Effects of Xiaoshuan enteric-coated capsule on neurovascular functions assessed by quantitative multiparametric MRI in a rat model of permanent cerebral ischemia.
BACKGROUND
Buyang Huanwu Decoction (BYHWD) is a Traditional Chinese Medicine (TCM) formula for treating stroke-induced disability. Xiaoshuan enteric-coated capsule (XSECC), derived from the formula BYHWD, is a drug approved by the China Food and Drug Administration (CFDA) for stroke management. To further investigate the potential protective effects of XSECC on neurovascular functions, we endeavour to monitor the neurovascular functions using multimodal magnetic resonance imaging (MRI) and evaluated histopathological changes of neurovascular unit (NVU) after stroke.


METHODS
Ischemic stroke was induced by permanent middle cerebral artery occlusion (pMCAO). XSECC (420 mg/kg) was orally administered 2 h after stroke and daily thereafter. T2-weighted imaging (T2WI), T2 relaxometry mapping and diffusion tensor imaging (DTI) were used to measure cerebral infarct volume, edema and white matter fiber integrity, respectively. Neurochemical metabolite levels were monitored by (1)H-magnetic resonance spectroscopy ((1)H-MRS). Arterial spin labeling (ASL) - cerebral blood flow (CBF) measurements and structural magnetic resonance angiography (MRA) images provided real-time and dynamic information about vascular hemodynamic dysfunction on the 3rd, 7th and 14th days after pMCAO. At the last imaging time point, immunohistochemistry, immunofluorescence as well as transmission electron microscopy (TEM) were used to test the microscopic and ultrastructural changes of NVU.


RESULTS
T2WI, T2 relaxometry mapping and Fractional anisotropy (FA) in DTI showed that XSECC significantly reduced cerebral infarct volume, relieved edema and alleviated nerve fiber injuries, respectively. (1)H-MRS provided information about improvement of neuronal/glial metabolism after XSECC treatment. Moreover, ASL - CBF measurements combined with MRA showed that XSECC significantly increased CBF and vascular signal strength and alleviated ischemia-induced morphological changes of arteries in ischemic hemisphere within 14 days after stroke. In addition, neuron specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), CD34 staining and TEM detection indicated that XSECC not only ameliorated neuronal injury, but also reduced endothelial damage and inhibited astrocyte proliferation.


CONCLUSIONS
Our results suggested that XSECC has multi-target neurovascular protective effects on ischemic stroke, which may be closely correlated with the improvement of cerebral blood supply and neuronal/glial metabolism.
['Zhang|Jian|J|', 'Zou|Haiyan|H|', 'Zhang|Qiuxia|Q|', 'Wang|Lei|L|', 'Lei|Jianfeng|J|', 'Wang|Yali|Y|', 'Ouyang|Junyao|J|', 'Zhang|Yi|Y|', 'Zhao|Hui|H|http://orcid.org/0000-0003-1327-2577']
D000818:Animals D001929:Brain Edema D002214:Capsules D002544:Cerebral Infarction D002560:Cerebrovascular Circulation D004195:Disease Models, Animal D004365:Drugs, Chinese Herbal D008279:Magnetic Resonance Imaging D008297:Male D009412:Nerve Fibers D018696:Neuroprotective Agents D051381:Rats D017207:Rats, Sprague-Dawley
Xiaoshuan enteric-coated capsule Magnetic resonance image Neurovascular unit Ischemic stroke Middle cerebral artery occlusion Cerebral blood flow