Abstract
The virus known to cause COVID-19, SARS-CoV-2, exhibits severe and complex neurological symptoms. These effects may be attributed to a virus-induced neuroinflammatory environment, warranting exploration of the respiratory centers of the brain, namely the pons and medulla, specifically in relation to neuroinflammation, demyelination, and neuronal death in response to COVID-19. Interestingly, older adults with neurological dysfunction maintained on N-methyl-d-aspartate receptor (NMDAR) antagonists, such as memantine, had reduced incidence and severity of COVID-19. Thus, the present study aimed to evaluate (1) the neuroinflammatory response to COVID-19 in the respiratory centers of the brain, and (2) to assess the extent to which NMDAR antagonists offer neuroprotective measures in the context of COVID-19. In a susceptible mouse model, animals inoculated with SARS-CoV-2 were pre-treated with either memantine or an alternative NMDAR antagonist, ifenprodil. Inoculated animals had poor survival and showed signs of neuroinflammation, evidenced by a reduction in morphological structure, demyelination, and changes in astrocyte and microglial expression in the pons and medulla. Mice pre-treated with memantine showed improved survival when challenged with COVID-19 and a reduction in virus-induced neuroinflammatory impairments. Our findings support the further investigation of memantine for the prevention of COVID-19 induced neuroinflammation and resultant neurological symptoms and shed light on the possible protective mechanism of memantine in the elderly maintained on NMDAR antagonists.
Original language | English |
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Article number | 19603 |
Journal | Scientific Reports |
Volume | 15 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2025 |
Bibliographical note
Publisher Copyright:© The Author(s) 2025.
Funding
The funding statement provided by National Institute on Drug Abuse, F31-DA-057812, American Foundation for Pharmaceutical Education, National Center for Advancing Translational Sciences (Grant No. UL1TR001998).
Funders | Funder number |
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American Foundation for Pharmaceutical Education | |
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse | F31-DA-057812 |
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse | |
National Center for Advancing Translational Sciences (NCATS) | UL1TR001998 |
National Center for Advancing Translational Sciences (NCATS) |
ASJC Scopus subject areas
- General