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J Med Virol. 2019 Jun;91(6):935-940. doi: 10.1002/jmv.25396. Epub 2019 Jan 17.

Memantine can relieve the neuronal impairment caused by neurotropic virus infection.

Author information

1
Department of Animal Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
2
Research and Development Department, State Key Laboratory of Development of Antibody Drugs, North China Pharmaceutical Group Corporation, Shijiazhuang, China.
3
Department of Science and Technology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
4
Department of Molecular, Cell and Developmental Biology, University of California-Santa Cruz, Santa Cruz, California.
5
Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.
6
Department of Microbiology, College of Life Sciences, Hebei Normal University, Shijiazhuang, China.

Abstract

Neurotropic viruses, such as the rabies virus (RABV) and Japanese encephalitis virus (JEV), induce neuronal dysfunction and complication, causing neuronal damage. Currently, there are still no effective clinical treatments for neuronal injury caused by neurotropic viruses. Memantine, a drug capable of passing through the blood-brain barrier, noncompetitively and reversibly binds to n-methyl- d-aspartic acid (NMDA) receptors. Memantine is used to treat Alzheimer's disease by blocking the activation of extra axonal ion channels, thus preventing neuronal degeneration by inhibiting the abnormal cytosolic Ca 2+ increase. To explore whether memantine can alleviate neurological disturbances caused by RABV and JEV, the following experiments were carried out: (1) for primary neurons cultured in vitro infected with RABV, the addition of memantine showed neuroprotection. (2) In the RABV challenge experiments, memantine had limited therapeutic effect, mildly extending the survival time of mice. In contrast, memantine significantly prolonged the survival time of mice infected with JEV, by reducing the intravascular cuff and inflammatory cell infiltration in mice. Furthermore, memantine decreases the amount of JEV virus in mice brain.

KEYWORDS:

Japanese encephalitis virus; memantine; neurological disturbance; neuroprotective drug; rabies virus

PMID:
30624794
DOI:
10.1002/jmv.25396

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