IMR Press / JIN / Volume 22 / Issue 2 / DOI: 10.31083/j.jin2202026
Open Access Original Research
Therapeutic Treatment with Pycnogenol® Attenuates Ischemic Brain Injury in Gerbils Focusing on Cognitive Impairment, Neuronal Death, BBB Leakage and Neuroinflammation in the Hippocampus
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1 Department of Food Science and Nutrition, Hallym University, 24252 Chuncheon, Gangwon, Republic of Korea
2 Department of Anatomy, College of Korean Medicine, Dongguk University, 38066 Gyeongju, Gyeongbuk, Republic of Korea
3 Department of Emergency Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, 24289 Chuncheon, Gangwon, Republic of Korea
4 Department of Physical Therapy, College of Health Science, Youngsan University, 50510 Yangsan, Gyeongnam, Republic of Korea
5 Department of Biochemistry and Molecular Biology, and Research Institute of Oral Sciences, College of Dentistry, Gangnung-Wonju National University, 25457 Gangneung, Gangwon, Republic of Korea
6 Department of Neurobiology, School of Medicine, Kangwon National University, 24341 Chuncheon, Gangwon, Republic of Korea
7 Department of Pharmacy, College of Pharmacy, Dankook University, 31116 Cheonan, Chungnam, Republic of Korea
8 Department of Surgery, Kangwon National University Hospital, School of Medicine, Kangwon National University, 24289 Chuncheon, Gangwon, Republic of Korea
*Correspondence: mhwon@kangwon.ac.kr (Moo-Ho Won); ijkang@hallym.ac.kr (Il Jun Kang)
These authors contributed equally.
J. Integr. Neurosci. 2023, 22(2), 26; https://doi.org/10.31083/j.jin2202026
Submitted: 14 October 2022 | Revised: 19 November 2022 | Accepted: 29 November 2022 | Published: 10 February 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: A gerbil model of ischemia and reperfusion (IR) injury in the forebrain has been developed for studies on mechanisms, prevention and therapeutic strategies of IR injury in the forebrain. Pycnogenol® (PYC), a standardized extract of French maritime pine tree (Pinus pinaster Aiton) has been exploited as an additive for dietary supplement. In the present study, we investigated the neuroprotective effects of post-treatment with PYC and its therapeutic mechanisms in gerbils. Methods: The gerbils were given sham and IR operation and intraperitoneally injected with vehicle and Pycnogenol® (25, 50 and 100 mg/kg, respectively) immediately, at 24 hours and 48 hours after sham and IR operation. Through 8-arm radial maze test and passive avoidance test, each spatial memory and short-term memory function was assessed. To examine the neuroprotection of Pycnogenol®, we conducted cresyl violet staining, immunohistochemistry for neuronal nuclei, and Fluoro-Jade B histofluorescence. Moreover, we carried out immunohistochemistry for immunoglobulin G (IgG) to investigate blood-brain barrier (BBB) leakage and interleukin-1β (IL-1β) to examine change in pro-inflammatory cytokine. Results: We found that IR-induced memory deficits were significantly ameliorated when 100 mg/kg Pycnogenol® was treated. In addition, treatment with 100 mg/kg Pycnogenol®, not 25 mg/kg nor 50 mg/kg, conferred neuroprotective effect against IR injury. For its mechanisms, we found that 100 mg/kg Pycnogenol® significantly reduced BBB leakage and inhibited the expression of IL-1β. Conclusions: Therapeutic treatment (post-treatment) with Pycnogenol® after IR effectively attenuated ischemic brain injury in gerbils. Based on these results, we suggest that PYC can be employed as an important material for ischemic drugs.

Keywords
immunoglobulin G
neuroprotection
proinflammatory cytokines
pyramidal cell
transient forebrain ischemia
Funding
NRF-2020R1F1A1071973/Basic Science Research Program through the National Research Foundation (NRF) of Korea
NRF-2020R1I1A3068251/Basic Science Research Program through the National Research Foundation (NRF) of Korea
NRF-2020R1I1A1A01070897/Basic Science Research Program through the National Research Foundation (NRF) of Korea
4220200913807/BK21 FOUR
Figures
Fig. 1.
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