Neuroprotective effects of novel phosphatidylglycerol‐based phospholipids in the 6‐hydroxydopamine model of Parkinson's disease

Administration of VP025 (Vasogen Inc.), a novel drug formulation based on phospholipid nanoparticles incorporating phosphatidylglycerol, has previously been shown to have a neuroprotective effect in the brain. We examined the effect of VP025 in a rat model of Parkinson's disease, the 6‐hydroxydopamine (6‐OHDA) lesion of the medial forebrain bundle. VP025 or phosphate‐buffered saline (PBS) was administered to rats 14 days, 13 days and 1 day before the unilateral 6‐OHDA lesion. Functional integrity of nigrostriatal dopaminergic neurons was assessed 7 and 21 days later by amphetamine‐induced rotational testing and we observed that rotational counts were significantly less in rats that were pretreated with VP025 compared with PBS‐pretreated 6‐OHDA‐lesioned rats. Neurochemical analysis at 10 and 28 days after lesion revealed that VP025 protected against a 6‐OHDA‐induced decrease in concentrations of striatal dopamine and its metabolites. Immunocytochemical studies of the ipsilateral substantia nigra showed that VP025 significantly inhibited 6‐OHDA‐induced loss of dopaminergic neurons. We also observed that increases in immunostaining for activated microglia and for activated p38 in dopaminergic neurons of 6‐OHDA‐lesioned rats were prevented by VP025. This study shows that VP025 has significant protective effects on the 6‐OHDA‐lesioned nigrostriatal pathway and may therefore have potential for the treatment of Parkinson's disease.

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