This article reports measurements of extracellular polyamines in rat brain. Microdialysis probes were implanted in the striatum and microperfusion samples were collected before, during, and after transient (20 min) global ischemia. Polyamine levels in microperfusates were measured by reverse-phase high-performance liquid chromatography after precolumn derivatization. No significant changes in extracellular polyamines were detected for up to 3 h following ischemia. We conclude that extracellular levels of polyamines (1) are comparable to the low levels in other extracellular compartments, and (2) do not change during the initial period of reperfusion, the period most critical for neuron survival after ischemia.

Animals↗

PubMedDate not supplied

Peroxidative damage to cell membranes following cerebral ischemia. A cause of ischemic brain injury?

Definitive evidence of oxygen radical-mediated lipid peroxidation as a cause of tissue injury in the setting of brain ischemia has proven elusive. We review the experimental data from our own and other laboratories on this subject. Spectroscopic detection of the conjugated diene structure, the earliest structural alteration produced by fatty acid radicalization, is an inconstant and highly focal observation in the recirculated ischemic brain. Alterations of lipid-soluble antioxidants offer an indirect indication of possible free radical reactions. Other inferences of lipid peroxidation have derived from studies of selective disappearance of free fatty acids. Recent studies of tissue conjugated diene in two rat models of thrombotic infarction with acute reperfusion yielded inconsistent evidence for lipid peroxidation, and in rats subjected to 25 min of diffuse forebrain ischemia, no evidence of conjugated diene formation was observed during early recirculation. We conclude that evolving parenchymal injury in these settings is unlikely to derive from spectroscopically observable lipid autoxidation.

Animals↗

PubMedDate not supplied

Adrenergic control of cerebral blood flow and energy metabolism in the rat.

Studies in rats were designed to separate and define the roles of the intrinsic and extrinsic adrenergic neurons in the control of cerebral blood flow (CBF) and cerebral energy metabolism. The data suggest several conclusions: 1. Arterial sympathetic innervation plays a role in the autoregulation of cerebral circulation. 2. The central adrenergic neurons have several functions: a) they enhance cerebral vascular tone by action on alpha receptor sites. b) They play an important role in the metabolic control of CBF. The proton-sensitive receptor sites on blood vessel walls require beta-adrenergic input in order to function. c) They influence metabolic rate of brain tissue by acting on beta-receptor sites on the cell membrane.

Adrenergic Fibers↗

PubMedDate not supplied

11C-Iodoantipyrine for the measurement of regional cerebral blood flow by positron emission tomography. Validation studies.

Positron emission tomography (PET) makes it possible to employ an in vivo autoradiographic paradigm to measure regional cerebral blood flow (rCBF) in man. In this study, we synthesized the positron-emitting radiopharmaceutical 11C-iodoantipyrine (11C-IAP) and validated its suitability as a CBF tracer. 11C ( T and one-half 20.4 min) was produced by the (p,alpha) nuclear reaction on 14N. 11C-methyl iodide was used to methylate 3-methyl-1-phenyl-2-pyrazolin-5-one to form 11C-antipyrine, which was iodinated. Radiochemical purity of the 11C-IAP product was 93-98% except as described below. rCBF was measured with 11C-IAP in nitrous oxide-anesthetized Wistar rats by the method of indicator fractionation, and values were compared with rCBF values measured with simultaneously administered commercially produced 14C-IAP. rCBF was studied over a range of arterial Pco2 values (31-58 mm Hg, mean 43.0 +/- 3.5). Mean rCBF data for the 2 tracers agreed to within 4.8% for cerebral hemispheral samples, 3.8% for cerebellum, and 5.3% for brainstem. Mean values (+/- SEM) for rCBF using 11C-IAP were 1.67 +/- 0.20 ml gm-1 min-1 for cerebral hemispheres; 1.32 +/- 0.17 for cerebellum; and 1.50 +/- 0.21 for brainstem. When chromatographic analysis revealed tracer impurity, rCBF, as measured with 11C-IAP, fell consistently below values obtained with 14C-IAP. The data indicate that 11C-IAP, when properly synthesized and submitted to batch-by-batch quality control, may be suitable for measuring rCBF in man by emission tomography.

Animals↗

PubMedDate not supplied

Verapamil: failure of metabolic amelioration following global forebrain ischemia in the rat.

The potential efficacy of the calcium channel blocker verapamil in modifying ischemic brain injury was evaluated in anesthetized rats subjected to 60 or 90 min of diffuse forebrain ischemia produced by bilateral occlusion of the carotid and vertebral arteries. Treated animals received verapamil, 2 mg/kg intravenously, prior to ischemia. Four hours of postischemic recirculation was permitted by reversing the carotid occlusions. Intermittent high-voltage slow-wave activity was noted on electroencephalograms shortly after verapamil infusion, prior to ischemia. The ischemic insult induced an isoelectric EEG, which tended to persist during recirculation in both treated and untreated animals. Similarly, verapamil pretreatment failed to influence brain water content or cerebral energy metabolites (phosphocreatine, ATP, ADP, AMP) or cerebral energy charge when assayed after four hours of recirculation. Thus, verapamil failed to confer a protective effect on brain electrical activity, water content, or energy metabolites following ischemia in this model.

Adenosine Diphosphate↗

PubMedDate not supplied

Graded focal cerebral ischemia in the rat by unilateral carotid artery occlusion and elevated intracranial pressure: hemodynamic and biochemical characterization.

Graded transient cerebral hemispheral ischemia was produced in nitrous oxide-anesthetized Wistar rats by a procedure combining unilateral common carotid artery occlusion; elevation of intracranial pressure to 40-45 mm Hg by infusion of mock cerebrospinal fluid; and maintenance of arterial blood pressure at 100-110 mm Hg by controlled hemorrhage. Cerebral perfusion pressure was thus reduced into the ischemic range ipsilateral to carotid occlusion but remained 55-70 mm Hg contralaterally. Regional cerebral blood flow, measured autoradiographically, fell by 85-90% in the ischemic dorsolateral and lateral neocortex, hippocampus and lateral striatum, but remained at 71% of control or higher contralaterally. Metabolite assay revealed a gradient of energy depletion, with profound reductions in ATP and phosphocreatine and marked elevations of lactate in lateral neocortex, lateral striatum, hippocampus and lateral thalamus. Importantly, dorsolateral neocortex proved to be a penumbral zone, with marked lactate elevation comparable to that of lateral cortex, yet only intermediate degrees of ATP and PCr reduction. Contralateral structures were metabolically unaffected apart from mild increases in lactate. The advantages of this focal ischemia model include the consistent topographic distribution of ischemia and its regional gradations of intensity; the avoidance of painstaking intracranial microsurgery and of systemic complications; preservation of intact energy state of the contralateral hemisphere; ease of reversibility of ischemia; and lack of seizures. The consistent metabolic penumbral zone is a unique feature of the model.

Animals↗

PubMedDate not supplied

Increased cerebral blood flow during hypercapnia is not affected by lesion of the nucleus locus ceruleus.

To test the hypothesis that the putative noradrenergic innervation of intraparenchymal cerebral blood vessels from the nucleus locus ceruleus mediates the vasodilatory response to hypercapnia, regional cerebral blood flow was measured by iodo-[14C]antipyrine autoradiography in awake and restrained rats with unilateral 6-hydroxydopamine lesion of the nucleus locus ceruleus and in unlesioned control rats. Hypercapnia, induced by the inhalation of 5% or 8% CO2 in air for 8 minutes caused a 2 to 5-fold increase in regional cerebral blood flow. However, despite a marked reduction of about 90% in cortical norepinephrine levels ipsilateral to the lesion, blood flow to the frontal and parietal cortex, hippocampus, striatum and cerebellum increased to the same extent in ipsilateral and contralateral regions. Thus, lesion of the locus ceruleus and the resultant depletion of endogenous cortical and hippocampal norepinephrine, does not influence the cerebrovascular response to hypercapnia.

Animals↗

PubMedDate not supplied

Failure of nimodipine to prevent ischemic neuronal damage in rats.

The efficacy of nimodipine in preventing ischemic brain injury was tested in rats subjected to a 20-minute period of high-grade forebrain ischemia by 4-vessel occlusion. Three minutes after restoration of circulation to the brain, an intravenous bolus of 5 micrograms/kg nimodipine or an equivalent amount of vehicle or saline was given, followed by continuous intravenous infusion of the respective solution at 1 microgram/kg/min for 2 hours. In a second series, a larger bolus (20 micrograms/kg of nimodipine) and longer infusion period (6 hours) were employed. Histopathology of the brain was evaluated blindly 72 hours later and graded on a conventional 3-point scale. There was no significant effect of treatment in either series. In the 6-hour series, the percent of cerebral hemispheres showing damage of Grades 2 or 3 in zone CA1 of the hippocampus and in the striatum, respectively, was 100 and 40% for the nimodipine-treated rats, 100 and 42% for rats receiving vehicle, and 75 and 25% for animals receiving saline. Thus, this study revealed no beneficial effect of nimodipine when given following a 20-minute period of severe forebrain ischemia.

Animals↗

PubMedDate not supplied

Hyperglycemia reduces the extent of cerebral infarction in rats.

Although hyperglycemia is known to exacerbate neuronal injury in the setting of reversible brain ischemia, its effect on irreversible thrombotic infarction is less well understood. In this study, unilateral thrombotic infarction was induced photochemically in the parietal cortex of Wistar rats. Seven days later, brains were perfusion-fixed for light microscopy. Infarct areas were measured by computer-assisted planimetry on multiple coronal sections at 250-micron intervals; these data were integrated to yield infarct volumes. Fasted, normoglycemic rats were compared with hyperglycemic rats that had received 1.2-1.5 ml of 50% dextrose i.p. 15 minutes prior to the induction of infarction. Infarct volume averaged 12.5 +/- 4.0 mm3 (mean +/- SD) in rats (n = 14) with plasma glucose levels of 72-184 mg/dl; this differed statistically from the average volume of 9.3 +/- 3.3 mm3 observed in rats (n = 13) with elevated plasma glucose (range 264-607 mg/dl). Spearman rank correlation analysis confirmed a significant correlation of larger infarct volumes with lower plasma glucose levels. In contrast, rats receiving mannitol i.p. to produce an osmotic load comparable with that of the dextrose-pretreated animals showed larger infarct volumes than saline-treated controls. The small but definite beneficial effect of hyperglycemia in this end-arteriolar thrombotic infarction model is possibly attributable to improved local energy metabolism at the periphery of the lesion during the early period of lesion expansion.

Animals↗

PubMedDate not supplied

The relation between cerebral oxygen consumption and cerebral vascular reactivity to carbon dioxide.

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Autonomic Nervous System↗