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Rama Khanian1 
, Somayeh Nazari2 , Mohamad Nekahi3 , Sepehr Edalatkhah4 , Davood Farzin5 , Maryam Pazhooha1 , Ali Siahposht-Khachaki *6
, Somayeh Nazari2 , Mohamad Nekahi3 , Sepehr Edalatkhah4 , Davood Farzin5 , Maryam Pazhooha1 , Ali Siahposht-Khachaki *6
1- Department of Physiology and Pharmacology, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Mazandaran, Iran
2- School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari Mazandaran, Iran
3- Department of Neuroscience, school of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran
4- Department of Physiology, Islamic Azad University of Tonekabon Brach, Sari, Mazandaran, Iran
5- School of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran
6- Immunogenetics Research center, Department of Physiology, Mazandaran University of Medical Siences, Sari, Iran
2- School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari Mazandaran, Iran
3- Department of Neuroscience, school of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran
4- Department of Physiology, Islamic Azad University of Tonekabon Brach, Sari, Mazandaran, Iran
5- School of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran
6- Immunogenetics Research center, Department of Physiology, Mazandaran University of Medical Siences, Sari, Iran
Abstract:
Introduction: Despite its substantial contribution to death and long-term neurological impairment worldwide, effective treatment strategies for traumatic brain injury (TBI) remain scarce. Therefore, this study examined the potential of memantine to reduce brain dysfunction following diffuse experimental TBI.
Materials and Methods: Male rats were randomly assigned to seven groups: intact, sham, vehicle (saline), and three memantine-treated groups receiving 10, 20, or 40 mg/kg. Diffuse TBI was induced, followed by intraperitoneal administration of memantine or vehicle 30 minutes post-injury. Neurological performance was assessed using the veterinary coma scale (VCS). Blood–brain barrier (BBB) disruption was evaluated 4–6 h after traumatic brain injury through Evans Blue extravasation analysis. In parallel, vestibulomotor deficits were monitored for 72 h using beam-balance and beam-walk assessments. Histopathological changes were examined with hematoxylin-eosin staining under light microscopy. Brain water content was determined using the wet/dry method, and cerebrospinal fluid (CSF) concentrations of matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were quantified by ELISA.
Results: Memantine treatment at 20 and 40 mg/kg significantly attenuated brain edema and BBB disruption while improving neurological performance compared with vehicle-treated animals (P<0.01 and P<0.001, respectively). CSF MMP-9 levels were markedly reduced in the 40 mg/kg group (P<0.001). In addition, these doses favorably regulated inflammatory markers by decreasing IL-1β and increasing IL-10 levels (P<0.01 and P<0.001, respectively). In contrast, the 10 mg/kg dose showed only modest effects across the measured outcomes.
Conclusion: The present study demonstrates that memantine significantly attenuates TBI-induced neurological deficits, reduces cerebral edema, preserves BBB integrity, and balances pro- and anti-inflammatory cytokines. These findings suggest that memantine may serve as a promising therapeutic strategy for enhancing functional recovery following TBI.
Materials and Methods: Male rats were randomly assigned to seven groups: intact, sham, vehicle (saline), and three memantine-treated groups receiving 10, 20, or 40 mg/kg. Diffuse TBI was induced, followed by intraperitoneal administration of memantine or vehicle 30 minutes post-injury. Neurological performance was assessed using the veterinary coma scale (VCS). Blood–brain barrier (BBB) disruption was evaluated 4–6 h after traumatic brain injury through Evans Blue extravasation analysis. In parallel, vestibulomotor deficits were monitored for 72 h using beam-balance and beam-walk assessments. Histopathological changes were examined with hematoxylin-eosin staining under light microscopy. Brain water content was determined using the wet/dry method, and cerebrospinal fluid (CSF) concentrations of matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were quantified by ELISA.
Results: Memantine treatment at 20 and 40 mg/kg significantly attenuated brain edema and BBB disruption while improving neurological performance compared with vehicle-treated animals (P<0.01 and P<0.001, respectively). CSF MMP-9 levels were markedly reduced in the 40 mg/kg group (P<0.001). In addition, these doses favorably regulated inflammatory markers by decreasing IL-1β and increasing IL-10 levels (P<0.01 and P<0.001, respectively). In contrast, the 10 mg/kg dose showed only modest effects across the measured outcomes.
Conclusion: The present study demonstrates that memantine significantly attenuates TBI-induced neurological deficits, reduces cerebral edema, preserves BBB integrity, and balances pro- and anti-inflammatory cytokines. These findings suggest that memantine may serve as a promising therapeutic strategy for enhancing functional recovery following TBI.
Keywords: Memantine, Neuroprotection, Blood-brain barrier, MMP-9, Interleukins Traumatic brain injury (TBI)
Type of Study: Original |
Subject:
Behavioral Neuroscience
Received: 2022/11/8 | Accepted: 2023/04/17
Received: 2022/11/8 | Accepted: 2023/04/17
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