Investigation of the effect of amantadine sulfate on the dynamics of neuroapoptosis in experimental traumatic brain injury
Keywords:amantadine sulfate, neuroapoptosis, traumatic brain injury
Background. Depending on the nature of brain injury and severity of the victims’ state, mortality in traumatic brain injury (TBI) ranges from 5 to 65 %. The share of necrotic and apoptotic neuron death in the total mass of damaged nerve tissue against the background of TBI is quite variable and depends on many conditions. The purpose: to characterize the effect of amantadine sulfate and 0.9% NaCl solution on DNA fragmentation (apoptosis) of rat cerebral cortex cells following TBI. Materials and methods. The experiments were performed on male rats. An experimental model of severe TBI was created using a pneumatic gun. The therapeutic effect of amantadine sulfate in TBI was evaluated at a dose of 5 mg/kg intravenously twice daily for 8 days. In the control group, 0.9% NaCl at a dose of 2 ml/kg was used. On day 8 after TBI and animal decapitation, samples of the cerebral cortex were taken to further evaluate DNA fragmentation in the cells. The studies were performed by flow cytometry. Results. In the control group, the intensity of DNA fragmentation in the nuclei of neurons of rat cerebral cortex significantly increased by 198.2 % on day 8 after TBI simulation. After the course introduction (for 8 days) of amantadine sulfate at a dose of 5 mg/kg to rats in the acute period of traumatic brain injury, lower values of Sub-G1, on average by 26.2 %, in the nuclei of the cells of the cerebral cortex of rats were determined compared to the same indicator in animals of the control group, but the studied index remained higher than in the group of pseudoperated animals — by 120.1 % (p < 0.05). Conclusions. The post-traumatic period of simulated TBI in rats is accompanied by a significant increase (on average 3-fold) in the level of DNA fragmentation in the nuclei of cortex cells of the brain on 8th experimental day compared to intact animals. By the size of anti-apoptotic effect in the conditions of post-traumatic damage to the brain, therapy with amantadine sulfate solution was significantly better than with the infusion of 0.9% NaCl solution — by an average of 26.2 % (p < 0.05).
Abou El Fadl MH, O'Phelan KH. Management of Traumatic Brain Injury: An Update. Neurosurg Clin N Am. 2018;29(2):213–221.
Smith C. Neurotrauma. Handb Clin Neurol. 2017;145:115–132.
Rickels E. Focus on traumatic brain injury. Eur J Trauma Emerg Surg. 2017;43(6):729–730.
Gardner RC, Dams-O'Connor K, Morrissey MR, Manley GT. Geriatric Traumatic Brain Injury: Epidemiology, Outcomes, Knowledge Gaps, and Future Directions. J Neurotrauma. 2018 Feb 15. doi: 10.1089/neu.2017.5371.
Llompart-Pou JA, Pérez-Bárcena J. Geriatric traumatic brain injury: An old challenge. Med Intensiva. 2019 Jan - Feb;43(1):44-46.
Arun P, Ariyannur PS, Moffett JR et al. Metabolic acetate therapy for the treatment of traumatic brain injury. J Neurotrauma. 2010;27(1):293–298.
Waring P, Kos FJ, Mullbacher A. Apoptosis or programmed cell death. Med. Res. Rev. 2008;11:219-236.
Manskikh VN. Morphological methods of verification and quantification of apoptosis. Bulletin of Siberian Medicine. 2004;1:63-70. (In Russian).
McGinn MJ, Povlishock JT. Pathophysiology of Traumatic Brain Injury. Neurosurgery Clinics of North America. 2016;27(4):397–407.
Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth. 2007;99:4–9.
Mettang M, Reichel SN, Lattke M et al. IKK2/NF–κB signaling protects neurons after traumatic brain injury. FASEB J. 2018;32(4):1916–1932. doi: 10.1096/fj.201700826R.
Khodakivskiy OA, Chereshnyuk IL. Study of the influence adamantane ademol derivatives on DNA fragmentation in the nuclei of neurons in the frontal lobe of the cortex by ischemia-reperfusion in the rat brain. Ukrainskiy visnyk psykhonevrologii. 2013;1(74):26-28. (In Ukrainian).
Carney N, Totten AM, O'Reilly C. Guidelines for the Management of Severe Traumatic Brain Injury 4th Edition Reviewed for evidence–based integrity and endorsed by the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. September 2016/https://braintrauma.org/uploads/03/12/Guidelines for Management of Severe TBI 4th_Edition.pdf.
Hatefi M, Behzadi S, Dastjerdi MM et al. Correlation of Homocysteine with Cerebral Hemodynamic Abnormality, Endothelial Dysfunction Markers, and Cognition Impairment in Patients with Traumatic Brain Injury. World Neurosurg. 2017;97:70–79. doi: 10.1016/j.wneu.2016.09.080.
Eroğlu O, Deniz T, Kisa Ü, Atasoy P, Aydinuraz K. Effect of hypothermia on apoptosis in traumatic brain injury and hemorrhagic shock model. Injury. 2017;48(12):2675–2682. doi: 10.1016/j.injury.2017.09.032.
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