Topical application of glial cell line-derived neurotrophic factor reduces ischemic brain injury after permanent middle cerebral artery occlusion in rats

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β (TGF-β) superfamily, plays important roles not only in the differentiation of neurons during normal development, but also in the survival and recovery of many populations of mature neurons. It has been reported that GDNF has protective effects on various injuries of the central and peripheral nervous systems in vitro and in vivo. However, a possible protective effect of GDNF in focal cerebral ischemia, and the exact mechanism of the ameliorative effect of GDNF in brain ischemic injury are not fully understood.

Caspase-1 (interleukin-1β converting enzyme (ICE)), caspase-2 and caspase-3 have been thought to play important roles in ischemic neuronal injury. Expression or upregulation of caspase mRNAs have been reported in some ischemic injury models. Inhibition of caspase family proteases reduced ischemic and excitotoxic neuronal damage, and expression of a dominant negative mutant of ICE or a mutant ICE inhibitory protein in transgenic mice prevented or attenuated ischemic brain injury. Therefore, the progression of ischemic neuronal injuries may be greatly associated with activation of these caspases through an apoptotic process. However, it has been uncertain whether caspases are also induced during, or involved in, neuronal death after permanent middle cerebral artery occlusion (MCAO).