CELLULAR DELIVERY OF CNTF BUT NOT NT-4 5 PREVENTS DEGENERATION OF STRIATAL NEURONS IN A RODENT MODEL OF HUNTINGTONS-DISEASE/

The delivery of neurotrophic factors to the central nervous system (CN S) has gained considerable attention as a potential treatment strategy for neurodegenerative disorders such as Huntington's disease (HD). In the present study, we directly compared the ability of two neurotroph ic factors, ciliary neurotrophic factor (CNTF), and neurotrophin-4/5 ( NT-4/5), to prevent the degeneration of striatal neurons following int rastriatal injections of quinolinic acid (QA). Expression vectors cont aining either the human CNTF or NT-4/5 gene were transfected into a ba by hamster kidney fibroblast cell line (BHR). Using a polymeric device , encapsulated BHK-control cells and those secreting either (BHK-CNTF) or NT-4/5 (BHK-NT-4/5) were transplanted unilaterally into the rat la teral ventricle. Seven days later, the same animals received unilatera l injections of QA (225 nmol) into the ipsilateral striatum, Nissl-sta ined sections demonstrated that the BHK-CNTF cells significantly reduc ed the volume of striatal damage produced by QA. Quantitative analysis of striatal neurons further demonstrated that both choline acetyltran sferase (ChAT)- and glutamic acid decarboxylase (GAD)-immunoreactive n eurons were protected by CNTF implants, In contrast, the volume of str iatal damage and loss of striatal ChAT and GAD-positive neurons in ani mals receiving BHK-NT-4/5 implants did not differ from control-implant ed animals, These results help better define the scope of neuronal pro tection that can be afforded following cellular delivery of various ne urotrophic factors, Moreover, these data further support the concept t hat implants of polymer-encapsulated CNTF-releasing cells can be used to protect striatal neurons from excitotoxic damage, and that this str ategy may ultimately prove relevant for the treatment of HD. (C) 1998 Elsevier Science Inc.