Intraventricular Implant of Encapsulated CNTF-Secreting Fibroblasts Ameliorates Motor Deficits in Aged Rats

Dwaine   F.   Emerich; Christopher   G.   Thanos; Paul   R.   Sanberg

doi:10.2174/1874609810801020105

Abstract

The impact of intraventricular ciliary neurotrophic factor (CNTF) on motor function in aged rats was evaluated. Spontaneous locomotion and motor coordination were quantified in young (5-6 months) and aged (24-25 months) rats. Relative to young animals, aged rats were significantly less active, fell more rapidly from a rotating rod, and were unable to maintain their balance on a wooden beam. Aged animals received bilateral intraventricular implants of polymerencapsulated fibroblasts that were genetically modified to secrete CNTF. Controls received either no implant or capsules loaded with mock transfected cells. One month after implantation the aged animals that received CNTF implants were significantly more active and were improved on the rotorod and beam balance tests. The improvement in performance on the rotorod and beam balance tests was dependant on the task difficulty and dissipated at higher rotations (rotorod) and smaller beam widths (beam balance). No recovery was seen in aged animals receiving control implants. Postmortem removal of the encapsulated cells confirmed that they continued to secrete CNTF. These data are the first to suggest that intracerebral delivery of CNTF might be useful for slowing or reversing age-related changes in motor function.

Keywords: CNTF, encapsulation, xenotransplantation, intraventricular delivery, trophic factor

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