Effects of coencapsulated NGF and GM1 in rats with cortical lesions.
Nerve growth factor (NGF) and monosialoganglioside GM1 were microencapsulated in biodegradable co-polymer poly(L-lactide):co-glycolide and administered locally to rats with unilateral cortical devascularizing lesions. Microcapsules were placed directly onto the lesioned cortical surface and rats were sacrificed 30 days post-operatively. Biochemical and quantitative immunocytochemical analyses revealed effective protection from degenerative changes of nucleus basalis magnocellularis (NBM) cholinergic neurones on the lesioned side as well as a significant increase in choline acetyltransferase activity in the frontoparietal cortex surrounding the lesion. Results of this study strongly suggest that the topical application of microcapsules of a biodegradable polymer containing a mixture of two neuroprotective factors is a viable alternative to the use of osmotic minipumps for delivery of these agents into the CNS. Indeed, this approach might find clinical applications.
Maysinger
D
D
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Filipovic-Grcic
J
J
Cuello
A C
AC
D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000293:injuries*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004339:Drug Compounding; D004343:Drug Implants; D004655:Emulsions; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D009410:Nerve Degeneration / Q000187:drug effects; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar
D004343:Drug Implants; D004655:Emulsions; D009414:Nerve Growth Factors; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005677:G(M1) Ganglioside; D002795:Choline O-Acetyltransferase