title: Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain.
abstract: Cytokines are important intercellular messengers involved in neuron-glia interactions and in the microglial-astroglial crosstalk, modulating the glial response to brain injury and the lesion outcome. In this study, excitotoxic lesions were induced by the injection of N-methyl-D-aspartate in postnatal day 9 rats, and the cytokines interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha) and transforming growth factor beta 1 (TGF-beta1) analysed by ELISA and/or immunohistochemistry. Moreover, cytokine-expressing glial cells were identified by means of double labelling with glial fibrillary acidic protein or tomato lectin binding. Our results show that both neurons and glia were capable of cytokine expression following different patterns in the excitotoxically damaged area vs. the nondegenerating surrounding grey matter (SGM). Excitotoxically damaged neurons showed upregulation of IL-6 and downregulation of TNFalpha and TGF-beta1 before they degenerated. Moreover, in the SGM, an increased expression of neuronal IL-6, TNFalpha and TGF-beta1 was observed. A subpopulation of microglial cells, located in the SGM and showing IL-1beta and TNFalpha expression, were the earliest glial cells producing cytokines, at 2-10 h postinjection. Later on, cytokine-positive glial cells were found within the excitotoxically damaged area and the adjacent white matter: some reactive astrocytes expressed TNFalpha and IL-6, and microglia/macrophages showed mild IL-1beta and TGF-beta1. Finally, the expression of all cytokines was observed in the glial scar. As discussed, this pattern of cytokine production suggests their implication in the evolution of excitotoxic neuronal damage and the associated glial response.
authors.affiliation: Unit of Histology, School of Medicine, Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Bellaterra 08193, Spain. lacarin@servet.uab.es
authors.forename: L
authors.initials: L
authors.lastname: Acarin
authors.forename: B
authors.initials: B
authors.lastname: González
authors.forename: B
authors.initials: B
authors.lastname: Castellano
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000033:anatomy & histology / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D016202:N-Methylaspartate / Q000009:adverse effects; D019579:Neocortex / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016202:N-Methylaspartate