Korean J Perinatol.  2008 Mar;19(1):42-53.

The neuroprotective effect of transforming growth factor-beta1 via anti-apoptosis on hypoxic-ischemic brain injury in neonatal rats

Affiliations
  • 1Department of Pediatrics, School of Medicine, Catholic University of Daegu, Daegu, Korea. wootykim@cu.ac.kr
  • 2Department of Opthalmology, Dongguk University College of Medicine, Gyeongju, Korea.

Abstract


OBJECTIVE
TGF-beta1 is an important neuronal survival factor to neurons from damage induced by cerebral ischemia. We examined whether treatment with the TGF-beta1 has neuroprotective effects on HI brain injury in neonatal rats using Rice-Vannucci model (in vivo) and in rat brain cortical cell culture induced by hypoxia (in vitro).
METHODS
Seven-day-old Sprague-Dawley (SD) rat pups were subjected to left carotid occlusion followed by 2 hour of hypoxic exposure. At the before and after 30 minutes of HI, the animals were injected intracerebrally with TGF-beta1 0.5 ng/kg. In addition, brain cortical cell culture model using pregnant SD rats for 19 days were experimented and induced for hypoxia cell injury. The cell were treated with TGF-beta1 1 ng/mL, 5 ng/mL and 10 ng/mL separately. and incubated in 1% O2 incubator. Apoptosis was measured in the injured hemispheres 7 days after the HI insults using western blot for pro-apoptotic marker-bax, caspase-3 and anti-apoptotic marker-Bcl-2.
RESULTS
In western blot and real-time PCR showed Caspase-3, Bax and Bax/Bcl-2 levels was reduced and Bcl-2 level was increased in vivo. In brain cortical cell culture, Bcl-2 expression was greater in the group with low dose of TGF-beta1 (1 ng/mL) in western blot.
CONCLUSION
This study thus suggests that the neuroprotective role of TGF-beta1 against HI brain injury is mediated through an anti-apoptotic effect, which offers the possibility of TGF-beta1 application for the treatment of neonatal HI encephalopathy.

Keyword

TGF-beta1; Hypoxic-ischemic; Brain; Apoptosis; Neonatal rat

MeSH Terms

Animals
Anoxia
Apoptosis
Blotting, Western
Brain
Brain Injuries
Brain Ischemia
Caspase 3
Cell Culture Techniques
Incubators
Neurons
Neuroprotective Agents
Rats
Real-Time Polymerase Chain Reaction
Transforming Growth Factor beta1
Caspase 3
Neuroprotective Agents
Transforming Growth Factor beta1
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