Cyclosporine A-Induced Hyperactivity in Rats: Is it Mediated by Immunosuppression, Neurotrophism, or Both?

Abstract

Cyclosporine A (CsA) immunosuppressive treatment has become an adjunctive therapy in neural transplanta tion of dopamine-secreting cells for treatment of Parkinson's disease (PD). Recently, CsA and its analogues have been shown to promote trophic effects against neurodegenerative disorders, and therefore CsA may have direct beneficial effects on dopaminergic neurons and dopamine-mediated behaviors. The present study examined the interaction between the reported CsA-induced hyperactivity and the possible alterations in nigral tyrosine hydroxylase (TH)-immunoreactive neurons in rats with damaged blood-brain barrier. CsA was administered at a therapeutic dose (10 mg/kg/day, IP, for 9 days) used in neural transplantation protocol for PD animal models. CsA-treated animals displayed significantly higher general spontaneous locomotor activity than control animals at drug injection days 7 and 9. Histological assays at day 9 revealed that there was a significant increase in TH-immunoreactive neurons in the nigra of CsA-treated rats compared to that of the vehicle-treated rats. The nigral TH elevation was accompanied by suppressed calcium-phosphotase calcineurin activity, indicating an inhibition of host immune response. This is the first report of CsA exerting simultaneous immunosuppressive and neurotrophic effects, as well as increasing general spontaneous loco motor behavior. These results support the utility of CsA as a therapeutic agent for PD and other movement disorders.

Infusion of Human Umbilical Cord Blood Cells in a Rat Model of Stroke Dose-Dependently Rescues Behavioral Deficits and Reduces Infarct Volume

“…After the infusion, all animals were injected with cyclosporin A daily (10 mg/kg intraperitoneally). Because cyclosporin has neuroprotective activity in MCAO, 12 animals that did not receive HUCBC were also injected daily with cyclosporin A.…”

A physical psychological factor in immunostimulation activity and homeostasis safeguarding

“…Because the mechanism by which cyclosporine induces hypertension is not well defined. In addition, recent studies have shown that cyclosporine plays a neuroprotective role (Friberg et al, 1998) , as well as trophic effects (Borlongan et al, 1999) and modifies behavioral activity in normal animals and models. Humans who have diseases of the neurodegenerative disorder (Tomac et al, 1999) .…”