Cerebral protective effects of gabapentin in a rat model of head injury

Year 2025, Volume: 38 Issue: 3, 273 - 277, 10.10.2025

Ömer Şahin , Fatma Karaca Kara

https://doi.org/10.5472/marumj.1800348

Abstract

Objective: Gabapentin reduces neuronal excitability, oxidative stress, release and/or synthesis of inflammatory mediators. The purpose
of our study is to explore the emerging biochemical and pathological effects of gabapentin in a rat model of head injury.
Materials and Methods: Thirty-two male Sprague-Dawley rats were used. The rats were randomly assigned into four distinct groups,
each consisting of eight subjects: a sham group, a control group, a dexamethasone-treated group, and a gabapentin-treated group. In
brain samples, assessment of malondialdehyde (MDA) levels, glutathione peroxidase (GPx), and superoxide dismutase (SOD) enzyme
activities were evaluated.
Results: Pathological examinations indicated that the cortical injury resulting from trauma was reduced in the group treated with
gabapentin. Traumatic brain injury (TBI) led to a substantial increase in MDA levels within the tissue. Conversely, when examining
the tissue SOD and GPx activities, a significant reduction was observed. The assessment of SOD and GPx activities illustrated that both
the dexamethasone and gabapentin groups exhibited significantly elevated levels in contrast to the control group.
Conclusion: These findings strongly suggest that gabapentin is effective in a head injury model.

Keywords

Gabapentin , Rat model , Head injury , Antioxidant

References

• Abdel-Salam OM, Sleem AA. Study of the analgesic, antiinflammatory, and gastric effects of gabapentin. Drug Discov Ther 2009;3:18-26.
• Rose MA, Kam PC. Gabapentin: pharmacology and its use in pain management. Anaesthesia. 2002;57:451-62. doi: 10.1046/j.0003-2409.2001.02399.x.
• Guedes RP, Bosco LD, Teixeira CM, et al. Neuropathic pain modifies antioxidant activity in rat spinal cord. Neurochem Res 2006;31:603-9. doi: 10.1007/s11064.006.9058-2.
• Lee BS, Jun IG, Kim SH, Park JY. Intrathecal gabapentin increases interleukin-10 expression and inhibits pro-inflammatory cytokine in a rat model of neuropathic pain. J Korean Med Sci 2013;28:308-14. doi: 10.3346/ jkms.2013.28.2.308.
• Dias JM, de Brito TV, de Aguiar Magalhães D, et al. Gabapentin, a synthetic analogue of gamma aminobutyric acid, reverses systemic acute inflammation and oxidative stress in mice. Inflammation 2014;37:1826-36. doi: 10.1007/ s10753.014.9913-2.
• Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 1994;80:291-300. doi: 10.3171/jns.1994.80.2.0291.
• Wodarski R, Clark AK, Grist J, et al. Gabapentin reverses microglial activation in the spinal cord of streptozotocininduced diabetic rats. Eur J Pain 2009;13:807-11. doi:10.1016/j. ejpain.
• Hickey RW, Ferimer H, Alexander HL, et al. Delayed, spontaneous hypothermia reduces neuronal damage after asphyxial cardiac arrest in rats. Crit Care Med 2000 ;28:3511- 6.
• Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-75.
• Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158-69.
• Krzywinski M, Altman N. Points of significance: Nonparametric tests. Nat Methods. 2014 May;11(5):467-8. PMID: 24820360.
• Haarbauer-Krupa J, Pugh MJ, Prager EM, Harmon N, Wolfe J, Yaffe K. Epidemiology of chronic effects of traumatic brain injury. J Neurotrauma 2021;38:3235-47. doi: 10.1089/ neu.2021.0062.
• Kuo GY, Tarzi FP, Louie S, Poblete RA. Neuroinflammation in Traumatic Brain Injury [Internet]. Frontiers In Traumatic Brain Injury. IntechOpen; 2022. Available from: http://dx.doi. org/10.5772/intechopen.105178. Accesed on: 04.03.2025
• Nag S, Manias JL, Stewart DJ. Expression of endothelial phosphorylated caveolin-1 is increased in brain injury. Neuropathol Appl Neurobiol 2009;35:417-26. doi: 10.1111/j.1365-2990.2008.01009.x.
• Tehse J, Taghibiglou C. The overlooked aspect of excitotoxicity: Glutamate-independent excitotoxicity in traumatic brain injuries. Eur J Neurosci 2019 ;49:1157-70. doi: 10.1111/ ejn.14307.
• Baracaldo-Santamaría D, Ariza-Salamanca DF, Corrales- Hernández MG, Pachón-Londoño MJ, Hernandez-Duarte I, Calderon-Ospina CA. Revisiting excitotoxicity in traumatic brain ınjury: from bench to bedside. pharmaceutics 20228;14:152. doi: 10.3390/pharmaceutics14010152.
• Viviani B, Boraso M, Marchetti N, Marinovich M. Perspectives on neuroinflammation and excitotoxicity: a neurotoxic conspiracy? Neurotoxicology 2014;43:10-20. doi: 10.1016/j. neuro.2014.03.004.
• Emmez H, Börcek AÖ, Kaymaz M, et al. Neuroprotective effects of gabapentin in experimental spinal cord injury. World Neurosurg 2010;73:729-34. doi: 10.1016/j.wneu.
• Janero DR. Malondialdehyde and thiobarbituric acidreactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 1990;9:515-40. doi: 10.1016/0891-5849(90)90131-2.
• Zhang W, Xiao S, Ahn DU. Protein oxidation: basic principles and implications for meat quality. Crit Rev Food Sci Nutr 2013;53:1191-201. doi: 10.1080/10408.398.2011.577540.
• Ighodaro OM, Akinloye OA. First line defense antioxidantssuperoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defense grid. Alex J Med 2018;54:287-93. doi:10.1016/j.ajme.2017.09.001
• Tsuru-Aoyagi K, Potts MB, Trivedi A, et al. Glutathione peroxidase activity modulates recovery in the injured immature brain. Ann Neurol 2009;65:540-9. doi: 10.1002/ ana.21600.
• Kale A, Börcek AÖ, Emmez H, et al. Neuroprotective effects of gabapentin on spinal cord ischemia-reperfusion injury in rabbits. J Neurosurg Spine 2011;15:228-37. doi: 10.3171/2011.4.SPINE10583. Erratum in: J Neurosurg Spine 2011;15:344.