Therapeutic Effect of Transforming Growth Factor (TGF)-beta1 in Neonatal Rat Model of Hypoxic-Ischemic Brain Damage

Kwan, Soon Lyoul; Kim, Heng Mi

Abstract

PURPOSE
TGF-beta1 has been shown to rescue cultured neurons from excitotoxic and hypoxic cell death and to reduce infarct size after focal and global ischemia in rats and rabbits. The present study investigated the therapeutic effects of TGF-beta1 in hypoxic ischemic brain damage of neonatal rats.
METHODS
Seven-day postnatal Sprague-Dawley rats underwent unilateral common carotid artery ligation and dissection followed thereafter by exposure to systemic hypoxia with 8% oxygen for 2 hours at 34 degrees C. In 19 rats, 0.05 microgram of TGF-beta1 was injected intracerebroventricularly just after hypoxia ischemia while the remaining 20 rats were injected with vehicle. Neuropathologic examination (Morphometric analyses of brain tissue specimens) were carried out at 30 days of postnatal age, and their brains were categorized as follow: 0=normal; 1=mild atrophy; 2=moderate atrophy; 3=atrophy with cystic cavitation <3 mm; 4=cystic cavitation >3 mm of the cerebral hemisphere ipsilateral to the carotid artery ligation. The width of the ipsilateral hemisphere also was determined on a posterior coronal section and compared with that of the contralateral hemisphere to ascertain the severity of cerebral atrophy/cavitation.
RESULTS
Neuropathologic results showed that 1/19 (5.3%) rats treated with TGF-beta1 showed no brain damage compared with 2/20 (10%) controls. Mild and moderate brain damage occurred in 4 (21%) and 4 (21%) TGF-beta1 treated rats and 6 (30%) and 7 (35%) controls respectively. Cystic cavitation occurred in 10 (53%) TGF-beta1 treated rats and 5 (25%) controls. Interhemispheric diameter ratio in rats treated with TGF-beta1 is 0.66+/- 0.17 and 0.69+/-0.18 in controls. There was no statistically significant difference of brain damage and interhemispheric diameter ratio between TGF-beta1 treated and control rats.
CONCLUSION
The results indicate that in neonatal rat model 0.05 microgram of TGF-beta1 treatment does not protect the hypoxic-ischemic brain damage.