BRAIN INJURY AND TUMOR NECROSIS FACTORS INDUCE CALBINDIN D-28K IN ASTROCYTES - EVIDENCE FOR A CYTOPROTECTIVE RESPONSE

Calbindin is a 28 kDa calcium-binding protein expressed in restricted neuronal populations in the mammalian brain where it may play a role in protecting neurons against excitotoxic insults. Recent findings indicate that electrical activity and some neurotropic factors can induce the expression of calbindin in neurons. We now report that brain injury, effected by systemic administration of the excitotoxin kainate or mechanical trauma, induces expression of calbindin in cells of the corpus callosum and subcortical white matter. Immunohistochemical analysis using antibodies to the astrocyte-specific proteins (glial fibrillary acidic protein and S-100beta) established the identity of calbindin immunoreactive cells as astrocytes. Because brain injury is known to induce the expression of several neurotrophic factors and cytokines, we employed cultures of hippocampal and neocortical astrocytes to test the hypothesis that such factors can induce expression of calbindin in astrocytes. Tumor necrosis factors (TNFalpha and TNFbeta), cytokines that are expressed in response to brain injury, induced the expression of calbindin in cultured rat hippocampal and neocortical astrocytes. Two neurotrophic factors, basic fibroblast growth factor and nerve growth factor, did not induce calbindin in astrocytes. TNF-treated, calbindin-expressing astrocytes were resistant to acidosis and calcium ionophore toxicity, suggesting that TNFs and calbindin may serve a cytoprotective role in astrocytes in the injured brain.