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TRANSFORMING growth factor-β1 (TGF-β1) mRNA is induced from 5 h to 3 days following hypoxic-ischaemic brain injury. Cell death also develops during this time suggesting that extracellular accumulation of this peptide may be involved in the processes that regulate cell loss. We examined the effect of rhTGF-β1 (0, 2.5, 10, 50 ng) injected into the cerebral lateral ventricle of rats 2 h after severe hypoxic-ischaemic brain injury. Histological outcome and B4-isolectin histochemistry were assessed 5 and 2 days, respectively following hypoxia.Treatment with 10 ng TGF-β1 reduced the microglia reaction (p < 0.05), the magnitude of neuronal loss (p < 0.01) and the area of cortical infarction (p < 0.05). Exogenous TGF-β1 given soon after hypoxic-ischaemic brain injury may have therapeutic potential and act by inhibiting the microglial reaction.