Showing papers on "Middle cerebral artery published in 1994"

Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia.

Abstract: We have demonstrated in a previous study that superoxide radicals play a role in the pathogenesis of cerebral infarction, using a transgenic mouse model of distal middle cerebral artery occlusion, permanent ipsilateral cerebral carotid artery occlusion, and 1-hour contralateral cerebral carotid artery occlusion that produced infarction only in the cortex. However, the role of superoxide radicals in reperfusion injury in transgenic mice overexpressing superoxide dismutase (SOD) is unknown. Using a mouse model of intraluminal blockade of middle cerebral artery that produced both cortical and striatal infarction, we now further examined the role of superoxide radicals in ischemic cerebral infarction after reperfusion in transgenic mice overexpressing human CuZn-SOD activity.Transgenic mice of strain Tg HS/SF-218, carrying human SOD-1 genes, and nontransgenic littermates were anesthetized with chloral hydrate (350 mg/kg IP) and xylazine (4 mg/kg IP). Physiological parameters were maintained at a normal range ...

Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk.

Abstract: PURPOSE To investigate the incidence and prognostic value of local brain swelling, the extent of parenchymal hypodensity, and the hyperdense middle cerebral artery sign as shown by CT within the first 5 hours after the onset of symptoms in patients with angiographically proved middle cerebral artery trunk occlusions. METHODS Fifty-three patients were studied prospectively with CT 46 to 292 minutes (median, 120; mean, 134 +/- 59) after symptom onset and scored clinically at admission and 4 weeks later. All patients were treated with recombinant tissue plasminogen activator (30 to 100 mg). RESULTS Early CT showed parenchymal hypodensity in 43 patients (81%), local brain swelling in 20 patients (38%), and hyperdensity of the middle cerebral artery trunk in 25 patients (47%). Hypodensity covering more than 50% of the middle cerebral artery territory had an 85%, local brain swelling a 70%, and the hyperdense middle cerebral artery sign a 32% positive predictive value for fatal clinical outcome. Specificity of these findings for fatal outcome was 94%, 83%, and 51%, respectively, and sensitivity was 61%, 78% and 44%, respectively. CONCLUSIONS Early CT in acute middle cerebral artery trunk occlusion is highly predictive for fatal clinical outcome if there is extended hypodensity or local brain swelling despite aggressive therapeutic attempts such as thrombolysis or decompressive surgery.

Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat).

Abstract: The results of several experimental studies of focal ischemia and anecdotal observations suggest that leukocytes may contribute to the injury initiated by an arterial occlusion. The timing and the nature of leukocyte responses in evolving brain infarcts (either human or experimental) are incompletely characterized. This is a study of experimental brain lesions in 96 Wistar rats that underwent occlusion of a large intracranial artery for variable intervals ranging between 30 minutes and 7 days. The experimental model, based on the occlusion of a middle cerebral artery ostium via the insertion of a nylon monofilament through the external carotid artery, does not require opening the skull; therefore, the inflammatory response is not influenced by the effects of craniotomy and changes in intracranial pressure are only those induced by the ischemic lesion. All 96 animals having the same type of arterial occlusion developed an ischemic brain lesion (limited to the territory of the corresponding artery) that evolved into an area of extensive neuronal necrosis over a period of 6 to 12 hours followed by pan-necrosis (infarct) approximately 60 hours later. In this study, leukocytes (in particular polymorphonuclear cells) were detected in the microvessels (capillaries and venules) of the ischemic hemisphere as early as 30 minutes after the arterial occlusion. Numbers of intravascular neutrophils peaked at 12 hours, whereas intraparenchymal granulocytes were most numerous at 24 hours; a few granulocytes were visible in the brain infarct as late as day 7. Circulating monocytes were first detected within the capillaries/venules of the ischemic area after 4 to 6 hours. Platelet aggregates were more abundant in the arterial than the venous side of the circulation, and luminal obstruction of arteries by platelet aggregates became noticeable only 48 hours after the arterial occlusion. Fibrin thrombi were conspicuous for their absence. These observations provide the background for studies that will attempt to unravel the relationship between the biological responses of leukocytes and neuronal necrosis secondary to focal ischemia.

Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.

Abstract: Neutrophils have been implicated in the pathogenesis of ischemia-reperfusion injury. The aim of the present study was to evaluate the correlation between neutrophil infiltration into ischemic tissues and brain injury after transient focal ischemia.We evaluated the effects of depletion of circulating neutrophils by administration of an antineutrophil monoclonal antibody (RP3) on brain edema formation, infarct size, and neutrophil infiltration (myeloperoxidase [MPO]-quantified) in rats with 1 hour of middle cerebral artery (MCA) occlusion.In the cerebral cortex perfused by the anterior cerebral artery (ACA area), there was a significant increase in MPO activity only 24 hours (P < .05) after reperfusion. In the cerebral cortex perfused by the middle cerebral artery (MCA area) and caudate putamen, MPO activity was significantly increased at 12 (MCA area, P < .01; caudate putamen, P < .05), 24 (MCA area, P < .05; caudate putamen, P < .01), and 72 hours (MCA area, P < .01; caudate putamen, P < .05) and returned...

Comparison of flow and velocity during dynamic autoregulation testing in humans.

Abstract: We compared relative changes in middle cerebral artery velocity and internal carotid artery flow during autoregulation testing to test the validity of using transcranial Doppler recordings of middle cerebral artery velocity to evaluate cerebral autoregulation in humans.Seven human volunteers had dynamic autoregulation tested during surgical procedures that included exposure of the internal carotid artery. The mean arterial blood pressure and middle cerebral artery velocity spectral outline (Vmax), using transcranial Doppler, and ipsilateral internal carotid artery flow, using an electromagnetic flowmeter, were continuously and simultaneously recorded during transient sharp decreases in blood pressure that were induced by rapid deflation of thigh blood pressure cuffs. The resulting responses of velocity in the middle cerebral artery and flow in the internal carotid artery were compared.Moderate decreases in blood pressure evoked responses in cerebral autoregulation. There were no significant (P = .97) diff...

Anti‐ICAM‐1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat

Abstract: Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein expressed on endothelial cells that facilitates leukocyte adhesion. To test the hypothesis that reduction of leukocytes in an ischemic lesion reduces ischemic brain damage, we measured the effect of administration of an anti-ICAM-1 monoclonal antibody on ischemic brain damage after transient middle cerebral artery occlusion in the rat. ICAM-1 expression increased in the ischemic lesion, and the lesion volume was significantly reduced by 41% in the anti-ICAM-1 antibody group compared with the control group (p < 0.05). Numbers of polymorphonuclear leukocytes (PMNs) were significantly reduced in the cortices of the anti-ICAM-1 antibody group compared with the control animals (p < 0.05). Our data indicate that administration of anti-ICAM-1 antibody results in a significant reduction of ischemic brain damage concomitant with a reduction of PMNs in the lesion after transient focal cerebral ischemia in the rat.

Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats.

Abstract: Postischemic cerebral inflammation may contribute to ischemic cell damage. The CD11b/18 (Mac-1) integrin mediates stimulated neutrophil binding to endothelia. We therefore investigated the effect of administration of an anti-Mac-1 monoclonal antibody on cerebral ischemic cell damage in the rat. Rats (n = 10) were subjected to 2 hours of middle cerebral artery occlusion; the anti-Mac-1 antibody was administered at a dose of 2 mg/kg i.v. at 1 hour of reperfusion and 1 mg/kg i.v. at 22 hours of reperfusion or an isotype-matched control antibody (n = 10) was administered using the same experimental protocol. Rats were killed at 46 hours of reperfusion, and brain sections were stained with hematoxylin and eosin for histological evaluation. In a separate population of rats given either vehicle (n = 8) or anti-Mac-1 antibodies (n = 9), intraparenchymal neutrophils were measured by means of a myeloperoxidase assay. The lesion volume was significantly smaller (28%) in the anti-Mac-1 antibody group compared with the vehicle control group (P < .01). Numbers of intraparenchymal polymorphonuclear cells were significantly reduced (P < .05) in the cortex of the anti-Mac-1 antibody group compared with the vehicle control group. Our data demonstrate that administration of anti-Mac-1 antibody 1 hour after onset of reperfusion results in significant reductions of ischemic cell damage and intraparenchymal neutrophils after transient (2-hour) focal cerebral ischemia in the rat.

Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats.

Abstract: The integrity of the blood-brain barrier may play an important pathophysiological role during postischemic reperfusion. To determine the factors that lead to exacerbation of brain injury by reperfu...

The NOS Inhibitor, 7-Nitroindazole, Decreases Focal Infarct Volume but not the Response to Topical Acetylcholine in Pial Vessels.

Abstract: We examined whether 7-nitroindazole (7-NI), a putative inhibitor of neuronal nitric oxide synthase (nNOS), decreases cerebral infarction 24 h after proximal middle cerebral artery (MCA) occlusion. In preliminary experiments, we determined that 7-NI (25, 50, and 100 mg/kg i.p.) decreased nitric oxide synthase (NOS) activity within cerebral cortex by 40-60% when measured up to 120 min, but not 240 min after administration. At 25 or 50 mg/kg, 7-NI did not alter the systemic arterial blood pressure or the dilation of pial arterioles after topical acetylcholine (10 and 100 microM). To examine the effect of 7-NI on infarct size, 55 Sprague-Dawley halothane-anesthetized rats were subjected to proximal MCA occlusion (modified Tamura method). Five minutes after occlusion, 7-NI (25 or 50 mg/kg i.p.) or vehicle was injected. Animals treated with 25 or 50 mg/kg showed 25 and 27% reductions in infarct volume, respectively. Coadministration of L-arginine (300 mg/kg i.p.) plus 7-NI (25 mg/kg i.p.) reversed the effect. If, indeed, the effects of 7-NI are mediated by inhibition of nNOS activity, these results suggest that enzymatic products of the neuronal isoform promote ischemic injury and that they do so at least within the first few hours after permanent occlusion. The results also emphasize the importance of developing strategies to selectively inhibit the neuronal isoform inasmuch as we observed previously that administering the less selective NOS inhibitor, N omega-nitro-L-arginine (L-NA), in the same model either caused no change or increased the volume of ischemic injury.

Cortical negative DC deflections following middle cerebral artery occlusion and KCl-induced spreading depression: effect on blood flow, tissue oxygenation, and electroencephalogram.

Abstract: In the periphery of ischemic brain lesions, transient spreading depression-like direct current (DC) deflections occur that may be of pathophysiological importance for determining the volume of the ischemic infarct. The effect of these deflections on cerebral blood flow, tissue oxygen tension, and electrophysiology was studied in rats submitted to intraluminal thread occlusion of the middle cerebral artery (MCA) and compared with the changes following potassium chloride (KCl)-induced spreading depression of intact animals. Immediately after MCA occlusion, cortical laser-Doppler flow (LDF) in the periphery of the MCA territory sharply decreased to 35 +/- 14% of control (mean +/- SD; p < 0.05), tissue PO2 declined from 28 +/- 4 to 21 +/- 3 mm Hg (p < 0.05), and EEG power fell to approximately 80% of control. During 7-h occlusion, 3-11 DC deflections with a mean duration of 5.2 +/- 4.8 min occurred at irregular intervals, and EEG power gradually declined to 66 +/- 16% of control (p < 0.05). During the passage of DC deflections, LDF did not change, but PO2 further declined to 19 +/- 4 mm Hg (p < 0.05). KCl-induced depolarizations of intact rats were significantly shorter (1.4 +/- 0.5 min; p < 0.05) and were accompanied by a 43% increase in LDF (p < 0.05) and a slight but significant increase in tissue PO2 from 22 +/- 4 to 25 +/- 4 mm Hg (p < 0.05). The comparison of periinfarct and KCl-induced depolarizations demonstrates that oxygen requirements are not coupled to an appropriate flow response in the periinfarct zone with severely reduced blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance imaging assessment of evolving focal cerebral ischemia. Comparison with histopathology in rats.

Abstract: Background and Purpose This study was performed to document the progression of ischemic brain damage after middle cerebral artery occlusion in the rat using magnetic resonance imaging and histopathologic methods.Methods Cerebral ischemia was induced through permanent tandem occlusion of ipsilateral middle cerebral and common carotid arteries. The evolution of magnetic resonance imaging and histopathologic parameter changes was studied, both short term (1.5 to 8 hours) and long term (24 to 168 hours), in five specific brain regions within the middle cerebral artery territory.Results Significant changes in proton nuclear magnetic resonance spin-lattice and spin-spin relaxation times and the ''apparent'' diffusion coefficient of water could be detected within hours after the onset of permanent focal cerebral ischemia, whereas significant alterations in proton spin-density ratios were not apparent until approximately 48 hours. Histological changes were evident within 12 hours, with a significant loss of neurons seen in the most severely damaged regions at 7 days. Diffusion-weighted imaging was the most sensitive technique for visualizing acute ischemic alterations. The water diffusion coefficient was the only magnetic resonance imaging parameter studied to indicate significant alterations within the first 4 hours after arterial occlusion in all five brain regions.Conclusions The degree of change for a particular magnetic resonance imaging parameter appeared to be related to the location and extent of neuronal injury, with the most dramatic changes occurring within the areas displaying the most severe histological damage. These results indicate that complete specification of all brain regions affected by ischemic brain injury may require a combination of imaging strategies applied over a period of days and suggest the possibility of using magnetic resonance imaging to distinguish between permanent and reversible cell damage.

Dynamic Penumbra Demonstrated by Sequential Multitracer PET after Middle Cerebral Artery Occlusion in Cats

Abstract: Experimental models of focal cerebral ischemia have provided important data on early circulatory and biochemical changes, but typically their correspondence with metabolic and hemodynamic findings in stroke patients has been poor. To fill the gap between experimental studies at early time points and rather late clinical studies, we repeatedly measured CBF, CMRO2, oxygen extraction fraction (OEF), cerebral blood volume (CBV), and CMRglc in six cats before and up to 24 h after permanent middle cerebral artery (MCA) occlusion (MCAO), using the 15O steady state and [18F]fluorodeoxy-glucose methods and a high-resolution positron emission tomography (PET) scanner. Likewise, three sham-operated control cats were studied during the same period. Final infarct size was determined on serial histologic sections. In the areas of final glucose metabolic depression that were slightly larger than the histologic infarcts, mean CBF dropped to approximately 40% of control values immediately on arterial occlusion. If further decreased to < 20% during the course of the experiment. This progressive ischemia was most conspicuous in border zones. CMRO2 fell to a lesser degree (55%), eventually reaching approximately 25% of its control level. At early stages, OEF increased mainly in the center of ischemia. With time, areas of increased OEF moved from the center to the periphery of the MCA territory. Concurrently, progressive secondary decreases in OEF in conjunction with further reductions of CBF and CMRO2 indicated the development of central necrosis. The findings are highly suggestive of a dynamic penumbra. In five cats with complete MCA infarcts, CBF decreased and OEF increased in the contralateral hemisphere after 24 h, suggesting whole-brain damage. This effect may be explained by the widespread brain edema found histologically in addition to the nonspecific CBF reductions and OEF elevations observed also in the sham-operated controls after 1 day in the experimental condition. In one cat, cortical OEF increased only transiently. Normal CMRO2 and CMRglc were eventually restored, and the final infarct was small. This study demonstrates that acute regional pathophysiologic changes can be repeatedly assessed by multivariate PET in cats. Viable tissue can be detected up to several hours after MCA occlusion, and the transition of misery-perfused regions into necrosis or preserved tissue can be followed over time. The present results support the concept of a dynamic penumbra, in which for up to 24 h tissue damage spreads progressively from the center to the periphery of ischemia. Sequential high-resolution PET provides insight into the dynamics of regional pathophysiology and may thus further the development of rational therapeutic strategies.

The incidence and treatment of asymptomatic, unruptured cerebral aneurysms

Abstract: The importance of early detection by various radiological techniques of asymptomatic, unruptured aneurysms as a means of preventing subarachnoid hemorrhage (SAH) is discussed in this report. Four hundred volunteers underwent clinical and radiological evaluations between March, 1988, and September, 1992. Studies included a neurological examination as well as digital subtraction cerebral angiography via a femoral arterial catheter, computerized tomography, T1- and T2-weighted magnetic resonance (MR) imaging of the whole brain, and MR angiography. The evaluation revealed 27 asymptomatic, unruptured intracranial aneurysms in 26 volunteers, for an incidence of 6.5%. The subjects ranged in age from 39 to 71 years, with an average of 55 years. The aneurysms were located on the internal carotid artery in 13 cases (48%), the anterior communicating artery in six (22%), the middle cerebral artery in six (22%), and the basilar artery in two (7%). Aneurysms ranged in size from 5 mm or less in 16 cases, 6 to 10 mm in nine, and 11 to 15 mm in one; one aneurysm was more than 15 mm, with a maximum diameter of 2 cm. Volunteers with a family history of SAH within the second degree of consanguinity showed a higher incidence of aneurysms (17.9%). Aneurysm clipping was performed on 20 of the 26 cases with no significant morbidity or mortality. These findings support the contention that aggressive early detection of unruptured aneurysms may improve the outcome in patients harboring cerebral aneurysms by preventing the devastating effects of SAH.

L-arginine infusion promotes nitric oxide-dependent vasodilation, increases regional cerebral blood flow, and reduces infarction volume in the rat.

Abstract: We previously reported that L-arginine infusion increased pial vessel diameter by nitric oxide-dependent mechanisms, improved regional cerebral blood flow (rCBF) distal to middle cerebral artery (MCA) occlusion, and reduced infarction volume in spontaneously hypertensive rats when administered intraperitoneally before and after MCA occlusion. In this report we extend our findings (1) by examining the time course of L-arginine on rCBF and pial vessel diameter under basal conditions and on rCBF after MCA occlusion and (2) by reproducing the protective effect of L-arginine on infarct volume when given intravenously immediately after the onset of MCA occlusion in both normotensive and hypertensive models of focal cerebral ischemia.Changes in pial vessel diameter (closed cranial window) and rCBF (laser-Doppler flowmetry) were measured over time after L-arginine infusion into anesthetized Sprague-Dawley rats. rCBF was also measured distal to MCA occlusion in a brain region showing rCBF reductions in the range o...

Nitric Oxide Donors Increase Blood Flow and Reduce Brain Damage in Focal Ischemia: Evidence That Nitric Oxide is Beneficial in the Early Stages of Cerebral Ischemia

Abstract: We studied whether administration of nitric oxide (NO) donors reduces the ischemic damage resulting from middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats (SHRs). In halothane-anesthetized and ventilated SHRs, the MCA was occluded. CBF was monitored using a laser-Doppler flowmeter. Three to five minutes after MCA occlusion, the NO donors sodium nitroprusside (SNP; 3 mg/kg/h) or 3-morpholino-sydnonimine (SIN 1; 1.5–6 mg/kg/h) were administered into the carotid artery for 60 min. As a control, the effect of papaverine (3.6 mg/kg/h), a vasodilator that acts independently of NO, was also studied. The hypotension evoked by these agents was counteracted by intravenous infusion of phenylephrine. At the end of the infusion, rats were allowed to recover. Stroke size was determined 24 h later in thionin-stained sections. In sham occluded rats, SNP (n = 5), SIN 1 (n = 5), and papaverine (n = 5) produced comparable increases in CBF (p > 0.05 from vehicle). After MCA occlusion, SNP (n = 5) and ...

Induction of ischemic tolerance following brief focal ischemia in rat brain.

Abstract: The objective of this study was to determine whether brief focal ischemia induces ischemic tolerance in rat brain. Focal ischemia was produced in Wistar rats by occluding the middle cerebral artery (MCA) for 20 min at a distal site. Following recovery for 24 h, the animals were subjected to a 10-min episode of forebrain ischemia using a combination of bilateral carotid artery occlusion and systemic hypotension. Histologic injury, assessed after a survival period of 3–4 days, consisted of selective neuronal necrosis bilaterally in cerebral cortex, striatum, hippocampus, and thalamus superimposed upon a small cortical infarct adjacent to the site of MCA occlusion. However, the intensity of neuronal necrosis in the MCA territory of the neocortex ipsilateral to MCA occlusion was markedly less than that in the contralateral MCA cortex. In contrast, the extent of neuronal necrosis in subcortical structures was similar in both hemispheres Unexpectedly, animals in which the MCA was manipulated, but not occluded, ...

Spontaneous dissections of cervicocephalic arteries in childhood and adolescence

Abstract: Among 263 consecutive patients with spontaneous cervicocephalic arterial dissections evaluated at the Mayo Clinic, 18 (6.8%) were 18 years of age or younger (mean age, 12 years). The dissection involved the cervical arteries in 11 patients and the intracranial arteries in seven. Extracranially, the internal carotid artery was involved in eight patients, the vertebral artery in two, and both arteries in one. Intracranially, only the anterior circulation was affected. All the patients had cerebral or retinal ischemic symptoms, usually preceded by headache. Death occurred in a 13-year-old boy with intracranial arterial dissection and coarctation of the aorta. For the 17 remaining patients, the follow-up period ranged from 1 to 21 years. A complete or good clinical recovery occurred in 10 of the 11 patients with cervical arterial dissection but in only four of the seven with dissection of intracranial arteries. Recurrent arterial dissection occurred in two patients with cervical arterial dissections and in one patients with intracranial arterial dissection.

Cerebral microembolism in symptomatic and asymptomatic high‐grade internal carotid artery stenosis

Abstract: Using transcranial Doppler (TCD) ultrasonography in patients with high-grade (> or = 70%) internal carotid artery (ICA) stenosis, we examined the relation between the rate of TCD-detected silent microembolism of the ipsilateral middle cerebral artery and a history of recent ( or = 2/h had a positive predictive value of 0.88 for a history of recent symptoms. Our data suggest that TCD monitoring can provide reliable paraclinical evidence of "unstable ICA disease."

p53-immunoreactive protein and p53 mRNA expression after transient middle cerebral artery occlusion in rats.

Abstract: We investigated the temporal distribution of the p53-immunoreactive protein in conjunction with cellular damage and the expression of the p53 mRNA after focal cerebral ischemia in rats.Male Wistar rats (n = 66; controls, n = 7) were subjected to 2 hours of middle cerebral artery occlusion and were killed at various times of reperfusion (0.5 to 168 hours) for p53 immunohistochemistry and Northern blot analysis.A cellular expression of mutant p53-immunoreactive protein was found localized to anatomic sites exhibiting severe neuronal damage. A maximal induction of mutant p53-immunoreactive protein was found at 12 hours after reperfusion and subsequently declined. No wild-type p53 protein expression was detected after ischemia. A time-dependent expression of p53 mRNA was observed in both hemispheres. The peak level of p53 mRNA occurred at 24 hours after reperfusion.Our data indicate that the expressions of p53-immunoreactive protein and p53 mRNA are upregulated after transient focal cerebral ischemic insult i...

Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat).

Abstract: The progression from ischemic injury to pannecrosis that occurs in the rat brain several hours after occluding a large artery may be partly attributable to a worsening of the circulation through the microvessels. The objective of this study was to quantitate selected structural changes involving astrocytes and endothelial cells within an area of focal brain ischemia created by the occlusion of a middle cerebral artery. The magnitude of these structural changes was correlated with alterations in the patency to a circulating macromolecule through the microvessels (< or = 15 mu in diameter) located within the territory of the occluded artery. One hundred eighty-five adult male Wistar rats had the right middle cerebral artery occluded after threading a nylon monofilament through the external carotid artery. Experiments were terminated by either cardiovascular perfusion or decapitation and immersion fixation at intervals ranging between 30 minutes and 7 days after the arterial occlusion. Randomly selected animals from each experimental subgroup were injected intravenously with horseradish peroxidase (molecular weight 44 kd) approximately 20 minutes before death. The progressive decline in the area fraction comprised by the vessels filled with horseradish peroxidase was preceded at 30 to 60 minutes by an increase in the surface area occupied (on a cross-section of a microvessel) by endothelial cells (both nucleus and cytoplasm). This was followed by an increase of 23.7% in the mean diameter of astrocytes nuclei and a decrease of approximately 35% in lumenal surface of the microvessels. These observations suggest that the occlusion of a large cerebral artery causes prompt swelling of endothelial cells and astrocytes; both of these early biological responses may interfere with erythrocyte circulation and oxygen delivery, which (after the arterial occlusion) are entirely dependent on the circulation provided by the collateral arterial connections. Through its interference with microvascular patency and oxygen delivery, cell swelling may influence the rate at which neurons become necrotic. In this model of brain infarct the number of necrotic neurons peaks approximately 72 hours after middle cerebral artery occlusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Diffusion nuclear magnetic resonance imaging in experimental stroke. Correlation with cerebral metabolites.

Abstract: Diffusion-weighted nuclear magnetic resonance imaging has been shown to detect early ischemia-related alterations in experimental stroke. This raises the question of whether the observed increase in signal intensity is correlated with changes in cerebral metabolism. After middle cerebral artery occlusion, nuclear magnetic resonance diffusion images were recorded and compared with the regional concentration of cerebral metabolites and with histology of identical planes.Seven anesthetized Fischer rats were subjected to permanent occlusion of the middle cerebral artery. T1, T2, and diffusion images (b factors ranging from 0 to 1500 s/mm2) were measured in three to five planes after 7 hours. Thereafter, brains were frozen in situ for histology and quantitative bioluminescence imaging of ATP, glucose, lactate, and for fluorescence imaging of tissue pH.Seven hours after middle cerebral artery occlusion, the apparent diffusion coefficient was reduced from 615 +/- 97 x 10(-6).mm2.s-1 (contralateral brain) to 359 ...

Transcranial color-coded sonography of the basal cerebral circulation. Reference data from 115 volunteers.

Abstract: Transcranial color-coded sonography is a new development in noninvasive cerebral vascular imaging. Reference data using this technique are described. Blood velocities and pulsatility and resistance indices were determined in the anterior cerebral, middle cerebral, posterior cerebral, vertebral, and basilar arteries in 115 volunteers after correction for the angle of insonation. Of 1265 basal arterial segments, 1053 were insonated (83%). The vertebral (98%), basilar (92%), middle cerebral (84%), and posterior (P1) cerebral arteries (84%) were the most successfully insonated, with the anterior (73%) and posterior (P2) cerebral arteries (72%) the least successfully insonated. Mean and end-diastolic blood velocities decreased significantly with age in all vessels (middle cerebral artery mean velocity: 20 to 39 years, 74 cm/s [71-76]; > 60 years, 58 cm/s [55-61], P 60-year group. Velocities showed the least interhemispheric asymmetry in the middle cerebral artery (r = .85 and r = .83, peak and mean velocities, respectively) and the greatest asymmetry in the posterior (P2) cerebral artery (r = .58 and r = .59, peak and mean velocities, respectively). Pulsatility and resistance indices increased significantly with age in all vessels (middle cerebral artery pulsatility index: 20 to 39 years, 0.84 [0.82-0.87], > 60 years, 0.97 [0.93-1.02], P 60 years, 0.62 [0.60-0.64], P < .0001). Transcranial color-coded sonography can image the basal cerebral arteries and distinguish vertebral from basilar artery flow and enables pulsed Doppler interrogation with correction for the angle of insonation.

Induction of c-fos, junB, c-jun, and hsp70 mRNA in cortex, thalamus, basal ganglia, and hippocampus following middle cerebral artery occlusion

Abstract: Middle cerebral artery (MCA) occlusion in halothane-anesthetized rats induced c-fos, junB, and c-jun immediate early gene mRNAs and hsp70 heat shock gene mRNA in brain. In situ hybridization studies showed that c-fos and junB were induced throughout all of the cortex at 1 and 4 h following MCA occlusion. hsp70 was induced in the core and margins of the MCA ischemia. By 24 h, there was little expression of c-fos, junB, c-jun, and hsp70 in the core of the MCA infarct; there was modest induction of hsp70 at the margins of the infarct; and there was diffuse induction of c-fos, junB, and c-jun in all of the cortex outside the infarct. MCA occlusion also induced these genes in subcortical structures. c-fos, junB, and hsp70 were induced in ipsilateral medial striatum, most of thalamus including medial and lateral geniculate nuclei, substantia nigra, and hippocampus. Most of these structures, except for the striatum, are not supplied by the MCA. These data show that changes in gene expression can occur in regions remote from an infarction.

Delayed induction of mild hypothermia to reduce infarct volume after temporary middle cerebral artery occlusion in rats

Abstract: Deep to moderate hypothermia (24 degrees to 30 degrees C) during focal cerebral ischemia reduces infarct volume but must be initiated before the onset of ischemia to be effective and has deleterious pulmonary, myocardial and neurological effects. It is not known whether mild hypothermia (32 degrees to 33 degrees C) protects against ischemic neuronal damage, whether hypothermia induced after the onset of ischemia has protective effects, or whether these effects are associated with alterations in cortical blood flow. In this study, mild whole-body hypothermia was induced in rats just before or 10, 30, or 60 minutes after the onset of 2 hours of temporary middle cerebral artery occlusion; rewarming began immediately after reversal of occlusion and normothermia was maintained throughout 22 hours of reperfusion. Infarct volume, measured 24 hours after the end of reperfusion, was significantly smaller in rats made hypothermic within 30 minutes after the onset of ischemia than in normothermic controls; hypothermia induced at 60 minutes of ischemia did not reduce infarct volume. Cortical blood flow, measured by laser Doppler ultrasound flowmetry, was not significantly different between groups during ischemia; however, postischemic cortical blood flow correlated positively with total infarct volume. These results indicate that mild hypothermia initiated during temporary focal ischemia in rats can reduce infarct volume without attenuating the reduction in cortical blood flow.

Blood Flow in Major Cerebral Arteries Measured by Phase-Contrast Cine MR

Abstract: PURPOSE To measure mean blood flow in individual cerebral arteries (carotid, basilar, anterior cerebral, middle cerebral, and posterior cerebral) using a cine phase contrast MR pulse sequence. METHODS Ten healthy volunteers (22 to 38 years of age) were studied. The cine phase-contrast section was positioned perpendicular to the vessel of interest using oblique scanning planes. This pulse sequence used a velocity encoding range of 60 to 250 cm/sec. From the velocity and area measurements on the cine images, mean blood flow was calculated in milliliters per minute and milliliters per cardiac cycle. In the same subjects, transcranial Doppler measurements of blood velocity in these same vessels were also obtained. RESULTS There was no difference in blood flow in the paired cerebral arteries. Carotid arteries had mean blood flow in the range of 4.8 +/- 0.4 ml/cycle, the basilar artery 2.4 +/- 0.2 ml/cycle, the middle cerebral artery 1.8 +/- 0.2 ml/cycle, the distal anterior cerebral artery 0.6 +/- 0.1 ml/cycle, and the posterior cerebral artery 0.8 +/- 0.1 ml/cycle. Overall, there was poor correlation between MR-measured and transcranial Doppler-measured peak velocity. CONCLUSION Although careful attention to technical detail is required, mean blood flow measurements in individual cerebral vessels is feasible using a cine phase-contrast MR pulse sequence.