Brain research
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Comparative Study
Relative effects of mannitol and hypertonic saline on calpain activity, apoptosis and polymorphonuclear infiltration in traumatic focal brain injury.
The purpose of this study was to compare the relative effects of mannitol and hypertonic saline (HTS) on calpain activity, apoptosis and neuroinflammatory response induced by experimental cortical contusion. Four groups of 5 Sprague-Dawley male rats were submitted to focal brain injury produced by exposing the parietal cortex to dynamic cortical deformation. Groups were defined by rescucitation fluids administered 30 min post-injury as follows: group 1-0.9% normal saline 2 ml/kg; group 2-mannitol 20% 0.5 g/kg; group 3-HTS 2 ml/kg; group 4-HTS 4 ml/kg. ⋯ Our results show that HTS promotes cell survival and reduces secondary brain damage following TBI. This protective effect was evidenced at rather small infused volumes, proved to encompass several cellular and molecular mechanisms involved in secondary cell death and could not be related to relief of intracranial pressure. These findings suggest that the high osmolality of HTS may have protective effects besides its impact on brain edema.
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Comparative Study
Hypoxic/Ischemic models in newborn piglet: comparison of constant FiO2 versus variable FiO2 delivery.
A comparison of a constant (continuous delivery of 4% FiO2) and a variable (initial 5% FiO2 with adjustments to induce low amplitude EEG (LAEEG) and hypotension) hypoxic/ischemic insult was performed to determine which insult was more effective in producing a consistent degree of survivable neuropathological damage in a newborn piglet model of perinatal asphyxia. We also examined which physiological responses contributed to this outcome. Thirty-nine 1-day-old piglets were subjected to either a constant hypoxic/ischemic insult of 30- to 37-min duration or a variable hypoxic/ischemic insult of 30-min low peak amplitude EEG (LAEEG <5 microV) including 10 min of low mean arterial blood pressure (MABP <70% of baseline). ⋯ The variable insult resulted in a greater number of piglets with neuropathological damage (undamaged = 12.5%, damaged = 68.75%, dead = 18.75%) while the constant insult resulted in a large proportion of undamaged piglets (undamaged = 50%, damaged = 22.2%, dead = 27.8%). A hypoxic insult varied to maintain peak amplitude EEG <5 microV results in a greater number of survivors with a consistent degree of neuropathological damage than a constant hypoxic insult. Physiological variables MABP, LAEEG, pH and arterial base excess were found to be significantly associated with neuropathological outcome.
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There is increasing evidence that neuronal cell death induced by seizures occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. Caspase-8 cleaves Bid, which releases cytochrome c, bridging the "extrinsic" and "intrinsic" pathways. Cleavage of Bid may amplify caspase-8-induced neuronal cell death following seizures. ⋯ Smac/DIABLO from mitochondria was not affected. These results suggest that seizures can lead the translocation of cytochrome c into the cytosol, and the activation of caspase-8 occurs upstream the mitochondria release of cytochrome c and Smac/DIABLO. Inhibition of caspase-8 attenuated neuronal cell death following seizures by decreasing mitochondria release of cytochrome c but not Smac/DIABLO.
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Uteroplacental vascular insufficiency in humans is a common cause of intrauterine growth restriction (IUGR) and is associated with an increased incidence of perinatal asphyxia and neurodevelopmental disorders compared to normal weight newborns. Experimental models that provide an opportunity to analyze the pathogenesis of these relationships are limited. Here, we used neonatal pigs from large litters in which there were piglets of normal birth weight (for controls) and of low birth weight (for uteroplacental vascular insufficiency). ⋯ Cellular positivity for Bcl-2 was consistently higher in the non-apoptotic white matter of the hypoxic IUGR animals compared with their littermates and reached significance at P < 0.05 in several pairs of littermates. Alterations in Bax showed a trend towards higher expression in the hypoxic IUGR littermates but rarely reached significance. The IUGR piglets showed a significantly greater amount of apoptosis in response to the hypoxia than the normal weight piglets, suggesting an increased vulnerability to apoptosis in the IUGR piglets.
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Hyperbaric oxygen therapy has been used to treat a variety of ailments from carbon monoxide poisoning to fibromyalgia. The purpose of this experiment was to explore the effect of hyperbaric oxygen treatment on carrageenan-induced inflammation and pain in rats. Hyperbaric oxygen treatment significantly decreased inflammation and pain following carrageenan injection. Clinically hyperbaric oxygen may be used in situations where NSAIDS are contraindicated or in persistent cases of inflammation.