Growth factors and gangliosides as neuroprotective agents in excitotoxicity and ischemia.
1. At least two different groups of molecules can be considered neurotrophic factors because they exert a variety of effects upon neural cells. 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 complexity of multiple forms, and consists of the sialic acid-containing glycosphingolipids or gangliosides. These molecules also take part in the transfer of information from the extracellular milieu to the cell interior, and, similarly to growth factors, are participants in such aspects as development, differentiation and functioning. 2. In this short overview, we consider the existing data on the neuroprotective effects of growth factors [e.g., basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and brain-derived neurotrophic factor] and one species of ganglioside (GM1) against retinal ischemia in vivo and cerebral excitotoxicity in vitro. 3. We used three different experimental models to investigate their relevance to ischemic and excitotoxic conditions in the retina and have shown that: (a) both bFGF and EGF show highly effective neuroprotection for rat retinal neurons exposed to toxic levels of glutamate or its nonphysiological agonist kainate in vitro (b) retinal glial cells suffer morphological perturbations after glutamate or kainate treatment, and this effect depends on neuron-glial interactions; (c) these glial changes can also be corrected by posttreatment with either bFGF or EGF in vitro; (d) with the use of an in vivo animal model involving anterior chamber pressure-induced ischemia in adult rats, either pretreatment by intraperitoneal injection of GM1 or posttreatment by intraocular injection of the same ganglioside significantly reduces histological damage to inner nuclear regions. 4. Hence both groups of trophic molecules show interesting features for retinal ischemic treatment.
Hicks
D
D
INSERM CJF 92-02, Centre Hospitalier et Universitaire Régional, Strasbourg, France. hicks@neurochem.u-strasbg.fr
Heidinger
V
V
Mohand-Said
S
S
Sahel
J
J
Dreyfus
H
H
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D005677:G(M1) Ganglioside / Q000627:therapeutic use*; D006133:Growth Substances / Q000627:therapeutic use*; D007511:Ischemia / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012164:Retinal Diseases / Q000188:drug therapy*; D012171:Retinal Vessels / Q000473:pathology
D006133:Growth Substances; D018696:Neuroprotective Agents; D005677:G(M1) Ganglioside