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Oxiracetam alleviates anti-inflammatory activity and ameliorates cognitive impairment in the early phase of traumatic brain injury

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Abstract

Background

We aimed to investigate the effects of oxiracetam on cognitive impairment in the early phase of traumatic brain injury (TBI), for which no specific treatment is currently available.

Methods

The in vitro study used a cell injury controller to damage SH-SY5Y cells and evaluate the effect of oxiracetam at a dosage of 100 nM. The in vivo study used a stereotaxic impactor to induce a TBI model in C57BL/6 J mice and analyzed immunohistochemical changes and cognitive function after an intraperitoneal injection of oxiracetam (30 mg/kg/day) for 5 days. The number of mice used in this study was 60. They were divided into three groups (sham, TBI, and TBI with oxiracetam treatment) (20 mice in each group).

Results

The in vitro study showed that oxiracetam treatment resulted in increased superoxide dismutase (SOD)1 and SOD2 mRNA expression. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and interleukin (IL)-1 β were decreased after oxiracetam treatment, along with decreases in intracellular reactive oxygen species production and apoptotic effects. TBI mice treated with oxiracetam exhibited the loss of fewer cortical damaged lesions, less brain edema, and fewer Fluoro-Jade B (FJB)-positive and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-positive cells compared to those without oxiracetam treatment. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and IL-1β were decreased significantly after oxiracetam treatment. These inflammation-related markers, which colocalized with Iba-1-positive or GFAP-positive cells after TBI, were also decreased after oxiracetam treatment. TBI mice treated with oxiracetam had a smaller decrease in preference and more latency time than those not treated with oxiracetam, suggesting the amelioration of impaired cognitive impairment.

Conclusions

Oxiracetam may be helpful in restoring cognitive impairment by ameliorating neuroinflammation in the early phase of TBI.

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Data Availability

Data is available upon possible request.

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Funding

This study is supported by research grants from the Samjin Pharmaceuticals (grant no. 6S190101937S000100), the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2022R1A5A8019303), and Hallym University Research Fund.

Author information

Author notes

  1. Dong Hyuk Youn and Sung Woo Han contributed equally.

Authors and Affiliations

  1. Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Korea

    Dong Hyuk Youn, Sung Woo Han, Jong-Tae Kim, Haesuk Choi, Aran Lee, Nayoung Kim, Harry Jung, Eun Pyo Hong, Chan Hum Park & Younghyurk Lee

  2. Department of Neurosurgery, Yonsei University Wonju College of Medicine, 20, Ilsan-RoGangwon-Do, Wonju, 26426, Korea

    Sung Min Cho

  3. Department of Neurosurgery, Hallym University College of Medicine, 77 Sakju-Ro, Chuncheon, 24253, Korea

    Jin Pyeong Jeon

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  1. Dong Hyuk Youn
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Correspondence to Sung Min Cho or Jin Pyeong Jeon.

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All experiments were approved by the Institutional Animal Care and Use Committee of the participating university (approval no. Hallym2020-51).

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Youn, D.H., Han, S.W., Kim, JT. et al. Oxiracetam alleviates anti-inflammatory activity and ameliorates cognitive impairment in the early phase of traumatic brain injury. Acta Neurochir 165, 2201–2210 (2023). https://doi.org/10.1007/s00701-023-05674-8

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