Phosphodiesterase-5 Inhibitor Attenuates Anxious Phenotypes and Movement Disorder Induced by Mild Ischemic Stroke in Rats

Yu, Yeon Hee; Kim, Seong-Wook; Kang, Juhyeon; Song, Yejin; Im, Hyuna; Kim, Seo Jeong; Yoo, Dae Young; Lee, Man-Ryul; Park, Dae-Kyoon; Oh, Jae Sang; Kim, Duk-Soo

doi:.0..

Journal of Korean Neurosurgical Society > Accepted Articles

Laboratory Investigation

doi: https://doi.org/10.3340/jkns.2021.0101 [Accepted]

Phosphodiesterase-5 Inhibitor Attenuates Anxious Phenotypes and Movement Disorder Induced by Mild Ischemic Stroke in Rats

Yeon Hee Yu^1,2, Seong-Wook Kim³, Juhyeon Kang^1,2, Yejin Song^1,2, Hyuna Im^1,2, Seo Jeong Kim^1,2, Dae Young Yoo^1,2, Man-Ryul Lee⁴, Dae-Kyoon Park^1,2, Jae Sang Oh⁵

, Duk-Soo Kim^1,2

¹Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea
²BK21 FOUR Project, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea
³Graduate School of New Drug Discovery & Development, Chungnam National University, Daejeon, Republic of Korea
⁴Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan 31151, Republic of Korea
⁵Department of Neurosurgery, College of Medicine, Soonchunhyang University, Cheonan Hospital, Cheonan 31151, Korea, Republic of Korea

Correspondence

Jae Sang Oh ,Tel: +82-41-570-3653, Email: metatron1324@hotmail.com
Duk-Soo Kim ,Tel: +82-41-570-2470, Fax: +82-41-574-1770, Email: dskim@sch.ac.kr

Received: April 20, 2021; Revised: November 17, 2021 Accepted: February 3, 2022. Published online: April 18, 2022.

ABSTRACT

Objective
Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil, a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke.
Methods
We divided the rats into four groups as follows (n = 20, respectively): group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30 + SIL-Pre; and group 4, MCAo30 + SIL-Post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-min before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations.
Results
Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke.
Conclusion
PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

Key Words: Infarction, Middle cerebral artery, Ischemic stroke, Phosphodiesterase 5 inhibitor, Sildenafil Citrate