Stock Ticker

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

  • Hung, E. C. et al. Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with severe acute respiratory syndrome. Clin. Chem. 49, 2108–2109. https://doi.org/10.1373/clinchem.2003.025437 (2003).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yeh, E. A., Collins, A., Cohen, M. E., Duffner, P. K. & Faden, H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics 113, e73–e76. https://doi.org/10.1542/peds.113.1.e73 (2004).

    Article 
    PubMed 

    Google Scholar
     

  • Umakanthan, S. et al. Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Postgrad. Med. J. 96, 753–758. https://doi.org/10.1136/postgradmedj-2020-138234 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, N. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 395, 507–513. https://doi.org/10.1016/S0140-6736(20)30211-7 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Harapan, B. N. & Yoo, H. J. Neurological symptoms, manifestations, and complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19). J. Neurol. 268, 3059–3071. https://doi.org/10.1007/s00415-021-10406-y (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shehata, G. A. et al. Neurological complications of COVID-19: Underlying mechanisms and management. Int. J. Mol. Sci. 22(8), 4081. https://doi.org/10.3390/ijms22084081 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mao, L. et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan China. JAMA Neurol. 77, 683–690. https://doi.org/10.1001/jamaneurol.2020.1127 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Meinhardt, J. et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat. Neurosci. 24, 168–175. https://doi.org/10.1038/s41593-020-00758-5 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, Y. C., Bai, W. Z. & Hashikawa, T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J. Med. Virol. 92, 552–555. https://doi.org/10.1002/jmv.25728 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Song, W. J. et al. Confronting COVID-19-associated cough and the post-COVID syndrome: Role of viral neurotropism, neuroinflammation, and neuroimmune responses. Lancet Respir. Med. 9, 533–544. https://doi.org/10.1016/S2213-2600(21)00125-9 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271–280. https://doi.org/10.1016/j.cell.2020.02.052 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cantuti-Castelvetri, L. et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 370, 856–860. https://doi.org/10.1126/science.abd2985 (2020).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Daly, J. L. et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 370, 861–865. https://doi.org/10.1126/science.abd3072 (2020).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Avdonin, P. P., Rybakova, E. Y., Trufanov, S. K. & Avdonin, P. V. SARS-CoV-2 receptors and their involvement in cell infection. Biochem. (Mosc) Suppl. Ser. A Membr. Cell Biol. 17, 1–11. https://doi.org/10.1134/S1990747822060034 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jackson, C. B., Farzan, M., Chen, B. & Choe, H. Mechanisms of SARS-CoV-2 entry into cells. Nat. Rev. Mol. Cell Biol. 23, 3–20. https://doi.org/10.1038/s41580-021-00418-x (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Butowt, R. & von Bartheld, C. S. The route of SARS-CoV-2 to brain infection: Have we been barking up the wrong tree? Mol. Neurodegener. 17, 20. https://doi.org/10.1186/s13024-022-00529-9 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bilinska, K., von Bartheld, C. S. & Butowt, R. Expression of the ACE2 virus entry protein in the nervus terminalis reveals the potential for an alternative route to brain infection in COVID-19. Front. Cell Neurosci. 15, 674123. https://doi.org/10.3389/fncel.2021.674123 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ortiz, M. E. et al. Heterogeneous expression of the SARS-coronavirus-2 receptor ACE2 in the human respiratory tract. EBioMedicine 60, 102976. https://doi.org/10.1016/j.ebiom.2020.102976 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gao, C. C. et al. Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques. Protein Cell 13, 920–939. https://doi.org/10.1007/s13238-022-00915-5 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wan, D. et al. Neurological complications and infection mechanism of SARS-COV-2. Signal Transduct. Target Ther. 6, 406. https://doi.org/10.1038/s41392-021-00818-7 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vitale-Cross, L., Szalayova, I., Scoggins, A., Palkovits, M. & Mezey, E. SARS-CoV-2 entry sites are present in all structural elements of the human glossopharyngeal and vagal nerves: Clinical implications. bioRxiv https://doi.org/10.1101/2021.12.30.474580 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ellenberger, H. H. & Feldman, J. L. Brainstem connections of the rostral ventral respiratory group of the rat. Brain Res. 513, 35–42. https://doi.org/10.1016/0006-8993(90)91086-v (1990).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Basinger, H. & Hogg, J. P. in StatPearls (2024).

  • Netland, J., Meyerholz, D. K., Moore, S., Cassell, M. & Perlman, S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J. Virol. 82, 7264–7275. https://doi.org/10.1128/JVI.00737-08 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Class, J. et al. Evolution of SARS-CoV-2 in the murine central nervous system drives viral diversification. Nat. Microbiol. 9, 2383–2394. https://doi.org/10.1038/s41564-024-01786-8 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Riyaz Tramboo, S. et al. The critical impacts of cytokine storms in respiratory disorders. Heliyon 10, e29769. https://doi.org/10.1016/j.heliyon.2024.e29769 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ragab, D., Salah Eldin, H., Taeimah, M., Khattab, R. & Salem, R. The COVID-19 cytokine storm; What we know so far. Front. Immunol. 11, 1446. https://doi.org/10.3389/fimmu.2020.01446 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, G. et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J. Clin. Invest. 130, 2620–2629. https://doi.org/10.1172/JCI137244 (2020).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. Lancet 395, 497–506. https://doi.org/10.1016/S0140-6736(20)30183-5 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fernandez-Castaneda, A. et al. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell 185, 2452–2468. https://doi.org/10.1016/j.cell.2022.06.008 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Woodburn, S. C., Bollinger, J. L. & Wohleb, E. S. The semantics of microglia activation: Neuroinflammation, homeostasis, and stress. J. Neuroinflam. 18, 258. https://doi.org/10.1186/s12974-021-02309-6 (2021).

    Article 

    Google Scholar
     

  • Skaper, S. D., Facci, L., Zusso, M. & Giusti, P. An inflammation-centric view of neurological disease: Beyond the neuron. Front. Cell Neurosci. 12, 72. https://doi.org/10.3389/fncel.2018.00072 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Paolicelli, R. C. et al. Synaptic pruning by microglia is necessary for normal brain development. Science 333, 1456–1458. https://doi.org/10.1126/science.1202529 (2011).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Lee, H. G., Lee, J. H., Flausino, L. E. & Quintana, F. J. Neuroinflammation: An astrocyte perspective. Sci. Transl. Med. 15, eadi7828. https://doi.org/10.1126/scitranslmed.adi7828 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lawrence, J. M., Schardien, K., Wigdahl, B. & Nonnemacher, M. R. Roles of neuropathology-associated reactive astrocytes: A systematic review. Acta Neuropathol. Commun. 11, 42. https://doi.org/10.1186/s40478-023-01526-9 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Joshi, A. U. et al. Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration. Nat. Neurosci. 22, 1635–1648. https://doi.org/10.1038/s41593-019-0486-0 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481–487. https://doi.org/10.1038/nature21029 (2017).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Monje, M. & Iwasaki, A. The neurobiology of long COVID. Neuron 110, 3484–3496. https://doi.org/10.1016/j.neuron.2022.10.006 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rejdak, K. & Grieb, P. Adamantanes might be protective from COVID-19 in patients with neurological diseases: Multiple sclerosis, Parkinsonism and cognitive impairment. Mult. Scler. Relat. Disord. 42, 102163. https://doi.org/10.1016/j.msard.2020.102163 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Artusi, C. A. et al. COVID-19 and Parkinson’s disease: What do we know so far? J. Parkinsons Dis. 11, 445–454. https://doi.org/10.3233/JPD-202463 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cortes-Borra, A. & Aranda-Abreu, G. E. Amantadine in the prevention of clinical symptoms caused by SARS-CoV-2. Pharmacol. Rep. 73, 962–965. https://doi.org/10.1007/s43440-021-00231-5 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Muller, T., Riederer, P. & Kuhn, W. Aminoadamantanes: From treatment of Parkinson’s and Alzheimer’s disease to symptom amelioration of long COVID-19 syndrome? Expert Rev. Clin. Pharmacol. 16, 101–107. https://doi.org/10.1080/17512433.2023.2176301 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Volbracht, C., van Beek, J., Zhu, C., Blomgren, K. & Leist, M. Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity. Eur. J. Neurosci. 23, 2611–2622. https://doi.org/10.1111/j.1460-9568.2006.04787.x (2006).

    Article 
    PubMed 

    Google Scholar
     

  • Wu, H. M. et al. Novel neuroprotective mechanisms of memantine: increase in neurotrophic factor release from astroglia and anti-inflammation by preventing microglial activation. Neuropsychopharmacology 34, 2344–2357. https://doi.org/10.1038/npp.2009.64 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Brison, E., Jacomy, H., Desforges, M. & Talbot, P. J. Novel treatment with neuroprotective and antiviral properties against a neuroinvasive human respiratory virus. J. Virol. 88, 1548–1563. https://doi.org/10.1128/JVI.02972-13 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rogawski, M. A. & Wenk, G. L. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer’s disease. CNS Drug Rev. 9, 275–308. https://doi.org/10.1111/j.1527-3458.2003.tb00254.x (2003).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mony, L., Kew, J. N., Gunthorpe, M. J. & Paoletti, P. Allosteric modulators of NR2B-containing NMDA receptors: Molecular mechanisms and therapeutic potential. Br. J. Pharmacol. 157, 1301–1317. https://doi.org/10.1111/j.1476-5381.2009.00304.x (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fischler, P. V., Soyka, M., Seifritz, E. & Mutschler, J. Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review. Front. Pharmacol. 13, 927703. https://doi.org/10.3389/fphar.2022.927703 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Paoletti, P. & Neyton, J. NMDA receptor subunits: Function and pharmacology. Curr. Opin. Pharmacol. 7, 39–47. https://doi.org/10.1016/j.coph.2006.08.011 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhou, Y. et al. Efficacy of ion-channel inhibitors amantadine, memantine and rimantadine for the treatment of SARS-CoV-2 in vitro. Viruses 13(10), 2082. https://doi.org/10.3390/v13102082 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Harandi, A. A. et al. A randomized open-label clinical trial on the effect of Amantadine on post Covid 19 fatigue. Sci. Rep. 14, 1343. https://doi.org/10.1038/s41598-024-51904-z (2024).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aranda-Abreu, G. E., Aranda-Martinez, J. D. & Araujo, R. Use of amantadine in a patient with SARS-CoV-2. J. Med. Virol. 93, 110–111. https://doi.org/10.1002/jmv.26179 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pharmaceuticals, A. (ed Novotech) (2020).

  • NIH. Guidelines for Endpoints in Animal Studies. (National Institute of Health, nih.gov, 2022).

  • Cohen, J. Statistical Power Analysis for the Behavioral Sciences 2nd edn. (Routledge, 1988).


    Google Scholar
     

  • Sullivan, G. M. & Feinn, R. Using effect size-or why the P value is not enough. J. Grad. Med. Educ. 4, 279–282. https://doi.org/10.4300/JGME-D-12-00156.1 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lier, J., Streit, W. J. & Bechmann, I. Beyond activation: Characterizing microglial functional phenotypes. Cells 10(9), 2236. https://doi.org/10.3390/cells10092236 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Parsons, C. G., Danysz, W. & Quack, G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist–a review of preclinical data. Neuropharmacology 38, 735–767. https://doi.org/10.1016/s0028-3908(99)00019-2 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lipton, S. A. Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond. Nat. Rev. Drug Discov. 5, 160–170. https://doi.org/10.1038/nrd1958 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Reisberg, B. et al. Memantine in moderate-to-severe Alzheimer’s disease. N. Engl. J. Med. 348, 1333–1341. https://doi.org/10.1056/NEJMoa013128 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dvoriantchikova, G., Fleishaker, M. & Ivanov, D. Molecular mechanisms of NMDA excitotoxicity in the retina. Sci. Rep. 13, 18471. https://doi.org/10.1038/s41598-023-45855-0 (2023).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Norris, C. M. et al. Electrophysiological mechanisms of delayed excitotoxicity: Positive feedback loop between NMDA receptor current and depolarization-mediated glutamate release. J. Neurophysiol. 96, 2488–2500. https://doi.org/10.1152/jn.00593.2005 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Haroon, E., Miller, A. H. & Sanacora, G. Inflammation, glutamate, and glia: A trio of trouble in mood disorders. Neuropsychopharmacology 42, 193–215. https://doi.org/10.1038/npp.2016.199 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Iovino, L., Tremblay, M. E. & Civiero, L. Glutamate-induced excitotoxicity in Parkinson’s disease: The role of glial cells. J. Pharmacol. Sci. 144, 151–164. https://doi.org/10.1016/j.jphs.2020.07.011 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rothstein, J. D. et al. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16, 675–686. https://doi.org/10.1016/s0896-6273(00)80086-0 (1996).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hardin-Pouzet, H. et al. Glutamate metabolism is down-regulated in astrocytes during experimental allergic encephalomyelitis. Glia 20, 79–85. https://doi.org/10.1002/(sici)1098-1136(199705)20:1%3c79::aid-glia8%3e3.0.co;2-0 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Werner, P., Pitt, D. & Raine, C. S. Multiple sclerosis: Altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Ann. Neurol. 50, 169–180. https://doi.org/10.1002/ana.1077 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Andrews, M. G. et al. Tropism of SARS-CoV-2 for human cortical astrocytes. Proc. Natl. Acad. Sci. U. S. A. 119, e2122236119. https://doi.org/10.1073/pnas.2122236119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Crunfli, F. et al. Morphological, cellular, and molecular basis of brain infection in COVID-19 patients. Proc. Natl. Acad. Sci. U. S. A. 119, e2200960119. https://doi.org/10.1073/pnas.2200960119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sofroniew, M. V. Astrogliosis. Cold Spring Harb. Perspect. Biol. 7, a020420. https://doi.org/10.1101/cshperspect.a020420 (2014).

    Article 
    PubMed 

    Google Scholar
     

  • Jordao, M. J. C. et al. Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science https://doi.org/10.1126/science.aat7554 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Boroujeni, M. E. et al. Inflammatory response leads to neuronal death in human post-mortem cerebral cortex in patients with COVID-19. ACS Chem. Neurosci. 12, 2143–2150. https://doi.org/10.1021/acschemneuro.1c00111 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sun, M. et al. Microglia-astrocyte interaction in neural development and neural pathogenesis. Cells https://doi.org/10.3390/cells12151942 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Matsudaira, T. & Prinz, M. Life and death of microglia: Mechanisms governing microglial states and fates. Immunol. Lett. 245, 51–60. https://doi.org/10.1016/j.imlet.2022.04.001 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • He, X. et al. NLRP3-dependent pyroptosis is required for HIV-1 gp120-induced neuropathology. Cell Mol. Immunol. 17, 283–299. https://doi.org/10.1038/s41423-019-0260-y (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hu, X. et al. Herpes simplex virus 1 induces microglia gasdermin D-dependent pyroptosis through activating the NLR family pyrin domain containing 3 inflammasome. Front. Microbiol. 13, 838808. https://doi.org/10.3389/fmicb.2022.838808 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou, T. et al. Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice. Nat. Commun. 13, 6233. https://doi.org/10.1038/s41467-022-33932-3 (2022).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Konishi, H. et al. Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction. EMBO J. 39, e104464. https://doi.org/10.15252/embj.2020104464 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ito, D. et al. Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res. Mol. Brain Res. 57, 1–9. https://doi.org/10.1016/s0169-328x(98)00040-0 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Walker, D. G. & Lue, L. F. Immune phenotypes of microglia in human neurodegenerative disease: Challenges to detecting microglial polarization in human brains. Alzheimers Res. Ther. 7, 56. https://doi.org/10.1186/s13195-015-0139-9 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shi, F. J. et al. Is Iba-1 protein expression a sensitive marker for microglia activation in experimental diabetic retinopathy. Int. J. Ophthalmol. 14, 200–208. https://doi.org/10.18240/ijo.2021.02.04 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hopperton, K. E., Mohammad, D., Trepanier, M. O., Giuliano, V. & Bazinet, R. P. Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: A systematic review. Mol. Psychiatry 23, 177–198. https://doi.org/10.1038/mp.2017.246 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Carmen, J., Rothstein, J. D. & Kerr, D. A. Tumor necrosis factor-alpha modulates glutamate transport in the CNS and is a critical determinant of outcome from viral encephalomyelitis. Brain Res. 1263, 143–154. https://doi.org/10.1016/j.brainres.2009.01.040 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Okada, K., Yamashita, U. & Tsuji, S. Modulation of Na(+)-dependent glutamate transporter of murine astrocytes by inflammatory mediators. J. UOEH 27, 161–170. https://doi.org/10.7888/juoeh.27.161 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Prow, N. A. & Irani, D. N. The inflammatory cytokine, interleukin-1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitis. J. Neurochem. 105, 1276–1286. https://doi.org/10.1111/j.1471-4159.2008.05230.x (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, T. L. & O’Banion, M. K. Interleukin-1 beta and tumor necrosis factor-alpha suppress dexamethasone induction of glutamine synthetase in primary mouse astrocytes. J. Neurochem. 71, 1436–1442. https://doi.org/10.1046/j.1471-4159.1998.71041436.x (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zou, J. et al. Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons. Neurochem. Int. 56, 577–584. https://doi.org/10.1016/j.neuint.2009.12.021 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Anderson, C. M. & Swanson, R. A. Astrocyte glutamate transport: Review of properties, regulation, and physiological functions. Glia 32, 1–14 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Albrecht, J., Sidoryk-Wegrzynowicz, M., Zielinska, M. & Aschner, M. Roles of glutamine in neurotransmission. Neuron Glia Biol. 6, 263–276. https://doi.org/10.1017/S1740925X11000093 (2010).

    Article 
    PubMed 

    Google Scholar
     

  • Norenberg, M. D. Distribution of glutamine synthetase in the rat central nervous system. J. Histochem. Cytochem. 27, 756–762. https://doi.org/10.1177/27.3.39099 (1979).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Norenberg, M. D. & Martinez-Hernandez, A. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 161, 303–310. https://doi.org/10.1016/0006-8993(79)90071-4 (1979).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chi, H., Chang, H.-Y. & Sang, T.-K. Neuronal cell death mechanisms in major neurodegenerative diseases. Int. J. Mol. Sci. 19(10), 3082. https://doi.org/10.3390/ijms19103082 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • J.A. Rumbaugh, A. N. in Encyclopedia of Neuroscience (ed M.D. Binder, Hirokawa, N., Windhorst, U.) (Springer, 2009).

  • Dorostkar, M. M., Zou, C., Blazquez-Llorca, L. & Herms, J. Analyzing dendritic spine pathology in Alzheimer’s disease: Problems and opportunities. Acta Neuropathol. 130, 1–19. https://doi.org/10.1007/s00401-015-1449-5 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Politi, L. S., Salsano, E. & Grimaldi, M. Magnetic resonance imaging alteration of the brain in a patient with coronavirus disease 2019 (COVID-19) and anosmia. JAMA Neurol. 77, 1028–1029. https://doi.org/10.1001/jamaneurol.2020.2125 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Zachary, M. A. M. a. J. F. in Pathologic Basis of Veterinary Disease (ed James F. Zachary) Ch. 1, (2017).

  • Reichard, R. R. et al. Neuropathology of COVID-19: A spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathol. 140, 1–6. https://doi.org/10.1007/s00401-020-02166-2 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ismail, I. I. & Salama, S. Association of CNS demyelination and COVID-19 infection: An updated systematic review. J. Neurol. 269, 541–576. https://doi.org/10.1007/s00415-021-10752-x (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Neumann, B., Segel, M., Chalut, K. J. & Franklin, R. J. Remyelination and ageing: Reversing the ravages of time. Mult. Scler. 25, 1835–1841. https://doi.org/10.1177/1352458519884006 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mei, F. et al. Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery. eLife https://doi.org/10.7554/eLife.18246 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Irvine, K. A. & Blakemore, W. F. Remyelination protects axons from demyelination-associated axon degeneration. Brain 131, 1464–1477. https://doi.org/10.1093/brain/awn080 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yick, L. W., Tang, C. H., Ma, O. K., Kwan, J. S. & Chan, K. H. Memantine ameliorates motor impairments and pathologies in a mouse model of neuromyelitis optica spectrum disorders. J. Neuroinflam. 17, 236. https://doi.org/10.1186/s12974-020-01913-2 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Alomar, S. Y. et al. Novel mechanism for memantine in attenuating diabetic neuropathic pain in mice via downregulating the spinal HMGB1/TRL4/NF-kB inflammatory axis. Pharmaceuticals 14(4), 307. https://doi.org/10.3390/ph14040307 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dong, H., Yuede, C. M., Coughlan, C., Lewis, B. & Csernansky, J. G. Effects of memantine on neuronal structure and conditioned fear in the Tg2576 mouse model of Alzheimer’s disease. Neuropsychopharmacology 33, 3226–3236. https://doi.org/10.1038/npp.2008.53 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fontaine, R. H. et al. Vulnerability of white matter towards antenatal hypoxia is linked to a species-dependent regulation of glutamate receptor subunits. Proc. Natl. Acad. Sci. U. S. A. 105, 16779–16784. https://doi.org/10.1073/pnas.0803004105 (2008).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Manousi, A. et al. Identification of novel myelin repair drugs by modulation of oligodendroglial differentiation competence. EBioMedicine 65, 103276. https://doi.org/10.1016/j.ebiom.2021.103276 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nabizadeh, F. et al. Autoimmune encephalitis associated with COVID-19: A systematic review. Mult. Scler. Relat. Disord. 62, 103795. https://doi.org/10.1016/j.msard.2022.103795 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Naidu, K. & Tayler, R. Anti N-Methyl-D-Aspartate receptor antibody associated acute demyelinating encephalomyelitis in a patient with COVID-19: A case report. J. Med. Case Rep. 17, 247. https://doi.org/10.1186/s13256-023-03979-x (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, H. et al. Anti-N-methyl-D-aspartate receptor encephalitis after coronavirus disease 2019: A case report and literature review. Medicine 101(35), e30464. https://doi.org/10.1097/MD.0000000000030464 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Oladunni, F. S. et al. Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice. Nat. Commun. 11, 6122. https://doi.org/10.1038/s41467-020-19891-7 (2020).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Malinowska, B., Napiorkowska-Pawlak, D., Pawlak, R., Buczko, W. & Gothert, M. Ifenprodil influences changes in mouse behaviour related to acute and chronic ethanol administration. Eur. J. Pharmacol. 377, 13–19. https://doi.org/10.1016/s0014-2999(99)00393-3 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Poleszak, E. et al. Effects of ifenprodil on the antidepressant-like activity of NMDA ligands in the forced swim test in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 46, 29–35. https://doi.org/10.1016/j.pnpbp.2013.06.001 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schidlitzki, A. et al. A combination of NMDA and AMPA receptor antagonists retards granule cell dispersion and epileptogenesis in a model of acquired epilepsy. Sci. Rep. 7, 12191. https://doi.org/10.1038/s41598-017-12368-6 (2017).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stazi, M. & Wirths, O. Chronic memantine treatment ameliorates behavioral deficits, neuron loss, and impaired neurogenesis in a model of Alzheimer’s disease. Mol. Neurobiol. 58, 204–216. https://doi.org/10.1007/s12035-020-02120-z (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Martinez-Coria, H. et al. Memantine improves cognition and reduces Alzheimer’s-like neuropathology in transgenic mice. Am. J. Pathol. 176, 870–880. https://doi.org/10.2353/ajpath.2010.090452 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, P. et al. Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal-CA1 projection. BMC Neurosci. 22, 41. https://doi.org/10.1186/s12868-021-00647-y (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Minkeviciene, R., Banerjee, P. & Tanila, H. Cognition-enhancing and anxiolytic effects of memantine. Neuropharmacology 54, 1079–1085. https://doi.org/10.1016/j.neuropharm.2008.02.014 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hsu, J. Multiple Comparisons: Theory and Methods (Chapman and Hall/CRC, 1996). https://doi.org/10.1201/b15074.

    Book 

    Google Scholar
     

  • Allen Reference Atlas – Mouse Brain [brain atlas].

  • Daigle, T. L. et al. A suite of transgenic driver and reporter mouse lines with enhanced brain-cell-type targeting and functionality. Cell 174, 465–480. https://doi.org/10.1016/j.cell.2018.06.035 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Harris, J. A. et al. Hierarchical organization of cortical and thalamic connectivity. Nature 575, 195–202. https://doi.org/10.1038/s41586-019-1716-z (2019).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lein, E. S. et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168–176. https://doi.org/10.1038/nature05453 (2007).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Oh, S. W. et al. A mesoscale connectome of the mouse brain. Nature 508, 207–214. https://doi.org/10.1038/nature13186 (2014).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Science, A. I. f. B. Allen Mouse Brain Atlas. (2004).

  • Source link

    Get RawNews Daily

    Stay informed with our RawNews daily newsletter email

    Guess The American Music Awards Nominee Behind This Spider Kid!

    3 exceptional AI stocks to consider buying in the next market pullback

    Iran says reached conclusion on many topics discussed but doesn’t mean deal is imminent

    Charlie Batch Predicts Huge Year From Aaron Rodgers, ‘He Has A PhD In This Offense’