Articles: traumatic-brain-injuries.
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Repeated blast exposures commonly induce traumatic brain injury (TBI) characterized by diffuse axonal injury (DAI). We hypothesized that degradation of cytoskeletal proteins in the brain can lead to DAI, and evaluated α-II spectrin degradation in the pathophysiology of blast-induced TBI using the tightly-coupled three repetitive blast exposure mice model with a 1-30 min window in between exposures. Degradation of α-II spectrin and the expression profiles of caspase-3 and calpain-2, the major enzymes involved in the degradation were analyzed in the frontal cortex and cerebellum using Western blotting with specific antibodies. ⋯ The expression of another α-II spectrin degrading enzyme, calpain-2, showed a rapid increase in the frontal cortex after blast exposure and it was significantly higher in the cerebellum at later time points. Neuropathological analysis showed significant levels of DAI at the frontal cortex and cerebellum at multiple time points after repeated blast injury. In summary, repeated blast exposure results in specific degradation of α-II spectrin in the brain along with differential expression of caspase-3/calpain-2 suggesting cytoskeletal breakdown as a possible contributor of DAI after repeated blast exposure.
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Neuronal loss is the most common and critical feature of a spectrum of brain traumas and neurodegenerative disorders such as Alzheimer's disease (AD). The capacity to generate new neurons in the central nervous system diminishes early during brain development and is restricted mainly to two brain areas in the mature brain: subventricular zone and subgranular zone. Extensive research on the impact of brain injury on endogenous neurogenesis and cognition has been conducted primarily using young animals, when neurogenesis is most active. ⋯ Our findings demonstrate that aged CaM/Tet-DTA mice that sustain severe neuronal loss exhibit an upregulation of endogenous neurogenesis. However, despite this significant upregulation, neurogenesis alone is not able to mitigate the cognitive deficits observed. Our studies suggest that the aged brain has the capacity to stimulate neurogenesis post-injury; however, multiple therapeutic approaches, including upregulation of endogenous neurogenesis, will be necessary to recover brain function after severe neurodegeneration.
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Progress in neurobiology · Feb 2014
ReviewRevisiting the roles of progesterone and allopregnanolone in the nervous system: resurgence of the progesterone receptors.
Progesterone is commonly considered as a female reproductive hormone and is well-known for its role in pregnancy. It is less well appreciated that progesterone and its metabolite allopregnanolone are also male hormones, as they are produced in both sexes by the adrenal glands. In addition, they are synthesized within the nervous system. ⋯ This lack of information about brain functions of PR is unexpected, as the protective and trophic effects of progesterone are much investigated, and as the therapeutic potential of progesterone as a neuroprotective and promyelinating agent is currently being assessed in clinical trials. The little attention devoted to the brain functions of PR may relate to the widely accepted assumption that non-reproductive actions of progesterone may be mainly mediated by allopregnanolone, which does not bind to PR, but acts as a potent positive modulator of γ-aminobutyric acid type A (GABA(A) receptors. The aim of this review is to critically discuss effects of progesterone on the nervous system via PR, and of allopregnanolone via its modulation of GABA(A) receptors, with main focus on the brain.
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Critically ill neurologic patients are common in the hospital practice of neurology and are often in extreme states requiring accurate and specific information. Imaging, especially using advanced imaging techniques, can provide an important means of garnering this information. This article focuses on the clinical utilization of selective imaging methods that are commonly used in critically ill neurologic patients to render diagnoses, to monitor effects of treatment, or have contributed to a better understanding of pathophysiology in the intensive care unit.
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Multicenter Study
Head injury and unclear mechanism of injury: initial hematocrit less than 30 is predictive of abusive head trauma in young children.
Head injury secondary to abusive head trauma (AHT) is a major cause of morbidity and mortality in susceptible young infants and children. Diagnosing AHT remains challenging and is often complicated by a questionable mechanism of injury. Concern of ionizing radiation risk to children undergoing head CT imaging warrants a selective approach. We aimed to evaluate initial findings that could direct further investigation of AHT. ⋯ In the setting of head injury and unclear history of trauma, a hematocrit of ≤ 30% on presentation increases the likelihood of abusive head trauma in children up to the age of 5 years.