Heparin-binding growth-associated molecule is a potent neurotrophic factor. To obtain a better understanding of its role in the central nervous system, we studied the changes of its expression in adult rat brain after two types of neuronal injury. In the control hippocampus, expression of heparin-binding growth-associated molecule messenger RNA was confined to CA1 pyramidal neurons and some hilar cells. Following transient forebrain ischaemia, the messenger RNA expression decreased within the first two days. On day 4, however, both the messenger RNA level and the number of expression-positive cells markedly increased in the CA1 subfield, where the selective neuronal losses were seen following ischaemia. Double-staining with a heparin-binding growth-associated molecule complementary RNA probe and an anti-glial fibrillary acidic protein antibody revealed that most of the expressing cells were reactive astrocytes. Moreover, the protein induction of heparin-binding growth-associated molecule after neuronal injury was demonstrated by immunohistochemistry using the affinity-purified antibodies. This molecule was also induced after intraventricular kainate injection, which is known to cause selective pyramidal cell necrosis in the CA3 region. Four days after the insult, the number of cells expressing the messenger RNA prominently increased in the CA3 subfield ipsilateral to the injection. As observed after the ischaemic insult, most of the expression-positive cells were identified as astrocytes. The data presented here suggest that heparin-binding growth-associated molecule, produced by the reactive astrocytes, may play important roles in the repair process after neuronal injury.
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