GROWTH-FACTORS AND GANGLIOSIDES AS NEUROPROTECTIVE AGENTS IN EXCITOTOXICITY ACID ISCHEMIA

1. At least two different groups of molecules can be considered neurot rophic factors because they exert a variety of effects upon neural cel ls. The first consists of the numerous families of polypeptide growth factors known to take part in almost all stages of neural cell growth and functioning, including development, differentiation, survival and pathology. The second group also is characterized by extensive complex ity of multiple forms, and consists of the sialic acid-containing glyc osphingolipids or gangliosides. These molecules also take part in the transfer of information from the extracellular milieu to the cell inte rior, and, similarly to growth factors, are participants in such aspec ts as development, differentiation and functioning. 2. In this short o verview, we consider the existing data on the neuroprotective effects of growth factors [e.g., basic fibroblast growth factor (bFGF), epider mal growth factor (EGF) and brain derived neurotrophic factor] and one species of ganglioside (GM1) against retinal ischemia in vivo and cer ebral excitotoxicity in vitro. 3. We used three different experimental models to investigate their relevance to ischemic and excitotoxic con ditions in the retina and have shown that: (a) both bFGF and EGF show highly effective neuroprotection for rat retinal neurons exposed to to xic levels of glutamate or its nonphysiological agonist kainate in vit ro (b) retinal glial cells suffer morphological perturbations after gl utamate or kainate treatment, and this effect depends on neuron-glial interactions; (c) these glial changes can also be corrected by posttre atment with either bFGF or EGF in vitro; (d) with the use of an in viv o animal model involving anterior chamber pressure-induced ischemia in adult rats, either pretreatment by intraperitoneal injection of GM1 o r posttreatment by intraocular injection of the same ganglioside signi ficantly reduces histological damage to inner nuclear regions. 4. Henc e both groups of trophic molecules show interesting features for retin al ischemic treatment. (C) 1998 Elsevier Science Inc.