Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.]
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Sickle cell disease (SCD) is a genetic blood disorder that impacts millions of individuals worldwide. SCD is characterized by debilitating pain that can begin during infancy and may continue to increase throughout life. This pain can be both acute and chronic. ⋯ Thus, pain management in SCD remains a major challenge. Humanized transgenic mice expressing exclusively human sickle hemoglobin show features of pain and pathobiology similar to that in patients with SCD. Therefore, these mice offer the potential for investigating the mechanisms of pain in SCD and allow for development of novel targeted analgesic therapies. © 2018 by John Wiley & Sons, Inc.
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Traumatic brain injury (TBI) is a major cause of death and disability world-wide. Following initial injury, TBI patients can face long-term disability in the form of cognitive, physical, and psychological deficits, depending on the severity and location of injury. This results in an economic burden in the United States estimated to be $60 billion due to health-care costs and loss of productivity. ⋯ Numerous pre-clinical animal models of TBI are used to characterize the anatomical and physiological pathways involved and to evaluate therapeutic interventions. Due to its flexibility and scalability, controlled cortical impact (CCI) is one of the most commonly used preclinical TBI models. This unit provides a basic CCI protocol performed in the rat. © 2017 by John Wiley & Sons, Inc.
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Curr Protoc Neurosci · Jan 2013
Blast traumatic brain injury in the rat using a blast overpressure model.
Traumatic brain injury (TBI) is a serious health concern for civilians and military populations, and blast-induced TBI (bTBI) has become an increasing problem for military personnel over the past 10 years. To understand the biological and psychological effects of blast-induced injuries and to examine potential interventions that may help to prevent, attenuate, and treat effects of bTBI, it is valuable to conduct controlled animal experiments. ⋯ This paper describes the detailed methods of a blast overpressure (BOP) paradigm that has been used to conduct experiments with rats to model blast exposure. This particular paradigm models the pressure wave created by explosions, including improvised explosive devices (IEDs).
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Curr Protoc Neurosci · Jan 2010
Generation of designer receptors exclusively activated by designer drugs (DREADDs) using directed molecular evolution.
G protein-coupled receptors (GPCRs) and their signal transductions are important for both physiological and pathological processes in neuron systems. Neuronal GPCRs activated by synthetic ligands have been created by designed mutagenesis for studying their functions and signal pathways. However, these engineered GPCRs have problems, such as their high constitutive activity. ⋯ This protocol provides detailed instructions for creating DREADDs using directed molecular evolution. The procedures to generate DREADDS include GPCR functional expression in yeast, mutant GPCR library generation, and high-throughput yeast screening. These methods are general and suitable for any GPCRs that can be functionally expressed in yeast.
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Obsessive-compulsive disorder (OCD) occurs with high prevalence, and the drugs used to treat OCD are limited in efficacy and have side-effect issues. The discovery of improved medicines for OCD has been hampered in part by the lack of predictive in vivo models. This unit provides a brief overview of two methods that might have such predictive utility. ⋯ Selective serotonin uptake inhibitors decrease these behaviors without producing motor side effects, as assessed by the behavior of walking on a rotating rod. In contrast, some other drugs (e.g., benzodiazepine anxiolytics) only affect marble burying and nestlet shredding at motor-impairing doses. The present methods might therefore provide one piece of in vivo information for the discovery of novel chemical treatment solutions for the symptoms of OCD.