]. Degradation of the cerebrovascular ZO-1 and claudin as well as the matrix metalloproteinase (MMP) has been shown to be highly correlated with the dynamic process of BBB disruption after cerebral ischemia [6, 7]. Among MMPs, MMP-9 has been most intensively studied for its
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