Abstract

Background/PurposeIschemic stroke is characterized by high morbidity and mortality worldwide. Matrix metalloproteinase 2 (MMP2), aquaporin (AQP) 4, and AQP9 are linked to permeabilization of the blood-brain barrier (BBB) in cerebral ischemia/reperfusion injury (CIRI). BBB disruption, tissue inflammation, and MMP/AQP upregulation jointly provoke brain edema/swelling after CIRI, while acupuncture and electroacupuncture can alleviate CIRI symptoms. This study evaluated the hypothesis that acupuncture and electroacupuncture can similarly exert neuroprotective actions in a rat model of middle cerebral artery occlusion (MCAO) by modulating MMP2/AQP4/APQ9 expression and inflammatory cell infiltration.MethodsEighty 8-week-old Sprague-Dawley rats were randomly divided into sham group S, MCAO model group M, acupuncture group A, electroacupuncture group EA, and edaravone group ED. The MCAO model was established by placement of a suture to block the middle carotid artery, and reperfusion was triggered by suture removal in all groups except group S. Acupuncture and electroacupuncture were administered at acupoints GV20 (governing vessel-20) and ST36 (stomach-36). Rats in groups A, EA, and ED received acupuncture, electroacupuncture, or edaravone, respectively, immediately after MCAO. Neurological function (assessed using the Modified Neurological Severity Score), infarct volume, MMP2/AQP4/AQP9 mRNA and protein expression, and inflammatory cell infiltration were all evaluated at 24 h post-reperfusion.ResultsAcupuncture and electroacupuncture significantly decreased infarct size and improved neurological function. Furthermore, target mRNA and protein levels and inflammatory cell infiltration were significantly reduced in groups A, EA, and ED vs. group M. However, MMP2/AQP levels and inflammatory cell infiltration were generally higher in groups A and EA than in group ED except MMP2 mRNA levels.ConclusionsAcupuncture and electroacupuncture at GV20 and ST36 both exercised neuroprotective actions in a rat model of MCAO, with no clear differences between groups A and EA. Therefore, acupuncture and electroacupuncture might find utility as adjunctive and complementary treatments to supplement conventional therapy for ischemic stroke.

Highlights

  • Ischemic stroke accounts for more than 80% of all stroke cases and has a high morbidity and mortality worldwide [1,2]

  • Reperfusion occupies an important position in the pathophysiology of cerebral ischemia [4], and many pathological events are associated with cerebral ischemia/reperfusion injury (CIRI)

  • The current study explored the hypothesis that acupuncture alone and electroacupuncture at GV20 and ST36 can confer neuroprotection in a rat model of middle cerebral artery occlusion (MCAO) via attenuation of Matrix metalloproteinase 2 (MMP2)/AQP4/ AQP9 expression and inflammatory cell infiltration in the ischemic brain

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Summary

Introduction

Ischemic stroke accounts for more than 80% of all stroke cases and has a high morbidity and mortality worldwide [1,2]. Reperfusion occupies an important position in the pathophysiology of cerebral ischemia [4], and many pathological events are associated with cerebral ischemia/reperfusion injury (CIRI). These events encompass inflammation, increased production of reactive oxygen species, blood-brain barrier (BBB) disruption, brain edema, necrosis, and apoptosis. Infiltrating leukocytes release interleukin-1b, tumor necrosis factor-a, and interleukin-6, and infiltrating macrophages and neutrophils join leukocytes to induce/activate MMPs. Cerebral inflammatory responses are amplified by the actions of cytokines and MMPs, the disruption of the BBB, and the development of brain edema [5]

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