Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.

Hyperfiltration is an important underlying cause of glomerular dysfunction associated with several systemic and intrinsic glomerular conditions leading to chronic kidney disease (CKD). These include obesity, diabetes, hypertension, focal segmental glomerulosclerosis (FSGS), congenital abnormalities and reduced renal mass (low nephron number). Hyperfiltration-associated biomechanical forces directly impact the cell membrane, generating tensile and fluid flow shear stresses in multiple segments of the nephron. Ongoing research suggests these biomechanical forces as the initial mediators of hyperfiltration-induced deterioration of podocyte structure and function leading to their detachment and irreplaceable loss from the glomerular filtration barrier. Membrane lipid-derived polyunsaturated fatty acids (PUFA) and their metabolites are potent transducers of biomechanical stress from the cell surface to intracellular compartments. Omega-6 and ω-3 long-chain PUFA from membrane phospholipids generate many versatile and autacoid oxylipins that modulate pro-inflammatory as well as anti-inflammatory autocrine and paracrine signaling. We advance the idea that lipid signaling molecules, related enzymes, metabolites and receptors are not just mediators of cellular stress but also potential targets for developing novel interventions. With the growing emphasis on lifestyle changes for wellness, dietary fatty acids are potential adjunct-therapeutics to minimize/treat hyperfiltration-induced progressive glomerular damage and CKD.

Background: Suicide rates are on the rise globally. Many suicide completers are previous attempters. Risk identification of attempters will provide an opportunity for prompt and targeted intervention towards suicide prevention. The aim of this study was to determine the incidence of suicide attempt and self-inflicted injury (SASI), and its associations with deployment-related PTSD and/or TBI and attempted suicide among a large national cohort of Veterans deployed pre and post-9/11 2001 who received care from the Veterans Health Administration (VHA) between 1998 - 2014. Methods: Clinical data from over 1,400 VHA establishments provided by the Veterans Administrations Informatics and Computing Infrastructure (VINCI) were used for descriptive and Cox regression analyses. Results: There were 1,327,604 patients in the study - PTSD only (1,121,818), TBI only (100,033), both PTSD and TBI (105,753). The incidence of SASI in the entire cohort was 351 per 100,000 person years; PTSD only (323), TBI only (181), both PTSD and TBI (835). Compared to TBI only group, the adjusted risk for SASI was higher in the PTSD only group (HR=1.129; 95% CI =1.063 - 1.200) and much higher in those with both PTSD and TBI (HR=2.283; 95% CI =2.136 - 2.441). The risk of SASI was higher if they were younger than 50 years, divorced or separated, non-Hispanic females, homeless, suffered adult abuse and neglect, had substance use, generalized anxiety and antisocial personality disorders, and if they were in the Pre-9/11 service period. Proportion of people attempting suicide increased every year post-diagnosis of PTSD and/or TBI. Conclusion: We recommend prioritizing resources to prevent suicide among at risk groups.

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.