Showing papers in "Journal of Cerebral Blood Flow and Metabolism in 1991"
TL;DR: In this paper, a distinction is made between using statistical parametric maps (SPMs) as images of change significance and using them to identify foci of significant change, where the SPM can be reported nonselectively as a single mathematical object with its omnibus significance.
Abstract: Statistical parametric maps (SPMs) are potentially powerful ways of localizing differences in regional cerebral activity. This potential is limited by uncertainties in assessing the significance of these maps. In this report, we describe an approach that may partially resolve this issue. A distinction is made between using SPMs as images of change significance and using them to identify foci of significant change. In the first case, the SPM can be reported nonselectively as a single mathematical object with its omnibus significance. Alternatively, the SPM constitutes a large number of repeated measures over the brain. To reject the null hypothesis, that no change has occurred at a specific location, a threshold adjustment must be made that accounts for the large number of comparisons made. This adjustment is shown to depend on the SPM's smoothness. Smoothness can be determined empirically and be used to calculate a threshold required to identify significant foci. The approach models the SPM as a stationary stochastic process. The theory and applications are illustrated using uniform phantom images and data from a verbal fluency activation study of four normal subjects.
1,658 citations
TL;DR: Very brief ischemia induces heat-shock proteins and, presumably, thereby renders neurons more tolerant to subsequent metabolic stress.
Abstract: Brief ischemia induced tolerance to subsequent ischemia in the hippocampal neurons. Male Mongolian gerbils were subjected to 2 min of ischemia in an awake condition. This ischemic insult only rarel...
590 citations
TL;DR: Hypothermia-treated rats had significantly less beam-walking beam-balance, and body weight loss deficits compared to normothermic (38°C) rats, and the greatest protection was observed in the 30°C hypothermia group.
Abstract: These experiments examined the effects of moderate hypothermia on mortality and neurological deficits observed after experimental traumatic brain injury (TBI) in the rat. Brain temperature was measured continuously in all experiments by intraparenchymal probes. Brain cooling was induced by partial immersion (skin protected by a plastic barrier) in a water bath (0 degrees C) under general anesthesia (1.5% halothane/70% nitrous oxide/30% oxygen). In experiment I, we examined the effects of moderate hypothermia induced prior to injury on mortality following fluid percussion TBI. Rats were cooled to 36 degrees C (n = 16), 33 degrees C (n = 17), or 30 degrees C (n = 11) prior to injury and maintained at their target temperature for 1 h after injury. There was a significant (p less than 0.04) reduction in mortality by a brain temperature of 30 degrees C. The mortality rate at 36 degrees C was 37.5%, at 33 degrees C was 41%, and at 30 degrees C was 9.1%. In experiment II, we examined the effects of moderate hypothermia or hyperthermia initiated after TBI on long-term behavioral deficits. Rats were cooled to 36 degrees C (n = 10), 33 degrees C (n = 10), or 30 degrees C (n = 10) or warmed to 38 degrees C (n = 10) or 40 degrees C (n = 12) starting at 5 min after injury and maintained at their target temperatures for 1 h. Hypothermia-treated rats had significantly less beam-walking, beam-balance, and body weight loss deficits compared to normothermic (38 degrees C) rats. The greatest protection was observed in the 30 degrees C hypothermia group.(ABSTRACT TRUNCATED AT 250 WORDS)
513 citations
TL;DR: In this paper, a pixel-by-pixel linear regression was performed to remove differences in global CBF between subjects, and pixels at which rCBF then showed a significant negative correlation with age were identified.
Abstract: Positron emission tomographic (PET) images of regional cerebral blood flow (rCBF) from 30 normal, resting volunteers aged 30 to 85 years were analysed to identify areas where rCBF fell with age. Images were anatomically normalised, and a pixel-by-pixel linear regression was performed to remove differences in global CBF between subjects. Pixels at which rCBF then showed a significant (p less than 0.01) negative correlation with age were identified. They were displayed as a statistical parametric map (SPM) of correlations. We demonstrate an age-related decrease in adjusted rCBF in the cingulate, parahippocampal, superior temporal, medial frontal, and posterior parietal cortices bilaterally, and in the left insular and left posterior prefrontal cortices (omnibus significance, chi 2 = 2,291, p less than 0.0001, df = 1). Decreases in rCBF suggest a regionally specific loss of cerebral function with age. The affected areas were all limbic, or association, cortices. Therefore, these decreases may constitute the cerebral substrate of the cognitive changes that occur during normal aging.
380 citations
TL;DR: A two-compartment, two-parameter configuration was found to adequately describe the kinetic behavior of [11C]FMZ in human brain, with stable estimates of the model parameters obtainable from as little as 20–30 min of data.
Abstract: The in vivo kinetic behavior of [11C]flumazenil ([11C]FMZ), a non-subtype-specific central benzodiazepine antagonist, is characterized using compartmental analysis with the aim of producing an optimized data acquisition protocol and tracer kinetic model configuration for the assessment of [11C]FMZ binding to benzodiazepine receptors (BZRs) in human brain. The approach presented is simple, requiring only a single radioligand injection. Dynamic positron emission tomography data were acquired on 18 normal volunteers using a 60- to 90-min sequence of scans and were analyzed with model configurations that included a three-compartment, four-parameter model, a three-compartment, three-parameter model, with a fixed value for free plus nonspecific binding; and a two-compartment, two-parameter model. Statistical analysis indicated that a four-parameter model did not yield significantly better fits than a three-parameter model. Goodness of fit was improved for three- versus two-parameter configurations in regions with low receptor density, but not in regions with moderate to high receptor density. Thus, a two-compartment, two-parameter configuration was found to adequately describe the kinetic behavior of [11C]FMZ in human brain, with stable estimates of the model parameters obtainable from as little as 20-30 min of data. Pixel-by-pixel analysis yields functional images of transport rate (K1) and ligand distribution volume (DV"), and thus provides independent estimates of ligand delivery and BZR binding.
343 citations
TL;DR: The results suggest that with increasing duration of ischemia, survival of brain tissue is determined by the high threshold of persisting inhibition of protein synthesis and not by the much lower one of acute energy failure.
Abstract: The ischemic threshold of protein synthesis and energy state was determined 1, 6, and 12 h after middle cerebral artery (MCA) occlusion in rats. Local blood flow and amino acid incorporation were measured by double tracer autoradiography, and local ATP content by substrate-induced bioluminescence. The various images were evaluated at the striatal level in cerebral cortex by scanning with a microdensitometer with 75 microns resolution. Each 75 x 75 microns digitized image pixel was then converted into the appropriate units of either protein synthesis, ATP content, or blood flow. The ischemic threshold was defined as the flow rate at which 50% of pixels exhibited complete metabolic suppression. One hour after MCA occlusion, the threshold of protein synthesis was 55.3 +/- 12.0 ml 100 g-1 min-1 and that of energy failure was 18.5 +/- 9.8 ml 100 g-1 min-1. After 6 and 12 h of MCA occlusion, the threshold of protein synthesis did not change (52.0 +/- 9.6 and 56.0 +/- 6.5 ml 100 g-1 min-1, respectively) but the threshold of energy failure increased significantly at 12 h following MCA occlusion to 31.9 +/- 9.7 ml 100 g-1 min-1 (p less than 0.05 compared to 1 h ATP threshold value; all values are mean +/- SD). In focal cerebral ischemia, therefore, the threshold of energy failure gradually approached that of protein synthesis. Our results suggest that with increasing duration of ischemia, survival of brain tissue is determined by the high threshold of persisting inhibition of protein synthesis and not by the much lower one of acute energy failure.(ABSTRACT TRUNCATED AT 250 WORDS)
328 citations
TL;DR: Greater emphasis on early detection of encephalopathy and aggressive treatment of minimal hyperammonemia may retard the development of ammonia-induced complications of severe liver disease and explain the emergence of toxin hypersensitivity as liver disease progresses.
Abstract: Cerebral ammonia metabolism was studied in five control subjects and five patients with severe liver disease exhibiting minimal hepatic encephalopathy The arterial ammonia concentration in the control subjects was 30 ± 7 μmol/L (mean ± SD) and 55 ± 13 μmol/L in the patients (p < 001) In the normal subjects, the whole-brain values for cerebral blood flow, cerebral metabolic rate for ammonia, and the permeability-surface area product for ammonia were 058 ± 012 ml g−1 min−1, 035 ± 015 μmol 100 g−1 min−1, and 013 ± 003 ml g−1 min−1, respectively In the patients, the respective values were 046 ± 016 ml g−1 min−1 (not different from control), 091 ± 036 μmol 100 g−1 min−1 (p < 0025), and 022 ± 007 ml g−1 min−1 (p < 005) The increased permeability-surface area product of the blood-brain barrier permits ammonia to diffuse across the blood-brain barrier into the brain more freely than normal This may cause ammonia-induced encephalopathy even though arterial ammonia levels are normal or near norm
319 citations
TL;DR: The examination of the microglial reaction provides an extremely sensitive indicator of subtle and morphologically nonapparent neuronal damage during the early stages of injury, consistent with the known serial pathological changes associated with cerebral ischemia.
Abstract: We have examined the distribution and time course of the microglial reaction in the rat dorsal hippocampus after 25-min transient forebrain ischemia (four-vessel occlusion model). Microglial cells ...
308 citations
TL;DR: A general algorithm for defining the affine transformation between two equivalent point ensembles has been adapted for the purpose of registering MRI and PET image volumes by means of a simple fiducial arrangement and previous MRI-based computerized atlas methodology to three dimensions is extended.
Abstract: Quantitative interpretation of functional images (PET or SPECT) is hampered by poor spatial resolution, low counting statistics, and, for many tracers, low contrast between different brain structures of interest Furthermore, normal tracer distributions can be severely disrupted by such gross pathologies as stroke, tumor, and dementia Hence, the complementary anatomical information provided by CT or MRI is essential for accurate and reproducible regional analysis of functional data We have developed methods for the simultaneous three-dimensional display and analysis of image volumes from MRI and PET A general algorithm for defining the affine transformation between two equivalent point ensembles has been adapted for the purpose of registering MRI and PET image volumes by means of a simple fiducial arrangement In addition, we have extended previous MRI-based computerized atlas methodology to three dimensions The native atlas planes were spaced at 2 mm intervals, sufficient axial sampling to permit the
292 citations
TL;DR: It is proposed that the lesser ischemic vulnerability of females may be based upon an antioxidant effect of endogenous estrogen, which was found to be a more potent inhibitor of iron-catalyzed lipid peroxidation in brain tissue than vitamin E.
Abstract: Twenty-four hour postischemic neuronal necrosis was compared in male vs. female Mongolian gerbils subjected to a 3-h period of severe incomplete hemispheric ischemia produced by unilateral carotid occlusion. The incidence of stroke-prone males was 42.9% versus 26.7% for the females. Among the stroke-prone animals, the males displayed significantly greater neuronal necrosis at 24 h after ischemia compared to the females in the cerebral cortex and CA1 region of the hippocampus. In the CA1 region of the stroke-prone males, only 2.0% of the normal neuronal population remained by 24 h compared to 36.8% in the stroke-prone females (p less than 0.02). In the cerebral cortex, the males had only 19.9% of normal versus 58.2% in the females (p less than 0.05). In a second series of mechanistic experiments, no differences in cortical blood flow (CBF) were disclosed between preselected male and female stroke-prone animals before, during, or for 2 h after ischemia. As with the CBF, the extent of cortical extracellular hypocalcia during ischemia did not differ significantly. However, the degree of postischemic recovery of cortical extracellular calcium was significantly better in the females from 30 min to 2 h after reperfusion. In the same experiments, hemispheric vitamin E levels were measured at the 2 h time point as an index of postischemic brain lipid peroxidation. No difference in baseline vitamin E levels was observed between male and female sham-operated gerbils. In the males subjected to 3 h of ischemia plus 2 h of reperfusion, the hemispheric vitamin E decreased by 43.5% compared to the sham-operated males.(ABSTRACT TRUNCATED AT 250 WORDS)
252 citations
TL;DR: The results show that dopamine D2 receptors can be clearly visualized with high resolution using the SPECT technique and S-(–)-IBZM as a ligand and is of clinical value for the diagnosis of degenerative neurological disorders such as Huntington's disease and for the monitoring of neuroleptic treatment.
Abstract: The purpose of the present study is to visualize and quantify dopamine D2 receptors in the living human brain using an 123I-labeled ligand and the single photon emission computerized tomography (SPECT) technique. S-(-)-Iodobenzamide [S-(-)-IBZM] has been shown to be a highly selective ligand with high affinity for D2 receptors in experimental studies. Five millicuries (185 MBq) of 123I-labeled S-(-)-IBZM was administered intravenously to 12 control subjects, 22 parkinsonian patients under L-Dopa therapy, 12 parkinsonian patients without L-Dopa, 10 unmedicated patients with Huntington's disease, and 12 patients under different neuroleptics. Data collection with a rotating double-head scintillation camera started 1 h after injection and lasted for 50 min. In a semiquantitative approach, a ratio was calculated between mean counts per pixel in the striatum and a region in the lateral frontal cortex, which was 1.74 +/- 0.10 in the control group. A marked reduction of this ratio was found in patients with Huntington's disease (1.38 +/- 0.12; p = 0.0001), no significant changes in untreated parkinsonian patients (1.67 +/- 0.14), but a reduction in L-Dopa-treated cases (1.59 +/- 0.13; p = 0.0014). A curvilinear relationship was found between total daily dose of neuroleptics and the reduction of this ratio. Estimated receptor blockade under full neuroleptic treatment was 75-80%. S-(-)-IBZM binding was reduced with increasing age (p less than 0.01). Specific binding was reduced markedly when the racemic mixture of IBZM was used, and no specific binding was seen with the R-(+)-isomer, demonstrating the stereoselectivity of IBZM binding.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: A prolonged postischemic stress response at the transcriptional level in vulnerable hippocampal neurons is demonstrated, and its utility as a marker for neuronal pathophysiology associated with mechanisms mediating delayed neuronal death is suggested.
Abstract: Induction of mRNA encoding the 70 kDa stress/heat shock protein, hsp70, was evaluated in post-ischemic gerbil brain by in situ hybridization using an oligonucleotide probe selective for stress-inducible members of this gene family. Expression of hsp70 sequences was most pronounced in hippocampal CA1 neurons that fail to accumulate immunoreactive hsp70 protein, and that are selectively lost following ischemia. Hybridizable RNA continued to be expressed in CA1 through at least 48 h, essentially until the onset of cell death in this model. In contrast, dentate granule cells and CA2 neurons destined to survive the insult showed transient induction of hsp70 mRNA during the first 24 h of recirculation that disappeared prior to the detection of maximal hsp70 immunoreactivity in these cell populations. Pretreatment with a single injection of MK-801 (10 mg/kg) considerably attenuated the induction of hsp70 mRNA in hippocampus at 6 h of recirculation, an effect apparently mediated by persistent drug-induced hypothermia. The drug did not prevent the later, selective appearance of hsp70 hybridization in CA1 neurons at 24 h, nor did it protect against the subsequent loss of these cells. These results demonstrate a prolonged postischemic stress response at the transcriptional level in vulnerable hippocampal neurons, and suggest its utility as a marker for neuronal pathophysiology associated with mechanisms mediating delayed neuronal death.
TL;DR: It is suggested that basic fibroblast growth factor prevents retrograde degeneration of thalamic neurons by working directly as a neurotrophic factor of these neurons or by activating astrocytes located in the thalamocortical pathway.
Abstract: In the focal infarction model of the rat middle cerebral artery (MCA), the thalamus of the occluded side becomes gradually atrophic, mainly because of retrograde degeneration. We determined whether basic fibroblast growth factor (bFGF) administered intracisternally could prevent this thalamic atrophy. We occluded the left MCA through a small cranial opening, and animals were then divided into two groups. One group received intracisternal injections of recombinant bFGF (1 microgram dissolved in 0.1 ml of saline with 2% rat serum) starting 1 day after occlusion and repeated once a week to a total dose of 4 micrograms by four injections. The other group received vehicle solution by the same schedule. The animals were perfused and fixed at 28 days after occlusion, and histological examination was made at the level of the caudoputamen and thalamus. In the bFGF-treated rats, the area of the posterior ventral thalamus of the occluded side was 93% of that of the contralateral side, i.e., significantly larger than in the normal saline-treated rats (75%, p less than 0.01). The infarction size was not statistically different in the two groups. Microscopic observation indicated that normal-saline-treated animals showed shrinkage and disappearance of thalamic neurons, whereas bFGF-treated groups showed preservation of thalamic neurons. Computerized analysis of the cell size substantiated this observation. To assess the effect of bFGF on astrocytes, bFGF or vehicle solution was injected into normal rats, and their histology was evaluated at 1, 2, and 4 weeks after injection. The bFGF-injected group showed a significant increase in glial fibrillary acidic protein-positive astrocytes in the brain tissue facing the ventriculocisternal system.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Evidence is provided of an in vivo abnormality of forward glucose transport in AD, however, this transport defect is probably not the cause of the diminution in glucose metabolism that has been widely found in AD patients, since a diminution of this magnitude should not lower intracerebral glucose content enough to alter rCMRglc.
Abstract: Dynamic positron emission tomography with (18F)fluorodeoxyglucose was used in six patients with Alzheimer's disease (AD) and seven healthy age-matched control subjects to estimate the kinetic parameters K1*, k2*, and k3* that describe glucose transport and phosphorylation. A high-resolution tomograph was used to acquire brain uptake data in one tomographic plane, and a radial artery catheter connected to a plastic scintillator was used to acquire arterial input data. A nonlinear iterative least-squares fitting procedure that included terms for the vascular fraction and time delay to the peripheral sampling site was used to fit a three-compartment model to the brain data. Regions studied included frontal, temporal, occipital, and the entire cortex and subcortical white matter. The values obtained for the individual rate constants and regional CMRglc (rCMRglc; calculated using regional values of the rate constants) were higher than those reported previously. A significant (p less than 0.05) decrease was found in K1* in frontal and temporal cortex in the AD patients compared with the controls, with values of 0.157 and 0.161 ml/g/min in frontal and temporal cortex, respectively, of controls and 0.127 and 0.126 ml/g/min in frontal and temporal cortex of the AD patients. rCMRglc was also significantly (p less than 0.02)more » lower in the AD patients than controls in all cortical brain regions. Lower values of k3* were found in all brain regions in the AD patients, although these were not statistically significant. These findings provide evidence of an in vivo abnormality of forward glucose transport in AD.« less
TL;DR: The results show that the binding of [3H]PK 11195 correlates in both time and spatial localisation with the appearance of macrophages around the lesion and that [C] PK 11195 could be used for imaging acute inflammatory response in human brain using PET.
Abstract: PK 11195 is a selective and specific ligand for the peripheral-type benzodiazepine binding site. Its potential for in vivo visualisation of lesioned human brain using positron emission tomography (PET) is currently being assessed. The present study examines the relationship between the temporal development of a local ischaemic lesion with its associated cell populations and the binding of [3H]PK 11195 in rat brain. Unilateral cortical infarcts were induced using the photosensitive dye Rose Bengal. At time intervals from 1 to 7 days after lesioning, the localisation of [3H]PK 11195 binding was determined using in vivo and in vitro autoradiography. Sections adjacent to those used for autoradiography were processed for immunohistochemistry using glial fibrillary acidic protein for astrocytes and ED-1 for macrophages. The results show that the binding of [3H]PK 11195 correlates in both time and spatial localisation with the appearance of macrophages around the lesion. Reactive astrocytes, although present, occupy a separate region in the tissue surrounding the lesion and lie outside the region defined by the [3H]PK 11195 binding. We conclude that the [3H]PK 11195 signal associated with this ischaemic lesion originates primarily from binding to macrophages and that [11C]PK 11195 could be used for imaging acute inflammatory response in human brain using PET.
TL;DR: An extension of the SSM technique to the generation of disease-specific covariance patterns is demonstrated for paraneoplastic cerebellar degeneration, the acquired immune deficiency syndrome dementia complex, and Parkinson's disease, and the importance of multidimensional descriptions of disease, such as may be obtained from PET data using SSM, is emphasized.
Abstract: This article provides a complete description of the subprofile scaling model (SSM) approach to the analysis of positron emission tomography (PET) data. The goals and assumptions underlying the development of SSM are outlined, and its strengths and weaknesses are discussed. It is demonstrated that all obtainable information about regional ratios can, in theory, be derived from the SSM regional covariance patterns. A general constraint on the ability to effectively remove global variation while identifying region-specific information about PET data sets is outlined and discussed within the SSM framework. Finally, an extension of the SSM technique to the generation of disease-specific covariance patterns is demonstrated for paraneoplastic cerebellar degeneration, the acquired immune deficiency syndrome dementia complex, and Parkinson's disease, and the importance of multidimensional descriptions of disease, such as may be obtained from PET data using SSM, is emphasized.
TL;DR: Results showed that a model consisting of three separate compartments for tissue FDOPA, tissue 6-[18F]fluorodopamine (FDA) and its metabolites, and tissue l-3,4-dihydroxy-6-[18f]fluoro-3-O-methylphenylalanine (3-OMFD) could describe adequately the striatal kinetics in humans.
Abstract: Kinetics of l-3,4-dihydroxy-6-[18F]fluorophenylalanine (FDOPA) in striatum and cerebellum were measured in 10 normal human subjects with positron emission tomography (PET) from 0 to 120 min after a...
TL;DR: It is demonstrated that, following the experimental traumatic brain injury in the rat, an initial global suppression of rCBF occurs up to 1 h postinjury; at the trauma site, a more persistent focal reduction of r CBF occurs; and these alterations in rCBf after trauma dissolve by 4 h post injury.
Abstract: To elucidate the temporal changes in regional cerebral blood flow (rCBF) after experimental traumatic brain injury, serial rCBF measurements were made during a 24-h period following fluid-percussion (F-P) traumatic brain injury in the rat. Brain injury of 2.2 atm was induced over the left parietal cortex and serial measurements of rCBF were performed using the radiolabeled microsphere method. rCBF values were obtained prior to injury and at 15 and 30 min and 1, 2, 4, and 24 h postinjury. At 15 min postinjury, there was a profound, wide-spread reduction in rCBF in all brain regions studied (p less than 0.05). At 30 min and 1 h postinjury, all brain regions except pons-medulla and cerebellum showed significantly reduced rCBF compared to the preinjury values (p less than 0.05). By 2 h postinjury, however, a significant focal reduction of rCBF was observed only in the cerebral tissue surrounding the trauma site (p less than 0.05); rCBF in the remaining brain regions had recovered to the preinjury levels. By 4 h postinjury, rCBF had returned to normal in all brain regions studied. This recovery of rCBF was still evident at 24 h postinjury. The present study demonstrates that, following the experimental traumatic brain injury in the rat, (a) an initial global suppression of rCBF occurs up to 1 h postinjury; (b) at the trauma site, a more persistent focal reduction of rCBF occurs; and (c) these alterations in rCBF after trauma dissolve by 4 h postinjury.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The results indicate that insulin acts directly on the brain, independent of hypoglycemia, to reduce ischemic brain necrosis.
Abstract: Insulin, an endogenously produced circulating peptide that enters the brain, has been shown to reduce ischemic brain and spinal cord damage in several animal models. Because of its potential clinical use in humans, the present study was undertaken to test the hypotheses that (a) survival and regional ischemic brain necrosis are improved by insulin; (b) insulin requires concomitant hypoglycemia to exert its neuroprotective effect; (c) insulin is still neuroprotective with delayed administration after an episode of postischemic hypotension; and (d) insulin is beneficial after normoglycemic, as well as hyperglycemic ischemia. Rats were subjected to 10.5 min two-vessel occlusion forebrain ischemia followed by 30 min of hypotension to increase the infarction rate. Insulin administered concomitantly with glucose significantly reduced the seizure rate, as well as cortical and striatal neuronal necrosis below that seen in untreated animals. Neuroprotection was seen whether insulin was given before or after a 30-m...
TL;DR: The effects of magnesium, an endogenous inhibitor of calcium entry into neurons, upon ischemic brain damage were investigated using a well-characterized model of focal cerebral ischemia in rats and no systemic effects of either treatment could account for the observed neuroprotection.
Abstract: The effects of magnesium, an endogenous inhibitor of calcium entry into neurons, upon ischemic brain damage were investigated using a well-characterized model of focal cerebral ischemia in rats. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride transcardiac perfusion 48 h after middle cerebral artery (MCA) occlusion. The area of ischemic damage was quantified by image analysis in coronal sections taken every 0.5 mm. MgCl2 (1 mmol/kg) was injected intraperitoneally just after MCA occlusion and again 1 h later. Posttreatment with MgCl2 (16 control and 16 treated rats) significantly reduced the cortical infarct volume. Compensation for the hyperglycemic effect of MgCl2 with insulin (17 rats) further reduced the infarct volume in the neocortex. No systemic effects of either treatment could account for the observed neuroprotection.
TL;DR: This transient and cumulative neuroprotective effect of hyperthermic pretreatment strongly suggested the involvement of stress reactions after hyperthermia in the protective mechanism against ischemic neuronal death.
Abstract: We investigated the effect of hyperthermic pretreatment before induction of ischemia using a gerbil model of 5-min forebrain ischemia. A single hyperthermic treatment 18 h before ischemia exhibited a partial protective effect, and repetitive hyperthermic pretreatments at 18-h intervals before ischemia showed clear protection against neuronal death in the CA1 area of the hippocampus, whereas single hyperthermic treatment 3, 6, 24, or 50 h before ischemia exhibited little protective effect. This transient and cumulative neuroprotective effect of hyperthermic pretreatment strongly suggested the involvement of stress reactions after hyperthermia in the protective mechanism against ischemic neuronal death.
TL;DR: The CBF increase in the associative visual area suggests that activation of cerebral structures processing complex visual material is correlated to visual dream experiences, and the reduced involvement of the inferior frontal cortex observed during REM sleep might explain the poor temporal organization and bizarreness often experienced in dreams.
Abstract: Owing to the coupling between CBF and neuronal activity, regional CBF is a reflection of neural activity in different brain regions In this study we measured regional CBF during polysomnographically well-defined rapid-eye-movement (REM) sleep by the use of single photon emission computerized tomography and the new tracer 99mTc-dl-hexamethylpropyleneamine Eleven healthy volunteers aged between 22 and 27 years were studied CBF was measured on separate nights during REM sleep and during EEG-verified wakefulness On awakening from REM sleep, all subjects reported visual dreams During REM sleep CBF increased by 4% (p less than 001) in the associative visual area, while it decreased by 9% (p less than 001) in the inferior frontal cortex The CBF increase in the associative visual area suggests that activation of cerebral structures processing complex visual material is correlated to visual dream experiences On the other hand, the reduced involvement of the inferior frontal cortex observed during REM sleep might explain the poor temporal organization and bizarreness often experienced in dreams
TL;DR: It is concluded that the initial aneurysm rupture produces a primary reduction in CMRO2, and that subsequent vasospasm causes ischemia, indicative of cerebral ischemIA without infarction.
Abstract: Previous studies of cerebral oxygen metabolism and extraction in patients with subarachnoid hemorrhage (SAH) have yielded conflicting results. We used positron emission tomography (PET) to measure ...
TL;DR: The results are useful in distinguishing the effects of age and simple atrophy from disease effects, when the 99mTc-d,l-HMPAO method is used.
Abstract: Single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethylpropyleneamine oxime (99mTc-d,l-HMPAO) was used to determine global and regional CBF in 53 healthy subjects aged 21–83 years For the whole group, global CBF normalized to the cerebellum was 864% ± 84 (SD) The contribution of age, sex, and atrophy to variations in global CBF was studied using stepwise multiple regression analysis There was a significant negative correlation of global CBF with subjective ratings of cortical atrophy, but not with ratings of ventricular size, Evans ratio, sex, or age In a subgroup of 33 subjects, in whom volumetric measurements of atrophy were performed, cortical atrophy was the only significant determinant for global CBF, accounting for 27% of its variance Mean global CBF as measured with the 133Xe inhalation technique and SPECT was 54 ± 9 ml/100 g/min and did not correlate significantly with age There was a preferential decline of CBF in the frontal cortex with advancing age The side-to-sid
TL;DR: It can be concluded that spreading depression caused an increase in cerebral O2 consumption that was adequately matched by a increase in local blood flow and oxygen delivery was not limited during spreading depression and its effects were quickly over as evidenced by the lack of alteration in oxygenation after the wave of spreading depression passed.
Abstract: We determined the effects of spreading depression on local cerebral O2 supply, oxygenation, and O2 consumption in the anesthetized rat. Spreading depression was induced by application of 0.5 M KCl to the frontal cortex. Regional cerebral blood flow was determined with [14C]iodoantipyrine and regional O2 extraction was determined microspectrophotometrically. The passage of the spreading depression wave was determined with a multiprobe assembly that recorded NADH redox state (surface fluorometry), extracellular K+ activity, and DC steady potential (surface minielectrodes). As the wave of spreading depression passed, there was an increase in extracellular K+ and a decrease in NADH. Cerebral blood flow was significantly increased (120 +/- 51 ml/min/100 g, mean +/- SD) during the wave as compared with other regions. In the affected cortex, blood flow was not different from that in the contralateral cortex (69 +/- 28 ml/min/100 g) either before or after the wave of spreading depression passed. Arterial and venous O2 saturation were unaffected by the wave and the histogram of O2 saturations of examined veins followed a similar normal distribution in all regions. Oxygen extraction was not altered by the wave of spreading depression. Oxygen consumption was significantly increased during the wave to 7.4 +/- 3.7 ml O2/min/100 g compared with the contralateral cortex (5.1 +/- 2.6 ml/min/100 g) and other regions. It can be concluded that spreading depression caused an increase in cerebral O2 consumption that was adequately matched by an increase in local blood flow. Oxygen delivery was not limited during spreading depression and its effects were quickly over as evidenced by the lack of alteration in oxygenation after the wave of spreading depression passed.
TL;DR: The similarity of the altered pattern of cerebral metabolism and flow in patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy.
Abstract: We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow andmore » metabolism and that this, in turn, causes the clinical expression of encephalopathy.« less
TL;DR: This work was carried out as part of a validation study with a view to the application of the compartmental model to data obtained in vivo in humans using positron emission tomography, when successive studies over a range of specific activities are not feasible.
Abstract: The regional binding of the opiate receptor ligand diprenorphine has been examined in rat brain both in vivo and in vitro. The time course of total label in specific brain regions was followed up to 2 h after intravenous bolus injection of [3H]diprenorphine, with or without a pulse chase of unlabelled diprenorphine at 30 min. In addition, total label was measured 30 min after injection of labelled diprenorphine at nontracer concentrations over a range of specific activities. Total data sets for each region were fitted simultaneously to a compartmental model to give estimates of maximal binding capacity (Bmax), the second-order apparent association rate constant, and the first-order dissociation rate constant of the receptor-ligand complex. The model incorporated the use of a reference region with low specific binding (cerebellum). The binding of diprenorphine to rat brain homogenates was measured in vitro under equilibrium conditions at 37°C, pH 7.4, in the presence and absence of naloxone, to give corres...
TL;DR: Results suggest differences in mechanisms of hsp72 induction in astrocytes compared to neurons, and these results suggest areas of focal infarction in the distribution of small cortical and lenticulostriate arteries.
Abstract: Transient global and transient focal ischemia induced the 72 kDa heat shock protein (hsp72) in neurons in cortex, striatum, and other regions known to be injured during transient ischemia. A novel finding was the induction of hsp72 in islands (cylinders in three dimensions) of cells composed of astrocytes around the perimeter and neurons in the interior. Since histology showed pale staining in these regions, it is proposed that these islands represent areas of focal infarction in the distribution of small cortical and lenticulostriate arteries. Although the factors responsible for hsp72 induction during ischemia and infarction are unknown, these results suggest differences in mechanisms of hsp72 induction in astrocytes compared to neurons.
TL;DR: The clustering of systematically placed cortical and subcortical ROIs has provided a normative data base forXe-CT CBF and a flexible and uncomplicated method for the analysis of CBF maps generated by Xe-enhanced CT.
Abstract: Normal reference values and a practical approach to CBF analysis are needed for routine clinical analysis and interpretation of xenon-enhanced computed tomography (CT) CBF studies. We measured CBF in 67 normal individuals with the GE 9800 CT scanner adapted for CBF imaging with stable Xe. CBF values for vascular territories were systematically analyzed using the clustering of contiguous 2-cm circular regions of interest (ROIs) placed within the cortical mantle and basal ganglia. Mixed cortical flows averaged 51 +/- 10ml.100g-1.min-1. High and low flow compartments, sampled by placing 5-mm circular ROIs in regions containing the highest and lowest flow values in each hemisphere, averaged 84 +/- 14 and 20 +/- 5 ml.100 g-1.min-1, respectively. Mixed cortical flow values as well as values within the high flow compartment demonstrated significant decline with age; however, there were no significant age-related changes in the low flow compartment. The clustering of systematically placed cortical and subcortical ROIs has provided a normative data base for Xe-CT CBF and a flexible and uncomplicated method for the analysis of CBF maps generated by Xe-enhanced CT.
TL;DR: There was good correlation between the metabolic maturation of various neuroanatomical regions and the emergence of behaviors mediated by the specific region, and at least in the kitten visual cortex the “critical period” corresponded to that portion of the lCMRglc maturational curve surrounding the 60-day metabolic peak.
Abstract: Previously, using positron emission tomography (PET), we showed that local cerebral metabolic rates for glucose (lCMRglc) in children undergo dynamic maturational trends before reaching adult values. In order to develop an animal model that can be used to explore the biological significance of the different segments of the lCMRglc maturational curve, we measured lCMRglc in kittens at various stages of postnatal development and in adult cats using quantitative [14C]2-deoxyglucose autoradiography. In the kitten, very low lCMRglc levels (0.14 to 0.53 mumol min-1 g-1) were seen during the first 15 days of life, with phylogenetically older brain regions being generally more metabolically mature than newer structures. After 15 days of age, many brain regions (particularly telencephalic structures) underwent sharp increases of lCMRglc to reach, or exceed, adult rates by 60 days. This developmental period (15 to 60 days) corresponds to the time of rapid synaptic proliferation known to occur in the cat. At 90 and 120 days, a slight decline in lCMRglc was observed, but this was followed by a second, larger peak occurring at about 180 days, when sexual maturation occurs in the cat. Only after 180 days did lCMRglc decrease to reach final adult values (0.21 to 2.04 mumol min-1 g-1). In general, there was good correlation between the metabolic maturation of various neuroanatomical regions and the emergence of behaviors mediated by the specific region. At least in the kitten visual cortex, which has been extensively studied with respect to developmental plasticity, the "critical period" corresponded to that portion of the lCMRglc maturational curve surrounding the 60-day metabolic peak. These normal maturational lCMRglc data will serve as baseline values with which to compare anatomical and metabolic plasticity changes induced by age-related lesions in the cat.