Korean J Pediatr.  2009 May;52(5):594-602. 10.3345/kjp.2009.52.5.594.

Expression of nitric oxide synthase isoforms and N-methyl-D-aspartate receptor subunits according to transforming growth factor-beta1 administration after hypoxic-ischemic brain injury in neonatal rats

• Go HY
• Seo ES
• Kim WT

• KMID: 2281464
• DOI: http://doi.org/10.3345/kjp.2009.52.5.594

Abstract

PURPOSE
Transforming growth factor (TGF)-beta1 reportedly increases neuronal survival by inhibiting the induction of inducible nitric oxide synthase (NOS) in astrocytes and protecting neurons after excitotoxic injury. However, the neuroprotective mechanism of TGF-beta1 on hypoxic-ischemic (HI) brain injury in neonatal rats is not clear. The aim of this study was to determine whether TGF-beta1 has neuroprotective effects via a NO-mediated mechanism and N-methyl-D-aspartate (NMDA) receptor modulation on perinatal HI brain injury. METHODS: Cortical cells were cultured using 19-day-pregnant Sprague-Dawley (SD) rats treated with TGF-beta1 (1, 5, or 10 ng/mL) and incubated in a 1% O2 incubator for hypoxia. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 h of hypoxic exposure (7.5% O2). TGF-beta1 (0.5 ng/kg) was administered intracerebrally to the rats 30 min before HI brain injury. The expressions of NOS and NMDA receptors were measured. RESULTS: In the in vitro model, the expressions of endothelial NOS (eNOS) and neuronal NOS (nNOS) increased in the hypoxic group and decreased in the 1 ng/mL TGF-beta1-treated group. In the in vivo model, the expression of inducible NOS (iNOS) decreased in the hypoxia group and increased in the TGF-beta1-treated group. The expressions of eNOS and nNOS were reversed compared with the expression of iNOS. The expressions of all NMDA receptor subunits decreased in hypoxia group and increased in the TGF-beta1-treated group except NR2C. CONCLUSION: The administration of TGF-beta1 could significantly protect against perinatal HI brain injury via some parts of the NO-mediated or excitotoxic mechanism.

Keyword

Transforming growth factor-beta1; Hypoxia; Ischemia; Excitotoxicity; Nitric oxide synthase; N-methy1-D-aspartate receptors

MeSH Terms

Animals
Anoxia
Astrocytes
Brain
Brain Injuries
Incubators
Ischemia
N-Methylaspartate
Neurons
Neuroprotective Agents
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Rats
Receptors, N-Methyl-D-Aspartate
Transforming Growth Factor beta1
Transforming Growth Factors
N-Methylaspartate
Neuroprotective Agents
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Receptors, N-Methyl-D-Aspartate
Transforming Growth Factor beta1
Transforming Growth Factors