bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstitial Fluid Adenosine and Sagittal Sinus Blood Flow during Bicuculline-Seizures in Newborn Piglets
Authors: Park T. S. , Van Wylen David G. L. , Rubio Rafael , Berne Robert M.
Published: April 2011

Changes of interstitial fluid adenosine concentrations and effects of O2 supply on interstitial fluid adenosine were studied by the brain dialysis technique in the frontal cortex of newborn piglets subjected to bicuculline-induced seizures. The O2 supply was changed globally by changing MABP and locally by varying PO2 in the artificial CSF perfusing the dialysis cannula. Sagittal sinus blood flow (SSBF), cerebrovascular resistance (CVR), and CMRO2 were also examined in the same animals. Seizures increased interstitial fluid adenosine 7.9-fold (p < 0.05) when ictal MABP was maintained at preictal level and perfusate PO2 was 24 mm Hg (group 1, n = 6). Interstitial fluid adenosine increased 11.8-fold (p < 0.05) during seizures associated with moderate systemic hypotension and the low perfusate PO2 (group 2, n = 6). By contrast, seizures increased interstitial fluid adenosine three-fold (p < 0. 05) when perfusate PO2 was increased to 182 mm Hg and ictal MABP was maintained at preictal level (group 3, n = 8). When ictal MABP was elevated from the preictal level and the perfusate was rich in oxygen, seizures failed to increase interstitial fluid adenosine (group 4, n = 7). In groups 1 and 3, the increase in interstitial fluid adenosine during seizures was associated with significant increases in SSBF and CMRO2, as well as significant decreases in CVR. These data suggest that the increase in O2 supply during seizures in piglets did not match completely the increase in O2 demand and resulted in enhanced release of adenosine into the interstitial space.
Evaluation of the 11CO2 Positron Emission Tomographic Method for Measuring Brain pH. I. pH Changes Measured in States of Altered PCO2
Authors: Buxton Richard B. , Alpert Nathaniel M. , Babikian Viken , Weise Steven , Correia John A. , Ackerman Robert H.
Published: April 2011

The 11CO2 method for measuring local brain pH with positron emission tomography (PET) has been experimentally evaluated, testing the adequacy of the kinetic model and the ability of the method to measure changes in brain pH. Plasma and tissue time/activity curves measured during and following continuous inhalation of 11CO2 were fit with a kinetic model that includes effects of tissue pH, blood flow, and fixation of CO2 into compounds other than dissolved gas and bicarbonate ions. For each of ten dogs, brain pH was measured with PET at two values of PaCO2 (range 21–67 mm Hg). The kinetic model fit the data well during both inhalation and washout of the label, with residual root mean square (RMS) deviations of the model from the measurements consistent with the statistical quality of the PET data. Brain pH calculated from the PET data shows a linear variation with log(PaCO2). These results were in good agreement with previously reported measurements of brain pH, both in absolute value and in variation with PCO2. The interpretation of these pH values in normal and pathological states is discussed.
Reduction of Cerebral Blood Flow in Subclinical Hepatic Encephalopathy and its Correlation with Plasma-Free Tryptophan
Authors: Rodriguez Guido , Testa Roberto , Celle Guido , Gris Arturo , Marenco Stefano , Nobili Flavio , Novellone Gianluca , Rosadini Guido
Published: April 2011

Cerebral blood flow (CBF), measured by the noninvasive xenon-133 inhalation method, EEG, and plasma levels of ammonia (NH3) and free tryptophan were determined in 18 hospitalized cirrhotic patients affected with subclinical hepatic encephalopathy, as diagnosed by the Kurtz test. CBF results were significantly lower (p < 0.001) in the patients' group as compared with a sex- and age-matched normal control population, although seven patients had values in the normal range. NH3 was increased only in six, while free tryptophan was increased in all but two patients. A significant negative correlation (p = 0.02) between CBF and free tryptophan was found, even though it appears to be difficult to interpret. We suggest that CBF impairment in some cirrhotic patients with subclinical hepatic encephalopathy may be related to the systemic metabolic derangement caused by the liver disease; free tryptophan could have some implication in producing CBF reduction.
Brain Phenobarbital Uptake during Prolonged Status Epilepticus
Authors: Simon Roger P. , Copeland James R. , Benowitz Neal L. , Jacob Peyton , Bronstein Jeff
Published: April 2011

The brain uptake of phenobarbital during prolonged status epilepticus (3 h) was studied in paralyzed, ventilated sheep. The first 30 min of status epilepticus was characterized by systemic hypertension, increased CBF, increased peripheral vascular resistance, a fall in brain pH, and an elevation in brain lactate concentrations. Subsequently, hemodynamic factors normalized and brain acidosis persisted. Phenobarbital administered during the early phase of status epilepticus produced higher levels of brain phenobarbital concentration, which was greatest at the earliest sample time (5 min following infusion), compared to nonseizure controls. This elevation persisted for the first 3 h following the infusion. Phenobarbital administration during the established phase of status epilepticus, when systemic blood pressure, peripheral vascular resistance, and CBF had returned to preseizure values, resulted in attenuated brain uptake not different from controls for the first 30 min. These results are explained by disruption of the blood-brain barrier to phenobarbital during the early (hypertensive) phase of status epilepticus.
Pial Artery Pressure after One Hour of Global Ischemia
Authors: Schmidt-Kastner R. , Hossmann K.-A. , Ophoff B. Grosse
Published: April 2011

Pial artery pressure was measured in anesthetized control cats and in animals subjected to 1 h of global ischemia and 6 h of recirculation. Cerebral blood flow (CBF) was measured with the intraarterial 133Xe technique before and after ischemia, and lumped segmental resistances upstream and downstream to the pial artery were calculated. In the control brain, upstream resistance was 1.30 ± 0.28 and downstream resistance 0.94 ± 0.1 mm Hg ml-1 100 g min. During the postischemic hypoperfusion period, both resistances significantly increased, indicating that hypoperfusion constitutes a dysregulation of both large extracerebral and small intracerebral vessels. Hypercapnia induced an increase of CBF in the control brain and was accompanied by a fall in downstream resistance, demonstrating intracortical vasodilation. By contrast, hypercapnia did not provoke changes in either CBF or segmental resistances in the hypoperfusion period. In conclusion, during the postischemic hypoperfusion period, both extra- and intracortical resistances are increased and vascular reactivity to CO2 is abolished.
A System for Cerebral Blood Flow Measurement Using an H215O Autoradiographic Method and Positron Emission Tomography
Authors: Kanno I. , Iida H. , Miura S. , Murakami M. , Takahashi K. , Sasaki H. , Inugami A. , Shishido F. , Uemura K.
Published: April 2011

A system for CBF measurement using an H215O autoradiographic method and positron emission tomography (PET) has been designed and installed as a clinical tool. Following an intravenous injection of H215O, a radioactivity accumulation in the brain tissue for 60 s and a continuous record of radioactivity in arterial blood were measured by a high counting speed PET device and a beta-ray detector, respectively, and CBF was calculated by a table-lookup procedure. First, this method was compared with the C15O2 inhalation steady-state method on 17 cerebrovascular disease patients and four normal subjects. The two values for CBF agreed with each other when H215O autoradiographic method was applied by correction for the dispersion in the measured arterial radioactivity–time curve. However, without the correction, the CBF by the H215O autoradiographic method revealed substantial overestimation by 30.6 ± 17.5%. A reduced gray/white ratio of CBF was also observed in the H215O autoradiographic method. Second, simulation was performed in order to determine optimal accumulation time by PET scan; the result was that errors due to dispersion and time mismatch became critical as the accumulation time was shortened to <60 s.
Increased Brain Interstitial Fluid Adenosine Concentration during Hypoxia in Newborn Piglet
Authors: Park T. S. , Van Wylen David G. L. , Rubio Rafael , Berne Robert M.
Published: April 2011

The effects of arterial hypoxia on interstitial fluid adenosine concentrations were studied in the frontal cortex and thalamus by the brain dialysis technique and in CSF from the cisterna magna of the newborn piglet. Acute hypoxia (PaO2 = 20 ± 1 mm Hg) increased the interstitial fluid adenosine concentrations significantly from 0.68 ± 0.29 (SEM) to 1.60 ± 0.35 μ M in the frontal cortex and from 1.03 ± 0.32 to 2.60 ± 0.86 μ M in the thalamus (n = 8). Interstitial fluid inosine and hypoxanthine also increased significantly during hypoxia. In separate groups of piglets, the adenosine concentration in the cisterna magna CSF under normoxic conditions was 0.04 ± 0.01 μ M (n = 5), which increased significantly to 0.17 ± 0.04 μ M (n = 6) with hypoxia (PaO2 = 4.7 ± 1.2 mm Hg). Cisterna magna CSF inosine levels did not change significantly during the severe hypoxia. Adenosine concentrations found in the interstitial space and CSF of newborn piglets under normoxic and hypoxic conditions are within the vasodilator range. These results thus suggest that in the neonatal brain adenosine may play a role in regulating blood flow during hypoxia.
Exogenous Norepinephrine Constricts Cerebral Arterioles via α2-Adrenoceptors in Newborn Pigs
Authors: Busija David W. , Leffler Charles W.
Published: April 2011

The purpose of this study was to determine whether exogenous norepinephrine mediates cerebrovascular constriction via α1- or α2-adrenoceptors in anesthetized neonatal pigs. Diameters of pial arterioles in anesthetized piglets, 1–6 days old, were investigated using a “closed” cranial window. We examined constrictor effects of norepinephrine on pial arterioles in the absence and presence of relatively selective α1,- (prazosin) and α2-(yohimbine) adrenoceptor antagonists (1 mg/kg i.v.). Yohimbine and prazosin inhibited pial arteriolar constriction induced by topical application of clonidine and phenylephrine (10−6 and 10−4 M, respectively), and yohimbine did not affect the response to topical phenylephrine. In one group diameter was 188 ± 13 (mean ± SEM) μm during control and 146 ± 12 (μm during 10−5 M norepinephrine (22 ± 5% constriction). Following yohimbine the same vessels did not constrict significantly. In another group 10−5 M norepinephrine constricted arterioles by 22 ± 5%, and this response was unaffected by prazosin (24 ± 5% constriction). We conclude that pial arterioles are responsive to both α1- and α2-adrenoceptor agonists, that intravenous administration of prazosin and yohimbine results in these drugs crossing the blood–brain barrier and inhibiting constrictor effects of agonists, and that norepinephrine constricts pial arterioles predominantly via α2-adrenoceptors.
Regional Cerebral Metabolic Activity in the Rat following Experimental Subarachnoid Hemorrhage
Authors: Solomon Robert A. , Lovitz Robert L. , Hegemann Margaret T. , Schuessler George B. , Young William L. , Chien Shu
Published: April 2011

A new experimental model was employed to investigate alterations of cerebral metabolic activity in rats subjected to extensive subarachnoid hemorrhage (SAH). The hemorrhages were produced in anesthetized animals by inserting 0.37 ml fresh autologous arterial blood into the subarachnoid space. Rats that underwent sham operations received subarachnoid injections of mock CSF to study the effects of sudden raised intracranial pressure (ICP). Forty-eight hours after subarachnoid injection, the unanesthetized rats were given intravenous injections of [14C]2-deoxyglucose. Experiments were terminated 45 min later by decapitation, and the brains were removed and frozen. Regional brain metabolic activity was studied employing quantitative autoradiography. In comparison with control animals, cerebral metabolic activity was diffusely decreased following SAH. Statistically significant decreases in metabolic activity of <34% were observed in 17 of 30 brain regions studied. The largest percentage reductions were in regions displaying the highest basal metabolic rates. Subarachnoid injections of mock CSF also produced depression of cerebral metabolic activity, but quantitatively these changes were not as pronounced as in the hemorrhage group. These studies demonstrate regional changes in brain function following SAH. The data relate these changes to both the presence of blood in the subarachnoid space and sudden raised ICP.
Mechanisms of Cerebrovascular Dilation by Ether in Monkeys
Authors: Kang Yoo Goo , Nemoto Edwin M. , Bleyaert Achiel L. , Winter Peter M. , Eidelman Benjamin H. , Taylor Floyd H.
Published: April 2011

We hypothesized that when the depth of ether anesthesia is increased from 2 to 5%, cerebral vessels dilate secondary to circulating catecholamine stimulation of cerebral metabolism. Cerebral blood flow (CBF) by 133Xe clearance and cerebral metabolic rate for oxygen (CMRO2) were measured on 2% and then 5% ether in air in two groups of seven monkeys each during mechanical ventilation. Propranolol, 0.5 mg/kg i. v., was infused over 5 min in one group, and the other received saline. All measurements were repeated on 5% and 2% ether. Cerebrovascular resistance (CVR) fell by 30%, from 2.28 2± 0.61 (mean ± SD) to 1.51± 0.28 mm Hg ml−1 100 g−1 min−1 (p < 0.01), with the increase in ether from 2 to 5%. CBF and CMRO2 were unaltered from values of about 45 ml 100 g−1 min−1 and 2.3 ml 100 g−1 min−1, respectively. During 5% ether anesthesia, propranolol had no effect on CBF, CMRO2, or CVR. On 2% ether, it increased CVR twofold, from 1.5 ± 0.30 to 3.0 ± 1.0 mm Hg ml−1 100 g−1 min−1, and decreased CBF by 33%, from 48 ± 8 to 32 ± 10 ml 100 g−1 min−1. Plasma epinephrine was twofold higher on 2% compared to 5% ether, both before and after saline or propranolol infusion. In monkeys, cerebrovascular dilation by ether at 5% compared to 2% is not secondary to catecholamine stimulation of CMRO2. It may result from a direct effect of either plasma catecholamines or ether on the cerebrovasculature.
Effect of Neonatal 6-Hydroxydopamine Treatment on Experimental Vasospasm following a Subarachnoid Hemorrhage in the Rat
Authors: Delgado Tia J. , Arbab Mohamed A.-R. , Rosengren Evald , Svendgaard Niels-Aage
Published: April 2011

Intracisternal injection of blood in the rat produces an angiographically demonstrable biphasic cerebral arterial vasospasm. Systemic 6-hydroxydopamine (6-OHDA) treatment in the neonatal stage, which causes a depletion of noradrenaline (NA) from both sympathetic and central NA-containing nerve fibers, prevents the development of the late spasm phase, while the acute spasm occurs to the same extent as in normal animals. The occurrence of acute spasm can be prevented by lesioning in the mesencephalon of the ascending catecholamine fibers originating in the lower brainstem and projecting to the hypothalamus. It is suggested that 6-OHDA treatment results in the altered spasm pattern via its effect on catecholamine fibers projecting between the medullary A1 and A2 nuclei and the hypothalamus. The occurrence of acute but not late spasm indicates that there is a different pathway underlying the two spasm phases.
The Effect of Hematocrit and Systolic Blood Pressure on Cerebral Blood Flow in Newborn Infants
Authors: Younkin D. P. , Reivich M. , Jaggi J. L. , Obrist W. D. , Delivoria-Papadopoulos M.
Published: April 2011

The effects of hematocrit and systolic blood pressure on cerebral blood flow were measured in 15 stable, low birth weight babies. CBF was measured with a modification of the xenon-133 (133Xe) clearance technique, which uses an intravenous bolus of 133Xe, an external chest detector to estimate arterial 133Xe concentration, eight external cranial detectors to measure cephalic 133Xe clearance curves, and a two-compartmental analysis of the cephalic 133Xe clearance curves to estimate CBF. There was a significant inverse correlation between hematocrit and CBF, presumably due to alterations in arterial oxygen content and blood viscosity. Newborn CBF varied independently of systolic blood pressure between 60 and 84 mm Hg, suggesting an intact cerebrovascular autoregulatory mechanism. These results indicate that at least two of the factors that affect newborn animal CBF are operational in human newborns and may have important clinical implications.
Effects of Insulin on Local Cerebral Glucose Utilization in the Rat
Authors: Lucignani Giovanni , Namba Hiroki , Nehlig Astrid , Porrino Linda J. , Kennedy Charles , Sokoloff Louis
Published: April 2011

The effects of hyperinsulinemia on local cerebral glucose utilization were studied by the quantitative autoradiographic 2-[14C]deoxyglucose method in normal conscious rats under steady-state normoglycemic conditions. Hyperinsulinemia and a steady state of normoglycemia were achieved and maintained during the experimental period by a continuous intravenous (i.v.) infusion of insulin given simultaneously with a programmed i.v. infusion of D-glucose. Hyperinsulinemia under normoglycemic conditions did not change the average rate of glucose utilization in the brain as a whole, but significant increases in local glucose utilization were found selectively in the ventromedial, dorsomedial, and anterior hypothalamic nuclei. The results suggest that a known anatomical pathway linking the dorsomedial and anterior nuclei with the ventromedial nucleus of the hypothalamus may be physiologically activated in response to hyperinsulinemia.
Tracer Disposition Kinetics in the Determination of Local Cerebral Blood Flow by a Venous Equilibrium Model, Tube Model, and Distributed Model
Authors: Sawada Y. , Sugiyama Y. , Iga T. , Hanano M.
Published: April 2011

Tracer distribution kinetics in the determination of local cerebral blood flow (LCBF) were examined by using three models, i.e., venous equilibrium, tube, and distributed models. The technique most commonly used for measuring LCBF is the tissue uptake method, which was first developed and applied by Kety (1951). The measurement of LCBF with the 14C-iodoantipyrine (IAP) method is calculated by using an equation derived by Kety based on the Fick's principle and a two-compartment model of blood–tissue exchange and tissue concentration at a single data point (Sakurada et al., 1978). The procedure, in which the tissue is to be in equilibrium with venous will be referred to as the tissue equilibration model. In this article, effects of the concentration gradient of tracer along the length of the capillary (tube model) and the transverse heterogeneity in the capillary transit time (distributed model) on the determination of LCBF were theoretically for the tissue sapling method. Similarities and differences among these models are explored. The rank order of the LCBF calculated by using arterial blood concentration time courses and the tissue concentration of tracer based on each model were tube model (model II) < distributed model (model III) < venous equilibrium model (model I). Data on 14C-IAP kinetics reported by Ohno et al. (1979) were employed. The LCBFs calculated based on model I were 45–260% larger than those in models II or III. To discriminate among three models, we propose to examine the effect of altering the venous infusion time of tracer on the apparent tissue-to-blood concentration ratio (Λapp). A range of the ratio of the predicted Λapp in models II or III to that in model I was from 0.6 to 1.3. In the future, there may be a need to determine which model should be used to calculate the LCBF based on this discriminator and to develop another discriminator by using multiple data points based on positron emission tomography.
Reduction of Cerebrospinal Fluid Pressure by Hypocapnia: Changes in Cerebral Blood Volume, Cerebrospinal Fluid Volume, and Brain Tissue Water and Electrolytes
Authors: Artru Alan A.
Published: April 2011

The study examined the role of cerebral blood volume (CBV), cerebrospinal fluid (CSF) volume, and brain tissue water and electrolytes on CSF pressure during 4 h of hypocapnia in dogs, Group I (n = 6) was examined during hypocapnia (PaCO2 20 mm Hg), with no intracranial mass being present Group II (n = 6) was examined with an intracranial mass present (epidural balloon, CSF pressure 35 cm H2O), but no hypocapnia. In group III (n = 6), an intracranial mass was present, and hypocapnia was used to lower CSF pressure. In group I, hypocapnia initially reduced CBV from 3.4 to 2.4 ml. With continued hypocapnia, CBV reexpanded to 3.4 ml by 4 h. CSF volume changed reciprocally, so that intracranial CSF pressure remained constant. In group II, CBV remained steady (2.7 ml), and CSF volume fell only slightly, so that CSF pressure remained elevated. In group III, hypocapnia initially reduced CBV from 2.8 to 2.2 ml, and CSF pressure fell from 35 to 19 cm H2O. With continued hypocapnia, CBV rose to 2.8 ml by 4 h, but CSF volume fell from 6.1 to 5.0 ml, so that CSF pressure remained low. Net intracranial absorption of CSF did not exceed net intracranial CSF production, suggesting that CSF volume fell because hypocapnia improved access of intracranial CSF to spinal sites of CSF reabsorption. Brain tissue composition was not different among groups. The indicate that hypocapnia lowers elevated CSF pressure initially by lowering CBV. This CSF pressure-lowering effect is sustained (despite reexpansion of CBV) by a further reduction of CSF volume. In this model, brain tissue water or electrolytes did not contribute to changes in CSF pressure.
Concentrations of Putative Neurovascular Transmitters in Major Cerebral Arteries and Small Pial Vessels of Various Species
Authors: Duverger D. , Edvinsson L. , MacKenzie E. T. , Oblin A. , Rouquier L. , Scatton B. , Zivkovic B.
Published: April 2011

The levels of noradrenaline, neuropeptide Y, 5-hydroxytryptamine, and substance P were measured and compared between the large arteries of the circle of Willis and the small cerebral vessels of the pia mater in the rat, rabbit, cat, and monkey. In all species, noradrenaline and neuropeptide Y concentrations were greater in the larger arteries than in small pial vessels. Noradrenaline concentrations were reduced following cervical sympathectomy, with the extent of diminution differing greatly in the various the effects of cervical ganglionectomy on neuropeptide Y concentrations were less pronounced. 5-Hydroxytryptamine concentrations in rats, cats, and rabbits were significantly greater in the small pial vessels, although measurable concentrations existed in the circle of Willis. In cats and monkeys, substance P was found in major arteries, but was not detectable at the level of the small pial vessels. The differences in the regional distribution of the various neurotransmitter candidates in the cerebrovascular bed may reflect their physiological significance.
Controlling for Cerebral Atrophy in Positron Emission Tomography Data
Authors: Clark Campbell , Hayden Michael , Hollenberg Susan , Li David , Stoessl A. Jon
Published: April 2011

This article outlines a simple method for estimating the degree of cerebral atrophy and subsequent experimental control for the effects of cerebral atrophy on regional metabolic values measured with positron emission tomography, It is suggested that rather than correcting derived values for atrophy, less potential error is introduced by experimentally controlling for regional atrophy when possible, By treating the derived metabolic rates and the measure of atrophy as two separate variables, it is also possible to establish whether there actually is a demonstrable relationship between the two measures.
Free Radical Reaction and Biological Defense Mechanism in the Pathogenesis of Prolonged Vasospasm in Experimental Subarachnoid Hemorrhage
Authors: Sakaki Saburo , Ohta Shinsuke , Nakamura Hisashi , Takeda Sadanori
Published: April 2011

The relationship between free radical reactions and the defense mechanisms against them was investigated in the pathogenesis of prolonged vasospasm following experimental subarachnoid hemorrhage (SAH) in dogs. The concentration of lipid peroxides in the cerebro spinal fluid (CSF) increased markedly up to the eighth day following SAH; the concentrations also rose in the arterial wall (p < 0.01) and the gray matter of the temporal lobe where the subarachnoid blood clots were (p < 0.01). On the other hand, the activity of superoxide dismutase (SOD) decreased significantly up to the eighth day after SAH (p < 0.01), and there was a gradual increase of glutathione peroxidase (GSH-px) in the CSF. In the arterial wall, there was a slight decrease in the activity of SOD, a significant decrease in the activity of GSH-px (p < 0.01), and also a significant decrease in the concentration of glutathione (p < 0.01) up to the eighth day following SAH. In conclusion, lipid peroxidation with insufficient biological defense mechanisms against it in the arterial wall, concomitant with that in the CSF, might take part in the genesis of prolonged vasospasm following SAH.
Changes in Vascular and Metabolic Reactivity as Indices of Ischaemia in the Penumbra
Authors: Strong A. J. , Gibson G. , Miller Susan A. , Venables G. S.
Published: April 2011

The reactivities of cerebral cortical blood flow (hydrogen clearance) and of compensated NADH fluorescence to local cortical electrical stimulation were examined on the marginal gyrus before and after transorbital occlusion of the middle cerebral artery in cats. Prestimulus cerebral blood flow (CBF) was 38.2 ± 12.9 (SD) ml 100 g−1 min−1 and fell to 19.8 ± 11.1 following occlusion (p < 0.02). Peak hydrogen clearance rate (percent increase above prestimulus clearance) was 81.6 ± 53.6 and fell to 19.9 ± 29.8 after middle cerebral artery occlusion (p < 0.01). Steady-state NADH fluorescence rose from 33.5 ± 10.7 to 40.5 ± 17.6% full-scale deflection following MCAO (p < 0.01). Latency from stimulus to maximal fluorescence depression in response to cortical stimulation increased from 12.2 ± 8.2 to 22.1 ± 11.9 s (p < 0.01). Hyperaemic responses at anteromedial sites on the marginal gyrus significantly exceeded those at posterolateral sites. The results are interpreted as indicating early ischaemic metabolic change; however, the presence of residual vasodilator responses to stimulation suggests that flow reduction and early ischaemic change in the territory studied are not simply due to inadequate collateral input, but may also reflect deafferentation or functional suppression. The possible significance of diminished vascular reactivity in the penumbra as a cause of increased vulnerability to extracellular release of excitatory amino acids is discussed.
The Transfer Coefficients for L-Valine and the Rate of Incorporation of L-[1-14C] Valine into Proteins in Normal Adult Rat Brain
Authors: Kirikae M. , Diksic M. , Yamamoto Y. L.
Published: April 2011

An autoradiographic method for the measurement of the rate of valine incorporation into brain proteins is described. The transfer coefficients for valine into and out of the brain and the rate of valine incorporation into normal rat brain proteins are given. The valine incorporation and the transfer constants of valine between different biological compartments are provided for 14 gray matter and 2 white matter structures of an adult rat brain. The rate of valine incorporation varies between 0.52 ± 0.19 nmol/g/min in white matter and 1.94 ± 0.47 in inferior colliculus (gray matter). Generally, the rate of valine incorporation is about three to four times higher in the gray matter than in the white matter structures.
Early Postischemic 45Ca Accumulation in Rat Dentate Hilus
Authors: Benveniste H. , Diemer N. H.
Published: April 2011

Several studies have found postischemic regional accumulation of calcium to be time-dependent and coincident with the progression of ischemic cell change. In the most vulnerable cells in the hippocampus one would therefore expect to find a primary and specific early uptake of calcium after ischemia. Autoradiograms of 45Ca and 3H-inulin distribution were investigated before and 1 h after 20 min ischemia in the rat hippocampus. Two different methodological approaches were used for administration of 45Ca: (a) administration via microdialysis probes, (b) intraventricular injection. During control conditions the 45Ca autoradiograms showed variations in distribution volume in accordance with 3H-inulin determination of extracellular space size. One hour after ischemia a massive accumulation of 45Ca was found in the dentate hilus. No change in the distribution pattern of 3H-inulin could be demonstrated 1 h after ischemia. We suggest that 45Ca accumulation in dentate hilus 1 h after ischemia is a result of increased Ca2+ uptake before irreversible cell damage occurs and is not due to passive influx of calcium across a leaky plasma membrane.
In situ Freezing of the Brain for Metabolic Studies: Evaluation of the “Box” Method for Large Experimental Animals
Authors: Obrenovitch T. P. , Bordi L. , Garofalo O. , Ono M. , Momma F. , Bachelard H. S. , Symon L.
Published: April 2011

The box method of freezing the brain in situ was assessed in baboons. The cooling rate of the tissue was monitored in several regions located at various depths from the skull surface. These measurements allowed us to examine the time required for the tissue to reach 0°C, in relation to its depth measured from the top of the skull. To define brain regions with proven ischaemia, frozen tissue sections were surveyed for areas of decreased pH. In addition, concentrations of ATP, phosphocreatine, and lactate were determined in gray matter located at various depths from the top of the brain surface. Normal tissue pH and low lactate concentration, without any significant decrease in high-energy phosphate levels, were found in regions at a depth < ∼10 mm from the brain surface. Deep structures including the inferiomedial aspect of the temporal lobe, the lateral geniculate body, and the limbic system (hippocampus) consistently showed mild tissue acidosis, indicating that these regions were subjected to some degree of ischaemia before they were reached by the freezing front. In some cases, acidosis was also detectable in the thalamus, basal ganglia, and in the deeper part of some sulci. We conclude that, with baboons, in situ freezing using the box method is valid for metabolic studies of the cerebral cortex and structures located at a depth <∼10 mm from the top of the brain surface.
Acute Cerebral Ischaemia: Concurrent Changes in Cerebral Blood Flow, Energy Metabolites, pH, and Lactate Measured with Hydrogen Clearance and 31P and 1H Nuclear Magnetic Resonance Spectroscopy. III. Changes following Ischaemia
Authors: Allen Kathryn , Busza Albert L. , Crockard H. Alan , Frackowiak Richard S. J. , Gadian David G. , Proctor Edward , Russell Ralph W. Ross , Williams Stephen R.
Published: April 2011

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anaesthesia. At the same time, intracellular pH and the concentrations of lactate and high-energy phosphates were measured in the brain using 1H and 31P nuclear magnetic resonance spectroscopy. Flow and metabolism have been followed during either a 15- or a 30-min ischaemic period (induced by bilateral carotid occlusion) and for up to 1 h of recovery. There was no significant difference between the flow characteristics of the two experimental groups. High-energy phosphate levels and pH returned to control within ∼20 min of the end of the ischaemic period. Lactate clearance, following a 30-min occlusion, was slower than the recovery of pH. The concentration of free ADP, calculated from the creatine kinase equilibrium, was lower during the recovery phase than under control conditions.
Calcium Accumulation during the Evolution of Hypoxic—Ischemic Brain Damage in the Immature Rat
Authors: Stein Dagmar T. , Vannucci Robert C.
Published: April 2011

An excessive accumulation of calcium in neuronal and other tissues has been postulated to represent a “final common pathway” for cell death arising from hypoxia-ischemia. To clarify the role of altered calcium flux into and distribution within the perinatal brain undergoing hypoxic-ischemic injury, 7-day postnatal rats underwent unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in >90% of the animals. Either before or after hypoxia-ischemia, the animals received a subcutaneous injection of [45Ca]Cl2, and their brains were subjected to 45Ca autoradiography at 0–1, 5, 24, and 72 h, 7 or 15 days thereafter. During hypoxia-ischemia, calcium flux into the ipsilateral cerebral hemisphere was prominent in 13 of 14 rat pups, especially in neocortex, hippocampus, striatum, and thalamus. Calcium accumulation also occurred to a variable degree (6 of 14 animals) in the contralateral cerebral hemisphere. During recovery, radioactivity in the contralateral cerebral hemisphere was no longer apparent, whereas in the ipsilateral hemisphere, the extent of calcium accumulation was mild in four of six at 1 h, moderate in three of six at 5 h, moderate to intense in six of seven and six of seven at 24 and 72 h, respectively, and intense in three of three and two of two animals at 7 and 15 days, respectively. As during hypoxia-ischemia, the distribution of the radioactivity was most prominent in those structures that are known to be vulnerable to hypoxic-ischemic injury. Thus, hypoxia-ischemia is associated with enhanced calcium uptake into the immature brain, which does not dissipate but rather progressively accumulates for up to 15 days of recovery. The findings implicate a disruption of intracellular calcium homeostasis as a major factor in the evolution of perinatal hypoxic-ischemic brain damage.
Brain Tissue Concentrations of ATP, Phosphocreatine, Lactate, and Tissue pH in Relation to Reduced Cerebral Blood Flow following Experimental Acute Middle Cerebral Artery Occlusion
Authors: Obrenovitch T. P. , Garofalo O. , Harris R. J. , Bordi L. , Ono M. , Momma F. , Bachelard H. S. , Symon L.
Published: April 2011

Local CBF (LCBF) was compared with the corresponding local tissue concentration of ATP, phosphocreatine (PCr), and lactate in anaesthetized baboons subjected to focal ischaemia produced by middle cerebral artery occlusion (MCAO). LCBF hydrogen electrodes were implanted in cortical regions where MCAO had been previously shown to produce severe and penumbral ischaemia and in posterior regions where blood flow is not altered. Metabolites were assayed in small tissue samples collected either by cryoprobe biopsy in the regions where LCBFs were measured (series 1) or by sampling appropriate regions of the rapidly frozen brain (series 2). Subsequent topographical study of brain tissue pH with umbelliferone was performed in this latter series. The results from these two series are compared and discussed in terms of the more appropriate way to perform simultaneous electrode measurements and analysis of tissue samples for studying focal ischaemia in the primate brain. They confirm that the concentrations of ATP and PCr decrease, and that lactate level increases, with decreasing blood flow. These metabolites tended to change more rapidly below a blood flow threshold, rather than showing a steady decrease as the blood flow was reduced, although the variability of the data precluded us from establishing this with confidence. Topographical study of tissue pH often showed sharp boundaries between zones of very low pH and regions with normal pH.
Effect of Stimulation of the Sphenopalatine Ganglion on Cortical Blood Flow in the Rat
Authors: Seylaz J. , Hara H , Pinard E. , Mraovitch S. , MacKenzie E. T. , Edvinsson L.
Published: April 2011

The effects of electrical stimulation of the sphenopalatine ganglion on cortical blood flow and gas partial pressures (Po2 and PCo2) were studied in the anesthetized rat. Tissue Po2, PCo2, and local CBF were measured simultaneously in both parietal cortices by means of mass spectrometry. Stimulation of the sphenopalatine ganglion increased CBF and tissue Po2 by —50 and 20%, respectively, in the ipsilateral parietal cortex. Smaller but significant increases in CBF and tissue Po2 were simultaneously seen in the contralateral parietal cortex. These variations were also accompanied by small decreases in PCo2 in both parietal cortices and a 5% increase in mean arterial pressure, whereas cortical electrical activity did not change. We conclude that the cholinergic (and vasoactive intestinal polypeptidergic) innervation of the cerebral blood vessels, arising from the sphenopalatine ganglion has significant vasomotor potential and that this system may be of functional importance.
Assessment of the Arterial Input Curve for [99mTc]-d,l-HM-PAO by Rapid Octanol Extraction
Authors: Andersen Allan R. , Friberg Hans , Lassen Niels A. , Kristensen K. , Neirinckx Rudi D.
Published: April 2011

The in vitro conversion of the lipophilic molecule [99mTc]– d,l-hexamethylpropyleneamine oxime ([99mTc]– d,l-HM-PAO) to a hydrophilic form was studied in saline, plasma, and blood at 37°C by paper chromatography and by octanol extraction. The octanol:saline ratio was 79.9. From this value and the corresponding octanol: plasma and octanol:blood partitioning values, an estimate of the transport of the lipophilic compound by various components of blood was made: 20% is carried in hemoglobin, 53% by the plasma proteins and 27% by the water phases of the red blood cell and plasma. Octanol extraction provided a rapid method for measuring the radiochemical purity (RCP) of lipophilic [99mTc]– d,l-HM-PAO. In saline, the RCP declined with a half-life of more than 1 h. In human plasma and whole blood, the conversion of [99mTc]– d,l-HM-PAO was biexponential due to the differences in the conversion rates of the d and l isomeric forms. The initial half-life representing the conversion rate of the l form was 1.7 min in blood and 1.4 min in plasma, while the conversion half-life of the d form was 7.4 and 24.4 min, respectively. In vivo, the RCP of arterial blood sampled after an i.v. bolus injection showed an initial peak value of 75% (68–79%) during the initial, first passage of the bolus. It declined to approximately 35% (29–40%) after 1.5 min and reached very low levels (about 1%) at 6 to 10 min. Quantitative measurements of cerebral blood flow using [99mTc]– d,l-HM-PAO necessitates a rapid method for RCP determination in arterial blood such as the one described here.
In vivo [3H]Spiperone Binding: Evidence for Accumulation in Corpus Striatum by Agonist-Mediated Receptor Internalization
Authors: Chugani Diane C. , Ackermann Robert F. , Phelps Michael E.
Published: April 2011

The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for β-adrenergic, muscarinic cholinergic, and δ-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist [3H]spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo [3H]spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of [3H]spiperone from microsomal membranes prepared from rat striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound [3H]spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to [3H]spiperone injection resulted in a selective increase of in vivo [3H]spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states.
The Quantification of Cerebral Infarction following Focal Ischemia in the Rat: Influence of Strain, Arterial Pressure, Blood Glucose Concentration, and Age
Authors: Duverger Danielle , MacKenzie Eric T.
Published: April 2011

Focal cerebral ischemia was induced by occlusion of the middle cerebral artery in rats. The volumetric assessment of infarcted tissue, 2 days following occlusion, was calculated from the examination of eight preselected coronal sections. Five differing rat strains were examined. A small and variable infarcted volume was seen in Wistar-Kyoto rats; Sprague-Dawley rats had a relatively large, but still variable, infarcted volume. Of the normotensive rat strains, the most reproducible volume of infarcted tissue was seen in Fischer-344 rats; also the absolute value of the infarcted volume did not vary from one series to another in this strain. Chronic arterial hypertension, studied in both normal and stroke-prone spontaneously hypertensive rats, was associated with significantly larger infarction volumes. Age does not change the volume of necrosis: Fischer-344 rats were studied at 3, 9, and 20 months of age, and no significant differences were noted between these ages. Experimental diabetes was induced by the administration of streptozotocin 3 days prior to middle cerebral artery occlusion. Severe hyperglycemia (>400 mg/dl) was associated with a considerably increased volume of infarction. The variability of the resultant lesion is high in the most commonly studied strains, but our results suggest that, for studies in normotensive rats, the use of the Fischer-344 strain produces a standardized and repeatable infarction that may be significantly modified by experimental interventions. Age is not a factor that affects the occlusion-induced infarction; in contrast, both chronic arterial hypertension and experimental diabetes aggravate the histological consequences of middle cerebral artery occlusion in the rat. We conclude that quantitative histological evaluation of infarct size allows a meaningful assessment of the gravity of focal cerebral ischemia.
Serotonin Potentiates Noradrenaline-Induced Vasoconstriction through 5-HT1-Type Receptors in Guinea Pig Basilar Artery
Authors: Chang Jing-Yu , Owman Christer
Published: April 2011

Based on the previous finding that 5-hydroxytryptamine (5-HT) co-exists with norepinephrine (NE) in cerebrovascular sympathetic nerve fibers and can be released during electrical nerve stimulation, the postjunctional interaction between the two amines was studied in isolated basilar artery of guinea pig. A low concentration of 5-HT, which in itself has little or no constrictive effect, potentiated the weak contraction of NE by almost 300%. The amplification was antagonized by methiothepin, but not by ketanserin, and it could be mimicked by methysergide. The marked potentiation is thus probably associated with the 5-HT1-like receptors, which earlier have been found to mediate the direct vasoconstrictive action of 5-HT in this vessel preparation.
Effect of the Serotonin Antagonist Ketanserin on the Hemodynamic and Morphological Consequences of Thrombotic Infarction
Authors: Dietrich W. Dalton , Busto Raul , Ginsberg Myron D.
Published: April 2011

The effect of the serotonin (5-hydroxytryptamine, 5-HT) antagonist ketanserin on the remote hemodynamic consequences of thrombotic brain infarction was studied in rats. Treated rats received an injection of 1 mg/kg ketanserin 30 min before and 1 h following photochemically induced cortical infarction. Local CBF (LCBF) was assessed autoradiographically with [14C]iodoantipyrine 4 h following infarction, and chronic infarct size was documented at 5 days. Thrombotic infarction led to significant decreases in LCBF within noninfarcted cortical regions. For example, mean LCBF was decreased to 63, 55, and 65% of control (nontreated normal rats) in ipsilateral frontal, lateral, and auditory cortices, respectively. In rats treated with ketanserin, significant decreases in LCBF were not documented within remote cortical areas compared with controls. In contrast to these hemodynamic effects, morphological analysis of chronic infarct size demonstrated no differences in infarct volume between treated (27 ± 3 mm3) and nontreated (27 ± 6 mm3) rats. These data are consistent with the hypothesis that 5-HT is involved in the widespread hemodynamic consequences of experimentally induced thrombotic infarction. Remote hemodynamic consequences of acute infarction can be inhibited without altering final infarct size.
Models for in vivo Kinetic Interactions of Dopamine D2-Neuroreceptors and 3-(2'-[18F]Fluoroethyl)Spiperone Examined with Positron Emission Tomography
Authors: Bahn Mark M. , Huang Sung-Cheng , Hawkins Randall A. , Satyamurthy Nagichettiar , Hoffman John M. , Barrio Jorge R. , Mazziotta John C. , Phelps Michael E.
Published: April 2011

The in vivo tracer kinetics of 3-(2apos;-[18F]fluoroethyl)spiperone (FESP) in the caudate/striatum and cerebellar regions of the human and monkey brain were studied with positron emission tomography (PET). The minimal model configuration that can describe the kinetics was determined statistically. Three two-compartment model configurations were found to be suitable for describing the kinetics in caudate/striatum and cerebellum: (1) a nonlinear model (five parameters) applicable to studies using nontracer (partially saturating) quantities of FESP in monkey striatum, (2) a linear four-parameter model applicable to the caudate/striatal and cerebellar kinetics in human and monkey studies with tracer quantities of FESP, and (3) a linear three-parameter model derived from the four-parameter model by assuming irreversible binding applicable to tracer studies of the human caudate. In the human studies, when the caudate kinetics ( n = 4) were fit by model 2 (with four parameters), the value of the in vivo ligand dissociation constant kd was found to be 0.0015 ± 0.0032/min. The three-parameter model (model 3) was found to fit the data equally well; this model is equivalent to model 2 with kd set to zero. In the monkey studies, it was found that for short (90 min) studies using tracer quantities of FESP, model 2 fit the striatal kinetics better than model 3. The parameters estimated using model 2 (four parameters) were in better agreement with those estimated by the nonlinear model (model 1) than those estimated using model 3 (three parameters). The use of a graphical approach gives estimates of the plasma–tissue fractional transport rate constant K1 and the net uptake constant K3 comparable to estimates using model 3 for both human and monkey studies.