Investigation of neuroprotective effects of amantadine on experimental traumatic brain injury model

Introduction & Objectives: Traumatic brain injury (TBI) is a leading cause of mortality and permanent or transient neurological disability worldwide. After primary damage, secondary damage processes begin, which last longer and cause loss of neurological function. Neuroinflammation, one of the responses to secondary damage, is an innate immune response to the pathogens or signaling molecules that result from cellular damage. The innate immune system is activated then an inflammatory response begins. In addition, later in the response, lymphocyte and microglia/macrophage activation are observed. The neuroprotective effects of Amantadine have been demonstrated in various experimental animal models and clinical trials. In this study, the objective was to assess the neuroprotective effects of Amantadine, given intraperitoneally, at the 24th hour in a traumatic brain injury model. Material & Methods: In this study, forty male Swiss Albino mice were divided into five groups: Naive (n=8), sham (n=8), control (n=8), 20 mg/kg AMA (n=8), and 40 mg/kg AMA (n=8) injected groups. Closed head trauma was performed by using a weight drop model (75 gr, 9 cm). An hour after the trauma, intraperitoneal saline was injected into the control group and intraperitoneal 20 and 40 mg/kg Amantadine were given to the experimental groups. Neurological evaluations of all the groups were performed with mNSS on the 1st and 24th. The mice were sacrificed 24 hours after the trauma and histopathologic and immunohistochemical findings of the brain tissues were examined and compared with the control group. Results: In the histopathological examinations: 1) Neuronal degeneration significantly decreased with 20 mg/kg Amantadine (p=0.0007, n=8/group). However, when 40 mg/kg Amantadine was administered, it was observed to be statistically not significant (p=0.1745, n=8/group). 2) Microglial activation significantly decreased with 20 mg/kg Amantadine (p=0.0073, n=8/group). When 40 mg/kg Amantadine was given, it was found to be statistically not significant (p>0.9999, n=8/group). 3) Astrocyte activation significantly reduced with 20 mg/kg Amantadine (p=0.0063, n=8/group). However, when 40 mg/kg Amantadine was given, it was determined to be statistically not significant (p=0.3566, n=8/group). 4) In histopathological evaluations, it was observed that cytotoxic edema was significantly reduced in the experimental group given 20 mg/kg Amantadine. Conclusion: In Swiss albino mice, using the weight-drop method, a mild traumatic brain injury model is established that does not cause deterioration in the neurological examination but leads to inflammation at the histopathological level. A single dose of 20 mg/kg Amantadine administered 1-hour post-trauma inhibits neuroinflammation and astrogliosis, contributing to the reduction of secondary damage.