Pallidal neuronal discharge in Parkinson's disease following intraputamenal fetal mesencephalic allograft

Abstract

Analysis of firing rate, bursting discharge and oscillatory activity showed that the graft corrected some, but not all, of the abnormalities associated with the off-medication state. Additionally, in the transplanted patient, voluntary hand movement produced a marked reduction in pallidal discharge rate at multiple GPi recording sites, which was not observed during active movement in other patients. These findings are consistent with a persistent effect of transplanted dopamine cells on basal ganglia outflow and suggest a mechanism for the graft-induced dystonic phenotype.

Reassessing Models of Basal Ganglia Function and Dysfunction

“…Interestingly, in the same study, patients subsequently developed dyskinesias, suggesting that soon after infusion, a “normal” firing rate in the STN was achieved, relieving parkinsonian symptoms, but later firing rates were further depressed, producing hyperkinesias. In the case of dyskinesias associated with grafting of fetal midbrain neurons, lower firing rates, as well as bursting, were observed in the GPi (Richardson et al 2011), also supporting the Rate Model.…”

Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)

“…The clinical guidelines presented in this document apply more to mature/functionally differentiated cell therapy. To date, clinical trials of treatments based on those categories of cells have been carried out in over 40 countries with documented safety and functional neurological improvement for patients with CNS diseases and damage 74 – 114 .…”

Facing the Unique Challenges of Dyskinesias In Parkinson‘s Disease

“…Some refractory cases of graft-induced dyskinesia have been treated with DBS. Intraoperative recording during these DBS implantation surgeries has indicated that similar to levodopa-induced dyskinesia, graft-induced dyskinesia is associated with overactivity of neurons in the direct striatal pathway [104].…”