bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Cerebral Blood Flow in Conscious Stroke-Prone Spontaneously Hypertensive Rats
Authors: Fredriksson Kent , Ingvar Martin , Johansson Barbro B.
Published: April 2011

Regional cerebral blood flow (rCBF) was measured autoradiographically with [14C]iodoantipyrine as a diffusible tracer in two strains of conscious normotensive rats (Wistar Kyoto and local Wistar) and in two groups of spontaneously hypertensive stroke-prone rats (SHRSP) with a mean arterial pressure (MAP) below or above 200 mm Hg. In spite of the large differences in arterial pressure, rCBF did not differ significantly between the hypertensive and the normotensive groups in any of the 14 specified brain structures measured. However, rCBF increased asymmetrically within part of the caudate-putamen in two of nine SHRSP with a MAP above 200 mm Hg, indicating a regional drop in the elevated cerebrovascular resistance.
Accumulation of Prostacyclin in Rat Brain during Haemorrhagic Hypotension—Possible Role of PGI2 in Autoregulation
Authors: Shohami E. , Sidi A.
Published: April 2011

The effect of haemorrhagic hypotension on the levels of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto prostaglandin F1α (6-keto-PGF1α) in cortical tissue of rats was studied. Lightly anesthetized rats were subjected to steady-state hypotension for 15 min, with a mean arterial blood pressure of 80, 60, and 40 mm Hg, and compared to a control group of normotensive rats. No significant change was found in the levels of PGE2 and TXB2. The level of 6-keto-PGF1α increased from 7.8 ± 0.9 to 14.1 ± 1.9 pg/mg protein (p < 0.02) at 80 mm Hg. Our findings suggest that prostacyclin, which is a potent vasodilator, might play a role in setting the lower limit of the autoregulation range.
Mechanisms of Regulation of Cerebral Microflow during Bicuculline-Induced Seizures in Anaesthetized Cats
Authors: Leniger-Follert Elfriede
Published: April 2011

Before, during, and after bicuculline-induced seizures, changes in microflow, local tissue Po2, and extracellular H+ and K+ activities were continuously recorded in the suprasylvian gyrus of the cat in parallel with electrical activity. Additionally, the patterns of microflow during seizures after blockade of the β-adrenergic and cholinergic receptors and after phentolamine application were studied. With the onset of discharges, microflow increased at all sites. The maximum increase was observed when the electrical activity was the strongest. During the period of alternating silent and nonsilent phases, microflow oscillated in parallel with functional activity. When the discharges ceased, microflow decreased to a new steady-state level. Tissue hypoxia was not responsible for the increase in flow because local tissue Po2 increased after the onset of seizures. H+ activity increased after a short delay and also oscillated during the period of oscillating functional activity. After the end of discharges, H+ activity decreased. K+ activity increased immediately with the onset of discharges and mirrored the electrical activity in the further course. The pattern of microflow was not changed by blockade of α-and β-adrenergic and cholinergic receptors. We conclude that besides the increase in systemic blood pressure, K+ and H+ activities could be the main factors responsible for the increase in flow during seizures.
Extracellular pH, Potassium, and Calcium Activities in Progressive Ischaemia of Rat Cortex
Authors: Harris Robert J. , Symon Lindsay
Published: April 2011

We measured the relationships between changes in extracellular pH (pHe), potassium (Ke), and calcium (Cae) activities and DC potential (DCe) in progressive ischaemia of rat cerebral cortex. pHe and Ke, or Cae and Ke, were measured at the same point simultaneously, using triple-barrelled, double-ion-sensitive microelectrodes. Ischaemia was produced using bilateral carotid artery occlusion and hypotension in rats under 50% N2O-0.4% halothane anaesthesia. Unilateral carotid artery occlusion did not affect blood flow, but bilateral occlusion reduced flow to ∼40% of normal. Autoregulation of blood pressure (BP) changes was lost after bilateral occlusion, and so progressive hypotension produced a linear decrease in flow. pHe began to decrease at high levels of flow (30–35 ml 100 g−1 min−1) and showed stepwise acidotic shifs with reductions in BP. Ke was affected at flows of ∼15 ml 100 g−1 min −1, during which time it was critically dependent on BP. When Ke reached 6 m M, it increased rapidly to 40 m M and was associated with a negative shift in DCe. When Ke reached ∼10 m M, Cae decreased rapidly to ∼0.1 m M. pHe had reached 6.87 when Ke increased rapidly and showed a transient alkalotic shift of ∼0.14 units at that time. Possible mechanisms for the sequence of ion changes described are discussed.
Extracellular pH Changes during Spreading Depression and Cerebral Ischemia: Mechanisms of Brain pH Regulation
Authors: Mutch W. A. C. , Hansen A. J.
Published: April 2011

We have examined the extracellular pH (pHe) during spreading depression and complete cerebral ischemia in rat parietal cortex utilizing double-barrelled H+ liquid ion exchanger microelectrodes. The baseline pHe of the parietal cortex was 7.33 at a mean arterial Pco2 of 38 mm Hg. Following spreading depression and cerebral ischemia, highly reproducible triphasic changes in pHe occurred, which were intimately related to the negative deflection in tissue potential (Ve). The changes in pHe for spreading depression (n = 23) were a small initial acidic shift, beginning before the rapid change in Ve, followed by a rapid transient alkaline shift of 0.16 pH units, the onset of which coincided with the negative deflection in Ve. A prolonged acidic shift of 0.42 pH units then occurred. The maximal decrease in pHe was to 6.97 and the mean duration of the triphasic pHe change was 7.8 min. The lactate concentration in brain cortex increased from baseline 1.2 m M to 7.0 m M (n = 6) during the maximal acidic change in spreading depression. In addition, lactate levels correlated well with resolution of the pHe changes during spreading depression. The triphasic pHe changes following complete cerebral ischemia were an initial acidic shift of 0.43 pH units which developed over 2 min, then an alkaline shift of 0.10 pH units coincident with the negative deflection in Ve, and a final acidic shift of 0.26 pH units. The terminal pHe was 6.75. Superfusion of the cortex with inhibitors of carbonic anhydrase (acetazolamide), Na+/H+ counter transport (amiloride), and Cl−/HCO3− countertransport (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) altered the triphasic pHe changes in a similar fashion for both spreading depression and cerebral ischemia, providing insights into the pHe regulatory mechanisms in mammalian brain.
Estimates of Michaelis-Menten Constants for the Two Membranes of the Brain Endothelium
Authors: Gjedde Albert , Christensen Ove
Published: April 2011

Tracer studies on facilitated diffusion across the blood–brain barrier lead to the calculation of Michaelis-Menten constants that describe the rate of transport. However, the barrier consists of two endothelial cell membranes, and the relevance of single Michaelis-Menten constants in relation to the two cell membranes is unknown. We have formulated a model of two endothelial cell membranes and show that the measured Michaelis-Menten constants are simple functions of the properties of the individual membranes when transport across the endothelium is rapid ( P1 > 10−6 cm s−1). We also show that the Michaelis-Menten constants determined in tracer experiments describe facilitated diffusion in the steady state only if the two membranes have similar transport properties. As an application of this observation, we have examined three experimental studies that measure glucose transport in the steady state and show that the Michaelis-Menten constants for glucose transport calculated from the tracer experiments are equal to the constants calculated from the steady-state experiments. We conclude that the luminal and abluminal membranes of brain capillary endothelial cells have equal glucose transport properties.
Reduction in Noradrenergic Perivascular Nerve Density in the Left and Right Cerebral Arteries of Old Rabbits
Authors: Saba H. , Cowen T. , Haven A. J. , Burnstock G.
Published: April 2011

With the use of fluorescence and acetylcholinesterase histochemistry, marked reductions have been shown in the noradrenergic and acetylcholinesterase-positive innervation of the right (RMC) and left (LMC) middle cerebral arteries of old compared with young adult rabbits. The decrease in noradrenergic nerve density tended to be greater in LMC than in RMC: Nerve density fell by ∼45% in LMC and by ∼30% in RMC. The reductions in acetylcholinesterase-positive nerves were similar in both LMC and RMC (29 and 33%, respectively). Vessel circumference and cross-sectional wall area appeared to increase in old age in LMC and RMC.
Intercorrelations of Glucose Metabolic Rates between Brain Regions: Application to Healthy Males in a State of Reduced Sensory Input
Authors: Horwitz Barry , Duara Ranjan , Rapoport Stanley I.
Published: April 2011

We use a correlational analysis of regional metabolic rates to characterize relations among different brain regions. Starting with rates of local glucose metabolism (rCMRglc) obtained by positron emission tomography using [18F]fluorodeoxyglucose, we propose that pairs of brain regions whose rCMRglc values are significantly correlated are functionally associated, and that the strength of the association is proportional to the magnitude of the correlation coefficient. Partial correlation coefficients, controlling for whole brain glucose metabolism, are used in the analysis. We also introduce a graphical technique to display simultaneously all the correlations, allowing us to examine patterns of relations among them. The method was applied to 40 very healthy males under conditions of reduced auditory and visual inputs (the “resting state”). Dividing the brain into 59 regions, and keeping only those partial correlation coefficients significant to p < 0.01, we found the following: (a) All regions were significantly correlated with their contralateral homologues. For the most part, the largest partial correlation coefficients were between homologous brain regions. (b) Generally, the pattern of significant correlations between any two lobes in the left hemisphere did not differ statistically from the corresponding pattern in the right hemisphere. (c) Strong correlations were observed between primary somatosensory areas and premotor association areas. Correlations between these association areas and primary visual and auditory regions were not statistically significant. (d) Significant correlations between inferior occipital and temporal areas were found. Metabolic rates in the superior part of the occipital lobe were not correlated significantly with metabolic rates in regions of the temporal lobe, nor with metabolism in the parietal lobe. (e) As a whole, there were numerous correlations among frontal and parietal lobe regions, on the one hand, and among temporal and occipital lobe regions, on the other, but few statistically significant correlations between these two domains. We relate our results to various aspects of known brain anatomy, physiology, and cognitive functioning.
Effect of Dihydroergocristine on Energy Metabolism Studied in the Isolated Perfused Rat Brain Affected by Ischemia and in Neuroblastoma Cells Deprived of Oxygen and Glucose
Authors: Rachman A. , Kellmann L. , Krieglstein J.
Published: April 2011

The effect of dihydroergocristine on energy metabolism was studied in the isolated perfused rat brain affected by ischemia and in cultivated C-1300 neuroblastoma cells deprived of oxygen and glucose. Creatine phosphate, ATP, ADP, AMP, glucose, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, and lactate were measured enzymatically. After a perfusion period of 30 min, the cortex of the isolated perfused rat brain exhibited an energy state not different from that in vivo. Dihydroergocristine added to the perfusion medium (5 μmol/L) did not influence these substrate levels under normal perfusion conditions. However, this drug was able to retard the breakdown of high-energy phosphates during ischemia and to accelerate the restoration of the energy state during the postischemic reperfusion period. The perfusion rate was not changed by the drug, and therefore it was assumed that dihydroergocristine could act directly on cell metabolism. This view was supported by the results obtained from experiments using cultivated N-2a neuroblastoma cells. These cells were incubated in a buffered salt solution deprived of glucose and oxygen for 15 min. Under these conditions, dihydroergocristine (2 μmol/L) added to the incubation medium caused changes in the concentrations of the high-energy phosphates similar to those in the isolated brain preparation: It increased the ATP concentration and decreased the ADP concentration significantly.
Estimation of Local Cerebral Glucose Utilization by Positron Emission Tomography of [18F]2-Fluoro-2-Deoxy-D-Glucose: A Critical Appraisal of Optimization Procedures
Authors: Wienhard K. , Pawlik G. , Herholz K. , Wagner R. , Heiss W.-D.
Published: April 2011

Various approaches estimating local cerebral glucose utilization by positron emission tomography of labeled deoxyglucose are compared. Autoradiographic methods that predict the glucose utilization rate from a single scan are unreliable in pathologic tissue because of abnormal values of the model rate constants. A normalization procedure using the ratio of measured tissue activity to activity calculated with standard rate constants is proposed to readjust the values of the rate constants. Reliable estimates of metabolic rates can be obtained from dynamic recordings of tracer uptake. In the graphic approach, metabolic rate can be derived from the slope of a segment of a transformed uptake curve, which becomes linear at 15–20 min after intravenous tracer injection, with an accuracy comparable with that in complete dynamic studies. However, by recording and analyzing full-length uptake curves, in addition to metabolic rate, the model rate constants can be determined regionally. The physiological significance of those parameters is demonstrated in crossed cerebellar deactivation in 30 patients with supratentorial infarcts. Mild hypometabolism both within the ischemic lesion and in the morphologically intact cerebellum is accompanied by a reduction of the phosphorylation rate only. Severe metabolic depression, by contrast, affects both cerebellar transport and phosphorylation processes, whereas in the cerebrum, only the rate constant k1 is significantly correlated with the degree of metabolic disturbance.
Positron Emission Tomography in Schizophrenic Patients with and without Neuroleptic Medication
Authors: DeLisi Lynn E. , Holcomb Henry H. , Cohen Robert M. , Pickar David , Carpenter William , Morihisa John M. , King A. Catherine , Kessler Robert , Buchsbaum Monte S.
Published: April 2011

Positron emission tomography using [18F]2-fluoro-2-deoxy-d-glucose was performed in nine chronic schizophrenic patients both when medication-free and when medicated with neuroleptics. Total brain cortex, temporal cortex, and basal ganglia glucose use was significantly increased with medication; however, there was no change in anterior/posterior metabolic gradients.
Lactic Acidosis and Recovery of Mitochondrial Function following Forebrain Ischemia in the Rat
Authors: Hillered Lars , Smith Maj-Lis , Siesjö Bo K.
Published: April 2011

The effect of different degrees of lactic acidosis on the recovery of brain mitochondrial function, measured as respiratory activity in isolated mitochondria or cortical concentrations of labile phosphates and carbohydrate substrates, was studied during 30 min of recirculation following 15 min of near-complete forebrain ischemia in rats. During ischemia, there was a marked decrease in mitochondrial State 3 respiration in vitro and a depletion of energy stores (i.e., phosphocreatine, ATP, glucose, and glycogen) in vivo that was similar in the high- and low-lactate ischemia groups. However, lactate concentrations differed markedly (20 and 10 μmol g−1, respectively). During recirculation, there was a near-complete recovery of both respiratory activity in vitro and adenylate energy charge (EC) in vivo regardless of the differences in lactic acidosis during ischemia. Respiratory activity and EC were well correlated. The changes in Ca2+ homeostasis during ischemia, an increase in tissue and a decrease in mitochondrial Ca2+ content, were reversed rapidly after ischemia in both high- and low-lactate ischemia animals and did not hinder an early recovery of mitochondrial function. It is concluded that lactic acidosis, with lactate levels reaching 20 μmol g−1 during 15-min ischemia, does not adversely affect early postischemic recovery of mitochondrial function.
Blood—Brain Barrier Transport of Butanol and Water Relative to N-Isopropyl-p-Iodoamphetamine as the Internal Reference
Authors: Pardridge William M. , Fierer Gary
Published: April 2011

The literature regarding the blood–brain barrier (BBB) transport of butanol is conflicting as studies report both incomplete and complete extraction of butanol by the brain. In this work the BBB transport of both [14C]butanol and [3H]water was studied using the carotid injection technique in conscious and in ketamine- or pentobarbital-anesthetized rats employing N-isopropyl- p-[125I]iodoamphetamine ([125I]IMP) as the internal reference and as a fluid microsphere. The three isotopes (3H, 125I, 14C) were conveniently counted simultaneously in a liquid scintillation spectrometer. IMP is essentially completely sequestered by the brain for at least 1 min in conscious rats and for 2 min in anesthetized animals. Butanol extraction by rat forebrain is not flow limited but ranges between 77 ± 1 and 87 ± 1% for the three conditions. The incomplete extraction of butanol by the forebrain is due to diffusion restriction of butanol clearance in some regions (frontal cortex, colliculi) but not in others (caudate, hippocampus, olfactory bulb). The permeability-surface area product/cerebral blood flow ratio of butanol and water in rat forebrain remains relatively constant, 1.7 ± 0.2 and 1.0 ± 0.1, respectively, despite a twofold increase in cerebral blood flow in conscious relative to pentobarbital-anesthetized rats. The absence of an inverse relationship between flow and butanol or water extraction is consistent with capillary recruitment being the principal mechanism underlying changes in cerebral blood flow in anesthesia. The diffusion restriction of BBB transport of butanol in some regions, but not in others, necessitates a careful regional analysis of BBB permeability to butanol prior to usage of this compound as a cerebral blood flow marker.
Cerebral Blood Flow and Blood—Brain Influx of Some Neutral Amino Acids in Control and Hypothyroid 16-Day-Old Rats
Authors: Lefauconnier J. M. , Lacombe P. , Bernard G.
Published: April 2011

Rats were made hypothyroid by a daily subcutaneous injection of propylthiouracil beginning the first day after birth. CBF, brain plasma volume, blood–brain extraction, and influx of some neutral amino acids were studied in 16-day-old animals. In hypothyroid rats, the brain plasma volume was decreased by ∼30%. CBF was decreased by >50%. This decrease was the highest in cerebellum. Blood–brain extraction of small neutral amino acids (alanine, serine, cysteine) was greatly enhanced. This greater extraction compensated for the decreased supply of alanine brought about by its decreased plasma concentration and the lower CBF. In contrast, the extraction of the large amino acids tested (leucine, phenylalanine) was hardly increased, and the influx of phenylalanine was slightly decreased. These results suggest an alteration in the maturation of the brain capillary bed and capillary transport for neutral amino acids in hypothyroidism. The differential effect of hypothyroidism on some small and large amino acids is an additional argument for the existence of two systems of transport for neutral amino acids at the luminal membrane of brain capillary endothelial cells of immature rats.
Nimodipine Has an Inhibitory Action on Neurotransmitter Release from Human Cerebral Arteries
Authors: Porter I. D. , Gardiner I. M. , de Belleroche J.
Published: April 2011

The effect of the dihydropyridine nimodipine was studied on the resting and K+-evoked release of [3H]acetylcholine (ACh) and [3H]5-hydroxytryptamine (5HT) from postmortem human cerebral arteries. Nimodipine, at a concentration of 30 μ M, significantly reduced the K+-evoked release of [3H]ACh from anterior and middle cerebral arteries by 36 and 70%, respectively, and the K+-evoked release of [3H]5HT from basilar and middle cerebral arteries by 55 and 66%, respectively. The mode of action of nimodipine is interpreted in terms of a specific effect on the depolarisation-induced calcium current occurring in neuronal elements present in these preparations but absent from brain.
Effect of Serotonin and its Antagonist Ketanserin on Pial Vessels
Authors: Auer Ludwig M. , Leber Klaus , Sayama Ichiro
Published: April 2011

The effect of serotonin (5-HT) and its antagonist ketanserin on the cerebral circulation was investigated in two series totaling 24 cats using the cranial window technique. 5-HT elicited a marked dilatation of small pial arteries, whereas large arteries tended to constrict. Intravenous administration of ketanserin reversed the constriction of large arteries, causing dilatation, and reduced the extent of small arteries' dilatation. In a randomized study, i.v. administration of ketanserin in its solvent versus the solvent alone revealed a strong dilatatory effect of the solvent on pial arteries (17 ± 1.8%), which partly jeopardized a possible constrictory effect of ketanserin, as ketanserin plus solvent induced less dilatation of small pial arteries than the solvent alone. The present data support the view that serotonin exerts a dual effect on cerebral arteries, namely, dilatation of small and constriction of large vessels. The antagonist ketanserin reverses this effect, but the strong dilatatory effect of the solvent alone masks the antiserotoninergic effect.
A Spatial Analysis of the Blood—Brain Barrier Damage in Experimental Allergic Encephalomyelitis
Authors: Juhler Marianne , Blasberg Ronald G. , Fenstermacher Joseph D. , Patlak Clifford S. , Paulson Olaf B.
Published: April 2011

Experimental allergic encephalomyelitis was induced in young male Lewis rats. Following the development of neurological signs, the local distribution of perivascular inflammatory cellular infiltrates and the local blood-to-tissue transfer constants ( K1) of α-aminoisobutyric acid (AIB) were determined, and these results were compared. Perivascular infiltrative lesions were generally found near areas of the CNS that normally lack an effective blood–brain barrier (BBB) such as the choroid plexus and the entry zones of the cranial and spinal nerve roots. This distribution pattern indicates that the entry of the causative agent into CNS tissue may be by way of the permeable microvessels of these structures. In tissue around inflamed veins, the mean transfer constant was slightly but significantly increased (2.8 ± 1.5 μl g−1 min−1) compared with uninvolved regions (0.9 ± 0.2 μl g−1 min−1) and similar areas in control animals (0.9 ± 0.3 μl g−1 min−1). Analysis of the autoradiographic method of determining transfer constants suggested that the AIB influx rate in the lesion areas may actually be manyfold larger than measured, that BBB permeability may be greatly increased at such sites, and that the areas of lymphocytic infiltration and increased K values may be virtually identical.
Early Postnatal Development of Transport Functions in the Rabbit Choroid Plexus
Authors: Lindvall-Axelsson M. , Owman Ch. , Winbladh B.
Published: April 2011

The development of transport functions in the rabbit choroid plexus was followed postnatally up to 2 months after birth. The activity of ouabain-sensitive Na+,K+-ATPase in newborn rabbit choroid plexus composes about one-fourth (lateral and third ventricle) to one-half (fourth ventricle) of the activity in the adult animal, and it increases markedly within the first 3 weeks of early life. A similar profile of postnatal changes is observed for the capacity to take up and accumulate the organic base choline, which is about three to five times higher for the adult rabbit than for the newborn animal. This coincides with the maturation of the epithelial cells as well as with the development of the sympathetic nerve supply in the choroid plexus. The results suggest that energy-dependent translocation systems influenced by local sympathetic nerves in the choroid plexus, at the interface between blood and CSF, have a functional role shortly after birth.
Circulating Catecholamines Modulate Ischemic Brain Damage
Authors: Koide Tohru , Wieloch Tadeusz W. , Siesjö Bo K.
Published: April 2011

In search of factors influencing the outcome of an ischemic insult, we induced 10 min of forebrain ischemia in rats and assessed neuronal necrosis by quantitative histopathology after 1 week of recovery. Procedures for inducing ischemia included bilateral carotid artery clamping and reduction of blood pressure to 40–50 mm Hg by bleeding. To facilitate rapid lowering of blood pressure, a ganglionic blocker, trimethaphan (TMP), was administered at the onset of ischemia. Omission of the ganglionic blocker proved to markedly ameliorate neuronal damage. Similarly favorable effects were obtained when a mixture of adrenaline and noradrenaline (1 μg kg−1 min−1 each) was infused during the early recirculation period in animals previously given TMP. Infusion of noradrenaline alone also ameliorated the damage, though the efficacy was somewhat less. The results suggest that catecholamines, released as a response to stress, ameliorate ischemic brain damage.
Changes in Extra- and Intracellular pH in the Brain during and following Ischemia in Hyperglycemic and in Moderately Hypoglycemic Rats
Authors: Smith M. -L. , von Hanwehr R. , Siesjö B. K.
Published: April 2011

Incomplete forebrain ischemia of 15-min duration was induced in rats made hyperglycemic or moderately hypoglycemic prior to ischemia. Tissue CO2 tension, CO2 content, labile tissue metabolites, and extracellular pH (pHe) were measured, and intracellular pH (pHi) was derived by calculation on the assumption that cerebral intracellular fluids can be lumped into one space. In hypoglycemic animals, mean tissue lactate content increased from 2 to 10 μmol g−1. Tissue CO2 content was virtually unchanged and the CO2 tension increased from ∼50 to ∼145 mm Hg. In hyperglycemic animals, tissue lactate content rose to 20 μmol g−1, and the CO2 content decreased by 25%, demonstrating that some CO2 was lost to the blood supplied by the remaining perfusion. Accordingly, tissue CO2 tension did not rise above 200 mm Hg. pHe was reduced in proportion to the amount of lactate accumulated, the values obtained in hypo- and hyperglycemic animals showing relatively little scatter (6.76 ± 0.03 and 6.25 ± 0.04, respectively). In hypoglycemic animals the extracellular HCO−3 concentration was virtually unchanged, demonstrating that any influx of lactic acid from the cells must have been accompanied by H+ efflux and/or HCO−3 influx via independent routes. In hyperglycemic animals [HCO−3]e fell by >10 μmol ml−1. In both groups [HCO−3]e was reduced during the first 5 min of recovery. Recovery of pHe was slower in hyper- than in hypoglycemic animals. During ischemia calculated pHi fell to 6.37 ± 0.04 and 5.95 ± 0.06 in hypo- and hyperglycemic animals, respectively. Differences in pHi were maintained for the first 15 min of recovery, but in both hypo- and hyperglycemic animals pHi had normalized after 30 min. It is concluded that preischemic hyperglycemia leads to a more pronounced intra- and extracellular acidosis than normo- and hypoglycemia, an acidosis that also resolves more slowly during recirculation.
Effect of γ-Hydroxybutyrate on the Reactivity of Pial Arteries before and after Ischemia
Authors: Haller Christlieb , Kuschinsky Wolfgang , Reimnitz Peter
Published: April 2011

The effect of γ-hydroxybutyrate (GHB) on the reactivity of pial arteries to local metabolic factors was tested in chloralose-anesthetized cats before or after a period of transient ischemia induced by air embolism. The vascular reactions were determined during the perivascular microapplication of artificial CSFs with increasing concentrations of adenosine (10−11–10−3 M), H+ (pH 5.1–7.6), or K+ (0–10 m M). During nonischemic conditions the pial arterial reactivity to adenosine and H+, but not to K+, was significantly increased by GHB (250 mg/kg i.v.) when compared with the control reactivity. After cerebral ischemia the reactivity to adenosine was abolished with and without the administration of GHB prior to air embolism. The reactivity to K+ was partly preserved but not increased by GHB when compared with previous results without GHB. In contrast GHB improved the postischemic reactivity to perivascular H+ that had been found to be abolished in previous experiments without GHB. The perivascular microapplication of GHB showed no influence of GHB on the vascular diameter. An important finding of the present study is the demonstration of an increase in cerebrovascular reactivity, which may give scope for therapeutic improvement of the regulation of CBF in pathophysiological conditions.
Cerebral Acidosis in Focal Ischemia: II. Nimodipine and Verapamil Normalize Cerebral pH following Middle Cerebral Artery Occlusion in the Rat
Authors: Hakim Antoine M.
Published: April 2011

The effects of prostacyclin, nimodipine, and verapamil on local cerebral pH (LCpH) and CBF (LCBF) in middle cerebral artery (MCA)–occluded rats were compared with those in controls and others receiving nimodipine carrier. LCpH and LCBF were determined simultaneously by a double-label autoradiographic technique. The infusions were intravenous, started 15 min following the occlusion, and ended at decapitation 4 h postocclusion. The dosages were 0.5 μg/kg/min for nimodipine, 40 μg/kg/min for verapamil, and 5 ng/kg/min for prostacyclin. Cortical LCpH in the MCA territory of control and carrier-infused rats varied between 6.72 ± 0.05 and 6.76 ± 0.05 (means ± SEM). These values were significantly lower than the LCpH in the same structures in the contralateral hemisphere (7.09 ± 0.06; p < 0.05). LCBF on the side of occlusion varied between 54 ± 5 ml/100 g/min for the parietal and 57 ± 7 ml/100 g/min for the sensorimotor cortex, while on the contralateral side, LCBF in these same structures was 190 ± 18 and 191 ± 4 ml/100 g/min, respectively. LCpH was not modified by prostacyclin treatment following MCA occlusion, but the pH in the structures that were acidotic in the controls became indistinguishable from contralateral values in nimodipine- and verapamil-treated animals. In contrast, LCBF was statistically higher than controls in many structures only in rats treated with prostacyclin. This suggested that the correction of LCpH produced by calcium blockers was not related to an effect they had on blood flow. Animals receiving calcium blockers tended to have smaller areas of infarction. These results may have therapeutic implications in cerebral ischemia.
The Effects of Nimodipine on Cerebral Blood Flow and Metabolism
Authors: Forsman Marianne , Fleischer Jerry E. , Milde James H. , Steen Petter A. , Michenfelder John D.
Published: April 2011

Nimodipine, a calcium entry blocker, was administered in increasing doses of 0.1–3.0 μg kg−1 min−1 to six dogs after they had recovered consciousness from a surgical preparation that was conducted under general anesthesia and while they were under the influence of total spinal anesthesia. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Nimodipine did not influence either CBF or CMRO2. There was a decrease in the cortical pyruvate level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with six control dogs. It has previously been reported that nimodipine increases the CBF in global ischemia with a potentially beneficial effect on the neurological outcome. With no effect on normal CBF or metabolism, this suggests that nimodipine may be useful in a variety of ischemic situations without fear of either a steal phenomenon or untoward effects on intracranial pressure.
Strategies for in vivo Measurement of Receptor Binding Using Positron Emission Tomography
Authors: Perlmutter Joel S. , Larson Kenneth B. , Raichle Marcus E. , Markham Joanne , Mintun Mark A. , Kilbourn Michael R. , Welch Michael J.
Published: April 2011

Dopaminergic ligands labeled with positron-emitting radionuclides have been synthesized for quantitative evaluation of dopaminergic binding in vivo. Two different methods, the explicit method and an operationally simplified ratio method, have been proposed for analysis of these positron emission tomographic (PET) data. The basis for both methods is the same three-compartment model. The two methods differ in the assumptions necessary for practical implementation. We have compared these two approaches using PET data obtained in our laboratory. Sequential scans and serial arterial blood samples from a baboon following intravenous injection of [18F]spiroperidol were collected. Application of the two methods to the same data yielded different values for corresponding parameters. Values calculated by the ratio method for the specific rate constant describing receptor binding varied depending upon the time after tracer injection, thus demonstrating an internal inconsistency in this approach. Tracer metabolism markedly affected the binding measurements calculated with either method and thus cannot be ignored. Our results indicate that the adoption of simplifying assumptions for operational convenience can lead to substantial errors and must be done with caution. Alternatively, we present simple new analytical solutions of the tracer conservation equations describing the complete, unsimplified three-compartment model that vastly reduce the computations necessary to implement the explicit method.
Recovery of Monkey Brain after Prolonged Ischemia. I. Electrophysiology and Brain Electrolytes
Authors: Hossmann K.-A. , Ophoff B. Grosse
Published: April 2011

Adult normothermic monkeys were submitted to 1 h of total cerebral ischemia, followed by blood recirculation for 1.5–24 h. During ischemia EEG and evoked potentials were suppressed within 12 s and 3 min, respectively. Upon recirculation, high-voltage EEG bursts began to reappear after 82–125 min, followed by gradual return of continuous background activity and near normalization of EEG frequency pattern within 24 h. Somatically evoked potentials, in contrast, exhibited only partial recovery, and consciousness did not return during the observation period. At the end of the experiments, tissue contents of sodium, potassium, calcium, and magnesium were measured in the gray and white matter of parietal lobe by atomic absorption spectros-copy. Gray matter sodium content gradually increased by ∼50% from 41.0 to 59.8 μmol/g wet wt during 24 h of recirculation. The other electrolytes including calcium did not change during the observation period. Postisch-emic recovery reported in this and the accompanying article is attributed to careful control of postischemic general physiological state and prevention or treatment of postischemic complicating side effects such as postischemic brain edema, hypotension, acidosis, pulmonary distress, and anuria. No specific drug treatment such as application of calcium antagonists or metabolic inhibitors was necessary to achieve this effect.
Photochemically Induced Cortical Infarction in the Rat. 1. Time Course of Hemodynamic Consequences
Authors: Dietrich W. Dalton , Ginsberg Myron D. , Busto Raul , Watson Brant D.
Published: April 2011

Alterations in local CBF (LCBF) were assessed autoradiographically in the rat at several time points following photochemically induced cortical infarction. Cortical infarction of consistent size and location was produced by irradiating the brain with green light through the intact skull for 20 min following the systemic injection of rose bengal. A consistent pattern of altered LCBF was recorded in both ipsilateral and contralateral brain regions over the course of the study. At 30 min, a severely ischemic zone surrounded by regions of cortical hyperemia was apparent. LCBF was also depressed relative to control values in ipsilateral cortical regions remote from the irradiated area, while contralateral cortical structures were mildly hyperemic. By 4 h, the zone of severe ischemia had enlarged and its margins were no longer hyperemic. Ipsilateral cortical and some subcortical structures demonstrated significantly depressed levels of LCBF. At 5 days, LCBF throughout both ipsilateral and contralateral cortices was depressed compared with control values. By 15 days, LCBF had returned to control levels in most brain structures shown histopathologically not to be irreversibly damaged. The temporal sequence and magnitude of these hemodynamic alterations are consistent with findings in clinical studies in which repeated measurements of CBF have been carried out in patients with acute stroke. The ability to produce a cortical infarct that results in a consistent pattern of altered CBF should facilitate the investigation of stroke mechanisms responsible for these hemodynamic abnormalities.
Antibodies to Blood—Brain Barrier Bind Selectively to Brain Capillary Endothelial Lateral Membranes and to a 46K Protein
Authors: Pardridge William M. , Yang Jing , Eisenberg Jody , Mietus Lawrence J.
Published: April 2011

To begin elucidating the biochemical basis of the polarized membrane features of the blood–brain barrier (BBB), a series of immunochemical and immunoperoxidase studies were initiated with bovine brain microvessels that make up the BBB in vivo. A rabbit antiserum was prepared against isolated bovine brain BBB plasma membranes. The bovine microvessel plasma membranes were radioiodinated with chloramine-T, and the antiserum selectively immunoprecipitated a 46K protein. The antibodies directed against the 46K protein were quantitatively absorbed with bovine brain capillaries but not with rat kidney or liver powder. Only the capillaries of brain reacted with the rat kidney-absorbed antiserum in immunoperoxidase studies of ethanol-fixed, 8-μm sections of bovine brain cortex, whereas the capillaries in heart, liver, and kidney did not react. This antiserum also strongly illuminated the lateral membranes of isolated bovine brain capillary endothelial cells grown in primary tissue culture. These studies provide evidence for a polarized distribution of a surface antigen in bovine brain capillary endothelial cells that is not present in capillary endothelia of liver, heart, or kidney. The correlation of the immunoperoxidase and immunoprecipitation techniques suggests that a candidate for the asymmetrically distributed surface antigen in the BBB is the 46K protein. The relationship between the 46K protein and the composition of BBB tight junctions remains to be determined.
Comparison between Pial and Intraparenchymal Vascular Responses to Cervical Sympathetic Stimulation in Cats. Part 1. Under Normal Resting Conditions
Authors: Gotoh Fumio , Fukuuchi Yasuo , Amano Takahiro , Tanaka Kortaro , Uematsu Daisuke , Suzuki Norihiro , Kobari Masahiro , Obara Katsuyuki
Published: April 2011

To investigate the role of sympathetic regulation in both resistance and capacitance vessels in cerebral circulation, the responses of pial and intraparenchymal vessels to sympathetic nerve stimulation were simultaneously examined in 14 cats by means of a newly developed video camera photoelectric system. The system consisted of a video camera system for measurement of pial vascular diameters and a photoelectric apparatus for estimating regional cerebral blood volume in the intraparenchymal vessels. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min. Initially, both the pial and intraparenchymal vessels constricted. The large pial arteries (173 ± 25 μm, mean ± SEM) remained constricted throughout the stimulation, whereas the intraparenchymal vessels began to dilate after the initial constriction and exceeded the control level at 175 ± 25 s despite continued stimulation. In conclusion, such sympathetic nerve stimulation is considered to exert a constrictive effect on the intraparenchymal as well as the pial vessels at the early stage. The compensatory dilation of the intraparenchymal vessels was delayed 3 min after initiation of the stimulation.
Comparison of Quantitative Autoradiographic and Xenon-133 Clearance Methods: Correlation of Gray and White Matter Cerebral Blood Flow with Compartmental Blood Flow Indices
Authors: Tuor U. I. , Fitch W. , Graham D. I. , Mendelow A. D.
Published: April 2011

The relationships between CBF in gray and white matter to those of the fast and slow components of xenon-133 clearance curves remain uncertain. CBF was measured in 13 anaesthetized baboons under a variety of conditions, using both the xenon-133 clearance technique and [14C]iodoantipyrine quantitative autoradiography. There was a linear relationship between CBF, as determined by the stochastic (height/area) analysis of the clearance curve, and mean CBF determined from the autoradiograms ( r = 0.94, p < 0.001, slope = 0.86 ± 0.09). There was also a linear correlation between the fast-flow component (measured with xenon-133) and blood flow in the cerebral gray matter (measured with [14C]iodoantipyrine) ( r = 0.92, p < 0.001, slope = 0.69 ± 0.15) and between the slow-flow component (with xenon-133) and blood flow in white matter (with [14C]iodoantipyrine) ( r = 0.79, p < 0.01, slope = 0.81 ± 0.10). In the primate brain, the fast- and slow-flow indices therefore appear to be representative of CBF in gray matter and white matter, respectively, whereas the stochastic analysis provides a stable measure of mean CBF within the tissue monitored.
Maximizing Precision in Quantitative Autoradiographic Determination of Tissue Tracer Concentration Using Exposure Optimization
Authors: Lear James L.
Published: April 2011

The relationships between tissue tracer concentrations, length of time of tissue contact with film, and the darkness of resulting autoradiographic images were explored. Operational equations were then developed relating ranges of film darkening to the ranges of tracer concentration contained within the sections. These equations were solved and used to define ranges of optical density that are optimal for precise determination of tracer concentration using digital image analyzers. The solutions indicated that optimal optical densities are a function of the range of tracer concentrations in the sections. For autoradiograms of typical cerebral blood flow and metabolism tracers, exposure should be controlled to produce images that are significantly less dark than what is generally considered pleasing to the eye.
Increases in Cerebral Interstitial Fluid Adenosine Concentration during Hypoxia, Local Potassium Infusion, and Ischemia
Authors: Van Wylen David G. L. , Park T. S. , Rubio Rafael , Berne Robert M.
Published: April 2011

This study used the brain dialysis technique to test the hypothesis that the adenosine concentration of cerebral interstitial fluid increases during situations in which cerebral oxygen supply is inadequate for oxygen demand. Sealed 300-μm hollow dialysis fibers were implanted in the caudate nucleus of pentobarbital-anesthetized rats and perfused at 2 μl/min with artificial cerebrospinal fluid. In vitro tests indicated the recovery of adenosine, inosine, and hypoxanthine from the external medium to be ∼20% at 2 μl/min and close to 100% at 0.1 μl/min. Three in vivo interventions were tested: hypoxia/hypotension (Pao2 = 41.9 mm Hg; MABP = 42.8 mm Hg; n = 9), local potassium infusion (n = 4), and cerebral anoxia/ischemia (n = 10). These interventions produced 10-, 4-, and 30-fold increases in perfusate adenosine concentration, respectively, as well as increases in perfusate concentrations of inosine and hypoxanthine. A separate group of rats (n = 9) perfused at 0.1 μl/min yielded estimates of cerebral interstitial fluid adenosine, inosine, and hypoxanthine concentrations of 1.26, 3.30, and 7.19 μ M, respectively. These results are consistent with the adenosine hypothesis for the regulation of CBF.
Studies on Regional Cerebral pH in Patients with Cerebral Tumours Using Continuous Inhalation of 11CO2 and Positron Emission Tomography
Authors: Brooks D. J. , Beaney R. P. , Thomas D. G. T. , Marshall J. , Jons T.
Published: April 2011

Regional cerebral pH (rpH) was measured in 12 patients with cerebral tumours and in 5 normal subjects using continuous inhalation of 11CO2 and positron emission tomography (PET). Cerebral tumours with a disrupted blood–brain barrier (BBB) on computed tomography scanning had a similar rpH to that of equivalent regions of contralateral brain tissue (mean tumour rpH, 6.98; mean contralateral brain pH, 6.99). Cerebral tumours with an intact BBB were consistently found to be more alkaline than contralateral brain tissue (mean tumour rpH, 7.09). There was no significant difference between the mean rpH values obtained for peripheral cortical gray and central white matter in normal subjects (7.02 and 6.98, respectively). It is concluded that in spite of reports of raised levels of aerobic glycolysis in neoplastic tissue, there is no evidence that cerebral tumour rpH values are depressed.
Simultaneous Determination of Regional Cerebral Blood Flow, Glucose Metabolism, and pH in Acute Experimental Allergic Encephalomyelitis
Authors: Juhler M.
Published: April 2011

Regional cerebral blood flow (rCBF), regional cerebral glucose metabolic rate (rCMR), and regional pH (r-pH) were measured simultaneously in fulminant acute experimental allergic encephalomyelitis (EAE) by the use of triple-label autoradiography. No changes were found in the absence of lesions (lymphocytic accumulations). In the lesions, rCBF was 79% increased and rCRM was 13% increased, whereas r-pH was unaltered compared to normal values. The reported changes result in a CBF/CMR ratio of almost 3 in the lesions compared to the normal value of 1.5. The changes may be interpreted as primary disturbances in glucose metabolism, resulting in a secondary increase in CBF. This theory is supported by quoted observations on abnormal morphology and abnormal enzyme content in brain mitochondria in EAE.
Reflectance Spectrophotometric Measurement of in vivo Local Oxygen Consumption in the Cerebral Cortex
Authors: Kinuta Yuji , Kikuchi Haruhiko , Ishikawa Masatsune , Hirai Osamu , Imataka Kiyoharu , Kobayashi Shuichi
Published: April 2011

A simple method was developed to measure in vivo local oxygen consumption quantitatively in the brain cortex. Reflectance spectra of tissue hemoglobin at the brain's surface were measured for assessment of both local tissue hemoglobin content and its oxygen saturation. Local oxygen consumption was calculated from the spectral changes of tissue hemoglobin during complete cessation of blood flow by compression of the cortical surface in the suprasylvian gyrus with the tip of an optic probe. This procedure was performed without any brain damage and only took ∼5 s. The calculated local oxygen consumption during this short period of compression remained constant for a few seconds. Then, it decreased rapidly, although the local tissue hemoglobin was not completely deoxygenated. The value of local cerebral oxygen consumption obtained by this method was 3.02 ± 0.61 mL O2/100 g brain/min; it was not influenced by the change in systemic blood pressure. The effect of pentobarbital on cerebral oxygen consumption was also studied. At the stage of burst and suppression on electrocorticogram, cerebral oxygen consumption decreased significantly (p < 0.001) to 1.03 ± 0.07 mL O2/100 g brain/min.