Abstract
Ischemic stroke is the primary cause of disability and mortality worldwide. Ischemia/reperfusion (I/R)-induced microcirculatory dysfunction and organ injury generally occur after ischemic stroke. Several studies have shown that intermedin (IMD) has a regulating function on cerebral microcirculation and blood-brain barrier via relaxing cerebral vessels and improving the local blood supply after cerebral ischemia. However, a unified conclusion has not been reached, and the underlying mechanism remains unclear. To observe and analyze the changes of cerebral microcirculation perfusion of cerebral IRI by IMD post-treatment in the rats and further explore the mechanism underlying the beneficial effect of IMD on cerebral IRI. Thirty-nine rats were divided into three groups: sham, I/R, and I/R + IMD groups. After IMD ischemia post-treatment, the rat cerebral infarction rate and the degree of neurological deficit were evaluated by TTC staining and neurological function score; the changes in the amount of cerebral microcirculation implantation on the injured side of the rats were observed by laser Doppler; the pathological changes and cell ultrastructure of rat cortex and hippocampus were observed by HE staining and transmission electron microscopy; the neuron apoptosis in the rat cortex and hippocampus was detected by TUNEL staining and immunohistochemical staining. Impaired neurological function, abnormal cortical/hippocampal neuron morphology, and the proportion of cerebral infarction were significantly improved in the IMD group compared with the I/R group, which suggested a possible neuroprotective role of IMD. IMD treatment also increased the average perfusion of cerebral surface microcirculation in rats by astonished 42.7 times. Finally, IMD administration decreased the caspase-3- and Bax-positive cell numbers and apoptotic cell ratio. IMD has a significant protective effect on neuronal damage caused by cerebral I/R in rats by improving cerebral microcirculation and inhibiting apoptosis.
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This work was supported by the Hebei Province Education Department Degree Office Higher Education Postgraduate Innovation Funding Project (No. CXZZBS 2020104).
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This study was approved by the Ethics Committee of the North China University of Science and Technology, China. And all experiments were conducted in accordance with the regulations on the management of laboratory animals promulgated by the Ministry of Science and Technology of the People’s Republic of China (1988, No. 134).
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Guo, X., Yuan, J., Li, M. et al. Neuroprotection of Intermedin Against Cerebral Ischemia/Reperfusion Injury Through Cerebral Microcirculation Improvement and Apoptosis Inhibition. J Mol Neurosci 71, 767–777 (2021). https://doi.org/10.1007/s12031-020-01697-3
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DOI: https://doi.org/10.1007/s12031-020-01697-3