Deborah J Clarke

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We have used a rat model of Parkinson's disease (PD) to address issues of importance for a future clinical application of dopamine (DA) neuron grafting in patients with PD. Human mesencephalic DA neurons, obtained from 6.5–8 week old fetuses, were found to survive intracerebral cell suspension xenografting to the striatum of rats immunosup-pressed with(More)
Light microscopic autoradiography was used to identify cells in the neostriatum that became labelled after the local injection of [3H]gamma-aminobutyrate (GABA). The GABA-accumulating cells comprised up to 15% of the total population of neurons. Thirty-seven of these cells were examined in the electron microscope and it was found that they all had similar(More)
A group of aged, behaviorally impaired rats received suspension grafts of fetal septal-diagonal band tissue into the otherwise intact hippocampal formation. Three months after grafting, behaviorally recovered rats were studied by immunocytochemistry by using monoclonal antibodies to choline acetyltransferase (ChAT) and electron microscopy. The innervation(More)
Human fetal mesencephalic dopamine (DA) neurons, obtained from 6.5–9 week old aborted fetuses, were grafted to the striatum of immunosuppressed rats with 6-hydroxydopamine lesions of the ascending mesostriatal DA pathway. The effects on amphetamine-induced motor asymmetry were studied at various timepoints after grafting. At eight weeks, functional graft(More)
Poor survival of transplanted dopaminergic (DA) neurons remains a serious obstacle to the success of cell replacement therapy as an alternative to the current treatments for Parkinson's disease. We have examined the temporal release profile of an inflammatory cytokine, interleukin-1 beta (IL-1 beta) following transplantation of fetal mesencephalic tissue(More)
Poor survival of transplanted dopaminergic (DA) neurons remains a serious obstacle to the success of cell replacement therapy as an alternative to the current treatments for Parkinson's disease (PD). We have examined the temporal release profile of an inflammatory cytokine, tumor necrosis factor-alpha (TNFalpha), following transplantation of fetal(More)
The effect of pretreating cell suspensions of embryonic rat ventral mesencephala (VM) with antioxidant combinations on the survival of dopaminergic (DA) neurons was studied in vitro and following transplantation into the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease. The in vitro experiments examined the effects of two(More)
Nitric oxide plays an important role in many biological processes including the cardiovascular, immune, reproductive and nervous systems. There is much interest surrounding this molecule and the enzyme responsible for its synthesis, nitric oxide synthase. In order to investigate the role of nitric oxide in various biological processes it is necessary to be(More)
Intrastriatal transplantation of foetal midbrain dopamine (DA) neurons ameliorates the fundamental symptoms of dopaminergic denervation in clinical and experimental parkinsonism despite providing only restricted reinnervation. To understand how DA function is restored by these grafts we used fast-scan cyclic voltammetry at a carbon-fiber microelectrode in(More)
Transplantation using fetal nigral grafts has been performed by various groups worldwide in over 200 Parkinson's disease (PD) patients in an attempt to restore dopaminergic (DA) input to the striatum. However, the proportion of the implanted DA neurons that survives, whether using suspension, partially dissociated, or solid grafts, is small, often as low as(More)