"NMDA receptor antagonists mitigate COVID-19-induced neuroinflammation " by Emily R. Prantzalos, Jane P. Chesser et al.
 

NMDA receptor antagonists mitigate COVID-19-induced neuroinflammation and improve survival in a mouse model

Authors

Emily R. Prantzalos, Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, 789 S. Limestone Street, 473 Lee T. Todd Jr. Building, Lexington, KY, 40536-0596, USA.
Jane P. Chesser, Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, 789 S. Limestone Street, 473 Lee T. Todd Jr. Building, Lexington, KY, 40536-0596, USA.
Judy Songrady Logan, Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, 789 S. Limestone Street, 473 Lee T. Todd Jr. Building, Lexington, KY, 40536-0596, USA.
Kristen A. McLaurin, Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, 789 S. Limestone Street, 473 Lee T. Todd Jr. Building, Lexington, KY, 40536-0596, USA.
Charles D. Anderson, Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY, USA.
Jon D. Gabbard, Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY, USA.
William E. Severson, Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY, USA.
Kenneth E. Palmer, Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY, USA.
Bobbi Jo Mullins, Advocate Health - MidwestFollow
Linda Dwoskin, Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, 789 S. Limestone Street, 473 Lee T. Todd Jr. Building, Lexington, KY, 40536-0596, USA.
Jill R. Turner, Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, 789 S. Limestone Street, 473 Lee T. Todd Jr. Building, Lexington, KY, 40536-0596, USA. Jill.Turner@uky.edu.

Affiliations

Advocate Condell Medical Center

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.

Document Type

Article

PubMed ID

40467606


 

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