Biomedical subjects

M Reivich

Publications and source records attributed to M Reivich.

At least 55 records · Page 3Linked to original sources

PubMed1991

Local cerebral tissue glucose utilization in graded arterial hemorrhagic hypotension, studied by the 14C-2-deoxyglucose method in rats.

The effect of hemorrhagic arterial hypotension on local cerebral glucose metabolism was studied on 33 rats. The mean arterial pressure was set with the aid of a reservoir at 80, 60, 50 and 40 mmHg pressures. Local cerebral glucose utilization was measured with the 14C-2-D-deoxyglucose accumulation autoradiographic technique. Local glucose consumption decreased somewhat in cortical structures when mean arterial pressure was reduced to 60-50 mmHg. Further decrease in mean arterial pressure to 50-40 mmHg caused inhomogeneity of tissue metabolism. Columns and patches of high glucose consumption interchanged with areas of very low glucose consumption in most telencephalic and cerebellar gray matter structures. Brain stem and white matter structures seem to be less sensitive to decreased mean arterial pressure in the range studied. We found a decrease in glucose utilization rather than an increase with decreasing mean arterial pressure down to 60-50 mmHg (in the range of the autoregulation of cerebral circulation). This finding makes it improbable that autoregulation would be connected with elevated anaerobic metabolism of the tissue. Patchy areas and columns of high glucose consumption found at 50-40 mmHg in all probability reflect areas of increased anaerobic metabolism of glucose. Here, circulation was not enough to transport adequate quantity of oxygen to the tissue, but still it transported relative large amount of glucose. Columns and patches of very low glucose consumption should reflect areas, where circulation was inadequate to transport both enough glucose and oxygen.

Animals↗

PubMed1991

Intracellular calcium and pathophysiological changes in cerebral ischemia.

The role of calcium as a mediator in neuronal death during ischemia is now quite strong. Evidence supporting this link included studies in cell cultures, measurements of calcium accumulation in the mitochondria during ischemia as well as direct measurements of shifts in extracellular calcium using microelectrodes. Since high concentrations of intracellular free calcium have been hypothesized to lead to neuronal damage, direct in vivo measurements of this parameter in ischemia are important. The studies outlined demonstrate that changes in intracellular free calcium occur in focal ischemia and describe the time course of these changes. They indicate that cellular damage can be attenuated by the use of agents that block calcium channels (both voltage-sensitive and receptor-operated) and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium.

Animals↗

PubMed1990

Relation of hyperglycemia early in ischemic brain infarction to cerebral anatomy, metabolism, and clinical outcome.

We studied the relation of serum glucose level measured in the first 12 hours of symptoms to the clinical findings, results of computed tomography (CT), and patterns of cerebral metabolism in 39 patients who had acute ischemic cerebral infarction. Structural damage was assessed by CT. Metabolic disruption was assessed using 18F-fluorodeoxyglucose and positron emission tomography (PET). Median initial serum glucose concentration was 155 mg/dl (6.7 mM). Clinical recovery was significantly poorer in patients with initial serum glucose levels higher than the median (p less than 0.05, chi square). PET tended to show normal results or minor abnormalities in patients with initial glucose levels less than the median, as opposed to lobar or multilobe abnormalities in patients with levels that were higher than the median (p less than 0.05, Kendall's Tau b). The severity of hypometabolism in the ischemic region, expressed as the percent asymmetry of local cerebral glucose metabolism between homologous brain regions, was greater in patients with initial glycemia concentrations higher than the median (p less than 0.001, t test). Relationships of serum glucose level with metabolic derangement and structural damage, but not outcome, held true in patients without a history of diabetes mellitus.

Aged↗

PubMed1990

Middle cerebral artery strokes causing homonymous hemianopia: positron emission tomography.

Eight patients were evaluated with 18F-fluorodeoxyglucose positron emission tomography between 3 and 30 days after isolated stroke involving the middle cerebral artery territory that caused homonymous hemianopia. Diffuse hypometabolism was present throughout the damaged cerebral hemisphere, even in cortical areas not obviously ischemic by clinical examination or neuro-imaging. Glucose metabolism in primary and association visual cortex of the damaged hemisphere was decreased by more than 47% (p less than 0.01). Metabolism in the undamaged hemisphere was less profoundly affected, but significant decrements were found in calcarine (40%; p less than 0.01) and lateral occipital cortex (35%; p less than 0.05).

Brain Ischemia↗

PubMed1990

Alterations in cytosolic free calcium in the cat cortex during bicuculline-induced epilepsy.

Influx of calcium ion (Ca++) into the neurons has recently been implicated in the generation of seizure activity. Utilizing indo-1, a fluorescent Ca++ indicator, changes in cytosolic free calcium ([Ca++]i), NAD/NADH redox state and hemodynamics were simultaneously measured in vivo from the cat cortex during bicuculline-induced seizure activity. A ratio of indo-1-Ca++ fluorescence at 400 and 506 nm during ultraviolet excitation (340 nm) was utilized as a measure of changes in [Ca++]i. Alterations in the NAD/NADH redox state and local cortical blood volume (1CBV) were assessed at 464 nm and 340 nm, respectively. Local cortical blood flow (1CBF) was calculated from 1CBV and mean transit time determined from cortical hemodilution curves. Electroencephalogram (EEG) was monitored from the same cortical region as the optical measurements. The [Ca++]i signal ratio started to increase 19 +/- 2 sec prior to the onset of seizure activity on the EEG and remained elevated until the activity was suppressed by an intravenous administration of diazepam (2 mg/kg). The early increase in [Ca++]i is presumably due to a synaptic Ca++ entry associated with facilitated excitatory neurotransmission. The NAD/NADH redox state became oxidized during the seizure activity and started to recover as the EEG activity was suppressed. The 1CBV and 1CBF increased by 17 +/- 8% and 68 +/- 16%, respectively, 10 min into the seizure activity. This study provides direct in vivo evidence suggesting a possible role of calcium entry into the neurons in the epileptogenesis.

Animals↗

PubMed1990

The effect of focal cerebral atrophy in positron emission tomographic studies of aging and dementia.

We used x-ray computed tomographic (XCT) scans to measure the degree of cerebral atrophy in brain regions defined by a region of interest (ROI) anatomy atlas. The same atlas was employed for quantitation of local cerebral glucose metabolic rates (LCMRglc) by PET. PET data were obtained from 9 young controls, 7 healthy elderly controls, and 10 patients with dementia. Cerebrospinal fluid (CSF) in atrophic brain regions was assumed to be metabolically inert, and LCMRglc measurements were corrected for the degree of atrophy. Significantly greater atrophy was seen for 7 of 8 regions in comparisons between demented patients and age-matched controls. This atrophy was most pronounced in superior parietal (SP) regions. Decreases in parietal LCMRglc in dementia patients and SP LCMRglc in old controls were no longer significant after correction for atrophy. These results emphasize the need to consider focal atrophy effects in regional quantitative analyses of emission tomographic data.

Aged↗

PubMed1990

Local cerebral blood flow during and after bilateral carotid artery occlusion in unanesthetized gerbils.

Using [14C]iodoantipyrine autoradiography, we measured regional cerebral blood flow in unanesthetized gerbils subjected to 2 (n = 5) or 30 (n = 6) minutes of bilateral carotid artery occlusion or 5 (n = 6), 30 (n = 6), or 120 (n = 5) minutes of reflow after 30 minutes of occlusion. Blood pressure, respiratory rate, and blood gases were recorded, and these and other gerbils were evaluated with periodic neurologic examinations. Blood flow to structures above the level of the diencephalon ceased almost totally during occlusion. The lateral thalamus, the rostral three quarters of the hypothalamus, and the superior colliculi were also markedly ischemic. Blood flow to the brainstem and cerebellum was only slightly affected. After release of the occlusion, blood flow was restored in some of the affected areas but to levels somewhat below that in eight sham-operated gerbils. In several areas, principally column-shaped areas in the cortex as well as patchy areas in other structures, blood flow did not recover. This inhomogeneous blood flow distribution lasted at least 30 minutes after release of the occlusion. Thereafter, the inhomogeneity slowly disappeared in such a manner that blood flow to originally well reperfused areas appeared to decrease while that to poorly reperfused areas increased. During reflow, blood flow in the brainstem and cerebellum slowly and continuously decreased. We show that there is an early no-reflow phenomenon that is inhomogeneous and appears to be of vascular origin and lasts approximately 30 minutes after release of the occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Cerebral blood flow variations in CNS lupus.

We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery.

Adult↗

PubMed1990

Cytosolic free calcium during focal cerebral ischemia and the effects of nimodipine on calcium and histologic damage.

The role of calcium as a mediator in neuronal death during ischemia is now quite strong. Evidence supporting this link includes studies in cell cultures and measurements of calcium accumulation in the mitochondria during ischemia, as well as direct measurements of shifts in extracellular calcium using microelectrodes. Since it is dangerously high concentrations of the intracellular free calcium that have been hypothesized to lead to neuronal damage, direct in vivo measurements of this parameter in ischemia are important. A technique for the measurement of intracellular free calcium is described, along with data from studies that dramatically demonstrate the time course of changes in intracellular free calcium induced by focal ischemia. Additional data are also presented that indicate that cellular damage can be attenuated by the use of agents that block calcium channels (nimodipine, which blocks voltage-sensitive calcium channels, and MK-801, which blocks receptor-operated channels) and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium.

Animals↗

PubMed1990

Validation studies of iodine-123-iodoamphetamine as a cerebral blood flow tracer using emission tomography.

We studied the radioisotope iodine-123-iodoamphetamine ([123I]IMP) and its performance in single-photon emission computed tomographic (SPECT) studies of cerebral blood flow (CBF). In seven normal volunteers, IMP/SPECT CBF measurements were calculated using a two-compartment model and were compared with the results of CBF measurements utilizing (O15)-H2O and positron emission tomography (PET). Calculated mean PET CBF was 57.6 ml/100 g/min while the SPECT CBF value was 47.3 ml/100 g/min. The response of IMP/SPECT CBF to alterations in arterial PaCO2 was studied in hypo-, eu- and hypercarbic subjects. SPECT CBF values showed a reactivity of 1.03 ml/100 g/min per mmHg PaCO2 change. These results show that the IMP/SPECT CBF technique may be used for quantitative imaging of CBF in man. They provide further support for IMP as a CBF tracer.

Amphetamines↗

PubMed1989

Positron emission tomography to study the effect of eye closure and optic nerve damage on human cerebral glucose metabolism.

We used 18F-2-fluoro-2-deoxyglucose and positron emission tomography to evaluate the effect of visual deprivation on brain glucose metabolism. In experiment 1, we compared local cerebral metabolic rates for glucose in seven normal volunteers studied with eyes closed to 11 age- and sex-matched normal volunteers studied with eyes open. Whole brain metabolism was similar in the two groups, and region/whole brain analysis of metabolic data showed that metabolism in the calcarine posterior cortex was decreased by 14% (P less than .05) with eye closure. Glucose metabolism in other regions was not different between the two groups. In experiment 2, we compared glucose metabolism in six patients with severe bilateral optic neuropathies to 12 age- and sex-matched normal controls. Whole brain glucose metabolism was unchanged in the optic neuropathy group compared to controls. However, statistically significant reductions in glucose metabolism in the optic neuropathy group were found in anterior calcarine cortex (17%), posterior calcarine cortex (27%), peristriate cortex (27%), and lateral occipital cortex (15%). The metabolic effects of damage to the pregeniculate visual system went well beyond those of simple eye closure.

Adolescent↗

PubMed1989

Cytosolic free calcium and NAD/NADH redox state in the cat cortex during in vivo activation of NMDA receptors.

Activation of the N-methyl-D-aspartate (NMDA) receptors and the concomitant Ca2+ entry have been implicated in neuronal injury in a variety of pathological states. The effects of extracellular Mg2+ concentrations and D,L-2-amino-5-phosphonovaleric acid (APV), a competitive NMDA receptor antagonist on the NMDA-induced responses were investigated in vivo. In vivo fluorometric measurements were made of changes in cytosolic free Ca2+ ([Ca2+]i) and NADH fluorescence directly from the cat cortex using indo-1, a fluorescent Ca2+ indicator. Changes in [Ca2+]i were assessed utilizing the ratio of indo-1 emission at two wavelengths (400 and 506 nm) during excitation with ultraviolet light (340 nm). Application of 100 microM NMDA to the cortex produced a significant increase in the [Ca2+]i signal ratio at physiological concentrations of Mg2+ (1.2 mM). This increase was enhanced in the absence of Mg2+ and was completely blocked either at 5 mM Mg2+ or in the presence of 50 microM APV. The NAD/NADH redox state was initially oxidized, which was also blocked by either high Mg2+ or APV. The application of NMDA elicited characteristic electroencephalogram (EEG) changes consisting of a marked reduction in amplitude and regular spikes (17-20 Hz). These EEG changes did not appear in the presence of APV. In addition to NMDA receptor antagonists, the level of extracellular Mg2+ is a potent physiological modulator of the NMDA response.

2-Amino-5-phosphonovalerate↗

PubMed1989

Direct evidence for calcium-induced ischemic and reperfusion injury.

Changes in cytosolic free calcium [( Ca2+]i) in the cat cortex were measured in vivo by indo-1 fluorometry during cerebral ischemia and reperfusion and were correlated to the histopathological ischemic changes. These changes were most pronounced in stroke cases with an increase in [Ca2+]i throughout the ischemic and reperfusion periods. Cases without a [Ca2+]i increase showed no histopathological change in the cortical gyrus in which [Ca2+]i was measured. The data support the hypothesis that an increase in [Ca2+]i during cerebral ischemia and reperfusion leads to neuronal damage.

Animals↗

PubMed1989

Alzheimer's disease with prominent visual symptoms. Clinical and metabolic evaluation.

The authors examined eight patients with dementia of the Alzheimer's type (DAT), five with prominent visual symptoms early in the illness (VS) and three with no visual symptoms (NVS). Results of neuro-ophthalmologic examinations on VS patients showed relatively consistent abnormalities in figure copying, color vision tested by isochromatic plates, and stereopsis. Cerebral glucose metabolism determined by 18F-fluoro-2-deoxyglucose positron emission tomography (PET) was unchanged in primary visual cortex of VS and NVS patients compared with 12 normal volunteers of similar age and sex. Glucose metabolism in VS patients was decreased by 45 and 34% in left and right visual association cortex (P less than 0.01 and P less than 0.05, respectively) and 34 and 37% in left and right inferior parietal cortex (P less than 0.05) compared with controls; NVS patients had no significant metabolic alteration in these areas. Symptoms, physical examination, and metabolic imaging imply that these patients are a heterogenous but distinct clinical subgroup of DAT often with mild dementia who have visual symptoms due primarily to visual agnosia.

Aged↗

PubMed1989

Cytosolic free calcium, NAD/NADH redox state and hemodynamic changes in the cat cortex during severe hypoglycemia.

Using indo-1, a fluorescent Ca2+ indicator, in vivo fluorometric measurements were made of changes in cytosolic free Ca2+, NAD/NADH redox state, and hemodynamics directly from the cat cortex during and after severe insulin-induced hypoglycemia. Cytosolic free Ca2+ started to increase when the EEG became isoelectric, remained at a significantly high level (p less than 0.05) during the period of isoelectric EEG (IEEG), and recovered to the control level 6 min following an intravenous infusion of glucose. The NAD/NADH redox state oxidized significantly during IEEG and then recovered rapidly to the control level after the glucose infusion. Local cortical blood volume (LCBV) increased gradually during the progression of hypoglycemia, reaching the maximal level (146 +/- 7%) at the end of IEEG, and then started to recover. The mean transit time (MTT) through the cortical microcirculation was shortened during the IEEG (control: 3.84 +/- 0.41 s versus IEEG: 2.73 +/- 0.17 s, p less than 0.05), whereas it was prolonged during the 30-min recovery period (5.68 +/- 0.58 s, p less than 0.05). Local cortical blood flow calculated from the LCBV and MTT showed a twofold increase 5 min into IEEG (201 +/- 27% of control, p less than 0.05), recovered 15 min into the recovery period, and then decreased to 77% of control (p less than 0.05) by 30 min. The data support the hypothesis that hypoglycemic brain damage might be mediated by an elevation of cytosolic free calcium.

Animals↗

PubMed1989

Local cerebral glucose utilization in chronic middle cerebral artery occlusion in the cat.

This study examines the correlation between local CMRglc (LCMRglc) alterations and clinicopathological changes in a chronic middle cerebral artery (MCA) occlusion model in the cat. The left MCA was occluded for a period of 2 h. The animals were grouped into mild, moderate, and severe ischemia based on the depression of the EEG 30 min after the MCA occlusion. Following release of the clip, the animals were allowed to recover for a week during which time daily neurological examinations were performed. On the seventh day [14C]2-deoxyglucose was injected for the determination of LCMRglc. Alternative blocks were processed for histological evaluation in which both neuronal and phagocytic changes were graded into four categories (0 = normal to 3 = severe). LCMRglc (mumol/100 g/min) in the ischemic hemisphere (all histological grades) was significantly lower than the metabolic rate in comparable regions of the sham MCA occlusion group. Regions with significant phagocytosis (grade 2 and 3) invariably exhibited activated glucose metabolism (57.4 +/- 8.4 and 105.9 +/- 6.8 mumol/100 g/min, respectively), which was significantly higher than in regions without phagocytosis (30.4 +/- 0.8 mumol/100 g/min). There was a significant gradient of metabolism in the central, peripheral, and boundary zone and the non-MCA territory in the animals with severe ischemic lesions. LCMRglc in the central MCA territory was well correlated with the EEG amplitude changes (r = 0.82, p less than 0.05) and the morphological score (r = -0.89, p less than 0.05). The metabolic rate was significantly depressed in both the ipsilateral and the contralateral central MCA territories in comparison with the sham occlusion animals. The depression in LCMRglc in the contralateral hemisphere correlated well with the concomitant depression in the contralateral EEG amplitude. These studies demonstrate that local heterogeneous metabolic alterations and contralateral cortical diaschisis exist chronically following temporary MCA occlusion and that the increases in local cerebral glucose metabolism seen in chronic stroke may be due to phagocytotic activity.

Animals↗

PubMed1989

Nimodipine attenuates both increase in cytosolic free calcium and histologic damage following focal cerebral ischemia and reperfusion in cats.

To clarify the mechanism of its effect on ischemic stroke, we investigated the effect of nimodipine, a dihydropyridine calcium antagonist, on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 14 cats. Using indo-1, a fluorescent intracellular Ca2+ indicator, we simultaneously measured changes in the Ca2+ signal ratio (400:506 nm), reduced nicotinamide adenine dinucleotide fluorescence (464 nm), and reflectance (340 nm) during an ultraviolet excitation (340 nm) directly from the cat cortex in vivo. In six cats treated with vehicle only, the calcium signal ratio increased from 5 minutes after middle cerebral artery occlusion to 30 minutes into reperfusion. The elevation of cytosolic free calcium was significantly attenuated by nimodipine, which was administered by intravenous infusion in eight cats starting 5 minutes after occlusion. Nimodipine had no effect on cortical blood flow during ischemia but induced a hyperperfused state following reperfusion. Nimodipine did not modify changes in the mitochondrial oxidation-reduction state. Nimodipine proved to have beneficial effects on recovery of the electroencephalogram following reperfusion as well as on the extent of focal histologic damage. Our results suggest that nimodipine, when administered during the early stage of focal ischemia, can favorably modify the outcome of stroke by reducing the Ca2+ entry during both the ischemic and reperfusion periods.

Animals↗

PubMed1989

Effect of GM1 ganglioside after focal cerebral ischemia in halothane-anesthetized cats.

The effect of the ganglioside GM1 was studied in a focal cerebral ischemia model in 30 cats consisting of 2 hours of middle cerebral artery occlusion followed by 4 hours of recirculation. The cerebrocortical electrical activity, extracellular potassium activity, and microcirculation indicated by NAD/NADH fluorescence were measured during occlusion as well as during recirculation in the core of the middle cerebral artery territory, while the cerebral metabolic rate for glucose (ICMRgl) was measured at the end of recirculation. The cats were classified into either mildly or moderately severe stroke groups based on the depression of the cerebrocortical electrical activity on the occluded side. Of 12 cats with only a mild stroke, six were administered GM1 intravenously 30 minutes after occlusion, while six cats were not treated. Of 12 cats with a moderate stroke, six were treated and six were left untreated. In six additional cats, only a sham insult was undertaken. In the cats with mild stroke, GM1 treatment significantly increased lCMRgl in the peripheral middle cerebral artery territory compared with the untreated cats; for the six treated cats, lCMRgl was normalized toward the control level, whereas it was depressed in the six untreated cats. There were no other significant effects of GM1 treatment on the other measured parameters. A potential protective effect of anesthesia is discussed.

Anesthesia↗