Effects of methylprednisolone on tumor-induced brain edema

Local cerebral blood flow (LCBF), local cerebral glucose utilization (LCGU) and capillary permeability were studied in rats with tumor-induced brain edema. Moreover, effects of methylprednisolone on these physiological parameters were studied to analyse a possible role of steroid on treatment of peritumoral brain edema. A cubic millimeter pellet of Walker 256 tumor was transplanted to the left sensorimotor cortex of the rat brain. Animals were randomly divided into two groups. One group was treated with methylprednisolone (15 mg/kg/day) for 5 days starting at 5 days after tumor inoculation, and the other group received no treatment. These rats were used for autoradiographic study at 10 days after tumor inoculation. Local CBF, LCGU and capillary permeability were measured with 14C-iodoantipyrine, 14C-deoxyglucose and 14C-alphaaminoisobutyric acid, respectively. In the untreated group, LCBF and LCGU were widely depressed in the cortex and deep structures of the hemisphere ipsilateral to the tumor. Of the methylprednisolone treated animals LCBF and LCGU were significantly better than that of untreated animals. Capillary permeability of the untreated animals were highly increased in the viable part of the tumor. Some increase was also noted in the peripheral edge of the tumor and adjacent brain. In the methylprednisolone treated groups, capillary permeability was significantly lower than that in untreated group. The data suggest that methylprednisolone decreases capillary permeability in the viable part of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental meningeal carcinomatosis selectively depresses local cerebral glucose utilization in rat brain

Using quantitative autoradiography, we investigated the effect of meningeal carcinomatosis on local cerebral glucose utilization (LCGU). A rat model of meningeal carcinomatosis using Walker 256 tumor was used. LCGU was evaluated using 14C-2-deoxy-D-glucose according to the Sokoloff method. Thirty-one neuroanatomic structures were evaluated, both separately and as part of five functional or neuroanatomic groups: olfactory, auditory, visual, limbic, and white matter. The relationship between tumor and LCGU of underlying brain was examined. Compared with controls, there was no global change of LCGU in the experimental group that applied to all structures. However, mean LCGU was significantly depressed in olfactory cortex, temporal cortex, olfactory tubercle, amygdala, caudate/putaman, inferior colliculus, medial geniculate, anterior commissure, and corpus callosum, and the functional groups that make up the olfactory and auditory systems. There was no correlation between extent of regional tumor burden and degree of depression of LCGU in underlying structures. In meningeal carcinomatosis, tumor results in selective regional depression of LCGU. This occurs both in structures underlying tumor and those anatomically remote, but in certain cases, functionally related to structures subadjacent to tumor. These data may help to explain the diversity of neurologic dysfunction seen in patients with meningeal cancer.     

Uncoupling of LCBF and LCGU in two different models of hydrocephalus: a review

We have used two different experimental models to examine the relationship between local cerebral blood flow and metabolism in hydrocephalus. In our first experiments local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured by quantitative autoradiographic methods in adult rats rendered hydrocephalic, though asymptomatic, by the injection of kaolin intracisternally at 3 weeks of age and in control animals. There were no significant differences in LCGU or LCBF in any of the 29 areas of grey matter examined, including layer IV of the cerebral cortex. Scanning across the cerebral cortex revealed an appreciable fall in LCGU and LCBF towards the inside and the outside of the mantle in control animals. Hydrocephalus had no significant effect on this transmantle pattern of reduction in cortical metabolism towards the periphery, but in contrast, significantly enhanced the reduction in cortical blood flow in 7 out of the 10 cortical regions examined. Hence, in this model of asymptomatic hydrocephalus there is relative uncoupling of LCBF and LCGU in the inner and outer layers of the cerebral mantle. In a study performed in congenitally hydrocephalic H-Tx rats at 10, 20 and 28 days we found that uptake of deoxyglucose was impaired in hydrocephalic rats compared with their non-hydrocephalic siblings. Small changes were seen at 10 and 21 days, but statistically significant changes were seen only at 28 days. A small reduction in LCBF was observed in all regions at 10 days, with statistically significant differences between control and hydrocephalic rats in auditory and parietal cortex. By 21 days, reductions of between 25% and 70% in local cerebral blood flow were observed in all regions, with statistically significant differences in visual, auditory and parietal cortex. At 30 days, a statistically significant difference was found between controls and hydrocephalic rats in pons, caudate nucleus and visual, auditory, parietal and sensorimotor cortex. This second study indicates that decreases in local cerebral blood flow precede decreases in cerebral metabolism and occur before the appearance of obvious symptoms. Our experiments suggest that in hydrocephalus a decrease in tissue perfusion precedes any impairment of cerebral glucose metabolism and may occur before the appearane of any gross symptoms.Presented at the Consensus conference: Hydrocephalus '92 Assisi, Italy, 26–30 April 1992     

Correlation of local cerebral blood flow, glucose utilization, and tissue pH following a middle cerebral artery occlusion in the rat

The use of three sets of the double-tracer autoradiographic technique to measure topographical changes of local cerebral blood flow (LCBF), glucose utilization (LCGU), and tissue pH following a 3 h middle cerebral artery (MCA) occlusion in the rat is described. In a sham-operated group of animals there was 10% reduction of LCBF and 7% reduction of LCGU in the most affected areas as compared to the contralateral homologous regions. However, the ratio of LCGU/LCBF in the affected areas remained within normal limits. In the MCA-occluded animals, LCGU showed a bimodal response to decreased LCBF. LCGU decreased with reduced LCBF until LCBF fell to 38% of normal. Below this LCBF level LCGU increased, most likely implying anerobic glycolysis. Decline of tissue pH corresponds to the mismatch of LCBF and LCGU. These results suggest that brain tissue pH change cannot be predicted on the basis of LCBF or LCGU alone.     

Effect of dexamethasone on tumorous brain edema--changes in regional cerebral blood flow and glucose utilization

An experimental brain tumor was produced by implanting a piece of A.A. ascites tumor into the parietal brain of rat. Local cerebral blood flow (LCBF) and glucose utilization (LCGU) were determined in this model with 14C-iodoantipyrine and 14C-deoxyglucose quantitative autoradiographic methods, respectively, to investigate the change of blood flow and glucose metabolism and the effect of dexamethasone in the brain with tumor. LCBF and LCGU in the peritumoral brain tissue were reduced 75% and 60%, respectively, compared with the values of the control. In the ipsilateral frontal and occipital cortical areas far from the tumor, 50% and 45% reduction of LCBF, respectively, was observed. More than 30% reduction of LCGU was seen in the same areas. In the caudate and corpus callosum ipsilateral to the tumor, LCBF was diminished 25% and 40%, respectively. LCGU was not significantly changed in these areas. No significant changes of LCBF and LCGU were observed in the contralateral hemisphere. In the dexamethasone-treated animal, the reduction of LCBF was less in all areas where it was reduced in the untreated animal. In the peritumoral brain tissue, LCBF was significantly higher compared to that of the untreated group, and 80% of the normal level. In the ipsilateral frontal and occipital cortical areas, caudate and corpus callosum, LCBF was about the same as that of the control group. In the animal treated with dexamethasone, quantitative analysis of LCGU could not be made because of high glucose levels in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Global increase in cerebral metabolism and blood flow produced by focal electrical stimulation of dorsal medullary reticular formation in rat

We sought to determine whether the increases in local cerebral blood flow (LBCF) elicited by focal electrical stimulation within the dorsal medullary reticular formation (DMRF), are secondary to or independent of, increased local cerebral glucose utilization (LCGU).Rats were anesthetized (chloralose), paralyzed, artificially ventilated and arterial pressure and blood gases controlled. LCBF and LCGU were determined in two separate groups of animals, using the autoradiographic [¹⁴C]iodoantipyrine and [¹⁴C]2-deoxyglucose methods, respectively. In unstimulated controls, LCBF (n= 5) and LCGU (n= 5) were linearly related (r = 0.780; P < 0.001) in the 27 brain regions studied. During DMRF stimulation LCGU increased significantly in 21 of the 27 regions, including cerebral cortex (up to 168% of control), thalamic nuclei (up to 161%) and selected ponto-medullary regions (e.g. parabrachial complex: 212%; vestibular complex: 147%). Along with LCGU, LCBF rose significantly in 25 regions (sensory motor cortex: 163%; anterior thalamus: 161%; parabrachial complex: 186%). Correlation analysis demonstrated that, during DMRF stimulation, the close relationship between LCBF and LCGU is preserved (r = 0.845; P < 0.001) and that, in addition, the increase in LCBF (δ LCBF) is proportional to the increase in LCGU (δ LCGU) (δLCGU+ 6.92; r = 0.7729; P < 0.001).Excitation of neurons or fibers within DMRF increases brain metabolism globally and blood flow secondarily. The DMRF appears to modulate cerebral metabolism globally, by as yet undefined pathways.     

Local cerebral glucose utilization in normoxemic and hypoxemic newborn lambs

To determine if hypoxemia altered local cerebral glucose utilization (LCGU) in newborn lambs, and where these alterations occurred, we measured LCGU using the 2-[14C]deoxyglucose [( 14C]DG) autoradiographic technique in lambs made hypoxemic by gradual reduction in inspired oxygen concentration. In 5 normoxemic control lambs, aged 3 days. LCGU of the cerebral cortex and white matter was higher than published values of LCGU in similar structures in near term normal fetuses and 2-4 times higher than reported values in normoxemic puppies. LCGU was highest in vestibular nuclei and auditory structures, followed by cerebellar nuclei, cerebral subcortical structures, and white matter. In 6 hypoxemic newborn lambs (paO2 14-18 torr) consistent increases in LCGU were noted only in the corona radiata compared to the values obtained in the normoxemic control lambs (36.5 +/- 8.1 vs. 23.9 +/- 1.7 mumol/100 per min, mean +/- S.D., P less than 0.02). This increase in LCGU in white matter was clearly noted in autoradiographs in which thin dark central regions within white matter often reached high into the gyri. In the hypoxic group. LCGU of the corona radiata superseded the value in many gray matter structures. In addition, patchy increases of [14C]DG utilization were present in the cerebral cortex of two hypoxemic lambs. Acute hypoxemia increases glucose utilization of the corona radiata to values equivalent to many gray matter structures, and leads to heterogeneous glucose metabolism in the cerebral cortex, but does not alter LCGU in other gray matter structures of newborn sheep.     

Quantitative double tracer autoradiographic technique for the simultaneous measurement of local cerebral blood flow and local cerebral glucose utilization using 14C-IAP and 18F-FDG

We have reported a quantitative double tracer autoradiographic technique for the simultaneous measurement of local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) using 14C-IAP and 18F-FDG respectively. Six awake normal rats and 3 left middle cerebral artery (MCA) occluded rats were used for this experiments. A 50-hold greater radioactivity of 18F was administered and the first exposure was done for 2 hours to obtain a 18F image. Three days later (39 half-lives of 18F), a second exposure was done for 5 to 6 days to obtain the 14C image. Tissue concentration of 14C was measured relative to the commercially available 14C-methyl methacrylate standards. 18F standards were prepared in each experiment. Cross contamination of 14C in the first exposure was less than 2% in the normal state and less than 4% even in the uncoupling condition. The values obtained by this methods for LCBF and LCGU agreed closely with those obtained by a single tracer technique previously reported in the literature. The technique outlined in this paper also provided local glucose utilization flow ratio (LGFR) for the first time. LGFR was obtained by dividing the LCGU image by LCBF image and was expressed as percent mumol/ml. The mean LGFR of control rats was 76 +/- 8% mumol/ml. In a MCA occlusion group, LGFR of ischemic cortex increased until 2 to 3 times higher than that of contralateral non-ischemic cortex. Oxygen glucose index image which was obtained from the LCGU and A-V differences of O2 showed that approximately half of the glucose was metabolized anerobically.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uncoupling of cerebral blood flow and metabolism after cerebral contusion in the rat.

Positron emission tomography scans of patients with head injuries often show discrete areas of increased 18F-fluorodeoxyglucose uptake ("hot spots") when performed hours to days after the initial ictus. Using quantitative autoradiographic methods, the authors have investigated whether cerebral blood flow and glucose metabolism are uncoupled 2 hours after controlled head injury in an animal model, and whether any "hot spots" are accompanied by changes in cerebral glucose concentration. Experiments were performed on 18 anesthetized, ventilated (1.5% halothane in 2:1 nitrous oxide:oxygen) Sprague-Dawley rats weighing 300 to 330 g. A burr hole was made over the left parietal cortex, and all animals received a piston impact on the intact dura (2 mm in diameter, 2.0 m/sec, 2 mm in depth). All animals remained anesthetized and ventilated for a further 2 hours, after which quantitative autoradiography was used to determine either (1) local cerebral blood flow (LCBF) using 14C-iodoantipyrine, (2) local cerebral glucose utilization (LCGU) using 14C-deoxyglucose, or (3) local cerebral glucose content (LCGC) using 14C-methylglucose. Local CBF, LCGU, and LCGC were measured in five regions adjacent to the contusion, and values then were normalized on the contralateral cortex. Normalized LCBF, LCGU, or LCGC varied in parallel in ipsilateral cortex (no change) and in the ischemic core of the contusion (reduced). However, there were marked changes in the patterns observed in the boundary zone (within 1 mm of the contusion). In all six rats used for LCGU measurement, there were discrete areas of high metabolism, whereas in all six rats used for LCBF measurement, flow was universally depressed in the boundary zone. Of the six rats used for LCGC determination, there was a discrete area of high signal in only one. The authors conclude that there are discrete areas of uncoupling of cerebral blood flow and metabolism after head injury within 2 hours of cerebral contusion in the rat that cannot be explained by changes in cerebral glucose content in the majority of animals.     

Use of short-lived 18F and long-lived 14C in double tracer autoradiography for simultaneous measurement of LCBF and LCGU

We have developed a quantitative autoradiographic technique for the simultaneous measurement of local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) using a combination of 14C-long-lived and 18F-short-lived radionuclides as labels. To obtain the LCGU image, a 50-fold greater radioactivity of 18F than of 14C was administered and the first exposure was done for 2 hours. Three days later, when most of the 18F had decayed, a second exposure was done for 5 to 6 days to obtain the LCBF image. 18F standards were prepared in each experiment. The technique provides, for the first time, the local glucose flow ratio (LGFR). LGFR, obtained by dividing the LCGU by the LCBF image, was expressed as percent mumol/ml (multiplied by 100). Measurement of these three values in the same animal is expected to prove useful in the investigation of the pathophysiology of the brain. The advantages of this method are that cross contamination is less than 4%, chemical or physical manipulation of the slices is unnecessary, and final results can be obtained within a week.     

Effect of thiamine deficiency and its reversal on cerebral blood flow in the rat. Observations on the phenomena of hyperperfusion, "no reflow," and delayed hypoperfusion

Local CBF (LCBF) was determined in the same rat model and at the same intervals of thiamine deficiency and reversal as in previous studies of local cerebral glucose utilization (LCGU) and pH (LCpH). The results showed that prior to the appearance of the clinical sequelae of thiamine deficiency (opisthotonus, which usually occurs on day 18 of deficiency) cerebral structures such as the mammillary body, vestibular nucleus, inferior colliculus, and thalamus showed significant hyperperfusion, reaching greater than 200% of control values. At opisthotonus, there was a general decline in LCBF, but, in addition, the larger of these structures developed inhomogeneous perfusion with patches of hyperperfusion adjacent to others of low flow. Seven days of thiamine replenishment at opisthotonus resulted in delayed hypoperfusion notably in the mammillary body, inferior colliculus, and thalamic nuclei. Superimposition of the LCBF, LCGU, and LCpH data reveals that structures known to be vulnerable to the development of histological lesions in this model showed an early phase of hyperperfusion uncoupled from declining LCGU and normal LCpH. Then, following a significant but only focal rise in LCGU between days 11 and 14 of deficiency, hyperperfusion persisted while the pH was dropping and LCGU was rapidly declining. The phase of patchy perfusion occurred only in the histologically vulnerable structures when LCGU was very low and acidosis was at its peak, suggesting that it may have resulted from these opposing influences on LCBF. Following replenishment with thiamine, the vulnerable structures showed delayed hypoperfusion coupled to LCGU.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral acidosis in focal ischemia: I. A method for the simultaneous measurement of local cerebral pH with cerebral glucose utilization or cerebral blood flow in the rat

We developed a technique for the simultaneous autoradiographic determination of local cerebral pH (LCpH) using [14C]dimethyloxazolidinedione ([14C]DMO) with either local cerebral glucose utilization (LCGU) using [14C]deoxyglucose ([14C]DG) or local CBF (LCBF) using [14C]iodoantipyrine ([14C]IAP). The method evolved from the observation that [14C]DMO is "unstable," which is shown here to be due to sublimation of the compound. Thus, the technique consists of administering to rats [14C]DMO followed by either [14C]DG or [14C]IAP. The first autoradiographic film that results contains both labeled compounds. The brain sections are then exposed in a fume hood until the complete disappearance of [14C]DMO, which usually required 10 days. The second film thus contains only the non-DMO isotope administered. Blood levels of the two isotopes are calculated from the total concentrations of isotope and the rate of decline of [14C]DMO in blood. This information is then used to determine cerebral pH and the other cerebral function of interest. Using this double-label technique in normal rats, LCpH, LCGU, and LCBF can be determined with the same accuracy as with single-label techniques. In rats with middle cerebral artery occlusion, this technique yielded LCpH and LCBF values 4 h after occlusion that were not statistically different from those obtained by separate determinations. Thus, interactions between LCpH and either LCBF or LCGU can be studied by this technique in normal and pathological conditions.     

The A1 receptor agonist R-Pia reduces the imbalance between cerebral glucose metabolism and blood flow during status epilepticus: Could this mechanism be involved with neuroprotection?

It is well known that the uncoupling between local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF), i.e. decrease in LCBF rates with high LCGU, is frequently associated with seizure-induced neuronal damage. This study was performed to assess if the neuroprotective effect of the adenosinergic A₁ receptor agonist R-N-phenylisopropyladenosine (R-Pia) injected prior to pilocarpine is able to reduce the uncoupling between LCGU and LCBF during status epilepticus (SE). Four groups of rats were studied: Saline, Pilo, R-Pia + Saline and R-Pia + Pilo. For LCGU and LCBF studies, rats were subjected to autoradiography using [¹⁴C]-2-deoxyglucose and [¹⁴C]-iodoantypirine, respectively. Radioligands were injected 4 h after SE onset. Neuronal loss was evaluated by Fluorojade-B (FJB) at two time points after SE onset (24 h and 7 days). The results showed a significant increase in LCGU in almost all brain regions studied in the Pilo and R-Pia + Pilo groups compared to controls. However, in R-Pia pretreated rats, the uncoupling between LCGU and LCBF was moderated in a limited number of structures as substantia nigra pars reticulata and hippocampal formation rather in favor of hyperperfusion. Significant increases in LCBF were observed in the entorhinal cortex, thalamic nuclei, mammillary body, red nucleus, zona incerta, pontine nucleus and visual cortex. The neuroprotective effect of R-Pia assessed by FJB showed a lower density of degenerating cells in the hippocampal formation, piriform cortex and basolateral amygdala. In conclusion our data shows that the neuroprotective effect of R-Pia was accompanied by a compensatory metabolic input in brain areas involved with seizures generation.     

Effect of the calcium antagonist nimodipine on local cerebral blood flow and metabolic coupling

The effects of a continuous infusion of the calcium antagonist nimodipine (1 microgram kg-1 min-1) on local CBF (LCBF) and local cerebral glucose utilisation (LCGU) were studied, using the quantitative autoradiographic [14C]iodoantipyrine and [14C]2-deoxyglucose techniques in 34 anatomically discrete regions of the brain in lightly restrained, conscious rats. The infusion of nimodipine at this concentration produced only a small (8%) reduction in the MABP. The administration of nimodipine did not alter the rate of glucose utilisation in any of the regions examined. By contrast, in 24 regions, CBF was increased significantly by 39-84% from control levels (for example, cerebral cortices, hippocampus, hypothalamus, and most thalamic nuclei). In vehicle-treated animals, there was an excellent correlation (p less than 0.01) between the local levels of CBF and glucose utilisation, with the ratio of flow to glucose use being approximately 1.5 ml mumol-1 in each brain region. During nimodipine treatment, there was a similarly excellent correlation (p less than 0.01) between LCBF and LCGU, but the median ratio between local flow and glucose use increased to 2.5 ml mumol-1.     

Influence of gamma-hydroxybutyrate on the relationship between local cerebral glucose utilization and local cerebral blood flow in the rat brain

The relationship between local cerebral glucose utilization (LCGU) and local CBF (LCBF) was examined during the action of gamma-hydroxybutyrate (GHB) (900 mg/kg i.v.) in conscious rats. GHB induced discrepant effects on blood flow and metabolism. LCGU was markedly depressed in all structures examined, whereas LCBF was differently affected in that no related changes were observed. Global glucose utilization was markedly depressed (-51%), whereas global blood flow was not significantly altered. The marked dissociation between the changes in global glucose utilization and global blood flow induced by GHB is reflected only to a minor degree in the local values inasmuch as the correlation between LCGU and LCBF was only slightly weakened and its heterogeneity was increased.     

Regional differences in local cerebral blood flow (LCBF) and glucose utilization (LCGU) in the basal ganglia after occlusion of the middle cerebral artery in rats

Summary Acute effects of occlusion of the middle cerebral artery on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were investigated quantitatively in separate groups of rats using (14C) iodoantipyrine (14C-IAP) or (14C) 2-deoxyglucose (14C-DG) respectively.LCBF was significantly decreased in the ipsilateral cerebral cortices (to less than 45 ml/100 g/min or 30% of the control side) and the lateral part of the striatum (to 22 ml/100 g/min or 10% of the control side) which were supplied by the middle cerebral artery. No significant changes in LCBF were found in any other of the subcortical regions. In contrast to the unanimous decrease of LCBF in the ipsilateral cortices and the lateral striatum, complexed changes in LCGU were found in not only the cortex and striatum but also in many other subcortical regions which were closely related to the distribution of the mesencephalic dopamine neurons, such as globus pallidus, substantia nigra, subthalamic nucleus, nucleus accumbens, olfactory tubercle and lateral habenular nucleus. Relevance of this putative neurotransmitter and GABA on the glucose metabolism in ischemic brain is discussed.     

Local cerebral glucose metabolism in newborn dogs: Effects of hypoxia and halothane anesthesia

Local cerebral glucose utilization (LCGU) was measured in 36 neuroanatomical structures of normal awake, halothane-anesthetized, and hypoxic newborn puppies by the autoradiographic 2-[¹⁴C]deoxyglucose method. In normal animals, LCGU was highest in the vestibular nucleus and in other gray matter nuclei of the brainstem and declined in a caudal-to-rostral progression through the neuraxis (i.e., LCGU of cerebellum > thalamus ? caudateputamen > cerebral cortex). Lowest rates of glucose metabolism were detected in white matter structures. Halothane anesthesia (1.5% inspired) caused few changes in local glucose metabolism, the most notable being decreased LCGU among structures of the auditory system (cochlear nucleus, lateral lemniscus, inferior colliculus) and increased LCGU in the interpeduncular nucleus. Acute systemic hypoxia (arterial oxygen tension of approximately 12 mm Hg) produced markedly heterogeneous effects on local glucose metabolism: LCGU was increased in some gray matter structures, decreased in the thalamus, and substantially increased in the subcortical white matter and corpus callosum. In puppies whose brains were frozen in situ after 55 minutes of hypoxia, the concentration of lactate was increased ten- to elevenfold in cortical gray and subcortical white matter, but the concentrations of glucose, adenosine triphosphate, and phosphocreatine declined to a greater extent in the white matter. The results suggest that during hypoxia the high rate of glycolysis in white matter exceeded substrate supply so that glucose availability became the limiting factor for local energy production. Such a mechanism may contribute to the white matter injury that often develops following hypoxic-ischemic insults in the perinatal period.     

Local cerebral blood flow with fentanyl-induced seizures

Local cerebral blood flow (LCBF) was evaluated with the [14C]iodoantipyrine quantitative autoradiographic technique in 29 brain structures in conscious control rats and during fentanyl-induced electroencephalographic (EEG) spike and/or seizure activity and in the postseizure EEG suppression phase. During spike activity, LCBF increased in all structures; the increase reached statistical significance (p less than 0.05) in the superior colliculus, sensorimotor cortex, and pineal body (+130%, +187%, and +185% from control, respectively). With progressive development of seizure activity, LCBF significantly increased in 24 brain structures (range, +58% to +231% from control). During the postseizure EEG suppression phase, LCBF remained elevated in all structures (+80% to +390% from control). The local cerebrovascular resistance (LCVR) significantly decreased in 10 of 29 structures with the onset of spike activity (range, -24% to -64%), and remained decreased in all brain structures during seizure activity (range, -34% to -67%) and during the EEG suppression phase (range, -24% to -74%). This reduction of LCVR represents a near maximal state of cerebrovasodilation during fentanyl-induced EEG seizure or postseizure suppression activity. The global nature of the LCBF elevation indicates that factors other than local metabolic control are responsible for CBF regulation during local seizure activity.     

The evaluation of quantitative autoradiogram processing systems for cerebrovascular research

The development of an image processing system for quantitative autoradiography (QAR) is described, with emphasis on the evaluation of image digitization systems independent of hardware or software design. Each step of converting the autoradiographic image to a functional image of a physiological variable such as local cerebral blood flow (LCBF) or local cerebral glucose utilization rate (LCGU) is evaluated. The autoradiograms are digitized, aligned, transformed to a tissue tracer concentrations image based on the gray value (GV) of calibrated 14C standards, subtracted from each other as required in double tracer QAR, and converted to an LCBF or LCGU image using the proper tracer kinetic model. Geometric size, mean and standard deviation of the LCBF, LCGU, and tracer concentration can be measured in regions of interest. These steps are evaluated separately for their contribution to the accuracy and precision of the final, functional image. The qualities important in the final image are spatial resolution, intensity linearity, and intensity sensitivity, as well as the noise level. Techniques for evaluating the LCBF image include: (1) optimization of the input linearity and dynamic range of the video camera to maximize relative intensity sensitivity of the final functional image; (2) visual inspection of the curves used to fit various functions that are important in the conversion of the GV image to an image of physiological interest; (3) consideration of the noise introduced by the input devices and during the image conversion; and (4) above all, the integration of the various parts of the system to produce an accurate image useful in cerebrovascular research.     

Ketamine effects on local cerebral blood flow and metabolism in the rat

The effects of an anesthetic dose (100 mg/kg) of ketamine, a phencyclidine derivative, on local rates of cerebral glucose utilization (LCGU) and CBF (LCBF) have been investigated by the quantitative [14C]2-deoxy-glucose and [14C]iodoantipyrine techniques in the unparalyzed, spontaneously breathing rat. In ketamine-injected animals, LCGU was significantly increased in some limbic structures and decreased in inferior colliculus, vestibular, and cerebellar nuclei. The degree and spatial distribution of drug-induced changes was similar for local blood flow rates, LCBF being increased in limbic regions and decreased in the inferior colliculus. Although Paco2 values were higher in anesthetized animals, the pattern of LCBF/LCGU ratios was not significantly affected by ketamine in the 36 brain regions examined in this study. So, at least in the rat and at the anesthetic level studied here, a net vasodilatory in vivo effect was not observed. These results support the hypothesis that CBF changes induced by the drug in animals and man are primarily related to the metabolic effects exerted by ketamine on cerebral structures.