Nicorandil Exerts Anticonvulsant Effects in Pentylenetetrazol-Induced Seizures and Maximal-Electroshock-Induced Seizures by Downregulating Excitability in Hippocampal Pyramidal Neurons

Zhao, Jing; Liang, Deqing; Xie, Tao; Qiang, Jing; Sun, Qian; Yang, Lan; Wang, Weiping

doi:10.1007/s11064-023-03932-w

Cited by 4 publications

(1 citation statement)

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“…Multiple mechanisms have been implicated in the development of cognitive dysfunction after TBI, including neuronal apoptosis, oxidative stress, inflammatory responses, and neurotransmitter abnormities (Paterno et al., 2017 ). Nicorandil, a K + ‐ATP channel opener, exhibits beneficent effects on the nervous system, including preventing seizures via reducing the excitability of pyramidal neurons (Zhao et al., 2023 ), decreasing cerebral ischemia/reperfusion (I/R) injury (Owjfard et al., 2020 ), improving neuronal mitochondrial dysfunction, antioxidative, and anti‐apoptosis effects (Ravindran et al., 2017 ). Notably, nicorandil has also been reported to improve cognitive impairment (Gupta et al., 2016 ; Singh et al., 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Nicorandil attenuates cognitive impairment after traumatic brain injury via inhibiting oxidative stress and inflammation: Involvement of BDNF and NGF

Tu,

Han,

Liu

et al. 2023

Brain and Behavior

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Background and purposeCognitive impairment is a prevalent adverse consequence of traumatic brain injury (TBI). The neuroprotective effects of nicorandil (N‐(2‐hydroxyethyl)‐nicotinamide nitrate) has been previously documented, yet its protective effects against cognitive dysfunction post‐TBI remain unclear. Hence, the present study was aimed to evaluate whether nicorandil attenuates cognitive dysfunction in TBI rats and the underlying mechanism behind this process.MethodsThe TBI model was established with a controlled cortical impact (CCI). The effects of nicorandil on cognitive dysfunction of rats with TBI were examined through Novel object recognition (NOR) test, Y‐maze test, and Morris water maze (MWM) task. After behavioral tests, hippocampal tissue was collected for Quantitative real‐time PCR, Western blot analysis, and Enzyme‐linked immunosorbent assay (ELISA) assay.ResultsWe observed that nicorandil administration effectively ameliorates learning and memory impairment in TBI rats. Alongside, nicorandil treatment attenuated oxidative stress in the hippocampus of TBI rats, characterized by the decreased reactive oxygen species generation, malondialdehyde, and protein carbonyls levels, and concurrent promotion of antioxidant‐related factors (including superoxide dismutase, glutathione peroxidase, and catalase) activities. Additionally, nicorandil treatment attenuated the inflammatory response in the hippocampus of TBI rat, as evidenced by the upregulated levels of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α (TNF‐α), as well as the downregulated level of IL‐10. Mechanistically, nicorandil treatment significantly enhanced the mRNA and protein levels of neurotrophic factors, brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus of TBI rats.ConclusionThese findings suggest that nicorandil mitigates cognitive impairment after TBI by suppressing oxidative stress and inflammation, potentially through enhancing BDNF and NGF levels.

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