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Effects of nicorandil on neurobehavioral function, BBB integrity, edema and stereological parameters of the brain in the sub-acute phase of stroke in a rat model

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Abstract

Blood–brain barrier (BBB) disruption, inflammation, and cell death are the pathogenic mechanisms of cerebral ischemia/reperfusion (I/R) injury. Nicorandil protects ischemic injury via some of these mechanisms. The aim of this study was to investigate the therapeutic effects of this drug on the brain ischemia after transient middle cerebral artery occlusion (MCAO) and clarify the NF-κB and Nrf2-dependent mechanisms modulated by this drug. Sixty-six rats were randomized into sham, MCAO and MCAO + nicorandil groups with oral gavage for 3 days. Cerebral I/R injury were induced by a transient MCAO for 1 h and neurobehavioral scores were performed for 3 days. In addition to measurement of BBB disruption and brain water content, the total and infarct volume, density, and total number of neurons, non-neurons and dead neurons in the right cortex were estimated by unbiased stereological methods. RT-PCR was performed to analyze the expression levels of NF-κB and Nrf2. Although nicorandil treatment in the sub-acute brain ischemia did not have a prominent effect on neurobehavioral function and number of neurons, non-neurons and dead neurons probably through up-regulation of NF-κB, it, however, improved ischemia-induced BBB disruption and brain edema and showed a significant reduction in the infarction volume probably through up-regulation of Nrf2.

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Acknowledgements

The authors wish to thank Mr. H Argasi at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for his invaluable assistance in editing this manuscript. The present article was extracted from a PhD thesis was written by MO, and was financially supported by Shahid Beheshti University, Tehran, Iran.

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Authors and Affiliations

  1. Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

    Maryam Owjfard & Mohammad Reza Bigdeli

  2. Institute for Cognitive and Brain Science, Shahid Beheshti University, Tehran, Iran

    Mohammad Reza Bigdeli

  3. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Anahid Safari

  4. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Reza Namavar

  5. Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Reza Namavar

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  1. Maryam Owjfard
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  2. Mohammad Reza Bigdeli
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Correspondence to Mohammad Reza Bigdeli or Mohammad Reza Namavar.

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Communicated by Neeraj Jain.

Corresponding editor: Neeraj Jain

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Owjfard, M., Bigdeli, M.R., Safari, A. et al. Effects of nicorandil on neurobehavioral function, BBB integrity, edema and stereological parameters of the brain in the sub-acute phase of stroke in a rat model. J Biosci 45, 49 (2020). https://doi.org/10.1007/s12038-020-0021-1

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