BackgroundNeuroinflammation and mitochondrial impairment play important roles in the neuropathogenesis of Parkinson’s disease (PD). The activation of NLRP3 inflammasome and the accumulation of α-synuclein (α-Syn) are strictly correlated to neuroinflammation. Therefore, the regulation of NLRP3 inflammasome activation and α-Syn aggregation might have therapeutic potential. It has been indicated that Dl-3-n-butylphthalide (NBP) produces neuroprotection against some neurological diseases such as ischemic stroke. We here intended to explore whether NBP suppressed NLRP3 inflammasome activation and reduced α-Syn aggregation, thus protecting dopaminergic neurons against neuroinflammation.MethodsIn our study, we established a MPTP-induced mouse model and 6-OHDA-induced SH-SY5Y cell model to examine the neuroprotective actions of NBP. We then performed behavioral tests to examine motor dysfunction in MPTP-exposed mice after NBP treatment. Western blotting, immunofluorescence staining, flow cytometry and RT-qPCR were conducted to investigate the expression of NLRP3 inflammasomes, neuroinflammatory cytokines, PARP1, p-α-Syn, and markers of microgliosis and astrogliosis.ResultsThe results showed that NBP exerts a neuroprotective effect on experimental PD models. In vivo, NBP ameliorated behavioral impairments and reduced dopaminergic neuron loss in MPTP-induced mice. In vitro, treatment of SH-SY5Y cells with 6-OHDA (100uM,24 h) significantly decreased cell viability, increased intracellular ROS production, and induced apoptosis, while pretreatment with 5uM NBP could alleviated 6-OHDA-induced cytotoxicity, ROS production and cell apoptosis to some extent. Importantly, both in vivo and in vitro, NBP suppressed the activation of the NLRP3 inflammasome and the aggregation of α-Syn, thus inhibited neuroinflammation ameliorated mitochondrial impairments.ConclusionsIn summary, NBP rescued dopaminergic neurons by reducing NLRP3 inflammasome activation and ameliorating mitochondrial impairments and increases in p-α-Syn levels. This current study may provide novel neuroprotective mechanisms of NBP as a potential therapeutic agent.

Objective: To characterize the clinical phenotypes associated with the “hot cross bun” sign (HCBs) on MRI and identify correlations between neuroimaging and clinical characteristics.Methods: Firstly, we screened a cohort of patients with HCBs from our radiologic information system (RIS) in our center. Secondly, we systematically reviewed published cases on HCBs and classified all these cases according to their etiologies. Finally, we characterized all HCBs cases in detail and classified the disease spectra and their clinical heterogeneity.Results: Out of a total of 3,546 patients who were screened, we identified 40 patients with HCBs imaging sign in our cohort; systemic literature review identified 39 cases, which were associated with 14 diseases. In our cohort, inflammation [neuromyelitis optica spectrum disorders (NMOSD), multiple sclerosis (MS), and acute disseminated encephalomyelitis (ADEM)] and toxicants [toxic encephalopathy caused by phenytoin sodium (TEPS)] were some of the underlying etiologies. Published cases by systemic literature review were linked to metabolic abnormality, degeneration, neoplasm, infection, and stroke. We demonstrated that the clinical phenotype, neuroimaging characteristics, and HCBs response to therapy varied greatly depending on underlying etiologies.Conclusion: This is the first to report HCBs spectra in inflammatory and toxication diseases. Our study and systemic literature review demonstrated that the underpinning disease spectrum may be broader than previously recognized.

Approximately 89% of patients with Parkinson’s disease (PD) suffer from dysarthria. Lee Silverman Voice Treatment (LSVT), a behavioral therapy, aims to improve speech and voice functions. The objective was to assess the effectiveness of LSVT compared with other/no speech interventions for dysarthria in patients with PD. Electronic databases, including PubMed, Embase and the Cochrane Library, were searched. The publication date of all included studies was before 6 March 2020. Only randomized controlled trials (RCTs) that evaluated the LSVT intervention compared with other/no speech intervention were considered. The data obtained from the included studies were described and the mean differences were calculated. Eight RCTs were included in this meta‐analysis comparing LSVT with other/no speech interventions. In the comparison of LSVT versus no intervention, vocal intensity for sustained ‘Ah’ phonation, reading the ‘Rainbow passage’, monologue and describing a picture increased by 8.87, 4.34, 3.25 and 3.31 dB, respectively, after 1 month of therapy. Compared with the respiratory therapy group, the LSVT group also showed significant improvement in vocal intensity for sustained ‘Ah’ phonation, reading the ‘Rainbow passage’ and monologue immediately after treatment (13.39, 6.66 and 3.19 dB). Positive improvement still existed after 24 months. There was no difference in the therapeutic effect between face‐to‐face and online LSVT. The effectiveness of LSVT for dysarthria in patients with PD was verified in these trials. However, future RCTs with sufficient participants are essential to evaluate the effectiveness of LSVT for dysarthria.