Achanta, S. | bioRxiv Science

bioRxiv2019

Accelerating Inflammation Resolution to Counteract Chemical Cutaneous Injury

Chemical exposure to vesicants such as sulfur mustard (SM), and electrophilic riot control agents such as 2-chlorobenzalmalononitrile (CS) tear gas agent, cause strong cutaneous inflammation. Classical anti-inflammatory treatments have focused on interference with target initiation and maintenance of inflammation, with mixed outcomes. Inflammation is broadly classified into three temporal phases, initiation, amplification and maintenance, and resolution. Resolution of inflammation was thought to be a passive process but the recent body of literature shows that resolution is an active process and is mediated by fatty acid-derived mediators (specialized pro-resolving mediators, SPMs). We hypothesized that accelerating resolution phase of inflammation may attenuate the exaggerated inflammatory response following chemical threat exposure, leading to decreased morbidity and improved recovery. In this study, SPMs, such as Resolvin D1 (RvD1) and Resolvin D2 (RvD2), were administered to mice at nanogram doses post-exposure to an SM analog, 2-chloroethyl-ethyl-sulfide (CEES) or CS tear gas agent. SPMs decreased edema (ear thickness and punch biopsy weights), pro-inflammatory cytokines (IL-1{beta}, CXCL1/KC, MIP2) and protease marker (MMP-9), and vascular leakage (determined by IRDye 800 CW PEG) while improving histopathology in cutaneous chemical injury mouse models. These results support our hypothesis and pave the way for SPMs for further development as potential medical countermeasures for chemical threat agents-induced skin injuries.

pharmacology and toxicology↗

bioRxiv2019

Comprehensive Integrated Anatomical And Molecular Atlas Of Rodent Intrinsic Cardiac Nervous System

In this study, we developed, coordinated, and integrated several technologies including novel whole organ imaging, software development to support the very first precise 3D neuroanatomical mapping and molecular phenotyping of the intracardiac nervous system (ICN). While qualitative and gross anatomical descriptions of the anatomy of the ICN have been presented, we here bring forth the first comprehensive atlas at large scale of the entire ICN in rat at a single cell resolution. Our work for the first time provides a novel 3D model to precisely integrate anatomical, functional and molecular data in the 3D digitally reconstructed whole heart with high resolution at the micron scale. This work represents the cutting edge in a long history of attempts to understand the anatomical substrate upon which the neuronal control of cardiac function is built. To our knowledge, there has not yet been a comprehensive histological mapping to generate a neurocardiac atlas at cellular and molecular level for the whole heart of any species. We now display the full extent and the position of neuronal clusters on the base and posterior left atrium, and the distribution of molecular phenotypes in that context. In addition we display in this context distinct molecular phenotypes that are defined along the base-to-apex axis, and the present novel discovery of their phenotypical spatial gradients, have not been previously described. The development of these approaches needed to acquire these data has produced method pipelines which can not only achieve the goals of anatomical and molecular mapping of the heart, but also provide the method pipelines for mapping other organs (e.g., stomach, lung, kidney, and liver).

neuroscience↗