AMELIORATION OF ISCHEMIA-INDUCED NEURONAL DEATH IN THE RAT STRIATUM BY NGF-SECRETING NEURAL STEM-CELLS

The objective of the present study was to explore whether grafted immo rtalized neural stem cells, genetically modified to secrete nerve grow th factor (NGF), can ameliorate neuronal death in the adult rat striat um following transient middle cerebral artery occlusion (MCAO), One we ek after cell implantation in the striatum, animals were subjected to 30 min of MCAO. Striatal damage was evaluated at the cellular level af ter 48 h of recirculation using immunocytochemical and stereological t echniques. The ischaemic insult caused an extensive degeneration of pr ojection neurons, immunoreactive for dopamine-and adenosine 3': 5'-mon ophosphate-regulated phosphoprotein with a molecular weight of 32 kilo daltons (DARPP-32). H-3-Thymidine autoradiography demonstrated survivi ng grafted cells in the lesioned striatum in all transplanted rats, Th e loss of striatal projection neurons was significantly reduced (by an average of 45%) in animals with NGF-secreting grafts, whereas control cells, not producing NGF, had no effect. The neuroprotective action o f NGF-secreting grafts was also observed when the total number of stri atal neurons immunopositive for the neuronal marker NeuN was quantifie d, as well as in cresyl violet-stained sections. The present findings indicate that administration of NGF by ex vivo gene transfer and graft ing of neural stem cells can ameliorate death of striatal projection n eurons caused by transient focal ischaemia.