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Abstract: Background: Reactive microgliosis, hallmark of neuroinflammation, may contribute to neuronal degeneration, as shown in several neurodegenerative diseases. We in vivo evaluated microglia activation in early dementia with Lewy bodies, still not reported, and compared with early Parkinson''s disease, to assess possible differential pathological patterns. Methods: We measured the [11C]-PK11195 binding potentials with Positron Emission Tomography, using a simplified reference tissue model, as marker of microglia activation, and cerebral spinal fluid protein carbonylation levels, as marker of oxidative stress. Six dementia with Lewy bodies and 6 Parkinson''s disease patients within a year from the onset, and eleven healthy controls were included. Clinical diagnosis was confirmed at a 4-year follow-up. Results: In dementia with Lewy bodies as well as in Parkinson''s disease, we found significant (p < 0.001) [11C]-PK11195 binding potential increases in the substantia nigra and putamen. Patients with Lewy bodies dementia had extensive additional microglia activation in several associative cortices. This was evident also at a single subject level. Significant increase of Cerebral Spinal Fluid protein carbonylation was shown in both patients'' groups. Conclusions: [11C]-PK11195 Positron Emission Tomography imaging revealed neuroinflammation in dementia with Lewy bodies and Parkinson''s disease, mirroring, even at a single subject level, the common and the different topographical distribution of neuropathological changes, yet in the earliest stages of the disease process. Focusing on those events that characterize parkinsonisms and Parkinson''s disease may be the key to further advancing the understanding of pathogenesis and to taking these mechanisms forward as a means of defining targets for neuroprotection. [Copyright &y& Elsevier]

Recombinant human erythropoietin (rHuEPO, epoetin alfa) is a 165-amino acid glycoprotein that has been shown to initiate response to hypoxia and is most widely known for its efficacy in the treatment of a variety of anemias. A series of experiments were conducted using rodent models to investigate the ability of systemically administered epoetin alfa to cross the blood-brain barrier (BBB) and affect the outcome of hypoxia and injury in the central nervous system. Results demonstrated that endogenous erythropoietin (EPO) and EPO receptors are expressed around animal brain capillaries and that systemically administered epoetin alfa crossed the BBB. The epoetin alfa group experienced significantly reduced (P <0.01) tissue damage in an ischemic stroke model when the study drug was administered 24 h before inducing stroke compared with control animals. Significant protective effects of epoetin alfa persisted when epoetin alfa was administered up to 6 h poststroke (P <0.05). Similarly, epoetin alfa reduced trauma-related brain injury when administered 24 h prior to and up to 6 h after blunt trauma when compared with the control group. The volume of tissue necrosis was significantly greater in control animals compared with those that received epoetin alfa (P <0.05). In addition, these studies led to the postulate that epoetin alfa may also have an effect on nervous system inflammation. This was confirmed using an experimental auto-immune encephalomyelitis model, where rats were shown to have significantly delayed onset (P <0.01) and reduced severity (P <0.05) of symptoms after treatment with epoetin alfa. Other studies demonstrated that epoetin alfa had an effect on the latency and severity of seizures and significantly increased (P <0.0002) survival versus controls when mice were exposed to the neurotoxin kainate (used to induce seizures). These findings suggest future potential therapeutic uses for epoetin alfa beyond its anemia-related effects. [Copyright &y& Elsevier]