ABSTRACT
The current study sought to characterize the pro-survival effects of erythropoietin (EPO) in a toxicant model of Parkinson's disease (PD). EPO treatment induced time-dependent elevations of antioxidant glutathione peroxidase (GPx) and anti-apoptotic factors (pAkt and pBad/Bad) within the striatum and substantia nigra pars compacta (SNc). Intriguingly, our results indicated a region- and lesion size- dependence of pro-survival effects of EPO. Indeed, intra-striatal (but not intra-nigral) infusion of EPO was effective at preventing dopaminergic terminal degeneration and sSNc neuronal loss induced by two different doses of 6-OHDA. These neuroprotective consequences were paralleled by a diminution of microglial morphological changes, along with enhanced motor functioning seen through a reduction in apomorphine-induced rotational behaviour. Finally, in the context of the 6-OHDA lesion, EPO again induced anti-apoptotic (Bcl-2) and antioxidant (GPx) factors within the striatum. Taken together, these results raise the possibility of EPO's potential use as an adjuvant therapy in the treatment of PD, or at least, suggest possible brain-region specific targets for the protective effects of EPO.
Subject(s)
Corpus Striatum/drug effects , Erythropoietin/therapeutic use , Neuroprotective Agents/therapeutic use , Oxidative Stress/drug effects , Parkinsonian Disorders/drug therapy , Animals , Apomorphine/pharmacology , Brain/drug effects , Brain/pathology , Cell Shape/drug effects , Corpus Striatum/pathology , Dopamine/metabolism , Erythropoietin/pharmacology , Humans , Male , Mice , Mice, Inbred C57BL , Microglia/drug effects , Microglia/ultrastructure , Neuroglia/drug effects , Neuroglia/ultrastructure , Neuroprotective Agents/pharmacology , Oxidopamine/toxicity , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/metabolism , Pilot Projects , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , Single-Blind Method , Video RecordingABSTRACT
The neutron field near the inflector of the 800-MeV electron storage ring was studied. Photon-induced neutrons are produced by 100-MeV electrons bombarding the inflector during injection into the synchrotron ring. Neutrons were measured with moderating detectors made of 15 X 15 X 20 cm Lucite blocks and Au activation foils. Detector response was established with a Pu-Be neutron source and a 25.4-cm polyethylene sphere and Au foil detector. The neutron yield was 0.97 +/- 0.14 X 10(12) kJ-1. For 1.38 W of electron pulse power, the dose equivalent rate 1 m aside and 1 m above the inflector was 4.35 +/- 0.47 mu Sv s-1 and 3.13 +/- 0.23 mu Sv s-1, respectively. A measured dose equivalent transmission curve for polyethylene yielded an attenuation coefficient of 15.7 m-1.
