Analytical study on the role of platelet-derived growth factor in developing and ischemic brain.

Current project was conducted to know the role of platelet-derived growth factor (PDGF) B-chain in either developing brain or brain subjected to injury.(1) We identified two PDGF-B mRNAs (3.5 and 2.6 kb) expressed in normal rat brain. It was found that the mRNA of 2.6 kb was a truncated form of that of 3.5 kb, and that truncated form of the gene is crucial for PDGF-B translation in the neuron during development or at a acute phase of ischemia of the brain.(2) In hypoxic / ischemic encephalopathy of neonatal rat brain, PDGF-B and β-receptor expression was induced in the neurons surrounding infarction. This fact revealed PDGF-B/β-receptor system plays a role in the survival of neurons in neonatal rat brain.(3) Regenerating renal tubular epithelial cells expressed both PDGF-B and β-receptor after ischemia/reperfusion insult. Inhibitors of PDGF-B, trapidil and Ki6896, prohibited recovery of renal function and suppressed epithelial regeneration. PDGF-B is important for the regeneration of renal tubular epithelial cells after acute injury.(4) Neuronal expression of PDGF-B disappeared prior to apoptotic neuronal death selectively in CA 1 lesion of hippocampus after transient forebrain ischemia, and in retinal ganglion cells after transection of optic nerve. PDGF-B is important for the survival of neurons.(5) Currently, we are testing the function of PDGF-B in neonatal rat brain by introducing anti-sense oligonucleotide, and are getting results to show the importance of PDGF-B in the normal maturation of the brain (unpublished data).(6) We have found that Heparin-binding epidermal growth factor is widely expressed in the brain, and is upregulated in neonate and in the brain after ischemia. Function as a ligand for EGF receptor is suspected in the brain.(7) We reported mutation in the microtubule-associated protein tau in a patient of pallido-nigra-luysian degeneration.(8) We detected mossy fiber sprout in the hippocampus of rat with hereditary epilepsy.