68 - Trophic Factors and Brain Cell Survival

Abstract

This chapter explains the role of trophic factors in protection and survival of brain cells. Several proteinaceous growth factors and cytokines, produced by neurons and/or glia in response to cerebral ischemia, have been shown to protect neurons against metabolic, excitotoxic, and oxidative insults in cell culture and animal models of ischemic stroke. The endogenous neuroprotective factors (ENFs) include fibroblast growth factors (FGFs), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factors (IGFs), platelet-derived growth factors (PDGFs), tumor necrosis factors (TNFs), transforming growth factor-β (TGFβ), secreted forms of β-amyloid precursor protein (sAPPs), and protease nexin-1. Early cell culture studies of embryonic rat hippocampus show that basic FGF (bFGF) could protect neurons against insults relevant to the pathogenesis of ischemic brain injury including glutamate excitotoxicity, glucose deprivation, hypoxia, and oxidative insults such as exposure to iron. Extension of the cell culture findings to in vivo rodent models of focal cerebral ischemia and transient global forebrain ischemia demonstrates profound neuroprotective actions of centrally administered bFGF. Additional neurotrophic factors that protect brain cells against metabolic, excitotoxic, oxidative, and ischemic insults in cell culture and in vivo include BDNF, neurotrophins 3 and 5, IGFs, and PDGFs.