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Item Bacterial Infections of the Central Nervous System(Lippincott, Williams, and Wilkins, 2015-12) Roos, Karen L.; Department of Neurological Surgery, IU School of MedicinePurpose of Review:: Bacterial infections of the central nervous system are neurologic emergencies. Prompt recognition and treatment are essential not only to prevent mortality, but also to decrease neurologic sequelae. This article focuses on the two most common central nervous system bacterial infections, bacterial meningitis and spinal epidural abscess. Recent Findings:: Two outbreaks of serogroup B meningococcal disease have occurred on US college campuses. The meningococcal vaccine given to young adults does not contain serogroup B. Summary:: In bacterial meningitis and in bacterial spinal epidural abscess, the identification of and eradication of the pathogen with antimicrobial therapy is the easy part. It is the recognition of the disorder, the understanding of which diagnostic studies to obtain and their limitations, and the management of the neurologic complications that require the expertise of a neurologist.Item Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets(MDPI, 2013-06-19) Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C.; Marrs, James A.; Biology, School of ScienceFetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.Item Purinergic Receptors of the Central Nervous System: Biology, PET Ligands, and Their Applications:(Sage, 2020-04-10) Zarrinmayeh, Hamideh; Territo, Paul R.; Radiology and Imaging Sciences, School of MedicinePurinergic receptors play important roles in central nervous system (CNS). These receptors are involved in cellular neuroinflammatory responses that regulate functions of neurons, microglial and astrocytes. Based on their endogenous ligands, purinergic receptors are classified into P1 or adenosine, P2X and P2Y receptors. During brain injury or under pathological conditions, rapid diffusion of extracellular adenosine triphosphate (ATP) or uridine triphosphate (UTP) from the damaged cells, promote microglial activation that result in the changes in expression of several of these receptors in the brain. Imaging of the purinergic receptors with selective Positron Emission Tomography (PET) radioligands has advanced our understanding of the functional roles of some of these receptors in healthy and diseased brains. In this review, we have accumulated a list of currently available PET radioligands of the purinergic receptors that are used to elucidate the receptor functions and participations in CNS disorders. We have also reviewed receptors lacking radiotracer, laying the foundation for future discoveries of novel PET radioligands to reveal these receptors roles in CNS disorders.Item The Signature Center Initiative for the Cure of Glioblastoma(Office of the Vice Chancellor for Research, 2015-04-17) Pollok, Karen E.; Cohen-Gadol, AaronGlioblastoma multiforme (GBM, World Health Organization/WHO grade IV) is the most common form of brain cancer in the central nervous system. Although conventional treatment-surgery, radiation, and temozolomide-is somewhat effective in adults, overall survival is still < 15 months. In pediatric patients, morbidity due to GBM is the highest among all pediatric cancers. In the context of brain cancers, new and existing therapeutics typically fail due to heterogeneity of genetic mutations within tumors, and because biologically effective doses of drug cannot be delivered to the primary site and invasive perimeter of the tumor due to the blood brain barrier. The Signature Center Initiative to Cure GBM is a funding mechanism that supports a research portal to foster investigations of the Brain Tumor Working Group for development of effective treatments for the eradication of GBM. The overall mission of the Signature Center Initiative is to: 1. Interrogate the molecular mechanisms of GBM biology and develop interventions that result in improved duration and quality of life for our patients. 2. Stimulate consistent and productive exchange of ideas between clinicians and basic scientists while employing bench-to-bedside and bedside-to-bench strategies to generate and prioritize scientific questions. 3. Provide infrastructure and mentorship needed to successfully compete for external funding. 4. Engage the community through patient advocacy to positively impact brain cancer patient outcomes and enhance philanthropic initiatives. The Brain Tumor Working Group brings together scientists committed to engaging in a team-based approach to study GBM biology. Infrastructure required to advance in vivo humanized intracranial tumor models, drug delivery, target validation, and development of new therapeutic strategies are in place. Additionally a patient sample pipeline to obtain, analyze, and distribute primary patient GBM specimens from the operating room to the research laboratory has been established. In year one of funding, over $70,000 in pilot project funding derived from the Signature Center Initiative and private donations has been distributed to the membership. The Brain Tumor Working Group meets in both small and large group formats to strategize experimental design and grant submissions. A network of basic scientists and clinicians has been developed that provides an effective forum for addressing clinically relevant questions related to GBM. A team-based approach, scientific expertise, and continued development of infrastructure provide our membership with a critical foundation to obtain new knowledge related to understanding how GBM cells evade therapy. In the future, this information can be applied to development of effective treatments that will cure GBM.