Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Jan 2007
Transgenic overexpression of adenosine kinase aggravates cell death in ischemia.
Adenosine is an endogenous neuromodulator with anticonvulsive and neuroprotective activity. Adenosine levels are normally kept in the range of 20 to 200 nmol/L by low basal expression of its main metabolic enzyme, adenosine kinase (ADK). Dysfunction of the adenosinergic system has been demonstrated to contribute to epileptogenesis. ⋯ Thus, low levels of ADK are essential to maintain adenosine-mediated neuroprotection. We conclude that pathologic overexpression of ADK as in epilepsy may also render the brain more susceptible to injury from ischemia. Consequently, ADK emerges as a rational therapeutic target to enhance neuroprotection.
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J. Cereb. Blood Flow Metab. · Jan 2007
Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model of thromboembolic stroke.
Uric acid is a natural antioxidant that protects the brain in a model of transient focal ischemia in rats. Here we sought to investigate whether uric acid was protective in a model of thromboembolic brain ischemia in rats, and whether the global benefit of recombinant tissue plasminogen activator (rt-PA) was improved by the combined treatment. Adult male Sprague-Dawley rats underwent either ischemia by thromboembolic middle cerebral artery occlusion (MCAO) or sham operation. ⋯ Uric acid strongly reduced ischemia-induced tyrosine nitration, but it was more effective alone than combined with rt-PA, suggesting that reperfusion enhances nitrotyrosine formation. All treatments reduced postischemic brain neutrophil infiltration. These results show that uric acid administered early after thromboembolic stroke is neuroprotective in the rat brain, as it reduces infarct volume, ameliorates the neurologic function, attenuates the inflammatory response, and extends the benefits of rt-PA.
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Hypothermia reduces cell death and promotes recovery in models of cerebral ischemia, intracerebral hemorrhage and trauma. Clinical studies report significant benefit for treating cardiac arrest and studies are investigating hypothermia for stroke and related conditions. Both local (head) and generalized hypothermia have been used. ⋯ A third experiment measured brain and body temperature along with heart rate and blood pressure. Brain cooling was produced for 24 h without significant alterations in pressure, heart rate or body temperature. In summary, our simple method allows for focal brain hypothermia to be safely induced in anesthetized or conscious rats, and is, therefore, ideally suited to stroke and trauma studies.
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J. Cereb. Blood Flow Metab. · Dec 2006
Activation of calcium/calmodulin-dependent protein kinases after traumatic brain injury.
A prominent cognitive impairment after traumatic brain injury (TBI) is hippocampal-dependent memory loss. Although the histopathologic changes in the brain are well documented after TBI, the underlying biochemical mechanisms that contribute to memory loss have yet to be thoroughly delineated. Thus, we determined if calcium/calmodulin-dependent protein kinases (CaMKs), known to be necessary for the formation of hippocampal-dependent memories, are regulated after TBI. ⋯ Two downstream substrates of alpha-CaMKII, the AMPA-type glutamate receptor GluR1, and cytoplasmic polyadenylation element-binding protein, concomitantly increased in phosphorylation in the hippocampus and cortex 1 h after TBI. These results demonstrate that several of the biochemical cascades that subserve memory formation are activated unselectively in neurons after TBI. As memory formation requires activation of CaMKII signaling pathways at specific neuronal synapses, unselective activation of CaMKII signaling in all synapses may disrupt the machinery for memory formation, resulting in memory loss after TBI.
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J. Cereb. Blood Flow Metab. · Nov 2006
The relationship between diffusion anisotropy and time of onset after stroke.
Diffusion anisotropy changes in stroke lesions less than 24 h after onset have been reported to be elevated, decreased, or both. To address these mixed findings, we sought to characterize temporal changes of diffusion anisotropy by analyzing anatomically distinct ischemic white matter (WM) regions at 3 time phases within the first 34 h of ischemic stroke onset in 26 stroke patients (2 to 5 h, N=7; 7 to 14 h, N=11; 18 to 34 h, N=8). Mean diffusivity (Trace/3 apparent diffusion coefficient (ADC)), fractional anisotropy (FA), and T2-weighted signal intensity were measured for major and subcortical WM in lesions defined by a >or=30% drop in Trace/3 ADC. ⋯ Of those patients with lesions in major WM, 4 of 8 patients