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The parallel placebo-controlled study examined the therapeutic effects of dual-target repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (bilaterally) and the left prefrontal cortex (dorsolaterally) on spontaneous and mitogen-stimulating synthesis of pro- and anti-inflammatory cytokines by the blood cells and the level of brain-derived neurotrophic factor (BDNF) in blood serum of patients with Parkinson's disease. The significantly steeper positive clinical dynamics (assessed by UPRSD scale) observed in rTMS group in comparison with the placebo group was accompanied by a significant drop in spontaneous production of proinflammatory cytokines IFNγ and IL-17A. rTMS produced no significant effect on serum BDNF. The possible mechanisms of rTMS therapeutic action on the level of cytokines associated with neuroinflammation in patients with Parkinson's disease are discussed.

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The present study demonstrates that: (1) activation of micro -opioid receptors by systemic administration of a highly selective agonist DAGO (100 microg/kg) results in a significant increase in the number of plaque- and rosette-forming cells in the spleen of CBA mice as well as Wistar rats on the 5th day following sheep red blood cells (5 x 10(8)) immunization, (2) the immunostimulatory effect of DAGO is mediated by central mechanisms including the hypothalamus-hypophysis complex; (3) the postsynaptic dopamine (DA) receptors of D2 type are involved in the DAGO-induced immunostimulation since the combined treatment of animals with haloperidol (2 mg/kg), a blocker of DA D2 receptors, and DAGO abolished this effect; (4) the nuclei caudatus and accumbens of the nigrostriatal and mesolimbic DAergic systems, respectively, are implicated in the immune response stimulation caused by DAGO.

Bilateral electrolytic destruction of the brain areas containing dopamine (DA) cell bodies (nuclei A9 and A10) as well as terminal regions of the nigrostriatal and mesolimbic DAergic systems (nuclei caudatus and accumbens) resulted in a considerable decrease in the intensity of the immune response in rats immunized with sheep red blood cells (SRBC). Administration of SRBC (5 x 10(8) i.p.) to rats produced a marked rise in activity of central DAergic system at early stage of the immune response formation. The most pronounced elevation in the concentration of DA and its metabolites, measured by the method of high performance liquid chromatography with electrochemical detection, was observed in the terminal regions of the nigrostriatal and mesolimbic DAergic systems (nuclei caudatus and accumbens), hypothalamus, hippocampus, amygdala within 20 min following antigen inoculation. By 60 min after immunization DA metabolism has been retained at a high level in all brain regions examined. The concentration of DA returned to control level in the amygdala and hypothalamus 24 hours after antigen administration and had a tendency to reach control values in the rest of the structures. The present results indicate that nigrostriatal and mesolimbic DAergic systems and DAergic structures of the hypothalamus are involved in the mechanisms of neuroimmunomodulation.

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