Electroacupuncture preconditioning reduces ROS generation with NOX4 down-regulation and ameliorates blood-brain barrier disruption after ischemic stroke.

BACKGROUND: Electroacupuncture (EA) is a modern application based on combination of traditional manual acupuncture and electrotherapy that is frequently recommended as an adjuvant treatment for ischemic stroke. EA preconditioning can ameliorate blood-brain barrier (BBB) dysfunction and brain edema in ischemia-reperfusion injury; however, its mechanism remains unclear. This study investigated the preventive effects of EA preconditioning, particularly on BBB injury, followed by a transient middle cerebral artery occlusion (MCAO) model in mice. RESULTS: Mice were treated with EA (20 min) at Baihui (GV20) and Dazhui (GV14) acupoints once a day for 3 days before ischemic injury. Infarct volume, neurological deficits, oxidative stress, Evans blue leakage and brain edema were evaluated at 24 h after ischemia-reperfusion injury. EA preconditioning significantly decreased infarct volume and improved neurological function even after ischemic injury. In addition, both Evans blue leakage and water content were significantly reduced in EA preconditioned mice. Whereas the expression of tight junction proteins, ZO-1 and claudin-5, were remarkably increased by EA preconditioning. Mice with EA preconditioning showed the reduction of astrocytic aquaporin 4, which is involved in BBB permeabilization. In addition, we found that EA preconditioning decreased reactive oxygen species (ROS) in brain tissues after ischemic injury. The expression of NADPH oxidase 4 (NOX4), not NOX2, was significantly suppressed in EA preconditioned mice. CONCLUSIONS: These results suggest that EA preconditioning improve neural function after ischemic injury through diminishing BBB disruption and brain edema. And, the reduction of ROS generation and NOX4 expression by EA preconditioning might be involved in BBB recovery. Therefore, EA may serve as a potential preventive strategy for patients at high risk of ischemic stroke.

Partially purified components of Uncaria sinensis attenuate blood brain barrier disruption after ischemic brain injury in mice.

BACKGROUND: 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; 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. METHODS: Focal 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. RESULTS: Infarct 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). CONCLUSIONS: PPUS prevents cerebral ischemic damage by BBB protection, and these effects were associated with inhibition of tight junction degradation and MMP-9 induction.