Abstract Piperine (PIP), an alkaloid from the Piper genus plants, presents biological properties, including potent anti-inflammatory actions. Since neuroinflammation plays a key role in Parkinson's disease (PD), the objectives were to evaluate the neuroprotective activity of PIP in a model of PD. Male Wistar rats were divided as: sham-operated (SO), untreated 6-OHDA (lesioned in the right striatum) and 6-OHDA lesioned and treated orally with PIP (5 and 10 mg/kg, 2 weeks). The SO group was injected with saline into the right striatum. The SO and untreated 6-OHDA groups were administered with water, for 2 weeks. All animals were subjected to behavioral (open field, rotarod, and apomorphine-induced rotations tests), neurochemical (DA and DOPAC determinations), histological (fluoro jade staining) and immunohistochemical analyses (TH, DAT, TNF-alpha and iNOS). The results showed that PIP reversed behavioral alterations observed in the untreated 6-OHDA group. DA and DOPAC contents decreased in the striatal lesioned side of the untreated 6-OHDA group, but this change was in part reversed by PIP, at the higher dose. The fluoro jade fluorescence, observed in the untreated 6-OHDA group was attenuated after PIP treatments. Furthermore, increased immunoreactivities for TH and DAT were completely reversed in the lesioned group after PIP treatments. In addition, a partial recovery of increased striatal immunoreactivies for TNF-alpha and iNOS was observed in the lesioned group after PIP treatments. In conclusion, PIP presented a neuroprotective action, probably a consequence of its anti-inflammatory and antioxidant properties, making the drug a potential candidate for the treatment of neurodegenerative diseases as PD.
Keywords: piperine; parkinson's disease; neuroinflammation; oxidative stress; neurodegeneration; neuroprotection

Abstract Importance: The term neuromyelitis optica spectrum disorders (NMOSD) currently includes neuromyelitis optica (NMO) and rare neurological disorders characterized by specific IgG autoantibodies directed against aquaporin 4 (AQP4); from a clinical perspective, optic nerves and spinal cord are the usual target tissues. The discovery and characterization of AQP4-IgG has revolutionized the diagnosis of NMOSD and can be used to predict relapses. Similarities with multiple sclerosis (MS) include immune-mediated demyelination and axonal damage but unlike MS, identification of AQP4 Ab positive and seronegative NMOSD (also called anti-MOG-Ab positive) have revolutionized the diagnosis of NMOSD leading to early diagnosis and therapeutic options. Similar to MS, the clinical presentation in NMOSD can have a relapsing-remitting disease course but some patients with NMOSD tend to run a more aggressive disease course. It is important to recognize that, despite the development of tests to identify specific autoantibodies, the diagnosis of NMOSD can be challenging and often missed, leading to delay in treatment options, particularly in the cohort of patients who do not have AQP4-IgG antibodies in serum (seronegative NMOSD). One cardinal difference in therapeutic options between NMOSD and MS is that there are no FDA-approved therapeutic interventions for NMOSD. Objectives: The aim of this study is to review recent changes in diagnostic criteria of NMOSD and outline challenges in characterizing patients with seronegative NMOSD. Findings: Depending on the assays used and the cohorts studied, 10% to 50% of NMOSD patients are AQP4-negative which can be challenging for the clinician treating the disease. Furthermore, identification of seronegative NMOSD or anti-MOG antibody positive patient cohorts can be difficult since antibody testing is available only in Japan and UK. Conclusions: The diagnostic criteria for NMOSD continue to evolve in this rapidly developing field. Concurrent diagnosis of systemic lupus erythematosus, Sjögren’s syndrome or myasthenia gravis increase the likelihood of diagnosis of NMOSD. As compared to the AQP4-IgG positive group, MOG-Ab positive patients with NMOSD or seronegative NMOSD have distinguishing characteristics that be exploited for early treatment. Recent breakthroughs, including the discovery of Fc receptor polymorphism, will likely aid in the medical management of NMOSD patients. Patients with clinical presentation with at least one core ‘syndrome’ should be evaluated for possible NMOSD. Some of these are seen in MS, such as optic neuritis and acute myelitis. Others include area postrema syndrome (APS) which presents with intractable nausea and vomiting, or hiccups, acute brainstem syndrome or symptomatic narcolepsy. As always, alternate diagnoses such as MS, sarcoidosis, malignancy, paraneoplasia, and infective etiologies affecting the brain should be sought and excluded.
Keywords: neuromyelitis optica; neuritis; myelitis; seronegative; Aquaporin-4 channelopathies; NMO spectrum disorders