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Neural stem cell depletion and CNS developmental defects after enteroviral infection.
Am J Pathol. 2012 Mar; 180(3):1107-1120.AJ

Abstract

Coxsackieviruses are significant human pathogens causing myocarditis, meningitis, and encephalitis. We previously demonstrated the ability of coxsackievirus B3 (CVB3) to persist within the neonatal central nervous system (CNS) and to target neural stem cells. Given that CVB3 is a cytolytic virus and may therefore damage target cells, we characterized the potential reduction in neurogenesis within the developing brain and the subsequent developmental defects that occurred after the loss of these essential neural stem cells. Neonatal mice were inoculated with a recombinant CVB3 expressing eGFP (eGFP-CVB3), and alterations in neurogenesis and brain development were evaluated over time. We observed a reduction in proliferating cells in CNS neurogenic regions simultaneously with the presence of nestin(+) cells undergoing apoptosis. The size of the brain appeared smaller by histology, and a permanent decrease in brain wet weight was observed after eGFP-CVB3 infection. We also observed an inverse relationship between the amount of virus material and brain wet weight up to day 30 postinfection. In addition, signs of astrogliosis and a compaction of the cortical layers were observed at 90 days postinfection. Intriguingly, partial brain wet weight recovery was observed in mice treated with the antiviral drug ribavirin during the persistent stage of infection. Hence, long-term neurological sequelae might be expected after neonatal enteroviral infections, yet antiviral treatment initiated long after the end of acute infection might limit virus-mediated neuropathology.

Authors+Show Affiliations

Cell and Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, California.Cell and Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, California.Cell and Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, California.Cell and Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, California.Cell and Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, California.Department of Psychology, San Diego State University, San Diego, California.Department of Psychology, San Diego State University, San Diego, California.Cell and Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, California.SDSU Heart Institute and Department of Biology, San Diego State University, San Diego, California.SDSU Heart Institute and Department of Biology, San Diego State University, San Diego, California.Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, California.Cell and Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, California. Electronic address: rfeuer@sciences.sdsu.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22214838

Citation

Ruller, Chelsea M., et al. "Neural Stem Cell Depletion and CNS Developmental Defects After Enteroviral Infection." The American Journal of Pathology, vol. 180, no. 3, 2012, pp. 1107-1120.
Ruller CM, Tabor-Godwin JM, Van Deren DA, et al. Neural stem cell depletion and CNS developmental defects after enteroviral infection. Am J Pathol. 2012;180(3):1107-1120.
Ruller, C. M., Tabor-Godwin, J. M., Van Deren, D. A., Robinson, S. M., Maciejewski, S., Gluhm, S., Gilbert, P. E., An, N., Gude, N. A., Sussman, M. A., Whitton, J. L., & Feuer, R. (2012). Neural stem cell depletion and CNS developmental defects after enteroviral infection. The American Journal of Pathology, 180(3), 1107-1120. https://doi.org/10.1016/j.ajpath.2011.11.016
Ruller CM, et al. Neural Stem Cell Depletion and CNS Developmental Defects After Enteroviral Infection. Am J Pathol. 2012;180(3):1107-1120. PubMed PMID: 22214838.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neural stem cell depletion and CNS developmental defects after enteroviral infection. AU - Ruller,Chelsea M, AU - Tabor-Godwin,Jenna M, AU - Van Deren,Donn A,Jr AU - Robinson,Scott M, AU - Maciejewski,Sonia, AU - Gluhm,Shea, AU - Gilbert,Paul E, AU - An,Naili, AU - Gude,Natalie A, AU - Sussman,Mark A, AU - Whitton,J Lindsay, AU - Feuer,Ralph, Y1 - 2011/12/31/ PY - 2011/07/01/received PY - 2011/10/26/revised PY - 2011/11/14/accepted PY - 2012/1/5/entrez PY - 2012/1/5/pubmed PY - 2012/4/28/medline SP - 1107 EP - 1120 JF - The American journal of pathology JO - Am J Pathol VL - 180 IS - 3 N2 - Coxsackieviruses are significant human pathogens causing myocarditis, meningitis, and encephalitis. We previously demonstrated the ability of coxsackievirus B3 (CVB3) to persist within the neonatal central nervous system (CNS) and to target neural stem cells. Given that CVB3 is a cytolytic virus and may therefore damage target cells, we characterized the potential reduction in neurogenesis within the developing brain and the subsequent developmental defects that occurred after the loss of these essential neural stem cells. Neonatal mice were inoculated with a recombinant CVB3 expressing eGFP (eGFP-CVB3), and alterations in neurogenesis and brain development were evaluated over time. We observed a reduction in proliferating cells in CNS neurogenic regions simultaneously with the presence of nestin(+) cells undergoing apoptosis. The size of the brain appeared smaller by histology, and a permanent decrease in brain wet weight was observed after eGFP-CVB3 infection. We also observed an inverse relationship between the amount of virus material and brain wet weight up to day 30 postinfection. In addition, signs of astrogliosis and a compaction of the cortical layers were observed at 90 days postinfection. Intriguingly, partial brain wet weight recovery was observed in mice treated with the antiviral drug ribavirin during the persistent stage of infection. Hence, long-term neurological sequelae might be expected after neonatal enteroviral infections, yet antiviral treatment initiated long after the end of acute infection might limit virus-mediated neuropathology. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/22214838/Neural_stem_cell_depletion_and_CNS_developmental_defects_after_enteroviral_infection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(11)01080-7 DB - PRIME DP - Unbound Medicine ER -