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Journal of Korean Neurosurgical Society > Epub ahead of print

doi: https://doi.org/10.3340/jkns.2021.0101    [Epub ahead of print]
Phosphodiesterase-5 Inhibitor Attenuates Anxious Phenotypes and Movement Disorder Induced by Mild Ischemic Stroke in Rats
Yeon Hee Yu1,2 , Seong-Wook Kim3 , Juhyeon Kang1,2 , Yejin Song1,2 , Hyuna Im1,2 , Seo Jeong Kim1,2 , Dae Young Yoo1,2 , Man-Ryul Lee4 , Dae-Kyoon Park1,2 , Jae Sang Oh5 , Duk-Soo Kim1,2
1Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan, Korea
2BK21 FOUR Project, College of Medicine, Soonchunhyang University, Cheonan, Korea
3Graduate School of New Drug Discovery & Development, Chungnam National University, Daejeon, Korea
4Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan, Korea
5Department of Neurosurgery, Cheonan Hospital, College of Medicine, Soonchunhyang University, Cheonan, Korea
Correspondence  Jae Sang Oh ,Tel: +82-41-570-3653, Fax: +82-41-574-1770, 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.
*Yeon Hee Yu and Seong-Wook Kim contributed equally to this work.
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 (SIL), 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-minute 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 inhibitors · Sildenafil citrate
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