Administration of transforming growth factor-alpha reduces infarct volume after transient focal cerebral ischemia in the rat

Growth factors promote cell growth and survival and protect the brain from developing injury after ischemia. In this article, the authors examined whe ther transforming growth factor-alpha (TGF-alpha) was protective in transie nt focal ischemia and whether alteration of cerebral circulation was involv ed. Rats received intraventricular TGF-alpha (50 ng, either split into 2 do ses given 30 minutes before and 30 minutes after middle cerebral artery occ lusion (MCAO), or 1 dose given 30 minutes after MCAO) or vehicle. Rats were subjected to 1-hour intraluminal MCAO and cerebral blood now was recorded continuously by laser-Doppler flowmetry. Infarct volume was measured 1 and 4 days later. The effects of TGF-alpha on arterial tone were assessed in is olated rabbit basilar and common carotid arteries. Transforming growth fact or-alpha before and after ischemia reduced infarct volume by 70% at 1 day a nd 50% at 4 days. Transforming growth factor-a given only after ischemia al so did reduce infarct volume by 70% at 1 day and 80% at 4 days, The protect ive effect was more marked in cortex than in striatum. Transforming growth factor-a did not change cortical microvascular perfusion and did not modify arterial passive tone nor agonist-induced active tone. It can be concluded that TGF-alpha reduces infarct volume, even when the factor is exclusively administered at reperfusion, and that this effect is not mediated by chang es in microvascular perfusion or cerebral arteries. It is therefore suggest ed that TGF-alpha has a protective effect against neuronal cell death after transient focal ischemia.