Can the neuroprotective effects of memantine prevent the complications of brain injuries? A systematic review of animal models

Memantine is thought to function as a neuroprotective agent because of its impact on the progression of various neurodegenerative diseases. This study examines memantine's neuroprotective effects in reducing complications resulting from brain injuries. The keywords were searched in the PubMed, Scopus, and Web of Science databases. Human studies were excluded. SYRCLE's RoB was utilized to assess the quality of the studies. Of 1543 articles reviewed up to November 20, 2024, 51 met the established inclusion and exclusion criteria. The results indicated a strong association between memantine administration and: 1) decreased infarct size, reduced number of apoptotic cells, less brain edema, lower oxidative stress index, and diminished inflammatory responses, alongside improved neurobehavioral outcomes in ischemic stroke models; 2) less hematoma expansion, reduced brain edema and damage, decreased inflammation, and notable enhancement in neurobehavioral function and survival in hemorrhagic stroke models, coupled with the prevention of delayed cerebral vasospasm in subarachnoid hemorrhage cases; and 3) diminished brain injury, reduced infarct volume, less oxidative stress, and marked improvement in neurofunctional recovery in traumatic brain injury models. Memantine's potential neuroprotective properties could improve neurofunctional outcomes for patients with acute brain injuries.