IMPLANTATION OF POLYMER-ENCAPSULATED HUMAN NERVE GROWTH FACTOR-SECRETING FIBROBLASTS ATTENUATES THE BEHAVIORAL AND NEUROPATHOLOGICAL CONSEQUENCES OF QUINOLINIC ACID INJECTIONS INTO RODENT STRIATUM

Delivery of neurotrophic molecules to the central nervous system has g ained considerable attention as a potential strategy for the treatment of neurological disorders. In the present study, a DHFR-based express ion vector containing the human nerve growth factor gene (hNGF) was tr ansfected into a baby hamster fibroblast cell line (BHK). Using an imm unoisolatory polymeric device, encapsulated BHK-control cells and thos e secreting hNGF (BHK-hNGF) were transplanted unilaterally into rat la teral ventricles. Three days later, the same animals received unilater al injections of quinolinic acid (QA, 225 nmol) or the saline vehicle into the ipsilateral striatum. Approximately 2 weeks following surgery , animals were tested for apomorphine-induced rotation behavior. Anima ls which received BHK-hNGF cells rotated significantly less than those animals receiving BHR-control cells or QA alone. Histological analysi s 29-30 days following capsule implantation demonstrated that BHK-hNGF cells attenuated the extent of host neural damage produced by QA as a ssessed by a sparing of ChAT- and NADPH-d-positive neurons. Moreover, a lessened GFAP reaction was apparent within the striatum of animals r eceiving BHK-hNGF cells. As measured by ELISA, hNGF was released by th e encapsulated BHK-hNGF cells prior to implantation and following remo val. Morphology of retrieved capsules revealed numerous viable and mit otically active BHK cells. These results suggest that implantation of polymer-encapsulated hNGF-releasing cells can be used to protect neuro ns from excitotoxin damage. (C) 1994 Academic Press, Inc.