Activation of microglia and astrocytes was also decreased, as well as infiltration of T cells into the substantia nigra. Some of these agents were shown to exert an anti-inflammatory action, decrease oxidative stress, and reduce lipid peroxidation products. All of the agents were effective in reducing the motor deficit and alleviating dopaminergic neurotoxicity and, when measured, preventing the decrease of dopamine upon being administered therapeutically after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 6-hydroxydopamine, rotenone-lesioning or delivery of adeno-associated virus-α-synuclein to the ventral midbrain of animals. Recent studies have identified several different agents with immunomodulatory properties that protected dopaminergic neurons from degeneration and death in animal models of PD. Many of these factors are proinflammatory and neurotoxic and harmful to nigral dopaminergic neurons.

Characteristic of neuroinflammation is the activation of brain glial cells, principally microglia and astrocytes that release various soluble factors. Studies in the last twenty years have indicated an important role for neuroinflammation in PD through degeneration of the nigrostriatal dopaminergic pathway. Both innate and adaptive immune responses may contribute to dopaminergic neurodegeneration and disease progression is potentially linked to these. The cell bodies of these neurons are present in the substantia nigra, with the nerve terminals being in the striatum. Parkinson’s disease (PD) is an age-related neurodegenerative disease for which the characteristic motor symptoms emerge after an extensive loss of dopamine containing neurons. Thus, the present finding of PYC-induced adaptation to oxidative stress and inflammation could suggest a novel avenue for clinical intervention in neurodegenerative diseases including PD.

These results suggest that PYC protects dopaminergic neurons from MPTP toxicity in the mouse model of PD. The MPTP-induced neuroinflammation, neurodegeneration and behavioral impairments were markedly repudiated by treatment with PYC. Additionally, there was significant upregulation of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) expression in the striata of MPTP injected mice compared to saline controls. This was associated with significantly increased inflammatory responses of astrocyte and microglia as assessed by ionized calcium binding adaptor molecule 1 (Iba 1) and glial fibrillary acidic protein (GFAP) immunohistochemistry, and nuclear transcription factor-κB (NF-kB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in the striata by Western blot. MPTP injected mice developed significantly severe oxidative stress and impaired motor coordination at day 1 and day 7 postinjection. Therefore, in the present study, using 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydro pyridine (MPTP)-induced mouse model of Parkinsonism, we investigated the neuroprotective potential of bioflavonoid compound Pycnogenol(®) (PYC), an extract of Pinus maritime bark. Flavonoids have been suggested to exert human health benefits by its anti-oxidant and anti-inflammatory properties. Current PD drugs provide only symptomatic relief and have limitations in terms of adverse effects and inability to prevent neurodegeneration.

Oxidative stress and inflammation play a crucial role in Parkinson's disease (PD) pathogenesis and may represent a target for treatment.

Queens medical associates shrook