UP-REGULATION OF PLEIOTROPHIN GENE-EXPRESSION IN DEVELOPING MICROVASCULATURE, MACROPHAGES, AND ASTROCYTES AFTER ACUTE ISCHEMIC BRAIN INJURY

Pleiotrophin (PTN) is a heparin-binding, 18 kDa secretory protein that functions to induce mitogenesis, angiogenesis, differentiation, and t ransformation in vitro. PTN gene (Ptn) expression is highly regulated during development and is highest at sites in which mitogenesis, angio genesis, and differentiation are active. In striking contrast, with th e exception of the neuron, the Ptn gene is only minimally expressed in adults. We now demonstrate that Ptn gene expression is strikingly upr egulated within 3 d in OX42-positive macrophages, astrocytes, and endo thelial cells in areas of developing neovasculature after focal cerebr al ischemia in adult rat. Ptn gene expression remains upregulated in t hese same cells and sites 7 and 14 d after ischemic injury. However, e xpression of the Ptn gene is significantly decreased in cortical neuro ns 6 and 24 hr after injury and is undetectable in degenerating neuron s at day 3. Neurons in contralateral cortex continue to express Ptn in levels equal to control, uninjured brain. It is suggested that PTN ma y have a vital role in neovascular formation in postischemic brain and that postischemic brain is an important model in which to analyze seq uential gene expression in developing neovasculature. In contrast, Ptn gene expression in injured neurons destined not to recover is strikin gly reduced, and potentially its absence may contribute to the failure of the neuron to survive.