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. · Nov 1994
Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats.
Experimental models of focal cerebral ischemia have provided important data on early circulatory and biochemical changes, but typically their correspondence with metabolic and hemodynamic findings in stroke patients has been poor. To fill the gap between experimental studies at early time points and rather late clinical studies, we repeatedly measured CBF, CMRO2, oxygen extraction fraction (OEF), cerebral blood volume (CBV), and CMRglc in six cats before and up to 24 h after permanent middle cerebral artery (MCA) occlusion (MCAO), using the 15O steady state and [18F]fluorodeoxy-glucose methods and a high-resolution positron emission tomography (PET) scanner. Likewise, three sham-operated control cats were studied during the same period. ⋯ Viable tissue can be detected up to several hours after MCA occlusion, and the transition of misery-perfused regions into necrosis or preserved tissue can be followed over time. The present results support the concept of a dynamic penumbra, in which for up to 24 h tissue damage spreads progressively from the center to the periphery of ischemia. Sequential high-resolution PET provides insight into the dynamics of regional pathophysiology and may thus further the development of rational therapeutic strategies.
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J. Cereb. Blood Flow Metab. · May 1994
Cerebral blood flow autoregulation in acute intracranial hypertension.
The present series of experiments was carried out to investigate CBF autoregulation during fixed levels of acute increased intracranial pressure (ICP). Three groups of six rats each, one with normal ICP (8 mmHg), one with moderately increased ICP (30 mmHg), and one with severely increased ICP (50 mmHg), were investigated. ICP was maintained by continuous infusion of lactated Ringer solution into the cisterna magna. ⋯ However, a significant shift of the lower limit of autoregulation (LL) toward lower CPP levels during severe intracranial hypertension was observed (p < 0.006). In the controls the LL was found at CPP = 73 +/- 6 mmHg, in moderately increased ICP the LL was 59 +/- 4 mmHg, and in severely increased ICP the LL was 51 +/- 4 mmHg. These results indicate that an acute elevation of ICP activates a reserve capacity of cerebral resistance vessels that dilate further below the normal physiological LL to maintain CBF at low levels of CPP.
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J. Cereb. Blood Flow Metab. · Jan 1994
Effects of MK-801 and NBQX on acute recovery of piglet cerebral metabolism after hypothermic circulatory arrest.
Brain protection during open heart surgery in the neonate and infant remains inadequate. Effects of the excitatory neurotransmitter antagonists MK-801 and NBQX on recovery of brain cellular energy state and metabolic rates were evaluated in 34 4-week-old piglets (10 MK-801, 10 NBQX, 14 controls) undergoing cardiopulmonary bypass and hypothermic circulatory arrest at 15 degrees C nasopharyngeal temperature for 1 h, as is used clinically for repair of congenital heart defects. MK-801 (dizocilpine) (0.75 mg/kg) or NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline] (25 mg/kg) was given intravenously before cardiopulmonary bypass. ⋯ Cerebral blood flow stayed significantly lower in group NBQX relative to control. Thus, MK-801 accelerates recovery of cerebral high-energy phosphates and metabolic rate after cardiopulmonary bypass and hypothermic circulatory arrest in the immature animal. At the dosage used NBQX exerts an adverse effect.
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J. Cereb. Blood Flow Metab. · Sep 1993
Comparative StudyHypothermia attenuates the loss of hippocampal microtubule-associated protein 2 (MAP2) following traumatic brain injury.
Traumatic brain injury (TBI) produces a tissue-specific decrease in protein levels of microtubule-associated protein 2 (MAP2), an important cross-linking component of the neuronal cytoskeleton. Because moderate brain hypothermia (30 degrees C) reduces certain neurobehavioral deficits produced by TBI, we examined the efficacy of moderate hypothermia (30 degrees C) in reversing the TBI-induced loss of MAP2 protein. Naive, sham-injured, and moderate (2.1 atm) fluid percussion-injured rats were assessed for MAP2 protein content 3 h post injury using quantitative immunoreactivity measurements. ⋯ Fluid percussion injury dramatically reduced MAP2 levels in the normothermic group (44.3 +/- 5.9%; p < 0.0005) compared with normothermic sham-injured controls. No significant reduction of MAP2 was seen in the hypothermic injured group (95.2 +/- 4.6%; compared with hypothermic sham-injured controls, p > 0.20). Although it is premature to infer any causal link, the data suggest that the attenuation of injury-induced MAP2 loss by hypothermia may contribute to its overall neuroprotective action.
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J. Cereb. Blood Flow Metab. · May 1992
Comparative StudyNeuronal damage after repeated 5 minutes of ischemia in the gerbil is preceded by prolonged impairment of protein metabolism.
The effect of single or repeated episodes of cerebral ischemia on protein biosynthesis and neuronal injury was studied in halothane-anesthetized gerbils by autoradiography of [14C]leucine incorporation into brain proteins and light microscopy. For quantification of the protein synthesis rate, the steady-state precursor pool distribution space for labeled and unlabeled free leucine was determined by clamping the specific activity of [14C]leucine in plasma, and by measuring free tissue leucine in samples taken from various parts of the brain. Control values of protein synthesis were 14.6 +/- 2.2, 5.8 +/- 2.3, 14.2 +/- 3.1, and 10.0 +/- 3.8 nmol g-1 min-1 (means +/- SD) in the frontal cortex, striatum, CA1 sector, and thalamus, respectively. ⋯ In animals submitted to a single episode of 5 or 15 min of ischemia, histological damage was restricted to the CA1 sector but injury occurred throughout the brain after three episodes of 5 min of ischemia. These observations demonstrate that persisting inhibition of protein synthesis following cerebral ischemia is an early manifestation of neuronal injury. Prevention of neuronal injury requires restoration of a normal protein synthesis rate.