Xenografting Human T2 Sympathetic Ganglion from Hyperhidrotic Patients Provides Short-Term Restoration of Catecholaminergic Functions in Hemiparkinsonian Athymic Rats

Abstract

Previous studies have suggested that allografting peripheral sympathetic ganglia, such as superior cervical ganglia, partially relieves clinical or behavioral deficits in parkinsonian patients and animals. However, removal of these ganglia can cause Homer's syndrome, which limits the utilization of this approach. Hyperhidrosis, a disease of excessive sweating, is commonly seen in young Orientals. Treatment of hyperhidrosis often involves surgical removal of the second thoracic sympathetic ganglia (T2G), which contain catecholaminergic neurons. The purpose of our study was to investigate behavioral responses and tyrosine hydroxylase (TH) immunoreactivity in hemiparkinsonian rats at different time points after transplantation of human T2G from hyperhidrotic patients. Athymic Fisher 344 rats were injected unilaterally with 6-hydroxydopamine into the medial forebrain bundle to destroy the nigrostriatal dopaminergic (DA) pathway. The effectiveness of lesions was tested by measuring methamphetamine (MA)-induced rotations. These unilaterally lesioned rats were later transplanted with T2G or T2 fiber tract (T2F) obtained from adult hyperhidrotic patients. Animals grafted with T2G showed a reduction in MA-induced rotation by 2 weeks; however, rotation returned to the pregrafting levels by 3 months. Animals receiving T2F grafts did not show any reduction of rotation over a 3-month period. Animals were later sacrificed for TH immunostaining at different time points. Tyrosine hydroxylase-positive [TH(+)] cell bodies and fibers were found in the lesioned striatum 2-4 weeks after T2G grafting, suggesting the survival of transplants. Two to 3 months after grafting, TH(+) fibers were still found in almost all the recipients. However, TH(+) cell bodies were found in only three of seven rats studied. Animals receiving T2F grafting did not show any TH immunoreactivity in the lesioned striatum over the 3-month period. These data indicate that T2G transplants from adult hyperhidrotic patients can survive and provide transient normalization of the motor behavior in the hemiparkinsonian athymic rats. Because of the short-term improvement in behavior after grafting, the use of T2G in human trials should be cautious at the present time. Further laboratory research is required.

Enhanced Survival of Dopaminergic Neuronal Transplants in Hemiparkinsonian Rats by the p53 Inactivator PFT-α

“…We found that treatment with PFT- α for 5 days significantly improved the survival of grafts, enhanced their viability and potentiated functional recovery of hemiparkinsonian animals. Our results differ from a previous study showing that the peptide caspase inhibitor, Ac-YVADCMK, which has minimal blood-brain barrier permeability, did not augment survival of TH-ir neurons in VM grafts (14). In Marchinoni’s study, Ac-YVAD-CMK was added to the graft cell suspension only prior to transplantation.…”

“…Rotational behavior (14,15) was evaluated using a multichannel rotometer system (RotoMax, AccuScan Instruments, Inc). Animals were individually placed in the test cylinder.…”

Early post-treatment with 9-cis retinoic acid reduces neurodegeneration of dopaminergic neurons in a rat model of Parkinson’s disease

“…Rotational behavior [42,43] was evaluated using a multichannel rotometer system (RotoMax, AccuScan Instruments, Inc). Six days after 6-OHDA lesioning, all animals were challenged with methamphetamine (2.5 mg/kg).…”

Enhanced survival of human-induced pluripotent stem cell transplant in parkinsonian rat brain by locally applied cyclosporine

“…Similar to the allogenic grafts, human dopaminergic cells have been grafted to 6-OHDA-lesioned rats. [456] To ensure the survival of xenografts in the host brain, the immunosuppressive agent cyclosporine A (CsA) was used as an adjunctive therapy to avoid xenograft rejection. [5] Chronic treatment with CsA improved the survival and function of transplanted human fetal ventromesencephalic cells in 6-OHDA-lesioned rats.…”