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The PDGF B-chain is involved in the ontogenic susceptibility of the developing rat brain to NMDA toxicity.

Authors: Egawa-Tsuzuki, T  Ohno, M  Tanaka, N  Takeuchi, Y  Uramoto, H  Faigle, R  Funa, K  Ishii, Y  Sasahara, M 
Citation: Egawa-Tsuzuki T, etal., Exp Neurol. 2004 Mar;186(1):89-98.
Pubmed: (View Article at PubMed) PMID:14980813
DOI: Full-text: DOI:10.1016/j.expneurol.2003.11.001

Hypoxic-ischemic (H-I) injury to neonatal brains can cause a life-long neuronal deficit because of increased susceptibility in the neonatal period. Excitotoxicity due to overstimulation of the N-methyl-d-aspartate receptor (NMDAR) is assumed to be the basis of the injury. However, the ontogenic profile of the susceptibility does not directly correlate with the levels of NMDAR expression. Platelet-derived growth factor B-chain (PDGF-B) has been reported to protect neurons by suppressing the NMDA-evoked current and translocating the glutamate transporter to the cell membrane. Thus, we assessed the relationship between the susceptibility to H-I injury and the expression of PDGF-B in neonatal rat brain. PDGF-B infusion before and after an intrastriatal NMDA injection significantly reduced the size of the lesions in 7-day-old rats, when they are most susceptible and the neuronal expression of PDGF-B is low. Fourteen-day-old neonatal rats were found to be resistant to NMDA injury, even though NMDARs are expressed at high levels in the brain at this age. Inhibition of PDGF-B protein synthesis by antisense oligodeoxynucleotides increased the size of the NMDA-induced lesions up to 6-fold at postnatal day 14, when PDGF-B is expressed at high levels in neurons. These data suggest that PDGF-B is an important physiological modulator of NMDAR excitability in the developing brain, and that the balance between the expression of NMDAR and PDGF-B partly determines the ontogenic susceptibility to brain injury. Enhancement of the PDGF-B/receptor signal pathway might rescue neonatal brains at risk of H-I injury.

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CRRD Object Information
CRRD ID: 1581758
Created: 2006-10-24
Species: All species
Last Modified: 2006-10-24
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.