INFUSION OF GDNF INTO THE CEREBRAL SPINAL-FLUID THROUGH 2 DIFFERENT ROUTES - EFFECTS ON BODY-WEIGHT AND CORTICOSPINAL NEURON SURVIVAL

SURVIVAL of axotomized adult rat corticospinal neurons (CSN) is suppor ted by glial cell line-derived neurotrophic factor (GDNF). We have eva luated the trophic effects of intrathecally applied GDNF on CSN surviv al and rat body weight. Body weight reduction is the major side effect of intracerebral neurotrophic factor treatment. GDNF was tested at to tal doses of 30, 100 and 300 mu g over 7 days after axotomy via differ ent application routes: intracerebroventricularly (i.c.v.) and cistern ally (cis). Animals injected i.c.v. displayed severe body weight reduc tion at all doses tested but CSN rescue only at the highest dose. In c ontrast, cis-infusion of GDNF promoted CSN survival at all doses and o nly the highest dose reduced the body weight. These results show that intracisternal, but not i.c.v., GDNF infusion at low doses can promote CSN survival without negatively affecting rat body weight. This findi ng may have implications for the clinic use of GDNF. (C) 1998 Lippinco tt Williams & Wilkins.