NLRP3 Inflammasome's Activation in Acute and Chronic Brain Diseases-An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes.

Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides the lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant neuroinflammation players such as microglia/monocytes typically exhibit a strong NLRP3 inflammasome activation. Hence the idea that NLRP3 suppression might solve neurodegenerative ailments. Here we review the recent Literature about this topic. First, we update conditions and mechanisms, including RNAs, extracellular vesicles/exosomes, endogenous compounds, and ethnic/pharmacological agents/extracts regulating NLRP3 function. Second, we pinpoint NLRP3-activating mechanisms and known NLRP3 inhibition effects in acute (ischemia, stroke, hemorrhage), chronic (Alzheimer's disease, Parkinson's disease, Huntington's disease, MS, ALS), and virus-induced (Zika, SARS-CoV-2, and others) human brain diseases. The available data show that (i) disease-specific divergent mechanisms activate the (mainly animal) brains NLRP3; (ii) no evidence proves that NLRP3 inhibition modifies human brain diseases (yet ad hoc trials are ongoing); and (iii) no findings exclude that concurrently activated other-than-NLRP3 inflammasomes might functionally replace the inhibited NLRP3. Finally, we highlight that among the causes of the persistent lack of therapies are the species difference problem in disease models and a preference for symptomatic over etiologic therapeutic approaches. Therefore, we posit that human neural cell-based disease models could drive etiological, pathogenetic, and therapeutic advances, including NLRP3's and other inflammasomes' regulation, while minimizing failure risks in candidate drug trials.

Anesthesia Management for Cesarean Delivery in a Woman With Aromatic L-Amino Acid Decarboxylase Deficiency: A Case Report.

Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare autosomal recessive disorder of neurotransmitter synthesis with lack of sympathetic autoregulation. Owing to hemodynamic regulatory dysfunction and impairment of sympathetic regulation of heart rate, anesthesia is challenging. We report the successful management of anesthesia in a 26-year-old pregnant woman presenting with a mild phenotype of AADCD. Neuraxial anesthesia was administered, as she had not developed complications previously. Thus, neuraxial anesthesia can also be used safely for a cesarean delivery with appropriate anticipation of potential autonomic disturbances and lack of adrenergic neurotransmission.

Two Case Reports of Upper Extremity Venous Thrombosis From Midline Catheter Placement in Pregnancy.

Midline catheters are often inserted in pregnant women for whom a prolonged hospital stay is anticipated to facilitate the administration of medications and for blood sampling. Midline catheters compared with peripheral intravenous catheters are associated with fewer venipunctures and scheduled line changes. We present 2 cases of pregnant women with no personal or family history of thrombosis who underwent midline catheter insertion and developed venous thromboembolism of the upper extremity requiring anticoagulation therapy. Studies are needed to evaluate the safety profile of midline catheters in pregnancy.