en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><span style="font-size:14px;"><span style="font-family:Tahoma;"><span style="line-height:2;"><strong>Introduction:</strong> 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.<br> <strong>Materials and Methods:</strong> 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&ndash;brain barrier (BBB) disruption was evaluated 4&ndash;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-1&beta; (IL-1&beta;), and interleukin-10 (IL-10) were quantified by ELISA.<br> <strong>Results:</strong> 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-1&beta; 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.<br> <strong>Conclusion:</strong> 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.</span></span></span></div> Memantine, Neuroprotection, Blood-brain barrier, MMP-9, Interleukins Traumatic brain injury (TBI) 0 0 http://bcn.iums.ac.ir/browse.php?a_code=A-10-788-2&slc_lang=en&sid=1 Rama Khanian khanianid.2019@gmail.com 13700319475328460058166 13700319475328460058166 No Department of Physiology and Pharmacology, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Mazandaran, Iran Somayeh Nazari snazari70@yahoo.com 13700319475328460058167 13700319475328460058167 No School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari Mazandaran, Iran Mohamad Nekahi ma.nekahi@gmail.com 13700319475328460058168 13700319475328460058168 No Department of Neuroscience, school of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran Sepehr Edalatkhah Sepehr.edalatkhah@gmail 13700319475328460058169 13700319475328460058169 No Department of Physiology, Islamic Azad University of Tonekabon Brach, Sari, Mazandaran, Iran Davood Farzin Davoodfarzin@gmail.com 13700319475328460058170 13700319475328460058170 No School of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran Maryam Pazhooha dr.mpazhooha@gmail.com 13700319475328460058171 13700319475328460058171 No Department of Physiology and Pharmacology, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Mazandaran, Iran Ali Siahposht-Khachaki a.siahposht@mazums.ac.ir 13700319475328460058165 13700319475328460058165 Yes Immunogenetics Research center, Department of Physiology, Mazandaran University of Medical Siences, Sari, Iran