Infusion of GDNF into the cerebral spinal fluid through two different routes: effects on body weight and corticospinal neuron survival

SURVIVAL of axotomized adult rat corticospinal neurons (CSN) is supported by glial cell line-derived neurotrophic factor (GDNF). We have evaluated the trophic effects of intrathecally applied GDNF on CSN survival and rat body weight. Body weight reduction is the major side effect of intracerebral neurotrophic factor treatment. GDNF was tested at total doses of 30, 100 and 300 mu g over 7 days after axotomy via different application routes: intracerebroventricularly (i.c.v.) and cisternally (cis). Animals injected i.c.v. displayed severe body weight reduction at all doses tested but CSN rescue only at the highest dose. In contrast, cis-infusion of GDNF promoted CSN survival at all doses and only 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 finding may have implications for the clinic use of GDNF. (C) 1998 Lippincott Williams & Wilkins.