The role of insulin-like growth factor-I in protection and regeneration after transient focal brain ischemia

Stroke represents the principle cause of invalidity in adults. Brain damage as a result of cerebral ischemia is a consequence of necrosis and apoptosis of neurons and glial cells and leads to upregulation of IGF-I expression in the central nervous system. However, maximal IGF-I concentrations are reached only after 5 days or longer. The literature shows that administration of the neurotrophic growth factor IGF-I after induction of focal cerebral ischemia in rats reduces cell death and tissue damage. The purpose of the current project is to investigate the therapeutic potential of IGF-I. We will study:
1) the mechanism involved in the neuroprotective effects of IGF-I administration after induction of focal cerebral ischemia by application of endothelin-1 in rats.
2) the effects of IGF-I on inflammatory responses in the brain.
3) the role of local IGF-I production in neuroprotection and regeneration using cell-specific knock out mice.
4) the therapeutic potential of different ways of IGF-I administration in the endothelin-1 rat model for focal cerebral ischemia.