Medical Sciences Commons^™

Clinical And Basic Research Investigations Into The Long‐Term Effects Of Prenatal Opioid Exposure On Brain Development, Taylor Boggess, W. Chris Risher

Biomedical Sciences

Coincident with the opioid epidemic in the United States has been a dramatic increase in the number of children born with neonatal abstinence syndrome (NAS), a form of withdrawal resulting from opioid exposure during pregnancy. Many research efforts on NAS have focused on short‐term care, including acute symptom treatment and weaning of the infants off their drug dependency prior to authorizing their release. However, investigations into the long‐term effects of prenatal opioid exposure (POE) on brain development, from the cellular to the behavioral level, have not been as frequent. Given the importance of the perinatal period for human brain development, …

Pyrosequencing Analysis Of Irs1 Methylation Levels In Schizophrenia With Tardive Dyskinesia, Yanli Li, Kesheng Wang, Ping Zhang, Junchao Huang, Ying Liu, Zhiren Wang, Yongke Lu, Shuping Tan, Fude Yang, Yunlong Tan

Pharmacology, Physiology and Toxicology

Tardive dyskinesia (TD) is a serious side effect of certain antipsychotic medications that are used to treat schizophrenia (SCZ) and other mental illnesses. The methylation status of the insulin receptor substrate 1 (IRS1) gene is reportedly associated with SCZ; however, no study, to the best of the authors' knowledge, has focused on the quantitative DNA methylation levels of the IRS1 gene using pyrosequencing in SCZ with or without TD. The present study aimed to quantify DNA methylation levels of 4 CpG sites in the IRS1 gene using a Chinese sample including SCZ patients with TD and without TD (NTD) and …

Regulation Of Synaptic Development By Astrocyte Signaling Factors And Their Emerging Roles In Substance Abuse, Christopher D. Walker, W. Chris Risher, Mary-Louise Risher

Biomedical Sciences

Astrocytes have critical functions throughout the central nervous system (CNS) and have emerged as regulators of synaptic development and function. With their highly complex morphologies, they are able to interact with thousands of synapses via peripheral astrocytic processes (PAPs), ensheathing neuronal axons and dendrites to form the tripartite synapse. In this way, astrocytes engage in crosstalk with neurons to mediate a variety of CNS processes including the regulation of extracellular matrix protein signaling, formation and maintenance of the blood-brain barrier (BBB), axon growth and guidance, homeostasis of the synaptic microenvironment, synaptogenesis, and the promotion of synaptic diversity. In this review, …

Thrombospondin Receptor Α2Δ-1 Promotes Synaptogenesis And Spinogenesis Via Postsynaptic Rac1, W. Chris Risher, Namsoo Kim, Sehwon Koh, Ji‑Eun Cho, Petar Mitev, Erin F. Spence, Louis‑Jan Pilaz, Dongqing Wang, Guoping Feng, Debra L. Silver, Scott H. Soderling, Henry H. Yin, Cagla Eroglu

Biomedical Sciences

Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus the TSP–α2δ-1 interaction is implicated in both synaptic development and disease pathogenesis. However, the mechanism by which this interaction promotes synaptogenesis and the requirement for α2δ-1 for connectivity of the developing mammalian brain are unknown. In this study, we show that global or cell-specific loss of α2δ-1 yields profound deficits in excitatory synapse numbers, ultrastructure, and activity and severely stunts spinogenesis in the mouse cortex. Postsynaptic but not presynaptic α2δ-1 …

Post-Traumatic Stress Disorder: Review Of Dsm Criteria And Functional Neuroanatomy, Cornelius W. Thomas

Marshall Journal of Medicine

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for post-traumatic stress disorder (PTSD) consist of over twenty possible symptoms that can be divided into six broad categories. These categories correlate with specific brain networks that regulate emotions, behaviors, and autonomic function. Normal functioning of these networks depends on two key regions; the prefrontal cortex and the amygdala. The prefrontal cortex provides top-down executive control over amygdala, whereas the amygdala is critical for threat detection and activation of the ‘fight or flight’ response. Events that trigger extreme and/or prolonged fear can cause persisting dysregulation within the prefrontal-amygdala circuit; resulting …

Spinal Cord Injury And Autonomic Dysreflexia- A Case Report, Apurva Bhatt, Brit Moore, Talal Asif, Kristy E. Steigerwalt, Rebecca R. Pauly

Marshall Journal of Medicine

Autonomic dysreflexia (AD) is a life threatening condition affecting patients with spinal cord lesions T6 level and above. A 51 year old male with a history of paraplegia due to a C6 spinal cord injury (30 years prior) presented with recurrent debilitating episodic diaphoresis, hypertension, low body temperature, and bradycardia. Previous hospitalizations presumed sepsis from UTI to be the etiology, however on further evaluation his symptoms were consistent with undiagnosed AD. This article describes a unique case presentation and reviews AD in depth, including the etiology, pathophysiology and management.

Dementia Care: Confronting Myths In Clinical Management, Shirley M. Neitch Md, Charles Meadows Md, Eva Patton-Tackett Md, Kevin W. Yingling Md

Internal Medicine

Enormous challenges of this pervasive life-changing condition. Seeking help, often grasping at straws, victims, and their care providers are confronted with misinformation and myths when they search the internet or other sources. When Persons with Dementia (PWD) and their caregivers believe and/or act on false information, proper treatment may be delayed, and ultimately damage can be done. In this paper, we review commonly misunderstood issues encountered in caring for PWD. Our goal is to equip Primary Care Practitioners (PCPs) with accurate information to share with patients and families, to improve the outcomes of PWD to the greatest extent possible.

While …

Intratracheal Instillation Of Cerium Oxide Nanoparticles Induces Hepatic Toxicity In Male Sprague-Dawley Rats, Siva Krishna Nalabotu, Madhukar Babu Kolli, William E. Triest, Jane Y. Ma, Nandini Dpk Manne, Anjaiah Katta, Hari S. Addagarla, Kevin M. Rice, Eric R. Blough

MIIR Faculty Research

Background: Cerium oxide (CeO₂) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO₂ nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats.

Methods and results: Compared with control animals, CeO₂ nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO₂nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and accumulation of granular material. No histopathological alterations were observed in the kidney, spleen, and heart. Analysis of serum biomarkers suggested an elevation of acute phase reactants and markers of hepatocyte injury in the rats exposed to CeO₂ nanoparticles.

Conclusion: Taken together, these data suggest that intratracheal instillation …