Frontiers in neurology
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Frontiers in neurology · Jan 2012
A Multiscale Approach to Blast Neurotrauma Modeling: Part II: Methodology for Inducing Blast Injury to in vitro Models.
Due to the prominent role of improvised explosive devices (IEDs) in wounding patterns of U. S. war-fighters in Iraq and Afghanistan, blast injury has risen to a new level of importance and is recognized to be a major cause of injuries to the brain. However, an injury risk-function for microscopic, macroscopic, behavioral, and neurological deficits has yet to be defined. ⋯ We have also injured a simplified in vitro model of the blood-brain barrier, which exhibits disrupted integrity immediately following exposure to 581 ± 10.0 kPa peak overpressure with a 1.067 ± 0.006-ms duration and 222 ± 6.9 kPa-ms impulse in-air. To better prevent and treat bTBI, both the initiating biomechanics and the ensuing pathobiology must be understood in greater detail. A well-characterized, in vitro model of bTBI, in conjunction with animal models, will be a powerful tool for developing strategies to mitigate the risks of bTBI.
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Frontiers in neurology · Jan 2012
Neuro-glial and systemic mechanisms of pathological responses in rat models of primary blast overpressure compared to "composite" blast.
A number of experimental models of blast brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and biomarkers difficult to analyze and compare. Recently, we showed the importance of rat position toward blast generated by an external shock tube. ⋯ In contrast, systemic IL-1, IL-10, fractalkine, neuroendocrine peptide Orexin A, and VEGF receptor Neuropilin-2 (NRP-2) were raised predominantly after primary blast exposure. In conclusion, biomarkers of major pathological pathways were elevated at all blast set-ups. The most significant and persistent changes in neuro-glial markers were found after composite blast, while primary blast instigated prominent systemic cytokine/chemokine, Orexin A, and Neuropilin-2 release, particularly when primary blast impacted rats with unprotected body.
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Frontiers in neurology · Jan 2012
Anesthesia-induced developmental neurodegeneration: the role of neuronal organelles.
Exposure to general anesthetics (GAs) and antiepileptics during critical stages of brain development causes significant neurotoxicity to immature neurons. Many animal, and emerging human studies have shown long-term functional sequelae manifested as behavioral deficits and cognitive impairments. Since GAs and antiepileptic drugs are a necessity, current research is focused on deciphering the mechanisms responsible for anesthesia-induced developmental neurotoxicity so that protective strategies can be devised. ⋯ By promoting significant release of intracellular calcium from the endoplasmic reticulum, anesthetics cause an increase in mitochondrial calcium load resulting in the loss of their integrity, release of pro-apoptotic factors, functional impairment of ATP synthesis, and enhanced accumulation of reactive oxygen species. The possibility that GAs may have direct damaging effects on mitochondria, resulting in the impairment of their morphogenesis, also has been proposed. This review will present evidence that neuronal organelles are critical and early targets of anesthesia-induced developmental neurotoxicity.
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Blast-induced traumatic brain injury (TBI) has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI). ⋯ Unlike the findings in nbTBI animal models, levels of the β-secretase, β-site APP cleaving enzyme 1, and the γ-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering Aβ production may not be effective for treating acute blast injury to the brain.
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Recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. However, the mechanisms that cause blast neurotrauma are unknown. Blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. ⋯ Intracranial pressures ranged from 80 to 390 kPa as a result of the blast and were notably lower than the shock tube reflected pressures of 300-2830 kPa, indicating pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations were measured from 385 to 3845 G's and were well correlated with peak incident overpressure (R(2) = 0.90). One SD corridors for the surface pressure, intracranial pressure (ICP), and head acceleration are presented to provide experimental data for computer model validation.