Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Effects of Sildenafil on the Recovery of Cognitive Function and the Protection of Neuronal Cell Death Following Transient Global Cerebral Ischemia in Gerbils

Version 1 : Received: 21 May 2024 / Approved: 21 May 2024 / Online: 21 May 2024 (12:49:16 CEST)

How to cite: Yu, Y. H.; Kim, G. W.; Lee, Y. R.; Park, D.-K.; Song, B.; Kim, D.-S. Effects of Sildenafil on the Recovery of Cognitive Function and the Protection of Neuronal Cell Death Following Transient Global Cerebral Ischemia in Gerbils. Preprints 2024, 2024051364. https://doi.org/10.20944/preprints202405.1364.v1 Yu, Y. H.; Kim, G. W.; Lee, Y. R.; Park, D.-K.; Song, B.; Kim, D.-S. Effects of Sildenafil on the Recovery of Cognitive Function and the Protection of Neuronal Cell Death Following Transient Global Cerebral Ischemia in Gerbils. Preprints 2024, 2024051364. https://doi.org/10.20944/preprints202405.1364.v1

Abstract

Cerebral ischemic stroke poses a significant global cause of death, with ischemia-reperfusion injury contributing to neuronal cell death and tissue damage. However, significant therapeutic approaches with meaningful treatment effects for patients with ischemic stroke in actual clinical practice are lacking. This study investigated the potential neuroprotective effects of sildenafil, a phosphodiesterase-5 inhibitor, in a global cerebral ischemia model. We explored the impact of sildenafil on GFAP and AQP-4 expression, which are markers associated with astrocyte activation and water homeostasis, respectively. The immunofluorescence analysis revealed that the number of cells co-expressing the markers, which increased in the ischemia-induced group, was significantly reduced in sildenafil-treated groups, suggesting a potential mitigating effect on ischemia-induced astrocyte activation. Additionally, we conducted diverse behavioral tests, including the open-field test, novel object recognition, Barnes maze, Y-maze, and passive avoidance tests, to assess the effect of sildenafil on the cognitive function impaired by ischemia. Cognitive improvements were observed following sildenafil administration (20mg/kg) compared to the untreated group. Taken together, the results presented here suggest sildenafil's potential as a neuroprotective agent for alleviating delayed neuronal cell death and cognitive function impaired by ischemia.

Keywords

global ischemia; reperfusion; sildenafil; behavioral test; neuroprotection

Subject

Medicine and Pharmacology, Neuroscience and Neurology

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