Glia
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Glial cell line-derived neurotrophic factor (GDNF) plays several important roles in the survival and recovery of mature neurons during ischemia. We examined the possibility that the expression of GDNF mRNA and the release of GDNF protein are regulated differentially in cultured astrocytes from the stroke-prone spontaneously hypertensive rat (SHRSP) compared with those from Wistar Kyoto rats (WKY) during hypoxia and reoxygenation (H/R) and after exposure to glutamate and hydrogen peroxide (H(2)O(2)). The mRNA expression was quantitated by reverse transcription-polymerase chain reaction (RT-PCR) based on the fluorescent TaqMan methodology. ⋯ Levels of GDNF mRNA and protein in SHRSP were significantly lower than in WKY. These findings indicate that GDNF production in SHRSP astrocytes was low in response to H/R, glutamate, and H(2)O(2), compared with that observed in WKY. We conclude that the attenuated production of GDNF in astrocytes is involved in neuronal vulnerability in SHRSP during H/R, as GDNF production, which is stimulated by glutamate and H(2)O(2), is closely related to the protective effect against H/R-mediated neurotoxicity.
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The striatum has been implicated as the site of action mediating neurotoxic effects of interleukin-1 (IL-1) during ischemia. However, the molecular mechanisms underlying these events have yet to be fully addressed. In the present study, primary cultures of rat striatal cells were used as a model for the study of IL-1 signaling pathways in the striatum. ⋯ The p38 MAP kinase inhibitor SB203580 failed to inhibit the effects of IL-1 on NF-kB translocation or gene transcription. These studies have demonstrated significant aspects of the IL-1 signaling cascade in cultured striatum. Of particular interest is the finding that IL-1 stimulated activation of p38 MAP kinase and NF-kB in striatal astrocytes exclusively.