Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain

Cytokines are important intercellular messengers involved in neuron-glia in teractions and in the microglial-astroglial crosstalk, modulating the glial response to brain injury and the lesion outcome. In this study, excitotoxi c lesions were induced by the injection of N-methyl-D-aspartate in postnata l day 9 rats, and the cytokines interleukin-1 beta (IL-1 beta), interleukin -6 (IL-6), tumour necrosis factor alpha (TNF alpha) and transforming growth factor beta 1 (TGF-beta 1) analysed by ELISA and/or immunohistochemistry. Moreover, cytokine-expressing glial cells were identified by means of doubl e labelling with glial fibrillary acidic protein or tomato lectin binding. Our results show that both neurons and glia were capable of cytokine expres sion following different patterns in the excitotoxically damaged area vs. t he nondegenerating surrounding grey matter (SGM). Excitotoxically damaged n eurons showed upregulation of IL-6 and downregulation of TNF alpha and TGF- beta 1 before they degenerated. Moreover, in the SGM, an increased expressi on of neuronal IL-6, TNF alpha and TGF-beta 1 was observed. A subpopulation of microglial cells, located in the SGM and showing IL-1 beta and TNF alph a expression, were the earliest glial cells producing cytokines, at 2-10 h postinjection. Later on, cytokine-positive glial cells were found within th e excitotoxically damaged area and the adjacent white matter: some reactive astrocytes expressed TNF alpha and IL-6, and microglia/macrophages showed mild IL-1 beta and TGF-beta 1. Finally, the expression of all cytokines was observed in the glial scar. As discussed, this pattern of cytokine product ion suggests their implication in the evolution of excitotoxic neuronal dam age and the associated glial response.