Neuroinflammation - A major cause for striatal dopaminergic degeneration in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNPc). Growing evidence suggests that neuroinflammation plays a critical role in the pathogenesis of PD. Activation of proinflammatory pathways have a deleterious effect on dopaminergic neurons and are key factors contributing to the development of disease pathology. Clinical and preclinical evidence show microglial activation, infiltration of lymphocyte, elevated levels of pro inflammatory cytokines in various regions of the brain. In this review, we have discussed the possible mechanisms which are responsible for neuroinflammatoin and the therapeutic strategies to rescue dopaminergic neurons from these deleterious events.

Beneficial effect of candesartan and lisinopril against haloperidol-induced tardive dyskinesia in rat.

INTRODUCTION: Tardive dyskinesia is a serious motor disorder of the orofacial region, resulting from chronic neuroleptic treatment of schizophrenia. Candesartan (AT1 antagonist) and lisinopril (ACE inhibitor) has been reported to possess antioxidant and neuroprotective effects. The present study is designed to investigate the effect of candesartan and lisinopril on haloperidol-induced orofacial dyskinesia and oxidative damage in rats. MATERIALS AND METHODS: Tardive dyskinesia was induced by administering haloperidol (1 mg/kg i.p.) and concomitantly treated with candesartan (3 and 5 mg/kg p.o.) and lisinopril (10 and 15 mg/kg p.o.) for 3 weeks in male Wistar rats. Various behavioral parameters were assessed on days 0, 7, 14 and 21 and biochemical parameters were estimated at day 22. RESULTS: Chronic administration of haloperidol significantly increased stereotypic behaviors in rats, which were significantly improved by administration of candesartan and lisinopril. Chronic administration of haloperidol significantly increased oxidative stress and neuro-inflammation in the striatum region of the rat's brain. Co-administration of candesartan and lisinopril significantly attenuated the oxidative damage and neuro-inflammation in the haloperidol-treated rat. CONCLUSIONS: The present study supports the therapeutic use of candesartan and lisinopril in the treatment of typical antipsychotic-induced orofacial dyskinesia and possible antioxidant and neuro-inflammatory mechanisms.