چکیده:
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.
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