Cerebral blood flow, cerebrovascular resistance and cerebral metabolic rate of oxygen in severe arterial hypoxia in dogs

Cerebral blood flow and cerebral oxygen uptake were studied during severe arterial hypoxia in anesthetized dogs. It was shown that the hypoxic vasodilatation in the brain reaches a limit at an arterial oxygen saturation at about 25% and that this vasodilatation is less than that which may be induced by hypercapnia. A further deepening of the arterial hypoxia at a maintained cerebral perfusion pressure is combined with a continuous decrease in cerebral venous oxygen tension and a reduced oxygen uptake.     

Cerebrovascular changes elicited by electrical stimulation of the centromedian-parafascicular complex in rat

Electrical stimulation of the centromedian-parafascicular complex (CM-Pf) in anesthetized (chloralose) and paralyzed (tubocurarine) rats elicites a widespread cerebrovascular dilatation. Regional cerebral blood flow (rCBF) was measured in dissected tissue samples of 10 brain regions (medulla, pons, cerebellum, inferior colliculus, superior colliculus, frontal parietal and occipital cortices, caudate-putamen and corpus callosum) by [¹⁴C]iodoantipyrine method. In unstimulated and sham-operated rats rCBF ranged from 40±3 (ml/100g/min) in corpus callosum to 86±6 (ml/100g/min) in inferior colliculus. During CM-Pf stimulation, rCBF increased significantly P < 0.05, analysis of variance and Scheffe's test) in all cerebral regions bilaterally ranging from +118% in parietal cortex to +38% in cerebellum. Although cerebral vasodilation elicited by CM-Pf stimulation persisted after unilateral transection of the cervical sympathetic trunk, the cortical CBF was significantly reduced (P < 0.05) on the denervated side. Acute adrenalectomy significantly (P < 0.05) decreased elevated rCBF during CM-Pf stimulation in all cortical regions (frontal −36%, parietal −34%, and occipital −27%) and in caudate nucleus (−37%). Thus, excitation of neurons originating in, or fibers passing through the CM-Pf can elicit a powerful cerebral vasodilation. The cerebral vasodilation is modulated by cervical sympathectomy and circulating adrenal hormones. We conclude that CM-Pf elicited vasodilation is at least partly mediated by intrinsic neural pathways.     

Trigeminal afferents and brainstem centers involved in the occurrence of cerebral vasospasm

Abstract

Cisternal injections of blood in the rat and squirrel monkey produce an angiographically demonstrable biphasic vasospasm with a maximal late spasm at two days in the rat and six days post-subarachnoid hemorrhage (SAH) in the monkey. The SAH induces a decrease in cerebral blood flow of about 25% and a corresponding increase in glucose uptake of between 30% and 50%. In about half of the animals low-flow areas were noted in the cortex and the basal ganglia with a corresponding marked increase in glucose uptake. Lesioning of the A2-nucleus/ its ascending pathway or the median eminence prevents the occurrence of spasm. Similarly; treatment with a substance P antagonist or gammaglobulin against substance P prevents or significantly reduces the degree of spasm. A unilateral post-ganglionic trigeminal lesion causes an ipsilateral constriction of the cerebral arteries of 27%, while a preganglionic lesion does not affect the baseline diameter. A pre- or post-ganglionic trigeminal lesion induces an increase in glucose uptake globally of about 50% without influencing cerebral blood flow. Following SAH the decrease in blood flow in both groups of lesioned animals is similar to that seen in controls. After SAH there is no further change in glucose uptake in the animals with a preganglionic lesion, while in the post- ganglionically lesioned animals there is an additional increase in glucose uptake of about 50% as compared to controls or the animals with a preganglionic lesion. [Neurol Res 1996; 18: 394-400]     

Widespread reductions in cerebral blood flow and metabolism elicited by electrical stimulation of the parabrachial nucleus in rat

We have studied the effect of electrical stimulation of the parabrachial nucleus (PBN) and adjacent areas of dorsal pons on regional cerebral blood flow (rCBF) and glucose utilization (rCGU) in anesthetized (chloralose), paralyzed (tubocurarine) rats. rCBF and rCGU were measured in dissected tissue samples of 9 brain regions by the [¹⁴C]iodoantipyrine and [¹⁴C]2-deoxyglucose method, respectively. Electrical stimulation restricted to the medial parabrachial nucleus (PBNm, n=5) elicited significant (P < 0.05) reductions in rCBF in 7 out of 9 brain regions. Reductions were greatest in cerebral cortex (up to 35% in occipital cortex) and least in the white matter of the corpus callosum (23%). The effect on rCBF persisted after transection of the cervical sympathetic trunk (n=5). In contrast, stimulation of the lateral portion of PBN (n=5), periventricular gray (n=5) and interestingly, the nucleus locus coeruleus (n=5) failed to elicit similar changes in rCBF. PBNm stimulation also elicited decreases in rCGU (n=4) in 5 out of 9 brain areas, most notably regions of cerebral cortex. The decreases in rCGU (ΔrCGU) were linearly related to the decreases in rCBF (ΔrCBF) according to the equationΔrCBF=2.37 ΔrCGU+2.1 (r=0.72; P<0.001). We conclude that excitation of neural pathways originating in, or passing through, PBNm elicits a widespread reduction in cerebral metabolism and secondarily in blood flow (secondary vasoconstriction). Since projections of the PBNm do not involve the entire cortex, it seems likely that the effect is mediated via inhibition of diffuse cortical projections through a subcortical site.     

Raphe region mediates changes in cutaneous vascular tone elicited by stimulation of amygdala and hypothalamus in rabbits

Raphe pallidus/parapyramidal neurons control cutaneous vasoconstriction induced by noxious stimuli. To determine whether they mediate forebrain-induced cutaneous vasoconstriction, we assessed changes in ear pinna blood flow elicited by electrical stimulation of amygdala and hypothalamus before and after injection of muscimol into the raphe/parapyramidal region. We compared ear flow with simultaneously recorded mesenteric flow. Experiments were performed in rabbits anesthetized with urethane (1.25-1.5 g/kg), paralysed and mechanically ventilated. Amygdala stimulation reduced skin conductance from 0.32+/-0.06 to 0.10+/-0.02 cm/s per mmHg (P<0.05, n=9), without effect on mesenteric conductance. Hypothalamic stimulation caused vasoconstriction in both cutaneous and mesenteric beds (conductances fell from 0.27+/-0.05 to 0.05+/-0.02 cm/s per mmHg and from 0.27+/-0.06 to 0.14+/-0.04 cm/s per mmHg (P<0.05, n=9), respectively). Muscimol microinjection (5 nmol in 100 nl) to raphe/parapyramidal region eliminated amygdala- and hypothalamus-induced skin vasoconstriction (pre-stimulus conductance 0.42+/-0.13 and 0.41+/-0.11 cm/s per mmHg, post-stimulus 0.41+/-0.12 and 0.39+/-0.10 cm/s per mmHg, respectively), but not hypothalamically-induced mesenteric vasoconstriction (pre-stimulus 0.29+/-0.06, post-stimulus 0.16+/-0.03 cm/s per mmHg, P<0.05, n=8). The latter was strongly attenuated by bilateral injection of muscimol to the rostral ventrolateral medulla. Data suggest that descending hypothalamo-spinal and amygdala-spinal pathways constricting the cutaneous vascular bed relay in the raphe/parapyramidal area. A relay in the rostral ventrolateral medulla contributes substantially to mesenteric vasoconstriction elicited from the hypothalamus.     

Muscarinic cholinergic receptors mediate the cerebrovasodilation elicited by stimulation of the cerebellar fastigial nucleus in rat

We have investigated the effects of systemic administration of atropine sulfate on the global cerebrovascular vasodilation elicited by electrical stimulation of the cerebellar fastigial nucleus (FN) in chloralose-anesthetized rat. Atropine (0.3 mg/kg, i.v.) abolished the cerebrovasodilation elicited from FN but did not affect the concomitant elevation in arterial pressure and the EEG changes. We conclude that the cerebrovascular effect of FN stimulation, but not the peripheral cardiovascular or EEG changes, are mediated by cholinergic muscarinic receptors associated with cerebral vessels and/or intrinsic neural pathways.     

Cerebral autoregulation during orthostatic stress in healthy controls and in patients with posturally related syncope

Abstract. Posturally related syncope (PRS) is a common and distressing problem, which frequently occurs in people with no apparent clinical disorder and is ultimately caused by a reduction in blood supply to the brain. The aim of this study was to compare cerebrovascular responses to orthostatic stress in otherwise healthy patients suffering from PRS, and who were shown to have a poor orthostatic tolerance (n=28), with those in healthy control subjects with good orthostatic tolerance (n=11). Responses of heart rate, arterial blood pressure, end tidal carbon dioxide and middle cerebral artery (MCA) blood flow velocity were determined during a progressive orthostatic stress test of combined head-up tilting and lower body suction, which was continued until presyncope. We assessed the efficiency of autoregulation of cerebral blood flow from the relationship between values of MCA velocity and pressure obtained over the expected range for autoregulation (> 55mmHg). All patients with PRS had a significant correlation between MCA velocity and pressure, but this was seen in only two of the controls. Furthermore, the values of the correlation coefficients were significantly higher in patients than controls, (p<0.001). We interpret these data as indicating that autoregulation in patients with PRS is less effective than in controls and suggest that this provides evidence for a link between abnormalities of regulation of the cerebral circulation and predisposition to syncope.     

Comparative analysis of regional brain blood flow and glucose metabolism in focal cerebrovascular disease measured by dynamic positron emission tomography of fluorine-18-labelled tracers

Summary Regional cerebral blood flow (rCBF) and glucose metabolism (rCMRglc) were measured in 44 patients with various kinds of focal vascular brain lesions, using multislice positron emission tomography (PET). Haemodynamic data were obtained by a recently developed, non-invasive clearance method utilizing (¹⁸F)-methyl fluoride as a diffusible, gaseous indicator. Shortly after completion of each flow study, rCMRglc was dynamically determined by standard procedures using 2(¹⁸F)-fluorodeoxyglucose. While blood flow and glucose consumption in the structurally damaged area were often uncoupled during the acute phase, metabolism-to-flow ratios were markedly less scattered at later stages of cerebrovascular disease. Individual maximum-likelihood cluster analysis of brain regions revealed remarkable similarity between deactivation patterns of rCBF and rCMRglc, with Tanimoto coefficients averaging 0.56. This similarity was inversely related to the residual rCMRglc of the lesion. These findings are in line with results obtained by PET of other tracers, suggesting that the pair of methods provides valuable and somewhat complementary information on brain function and mechanisms of cerebral vascular disease.     

Cerebral metabolic and circulatory changes in the rat during sustained seizures induced by DL-homocysteine

Sustained, generalized seizure activity was induced in anaesthetized (70% N2O), paralyzed and artifically ventilated rats by i.p. DL-homocysteine thiolactone in a dose of 11 mmol/kg. Epileptic discharges in the EEG were accompanied by marked perturbation of tissue metabolites. There was a fall in phosphocreatine concentration to 40% of control but only moderate changes in adenine nucleotides, a marked rise in lactate concentration, and a pronounced increase in the lactate/pyruvate ratio. Excessive amounts of dihydroxyacetone phosphate (and glyceraldehyde phosphate) accumulated, indicating that depletion of NAD+ occurred. There was marked accumulation of ammonia, glutamine and alanine, and reduction in glutamate and aspartate concentrations. Administration of a subconvulsive dose of homocysteine (7.5 mmol/kg) gave rise to changes in ammonia and amino acids, qualitatively similar to those occurring during seizures. It is concluded that although changes in the metabolites of the energy reserve were mainly caused by the induced seizures, those affecting amino acid concentrations were significantly influenced by accumulation of ammonia, secondary to metabolism of injected homocysteine. Cerebral blood flow (CBF) and oxygen utilization (CMRO2) were measured during sustained seizures. CMRO2 rose to 150% of control, with a corresponding increase in CBF.     

Principles of cerebral oxygenation and blood flow in the neurological critical care unit

Cerebrovascular disease and trauma are leading causes of death in the United States. In addition to the initial insult to the brain, disturbances of cerebral oxygenation and metabolism underlie many of the secondary pathophysiological processes that increase both morbidity and mortality. Therefore, researchers and clinicians have sought to obtain a more thorough understanding of the physiological and biochemical principles of cerebral oxygenation and metabolism. New technologies capable of offering continuous and quantitative assessment of cerebral oxygenation may improve clinical outcomes. In this article, we review the physiological principles of cerebral metabolism, cerebral blood flow and their metabolic coupling, and cerebral oxygenation, with particular emphasis on variables that could be monitored and managed in an intensive care unit setting. BWH Neurosurgery Group in alphabetical order are Ian F. Dunn, Dilantha B. Ellegala, Jonathan F. Fox, and Dong H. Kim.     

Determination of the rate of cerebral oxygen consumption and regional cerebral blood flow by non-invasive 17O in vivo NMR spectroscopy and magnetic resonance imaging: Part 1. Theory and data analysis methods Daniel Fiat and Seho Kang

Abstract

Theory and novel data analysis methods of 170 inhalation measurements are presented for the calculation of CMR02, regional cerebral blood flow (rCBF), the reflow (R), the arterial venous difference (AVD) and the partition coefficient (X). Several of the methods proposed for the determination of CMR02 do not require measurements of regional cerebral blood flow and H2170 arterial concentration. All methods'of analysis are based on the Kety-Schmidt approach. [Neurol Res 1992; 14: 303-311]     

Haemodynamic and metabolic disturbances in the acute stage of subarachnoid haemorrhage demonstrated by PET

OBJECTIVE: To investigate the occurrence of early haemodynamic and metabolic changes in the acute stage of subarachnoid haemorrhage (SAH). MATERIAL AND METHODS: Eleven SAH patients were studied. Regional cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and oxygen extraction ratio (OER) were measured with positron emission tomography (PET) 22-53 h after haemorrhage, utilizing 15O-labelled water bolus and the 15O-inhalation technique. Ten volumes of interest (VOIs) representing vascular territories were outlined in each patient according to a standardized procedure. The occurrence of irreversible ischaemia, penumbra, oligaemia, hyperperfusion and normal haemodynamics according to PET criteria was investigated. These pathophysiological categories were related to final tissue outcome as determined by follow-up computed tomography (CT). RESULTS: All five tissue subtypes were represented in the vascular region VOIs; oligaemia was the predominant pathophysiological pattern. When global changes were analysed, blood flow was reduced in three, oxygen metabolism was reduced in four, and OER was increased in four of seven unsedated patients, respectively. The sedated patients all had markedly reduced CBF and CMRO2 and OER in the high or supranormal range. CONCLUSION: Haemodynamic and metabolic disturbances proved to be common after SAH. These abnormalities probably reflect the primary brain injury caused by the initial haemorrhage. The impact of secondary insults such as acute hydrocephalus, brain oedema, vasospasm, seizures, hypotension and hypoxaemia are likely to be dependent on the degree of primary injury, which can be assessed by PET.     

Three-dimensional remodeling of functional cerebrovascular architecture and gliovascular unit in leptin receptor-deficient mice

The cerebrovascular sequelae of diabetes render victims more susceptible to ischemic stroke, vascular cognitive impairment, and Alzheimer''s disease. However, limited knowledge exists on the progressive changes in cerebrovascular structure and functional remodeling in type 2 diabetes. To ascertain the impact of diabetes on whole-brain cerebrovascular perfusion, leptin-receptor-deficient mice were transcardially injected with tomato-lectin before sacrifice. The whole brain was clarified by the Fast free-of-acrylamide clearing tissue technique. Functional vascular anatomy of the cerebrum was visualized by light-sheet microscopy, followed by analysis in Imaris software. We observed enhanced neovascularization in adult db/db mice, characterized by increased branch level and loop structures. Microvascular hypoperfusion was initially detected in juvenile db/db mice, suggesting early onset of insufficient microcirculation. Furthermore, gliovascular unit remodeling was verified by loss of pericytes and overactivation of microglia and astrocytes in adult diabetic mice. However, the integrity of the blood-brain barrier (BBB) was fundamentally preserved, as shown by a lack of extravasation of IgG into the brain parenchyma. In summary, we, for the first time, reveal that functional cerebrovascular remodeling occurs as early as four weeks in db/db mice and the deficit in gliovascular coupling may play a role in cerebral hypoperfusion before BBB breakdown in 16-week-old db/db mice.     

Cerebral blood flow, cerebrovascular resistance, cerebral metabolic rate of oxygen and intracranial pressure during and after severe prolonged arterial hypoxia in dogs. The role of dopamine in the deep hypoxic state

The effect of extreme, prolonged arterial hypoxia on cerebral blood flow, oxygen uptake and intracranial pressure was studied in anesthetized dogs. The experiments were performed along two lines. Both started with a period of hypoxia of about 40 minutes to 2 hours. Thereafter normoxia was restituted in one group and the animals were studied for another 1-2 hours. In the other group with continued hypoxia dopamine was administered. During the hypoxic period the cerebral blood flow decreased mainly as a result of vasoconstriction after an initial marked flow increase. Cerebral oxygen uptake was reduced. Intracranial pressure increased, largely in proportion to blood flow changes, and no indication of important brain edema appeared. In the "recovery" period at normoxia the cerebral oxygen uptake showed an increase during the observation time. The blood flow, initially high, returned to the control level within the observation period. Dopamine infusion during continued hypoxia induced a vasodilatation, with reduction of vascular resistance to the values found at the induction of hypoxia, and with an increase of the cerebral oxygen uptake. An important role of endogenous dopamine in the hypoxic vasodilatation is suggested.     

Effects of microbial invasion on cerebral hemodynamics and oxygenation monitored by near infrared spectroscopy in experimental Escherichia coli meningitis in the newborn piglet

Abstract

This study was carried out to elucidate the pathophysiologic mechanism of cerebral hyperemia observed during the early phase of bacterial meningitis. We tested the hypothesis that microbial invasion through the blood-brain barrier is responsible for cerebral vasodilation and hyperemia in meningitis. Escherichia coli was given either intravenously (i.v.) or intracisternally (i.e.) to closely mimic the primary or secondary bacterial invasion occurring in meningitis and newborn piglets were grouped according to their invasion results (+ or -); 7 2 in the i. v. (+) group, 14 in the i. v.{-) group, 73 in the i. c.( + ) group, 7 5 in the i. c. (-) group. The results were compared with eight animals in the control group. Near infrared spectroscopy (NIRS) was employed to monitor changes in total hemoglobin (HbT), oxygenated hemoglobin (HbO), deoxygenated hemoglobin (Hb), deduced hemoglobin (HbD), and oxidized cytochrome aa3 (Cyt aa3). HbT, as an index of cerebral blood volume, increased progressively in both i.v. (+) and i.v. (-) groups and became significantly different from control and baseline values at 2 h. Hb significantly increased only in i.v. ( + ) group. HbD, as an index of cerebral blood flow, decreased significantly in i.v. ( + ), i.v.(-) and i.e. (-) groups and this change was mitigated in i.e. ( + ) group. HbO was reduced in i.e. (-) group and this decrease was attenuated in i.e. ( + ) group. Increased Cyt aa3 was observed in all experimental groups after bacterial inoculation. Changes in ICP, blood pressure, cerebral perfusion pressure, blood or CSF glucose or lactate, CSF TNF-a level, or CSF leukocytes number were not associated with changes in NIRS findings. These findings suggest that primary or secondary bacterial invasion across the blood-brain barrier is primarily responsible for cerebral vasodilation and hyperemia observed during the early phase of bacterial meningitis. [Neurol Res 1999; 21: 391-398]     

Effect of memantine on CBF and CMRO2 in patients with early Parkinson's disease

Objectives –  Parkinson's disease (PD) may be associated with increased energy metabolism in overactive regions of the basal ganglia. Therefore, we hypothesized that treatment with the N -methyl- d -aspartate receptor (NMDAR) antagonist memantine would decrease regional cerebral blood flow (rCBF) and oxygen metabolism in the basal ganglia of patients with early-stage PD.
Methods –  Quantitative positron emission tomography (PET) recordings were obtained with [¹⁵O]water and [¹⁵O]oxygen in 10 patients, scanned first in a baseline condition, and again 6 weeks after treatment with a daily dose of 20 mg memantine. Dynamic PET data were analyzed using volume of interest and voxel-based approaches.
Results –  The treatment evoked rCBF decreases in basal ganglia, and in several frontal cortical areas. The regional cerebral metabolic rate of oxygen (rCMRO₂) did not decrease in any of the a priori defined regions, and consequently the oxygen extraction fraction was increased in these regions. Two peaks of significantly decreased rCMRO₂ were detected near the frontal poles in both hemispheres, using a posteriori voxel-based analysis.
Conclusions –  Although we did not find the predicted decrease in basal ganglia oxygen consumption, our data suggest that treatment with memantine actively modulates neuronal activity and/or hemodynamic response in basal ganglia of PD patients. This finding may be relevant to the putative neuroprotective properties of NMDAR antagonists.     

Local cholinergic mechanisms participate in the increase in cortical cerebral blood flow elicited by electrical stimulation of the fastigial nucleus in rat

We sought to determine whether the increase in regional cerebral blood flow (rCBF) elicited within the cerebral cortex (CX) by electrical stimulation of the fastigial nucleus (FN) of the cerebellum is: prevented by local application of the muscarinic cholinergic receptor antagonist, atropine and temporally correlated with a stimulus-locked release of acetylcholine (ACh) from the cortical surface. Rats were anesthetized, paralyzed, ventilated, with arterial blood gases controlled and arterial pressure maintained within the autoregulated range. Bilateral craniotomies were performed over a standardized region of the sensory motor CX and superfusion devices stereotaxically positioned on the cortical surface. Cortical surface temperature, as well as pH, pCO2 and pO2 of the solutions applied to the cortex were also carefully controlled. rCBF was measured in dissected regions of frontal (FCX), parietal (PCX), and occipital cortices (OCX), caudate nucleus (CN), and hippocampus (HIPP) by the Kety principle using [14C]iodoantipyrine as indicator. Resting rCBF (ml/100 g/min) in unoperated control animals ranged from 70 +/- 5 in HIPP to 95 +/- 7 in PCX and was unaffected by bilateral craniotomies and placement of superfusion devices containing Kreb's bicarbonate buffer (vehicle) on the cortical surface. Local application of atropine (ATR, 100 microM) to the right PCX via the superfusion device did not affect resting rCBF. With FN stimulation rCBF increased bilaterally and symmetrically in all areas up to 227% in PCX. ATR application attenuated by 59% the FN-elicited increase in rCBF on the ipsilateral frontoparietal CX, without affecting blood flow in adjacent structures. ATR did not affect cortical cerebrovasodilation produced by hypercarbia (arterial pCO2 = 59.0 +/- 1.4 mm Hg). FN-stimulation resulted in a small (22%) but significant (P less than 0.05, n = 9) reduction in the release of [3H]ACh from the cortical surface, while supramaximal depolarization with 55 mM K+ increased [3H]ACh release by 251%. These studies indicate that: increases in cortical rCBF elicited by FN stimulation, but not hypercarbia, are in large part mediated by local muscarinic cholinergic receptors; resting rCBF is not tonically affected by muscarinic receptor activation; and the release of ACh from the cortical surface is, in general, reduced during FN-stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cerebral blood flow and metabolism following subarachnoid haemorrhage: cerebral oxygen uptake and global blood flow during the acute period in patients with SAH

Forty-eight patients with subarachnoid haemorrhage were studied with repeated rCBF and CMRO2 measurements. Cortical rCBF was measured using xenon-inhalation technique. CMRO2 was calculated as AVDO2 x CBF. When first studied the 29 conscious patients showed relative hyperaemia with CBF at 50 ml and reduced CMRO2 at 2.17 ml. In the following week CBF decreased to 41. CMRO2 remained reduced and constant. The 19 unconscious patients showed initially pronounced reduction in CMRO2 to 1.26, followed by gradual increase to 1.73 in 4-5 days. Simultaneously CBF increased from 18 ml to slightly above 30 ml. In the conscious patients the early reduction in CMRO2 and the concomitant luxury perfusion may be explained by global ischaemia because of very high ICP at the time of the haemorrhage. The reduced CBF in the unconscious group could be due to increased ICP, as ventricular drainage increased CBF to levels of relative hyperaemia as demonstrated in one case. As no decrease in CMRO2 was seen during the first 2 weeks, it is suggested that ischaemia at the time of aneurysm rupture is the most important single factor in reduction of global CMRO2.     

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.     

Assessment of cerebrovascular reserve in unilateral middle cerebral artery stenosis using perfusion CT and CO2 inhalation tests

Purpose/Aim of the study: Cerebrovascular reactivity (CVR) is an important marker for assessing cerebrovascular disease. This study assessed the CVR by perfusion computed tomography (CT) and CO₂ inhalation tests in patients with unilateral middle cerebral artery (MCA) stenosis disease. Materials and Methods: Thirty-one patients with unilateral MCA stenosis disease diagnosed by digital subtraction angiography were studied. Patients were divided into two groups according to the degree of stenosis: severe and moderate. The regional cerebral blood flow (CBF) before and after CO₂ inhalation was determined by perfusion CT. Regional CVR values were obtained by the following formula: increase (%) = (post-CBF) ? (pre-CBF)/(pre-CBF) × 100%. Results: No significant differences in the mean CBF in the MCA stenosis region were found between the affected and contralateral sides before the CO₂ inhalation test; after the test, CBF was more significantly decreased on the affected side than on the contralateral side. The changes in CBF on the affected side were categorized into three types: increased CBF (17 cases), decreased CBF (12 cases) and no change in CBF (2 cases). The rate of CVR impairment among severe stenosis patients (13/19) was higher than that among moderate stenosis patients (3/12). CVR was significantly correlated with the degree of stenosis (r = 0.423, P = 0.018). Conclusion: CVR impairment was found in approximately half of patients with unilateral MCA stenosis. Along with an increase in the degree of stenosis, patients with unilateral MCA stenosis were more likely to exhibit CVR impairment. It is important to assess the CVR in patients with unilateral MCA stenosis, especially those with severe stenosis.