Journal of neurotrauma
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Journal of neurotrauma · Jul 2011
Contribution of Ih to neuronal damage in the hippocampus after traumatic brain injury in rats.
Traumatic brain injury (TBI) causes selective neuronal damage in the hippocampus; however, the underlying mechanisms are still unclear. Post-traumatic alterations of ion channel activity, which actively regulate neuronal excitability and thus impact on excitotoxicity, may be involved in TBI-induced neuronal injury. Here we report that hyperpolarization-activated cation current (I(h)) contributes to the distinct vulnerability of hippocampal neurons in TBI. ⋯ Moreover, blocking I(h) led to an increase of neuronal excitability, with greater effects seen in post-traumatic CA1 pyramidal cells than in CA3 neurons. In addition, the I(h) in mossy cells was dramatically inhibited early after TBI. Our findings indicate that differential changes of I(h) in hippocampal neurons may be one of the mechanisms of selective cell death, and that an enhancement of functional I(h) may protect hippocampal neurons against TBI.
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Journal of neurotrauma · Jul 2011
Post-stroke hypothermia provides neuroprotection through inhibition of AMP-activated protein kinase.
Hypothermia is robustly protective in pre-clinical models of both global and focal ischemia, as well as in patients after cardiac arrest. Although the mechanism for hypothermic neuroprotection remains unknown, reducing metabolic drive may play a role. Capitalizing on the beneficial effects of hypothermia while avoiding detrimental effects such as infection will be the key to moving this therapy forward as a treatment for stroke. ⋯ These effects were mediated by a reduction in AMPK activation rather than a reduction in LKB1, an upstream AMPK kinase. In summary, these studies provide evidence that hypothermia exerts its protective effect in part by inhibiting AMPK activation in experimental focal stroke. This suggests that AMPK represents a potentially important biological target for stroke treatment.
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Journal of neurotrauma · Jul 2011
The combination of either tempol or FK506 with delayed hypothermia: implications for traumatically induced microvascular and axonal protection.
Following traumatic brain injury (TBI), inhibition of reactive oxygen species and/or calcineurin can exert axonal and vascular protection. This protection proves optimal when these strategies are used early post-injury. Recent work has shown that the combination of delayed drug administration and delayed hypothermia extends this protection. ⋯ These studies illustrate the potential benefits of Tempol coupled to delayed hypothermia. However, these findings do not transfer to the use of FK506, which in previous studies proved beneficial when coupled with hypothermia. These divergent results may be a reflection of the different animal models used and/or their associated injury severity.
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Journal of neurotrauma · Jul 2011
Selective brain cooling in rats ameliorates intracerebral hemorrhage and edema caused by penetrating brain injury: possible involvement of heme oxygenase-1 expression.
Brain edema formation associated with trauma-induced intracerebral hemorrhage (ICH) is a clinical complication with high mortality. Studies have shown that heme oxygenase-1 (HO-1) plays an important role in ICH-induced brain edema. In order to understand the role of HO-1 in the protective effect of selective brain cooling (SBC), we investigated the time course of HO-1 changes following penetrating ballistic-like brain injury (PBBI) in rats. ⋯ SBC significantly decreased PBBI-induced heme concentration, attenuated HO-1 upregulation, and concomitantly reduced brain water content. These results suggest that the neuroprotective effects of SBC may be partially mediated by reducing the heme accumulation, which reduced injury-mediated upregulation of HO-1, and in turn ameliorated edema formation. Collectively, these results suggest a potential value of HO-1 as a diagnostic and/or therapeutic biomarker in hemorrhagic brain injury.