Background:NLRP3 inflammasome plays a prominent role in the pathogenesis and progression of many diseases, such as type 2 diabetes mellitus, obesity, atherosclerosis, and Alzheimer's disease. However, little knowledge is known about the role of NLRP3 inflammasome in central post-stroke pain (CPSP).Methods:We selected relevant studies by searching PubMed, Embase, and Medline from inception through February, 2018. We systematically reviewed available publications according to the terms “NLRP3 inflammasome” and “stroke” or “central post-stroke pain” in the title/abstract field.Results:We reviewed the articles and put forward two possible ways for NLRP3 inflammasome in CPSP. One way is that NLRP3 activation causes cerebral cortex injure, decreasing descending projection fiber to thalamus. Such condition may let GABAergic releases reduce, making the ventral basal (VB) neurons excitability increased. Finally, CPSP occur. Another way is that NLRP3 inflammasome leads to thalamic lesion and strengthens inflammatory response of microglia at the same time. Persistent inflammation causes GABAergic alteration in thalamus reticular neurons (TRN) to restrain VB interneurons functions, contributing to CPSP.Conclusions:These possible mechanisms will help become knowledgeable about the occurrence CPSP and provide potential therapy for CPSP.

Touch and itch sensations are crucial for evoking defensive and emotional responses, and light tactile touch may induce unpleasant itch sensations (mechanical itch or alloknesis). The neural substrate for touch-to-itch conversion in the spinal cord remains elusive. We report that spinal interneurons expressing Tachykinin 2-Cre (Tac2Cre) receive direct Aβ low threshold mechanoreceptor (LTMR) input and form monosynaptic connections with GRPR neurons. Ablation or inhibition markedly reduces mechanical but not acute chemical itch nor noxious touch information. Chemogenetic inhibition of Tac2Cre neurons also displays pronounced deficit in chronic dry skin itch, a type of chemical itch in mice. Consistently, ablation of gastrin-releasing peptide receptor (GRPR) neurons, which are essential for transmitting chemical itch, also abolishes mechanical itch. Together, these results suggest that innocuous touch and chemical itch information converge on GRPR neurons and thus map an exquisite spinal circuitry hard-wired for converting innocuous touch to irritating itch.

Chloral hydrate preconditioning protects against ischemic injuries through upregulating the expression of ANXA1, and the followed antiinflammatory mechanisms.

Ischemic stroke, which accounts for 87% of all strokes, constitutes the leading cause of morbidity and mortality in China. Although the genetics and epigenetics of stroke have been extensively investigated, few studies have examined their relationships at different stages of stroke. This study assessed the characteristics of transcriptome changes at different stages of ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO) and bioinformatics analyses. Cerebral cortex tissues from tMCAO mice at days 1, 3, 7, 14, and 28 were removed for RNA-Seq and small RNA-Seq library construction, sequencing, and bioinformatics analysis. We identified differentially expressed (DE) genes and miRNAs and revealed an association of the up-regulated or down-regulated DEmiRNAs with the correspondingly altered DEgene targets at each time point. In addition, different biological pathways were activated at different time points; thus, three groups of miRNAs were verified that may represent potential clinical biomarkers corresponding to days 1, 3, and 7 after ischemic stroke. Notably, this represents the first functional association of some of these miRNAs with stroke, e.g., miR-2137, miR-874-5p, and miR-5099. Together, our findings lay the foundation for the transition from a single-point, single-drug stroke treatment approach to multiple-time-point multi-drug combination therapies.

Background Annexin A1 (ANXA1) exerts anti-nociceptive effect through ANXA1 receptor formyl peptide receptor 2 (FPR2/ALX (receptor for lipoxin A4), FPR2) at the dorsal root ganglia (DRG) level. However, the mechanisms remain elucidated. By using radiant heat, hot/cold plate, tail flick, von Frey, and Randall-Selitto tests to detect nociception in intact and chemical (capsaicin, menthol, mustard oil, formalin or CFA) injected AnxA1 conditional knockout (AnxA1−/−) mice, applying calcium imaging and patch clamp recordings in cultured DRG neurons to measure neuronal excitability, conducting immunofluorescence and western blotting to detect the protein levels of TRPV1, FPR2 and its downstream molecules, and performing double immunofluorescence and co-immunoprecipitation to investigate the interaction between Calmodulin (CaM) and TRPV1; we aim to uncover the molecular and cellular mechanisms of ANXA1’s role in antinociception. Results AnxA1−/− mice exhibited significant sensitivity to noxious heat (mean ± SD, 6.2 ± 1.0 s vs. 9.9 ± 1.6 s in Hargreaves test; 13.6 ± 1.5 s vs. 19.0 ± 1.9 s in hot plate test; n = 8; P < 0.001), capsaicin (101.0 ± 15.3 vs. 76.2 ± 10.9; n = 8; P < 0.01), formalin (early phase: 169.5 ± 32.8 s vs. 76.0 ± 21.9 s; n = 8; P < 0.05; late phase: 444.6 ± 40.1 s vs. 320.4 ± 33.6 s; n = 8; P < 0.01) and CFA (3.5 ± 0.8 s vs. 5.9 ± 1.4 s; n = 8; P < 0.01). In addition, we found significantly increased capsaicin induced Ca2+ response, TRPV1 currents and neuronal firing in AnxA1 deficient DRG neurons. Furthermore, ANXA1 mimic peptide Ac2-26 robustly increased intracellular Ca2+, inhibited TRPV1 current, activated PLCβ and promoted CaM-TRPV1 interaction. And these effects of Ac2-26 could be attenuated by FPR2 antagonist Boc2. Conclusions Selective deletion of AnxA1 in DRG neurons enhances TRPV1 sensitivity and deteriorates noxious heat or capsaicin induced nociception, while ANXA1 mimic peptide Ac2-26 desensitizes TRPV1 via FPR2 and the downstream PLCβ-Ca2+-CaM signal. This study may provide possible target for developing new analgesic drugs in inflammatory pain.

Dementia is known to be induced by vascular dementia and certain neurodegenerative diseases. The presenting features of disordered memory, intellect and personality often result in referral to a neurologist initially. Septum pellucidum cyst (SPC) is a rare clinical finding and defined as a cystic structure between the lateral ventricles. SPC induced memory disorder and dementia has been seldom reported in which the clinical features are atypical and can be misdiagnosed. The main difficulty is to establish a correlation between symptoms and the cyst. When indicated, the treatment is essentially surgical and the ideal operative technique is also a matter of debate. Here, we reported a 58-year-male Chinese patient who presented with memory impairment 1 year ago. Both the physical and laboratory examinations were performed to evaluate the general conditions of the patient. Brain magnetic resonance imaging (MRI) was applied to observe SPC and the neighboring brain structures. Mini-Mental State Exam (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess cognitive function. The results of the patient’s laboratory examinations were normal. However, the patient exhibited severe sleeplessness along with cognitive deteriorations despite short-term (less than 2 weeks) use of benzodiazepines with regular dose. MRI fulfills the consensus criteria for clinical diagnosis of SPC. Furthermore, the results of MMSE and MoCA were showed mild cognitive impairment (MCI) before the treatment of SPC. After neuroendoscopic fenestration of SPC, the patient’s syndromes were disappeared, and his cognitive function was improved. In conclusion, the patient’s symptoms were due to a secondary lesion attributed to the cyst. Comprehensive clinical evaluation and MRI help diagnose SPC induced dementia.

Background The Patient-Reported Outcomes Measurement Information System 29-item Profile (PROMIS-29) has been widely used to measure health outcomes from the patient’s perspective. It has not been validated in adults with aortic disease. The aim of this study was to explore the reliability and validity of the Chinese PROMIS-29 among patients undergoing surgery for aortic dissection (AD). Methods A cross-sectional design was applied. Eligible patients completed a questionnaire that contained the PROMIS-29 and legacy measures, including the Short Form-12 Health Survey (SF-12), 8-item Somatic Symptom Scale (SSS-8), Generalized Anxiety Disorder–2 (GAD-2), and Patient Health Questionnaire-2 (PHQ-2). The structural validity of the PROMIS-29 was evaluated using confirmatory factor analysis (CFA). Reliability was evaluated with Cronbach’s α. Construct validity was assessed by calculating Spearman’s rank correlations and comparing known-group differences. Results In total, a sample of 327 AD patients was included in the final analysis. Most of them were male (89%) with a mean age of 52.7 (± 10.3). CFA revealed good model fit of the seven-factor structure within PROMIS-29, as well as most domains in single-factor analysis. Reliability was confirmed with Cronbach’s α > 0.90. Correlations between comparable domains of the PROMIS-29 and those of legacy questionnaires and most know-group comparisons were observed as hypothesized. Conclusions This study found evidence for acceptable structural validity, construct validity and internal consistency of the PROMIS-29 in a sample of AD patients. It can be applied to AD survivors by researchers or clinicians, measuring outcomes after surgery and identifying those with worse health status.