Hydrogen improves neurological function through attenuation of blood-brain barrier disruption in spontaneously hypertensive stroke-prone rats.

Satoru Takeuchi,Kentaro Mori,Kimihiro Nagatani,Hiroshi Nawashiro,Takashi Sugawara,Naoki Otani,Kojiro Wada

doi:10.1186/s12868-015-0165-3

Abstract

BackgroundEnhanced oxidative stress occurs in spontaneously hypertensive stroke-prone rats (SHRSP), and is important in blood–brain barrier (BBB) disruption. Hydrogen can exert potent protective cellular effects via reduction in oxidative stress in various diseases. The present study investigated whether long-term hydrogen treatment can improve neurological function outcome in the SHRSP model, and the effects of hydrogen on BBB function, especially the oxidative stress and the activity of matrix metalloproteinases (MMPs) in this model. Fifty-six animals were randomly assigned to 2 groups and treated as follows: SHRSP treated with hydrogen-rich water (HRW) (HRW group, n = 28); and SHRSP treated with regular water (control group, n = 28). The effect of HRW on overall survival and neurological function, and the effects of HRW on reactive oxygen species, BBB function, and MMP activities were examined.ResultsHRW treatment improved neurological function and tended to improve overall survival but without significant difference. The numbers of bleeds and infarcts were lower in the cortex and hippocampus in the HRW group. The HRW group exhibited a significantly lower number of 8-hydroxy-2'-deoxyguanosine-positive cells and vessels of extravasated albumin in the hippocampus compared with the control group. MMP-9 activity was reduced in the hippocampus in the HRW group compared with the control group.ConclusionsThe present study suggests that ingestion of HRW can improve neurological function outcome in the SHRSP model. This beneficial effect may be due to attenuation of BBB disruption via reduction in reactive oxygen species and suppression of MMP-9 activity in the hippocampus.

Highlights

Enhanced oxidative stress occurs in spontaneously hypertensive stroke-prone rats (SHRSP), and is important in blood–brain barrier (BBB) disruption
Physiological data Age-related increases in body weight and blood pressure were observed in both groups, but the physiological data showed no significant differences between the control group and the hydrogen-rich water (HRW) group (Table 1)
Neurological function and overall survival Neurological score was higher in the control group than in the HRW group from 9 to 16 weeks after treatment (Figure 1)

Summary

Introduction

Enhanced oxidative stress occurs in spontaneously hypertensive stroke-prone rats (SHRSP), and is important in blood–brain barrier (BBB) disruption. Hypertensive stroke-prone rats (SHRSP), a substrain of spontaneously hypertensive rats (SHR) derived from Wistar Kyoto rats, develop malignant hypertension at an early age and have an increased incidence of spontaneous hemorrhagic and ischemic strokes [1,2,3]. In this model, cerebral hemorrhage or infarction occurs in 82% of males over 100 days of age and 58% of females over 150 days of age [1]. Several studies showed that MMP activities may be regulated by reactive oxygen species (ROS) [19,20,21]

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