title: Reactive astrogliosis in the neonatal mouse brain and its modulation by cytokines.
abstract: Reactive astrogliosis is a characteristic response of astrocytes to inflammation and trauma of the adult CNS. To assess the hypothesis that cytokines from inflammatory mononuclear cells that accumulate around lesion sites have a role in modulating astrogliosis, this study sought to take advantage of the neonatal system in which astrogliosis is reported to be minimal following injury and in which the immune system is relatively immature compared to adult animals. A nitrocellulose membrane implant into the cortex of postnatal day 3 mice resulted in a tremendous astrogliotic response 4 d later, as measured by glial fibrillary acidic protein (GFAP) immunoreactivity and GFAP content. In contrast, a neonatal stab wound produced limited astroglial response when compared to the adult stab wound. Utilizing the neonatal stab wound model, cytokines were microinjected into the wound site at the time of injury. All cytokines tested (gamma-IFN, IL-1, IL-2, IL-6, TNF-alpha, and M-CSF) resulted in a significantly increased astrogliosis. The specificity of the cytokine response was demonstrated by the inability of human gamma-IFN, but not mouse gamma-IFN, in enhancing neonatal mouse astrogliosis, in accordance with reports that the interaction of gamma-IFN with its receptor occurs in a species-specific manner. We conclude that neonatal astrocytes can become reactive if an adequate injury stimulus is presented, and that the release of immunoregulatory cytokines by cells around lesion sites may be a mechanism that contributes to the production of gliosis.
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Balasingam
authors.forename: T
authors.initials: T
authors.lastname: Tejada-Berges
authors.forename: E
authors.initials: E
authors.lastname: Wright
authors.forename: R
authors.initials: R
authors.lastname: Bouckova
authors.forename: V W
authors.initials: VW
authors.lastname: Yong
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008845:Microinjections; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014951:Wounds, Stab / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D004247:DNA; D013936:Thymidine