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

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.

• Authors: 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, Sung Min Cho, Jin Pyeong Jeon
• Journal: Acta neurochirurgica (Acta Neurochir (Wien)) Vol. 165 Issue 8 Pg. 2201-2210 (08 2023) ISSN: 0942-0940 [Electronic] Austria
• PMID: 37380907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.

Chemical References

• oxiracetam
• NLR Family, Pyrin Domain-Containing 3 Protein
• Cyclooxygenase 2
• Anti-Inflammatory Agents
• RNA, Messenger
• Caspases

Topics

• Rats
• Mice
• Humans
• Animals
• NLR Family, Pyrin Domain-Containing 3 Protein
• Rats, Sprague-Dawley
• Cyclooxygenase 2
• Mice, Inbred C57BL
• Neuroblastoma
• Brain Injuries, Traumatic (complications, drug therapy, metabolism)
• Anti-Inflammatory Agents (therapeutic use)
• Cognitive Dysfunction (drug therapy, etiology)
• RNA, Messenger (genetics, metabolism, therapeutic use)
• Caspases (therapeutic use)
• Disease Models, Animal