Nerve growth factor increases survival of dopaminergic graft, rescue nigral dopaminergic neurons and restores functional deficits in rat model of Parkinson's disease

In the present study, an attempt has been made to explore the neuroprotective and neurorescue effects of nerve growth factor (NGF) on grafted cells and on host nigral dopaminergic neurons, respectively. NGF was co-transplanted with fetal ventral mesencephalic cells (VMC) in the striatum of 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease (PD). In the other groups fetal VMC and NGF were transplanted alone. Twelve weeks post-transplantation, a significant restoration was observed in d-amphetamine induced rotations (stereotypy), spontaneous locomotor activity, striatal and nigral dopamine (DA) and 3,4-dihydroxy-phenyl acetic acid (DOPAC) levels in co-transplanted rats as compared to VMC alone transplanted rats. Higher number of surviving tyrosine hydroxylase immunoreactive (TH-ir) neurons and significantly increased fiber outgrowth from graft was evident in co-transplanted rats as compared to VMC alone transplanted rats. Further, a significant increase was also observed in substantia nigra TH-ir neurons count in co-transplanted rats, exhibiting a potential neuroprotective and neurorescue effects of NGF on nigrostriatal dopaminergic neurons. The results suggest that NGF at the time of transplantation exhibits neuroprotective effect on transplanted VMC as well as neurorescue effect on remaining host nigral dopaminergic neurons, leading to better functional restoration.