Middle Cerebral Artery Occlusion Time Research Articles

Identification of dynamic co-expression networks in peripheral blood of rats after middle cerebral artery occlusion

To identify the time dependent profiles of gene expression and featured co-expression network modules in peripheral blood of rats after middle cerebral artery occlusion (MCAO). Microarray GSE119121 from GEO database was analyzed by R language to identify the significantly changed genes in peripheral blood at different time points (0, 1, 2, 3, 6 and 24 h) after MCAO. Gene expression patterns at different time courses were screened by STEM tools. Then, function annotation and pathway enrichment of differentially expressed genes (DEGs) were performed using the Gene Ontology (GO) database and the Kyoto Gene and Genomic Encyclopedia (KEGG) database. Depending on CEMiTool package, gene expression profile matrix was inputted into R to construct the co-expression networks and to analyze modules, and enrichment analysis was conducted to evaluate the correlation between the modules and different time points. Comparing with gene at 0 h, the numbers of DEGs in peripheral blood at different time points after MCAO were 163 (1 h), 502 (2 h), 527 (3 h), 550 (6 h), and 75 (24 h), respectively. Moreover, a total of 38 gene expression patterns were enriched, and pattern 65 and pattern 34 were specifically up-regulated or down-regulated at 2-6 h. Hp, Nos2, P2ry10, and Klf12 were representative genes of these two models. The co-expression network module analysis showed that the gene status in the early acute phase (1-6 h) was positively correlated with the Module 2. Module 3 and Module 4 was positively correlated with phase phase 1-3 h and 2-6 h, respectively. Noteworthy, Module 6 gradually changed from positive correlation (0-2 h) to negative correlation (3-24 h) with the MCAO time course, and Module 6 was mainly related to viral response and innate immune response. The hub genes of Module 6 included Mx1, Mx2, and Rtp4. Our study has identified the featured genes and dynamic co-expression network modules in peripheral blood after acute ischemic stroke, which provides a potential basis for judging the onset time of ischemic stroke.

Therapeutic Vaccine Against S100A9 (S100 Calcium-Binding Protein A9) Inhibits Thrombosis Without Increasing the Risk of Bleeding in Ischemic Stroke in Mice.

Decreased adherence to daily ingestion of antiplatelet drugs is a critical issue, increasing mortality and morbidity in poststroke patients. As vaccination could be a promising approach to solving this, we designed an antiplatelet vaccine that inhibited S100A9 (S100 calcium-binding protein A9)/CD36 (cluster of differentiation 36) signaling in platelets, which was reported to be a key signal in arterial thrombosis, but not hemostasis. Immunization with this vaccine induced a sustainable increase in the anti-S100A9 antibody titer for >2 months and an additional booster immunization enhanced the antibody production further. The middle cerebral artery occlusion time was successfully prolonged in the vaccinated mice, which was comparable to that in mice treated with clopidogrel. The antithrombotic effect lasted for 84 days after the last vaccination, as well as after the booster immunization. Importantly, the bleeding time was not affected in the immunized mice. The antithrombotic effect was also observed in the common carotid artery, which was similar to that found in CD36-/- mice. Vascular injury increased the expression of S100A9 in the serum and phosphorylation of JNK (c-Jun N-terminal kinase) and VAV1 in the platelets, but these increases were inhibited in the immunized mice. Moreover, the S100A9 vaccine did not induce cell-mediated autoimmunity, as demonstrated by the enzyme-linked immunosorbent spot assay. Thus, immunization with the S100A9 vaccine resulted in long-term inhibition of thrombus formation through inhibition of increased S100A9/CD36 signaling without risk of bleeding or adverse autoimmune responses. Vaccination against S100A9 might be a novel therapy to prevent recurrent ischemic stroke.

Abstract WMP44: Functional Recovery Following a Combination of Thrombin Inhibitor Argatroban and Tissue Plasminogen Activator (tPA) in Thromboembolic Stroke in Nonhuman Primates

Introduction: Early treatment following an acute stroke with the thrombolytic tissue plasminogen activator (tPA) increases functional recovery. Complications of tPA treatment include hemorrhaging and narrow therapeutic time window. Thus, better treatments for acute stroke are needed. While a number of novel treatments for acute ischemic stroke have been derived from preclinical rodent stroke models, to date, none have succeeded in clinical studies. Nonhuman primates are phylogenetically closer to humans than rodents, which could narrow the current translational shortfall between preclinical and clinical findings. The goal of the current study was to test the effect of a combination of argatroban, a thrombin inhibitor, and tPA on functional recovery and brain infarction size following thromboembolic ischemia in nonhuman primates. Methods: Autologous blood clots were injected into the internal carotid artery of cynomolgus macaques to induced a thromboembolic stroke. Either tPA (0.9 mg/kg; n = 8) or vehicle (n = 8) was intravenously infused for one hour an hour following the induction of ischemia. In a third group, after completion of tPA infusion, argatroban (0.6 mg/kg; n= 7) was intravenously infused for 22 hours. Doppler ultrasound recorded middle cerebral artery (MCA) blood flow for six hours following induction of stroke. In addition, brain infarct volume (TTC staining) and functional assessment (Neurologic Deficit Score; NDS) were determined 24 hours after ischemia. Results: Compared to vehicle treatment, tPA treatment significantly decreased MCA occlusion time, brain infarct volume and NDS. Treatment with the combination of argatroban and tPA decreased occlusion time, brain infarct volume and NDS similar to tPA treatment alone. Conclusion: The current study suggests that the addition of argatroban could enhance recanalization rates observed with tPA treatment alone. However, in contrast to previous findings in rats, the combination of argatroban and tPA does not appear to further enhance tissue or functional recovery from a thromboembolic stroke compared to tPA treatment alone.

Automated end-to-side anastomosis to the middle cerebral artery with C-Port xA: A feasibility study on human cadavers

Background:Anastomosis to the superficial temporal artery is suitable in patients with functional and structural impairment of the middle cerebral artery (i.e., complex aneurysms and skull base tumors), as either definitive treatment or an additional safety measure. A shorter occlusion time or a non-occlusive technique is expected to reduce the risk of cerebral ischemia following the procedure. In this cadaver study, we assessed the fitness of C-Port xA® device for use in superficial temporal artery (STA)–middle cerebral artery (MCA) bypass.Materials and Methods:Seven fixed human head specimens were prepared through eight pterional craniotomies. The superficial temporal artery was dissected and the sylvian fissure was opened to access the MCA. The C-Port xA was tested on each of the eight exposures. We recorded the lengths of both donor and recipient vessel, the durations of the procedure and the craniotomy, and sylvian scissure opening sizes. The bypass was then assessed by pressure injection of methylene blue in the donor vessel.Results:C-Port xA-assisted STA–MCA anastomosis was successfully accomplished in seven dissections. A minimum STA length of 7 cm, a sylvian scissure opening larger than 5 cm, and a craniotomy size of at least 6 × 6 cm appeared to be the requisites for a safe maneuverability of the device. The MCA occlusion time lasted in all cases less than 4.5 min, and we observed a clear improvement in time performance with growing experience.Conclusions:The results suggest that the C-Port xA device is suitable for STA–MCA bypass. We experienced a shorter occlusion time and a shorter learning curve compared to conventional techniques. Further miniaturization and special adaptation of this device may allow a future application even to deeper intracranial vessels. Clinical trials will have to assess the long-term results and benefits of this minimal occlusive technique.

K-134, a Phosphodiesterase 3 Inhibitor, Prevents Brain Damage by Inhibiting Thrombus Formation in a Rat Cerebral Infarction Model

BackgroundK-134 is a more potent antiplatelet drug with a selective inhibitory effect on phosphodiesterase 3 (PDE3) compared with its analogue, cilostazol.ObjectivesThis study was performed to compare the ameliorating effects of K-134 and cilostazol on brain damage in an experimental photothrombotic cerebral infarction model.Methods and ResultsWe investigated the effects of oral preadministration of PDE3 inhibitors in a rat stroke model established by photothrombotic middle cerebral artery (MCA) occlusion. K-134 significantly prolonged MCA occlusion time at doses >10 mg/kg, and reduced cerebral infarct size at 30 mg/kg in the stroke model (n = 12, 87.5±5.6 vs. 126.8±7.5 mm3, P<0.01), indicating its potent antithrombotic effect. On the other hand, the effects of cilostazol on MCA occlusion time and cerebral infarct size are relatively weak even at the high dosage of 300 mg/kg. Furthermore, K-134 blocked rat platelet aggregation more potently than cilostazol in vitro. Also in an arteriovenous shunt thrombosis model, K-134 showed an antithrombotic effect greater than cilostazol.ConclusionsThese findings suggest that K-134, which has strong antithrombotic activity, is a promising drug for prevention of cerebral infarction associated with platelet hyperaggregability.

Hypoxia-Inducible Factor-1&amp;#945; Contributes to Brain Edema after Stroke by Regulating Aquaporins and Glycerol Distribution in Brain

Brain edema following stroke is a critical clinical problem due to its association with increased morbidity and mortality. Despite its significance, present treatment for brain edema simply provides symptomatic relief due to the fact that molecular mechanisms underlying brain edema remain poorly understood. The present study investigated the role of hypoxia-inducible factor-1α (HIF-1α) and aquaporins (AQP-4 and -9) in regulating cerebral glycerol accumulation and inducing brain edema in a rodent model of stroke. Two-hours of middle cerebral artery occlusion (MCAO) followed by reperfusion was performed in male Sprague-Dawley rats (250-280 g). Anti-AQP-4 antibody, anti-AQP-9 antibody, or 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1α) was given at the time of MCAO. The rats were sacrificed at 1 and 24 hours after reperfusion and their brains were examined. Extracellular and intracellular glycerol concentration of brain tissue was calculated with an enzymatic glycerol assay. The protein expressions of HIF-1α, AQP-4 and AQP-9 were determined by Western blotting. Brain edema was measured by brain water content. Compared to control, edema (p < 0.01), increased glycerol (p < 0.05), and enhanced expressions of HIF-1α, AQP-4, and AQP-9 (p < 0.05) were observed after stroke. With inhibition of AQP-4, AQP-9 or HIF-1α, edema and extracellular glycerol were significantly (p < 0.01) decreased while intracellular glycerol was increased (p < 0.01) 1 hour after stroke. Inhibition of HIF-1α with 2ME2 suppressed (p < 0.01) the expression of AQP-4 and AQP-9. These findings suggest that HIF-1α serves as an upstream regulator of cerebral glycerol concentrations and brain edema via a molecular pathway involving AQP-4 and AQP-9. Pharmacological blockade of this pathway in stroke patients may provide novel therapeutic strategies.

Effect of vineatrol in focal cerebral ischemia in rats

The present study was carried out to examine the effect of administration of vineatrol in the middle cerebral artery (MCA) occlusion model of stroke in rats. Rats were anesthetized using chloral hydrate (400 mg/kg i.p.) and subjected to 2 h of transient MCA occlusion. Vineatrol was administered at doses of 10, 20 and 40 mg/kg i.p. to different groups. In total, four injections of vineatrol were given, i.e., at the time of MCA occlusion, 1 h after MCA occlusion, at the time of reperfusion and 30 min after reperfusion. Neurological deficit and motor performance tests (grip, foot fault, rotarod performance, spontaneous locomotor activity tests) were carried out 24 h after MCA occlusion. Thereafter, the rats were sacrificed to estimate markers of oxidative stress: malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD). A vehicle-treated group was also run in parallel. Vineatrol at the dose of 10 mg/kg i.p. neither improved neurological deficits nor decreased the elevated level of MDA compared with vehicle-treated MCA-occluded rats. However, higher doses of vineatrol (20 and 40 mg/kg i.p.) afforded significant protection, as shown by the increase in scoring on motor performance tests and significant attenuation of the elevated MDA level observed after MCA occlusion. Levels of GSH and SOD were significantly increased. The results demonstrate that administration of vineatrol is able to reduce the neuronal damage caused by focal ischemia in the MCA occlusion model of stroke in rats.

Plasminogen activator inhibitor-1 contributes to the deleterious effect of obesity on the outcome of thrombotic ischemic stroke in mice.

It is widely accepted that obesity is a risk factor for ischemic heart disease, but the association with stroke is less clear. Adipose tissue is an important source of plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of plasminogen activation. To test the hypothesis that elevated PAI-1 levels associated with obesity negatively affect the outcome of thrombotic ischemic stroke. Middle cerebral artery (MCA) occlusion was induced photochemically in mice with nutritionally induced or genetically determined obesity and their lean counterparts. The MCA occlusion time (to obtain complete occlusion) was significantly shorter in obese (nutritionally induced) than in lean wild-type (WT) C57Bl/6 mice, whereas the infarct size was significantly larger and intracranial hemorrhage (ICH) was enhanced (all P < 0.05). Similar observations were made in genetically obese ob/ob mice, as compared to lean WT littermates. In both strains, obesity was associated with markedly elevated circulating PAI-1 levels, probably originating from the fat tissue. In contrast, PAI-1-deficient lean and obese mice did not display significant differences in MCA occlusion time, infarct volume or ICH. Plasminogen activator inhibitor-1 may play a functional role in the deleterious effect of obesity on the outcome of thrombotic ischemic stroke in mice.

Restoration of middle cerebral artery thrombosis by novel glycoprotein IIb/IIIa antagonist FK419 in guinea pig

We compared the antithrombotic efficacy of FK419 [( S)-2-acetylamino-3-[( R)-[1-[3-(piperidin-4-yl)propionyl]piperidin-3-ylcarbonyl]amino] propionic acid trihydrate], a novel nonpeptide glycoprotein IIb/IIIa antagonist, with recombinant tissue plasminogen activator (rt-PA) and other antithrombotic agents (aspirin, ozagrel, argatroban and heparin). FK419 not only inhibited ADP- and collagen-induced guinea pig platelet aggregation, but also induced disaggregation for ADP-induced aggregated platelets in vitro. In the photochemically induced middle cerebral artery thrombosis model in guinea pigs, FK419 dose-dependently shortened the time to first reperfusion and the total middle cerebral artery occlusion time and reduced ischemic brain damage and ameliorated neurological deficits measured 24 h after middle cerebral artery occlusion. Rt-PA similarly improved the middle cerebral artery patency, brain damage and neurological deficits. Neither aspirin, ozagrel, argatroban nor heparin restored the middle cerebral artery blood flow and improved the brain damage or neurological deficits. These results demonstrated that novel glycoprotein IIb/IIIa antagonist FK419 could disperse thrombus and ameliorated ischemic brain damage, suggesting that FK419 would be an attractive intervention for stroke patients.

Tamoxifen, a Selective Estrogen Receptor Modulator, Reduces Ischemic Damage Caused by Middle Cerebral Artery Occlusion in the Ovariectomized Female Rat

Previous work has demonstrated that physiological concentrations of 17β-estradiol can protect the female rat brain against middle cerebral artery occlusion (MCAO)-induced ischemic damage. The present study examined whether therapeutic doses of the clinically relevant selective estrogen receptor modulator (SERM), tamoxifen, can similarly protect the female rat brain against ischemic stroke damage. Adult female rats were bilaterally ovariectomized and implanted subcutaneously with either a placebo or tamoxifen time-release pellet (0.1, 0.8 or 2.4 mg/kg/day). One week later, the animals underwent permanent MCAO to assess the protective ability of the different tamoxifen doses on brain infarct size. As expected, MCAO produced a large infarct (∼53%) of the affected cerebral hemisphere in placebo (control) animals. The 0.1 mg/kg/day dose of tamoxifen did not exhibit any significant protective effects, however; the 0.8 and 2.4 mg/kg/day doses of tamoxifen, which are in the therapeutic range, dramatically reduced infarct of the affected cerebral hemisphere (∼70% reduction) as compared to the controls. The reduction of infarct size was primarily due to protection of two major structures, the cerebral cortex and striatum. Laser Doppler analysis further revealed that tamoxifen had no significant effect on cerebral blood flow either before or after MCAO, suggesting that tamoxifen protection is independent of cerebral blood flow changes. Further studies showed that tamoxifen pellets implanted at the time of MCAO did not reduce infarct size, suggesting that pretreatment with tamoxifen is necessary to observe a protective effect. These studies suggest that clinically important SERMs may have an additional unrecognized beneficial effect of protection of the female brain.

Protective effect of adenosine against neuronal injury induced by middle cerebral artery occlusion in rats as evidenced by diffusion-weighted imaging

In the present study, adenosine, an inhibitory neuromodulator, was studied in male Wistar rats subjected to 2 h of transient middle cerebral artery (MCA) occlusion. Adenosine (500 mg/kg ip) was administered twice—once at the time of MCA occlusion and again at the time of reperfusion—and evaluated for its protective effect by using diffusion-weighted imaging (DWI) (30 min after reperfusion). After the DWI experiments, one group of animals was euthanized 2 h after reperfusion for the estimation of oxidative stress markers, while in another group, neurological deficit was assessed 24 h after MCA occlusion. In the adenosine-treated group, percent hemispheric lesion area (%HLA) in DWI was significantly attenuated (11.7±5.2) as compared to vehicle-treated group (21.4±4.7). The level of malondialdehyde (MDA) (301.8±22 nmol/g wet tissue) in the adenosine-treated group was significantly decreased as compared to that in the vehicle-treated MCA-occluded rats (420±20 nmol/g wet tissue). An insignificant change was observed in the levels of glutathione in both the vehicle-treated MCA-occluded and the adenosine-treated groups. The neurological deficit was significantly improved in the adenosine-treated group (1.8±0.06) as compared to the vehicle-treated (2.9±0.38) group. This is the first study to demonstrate the effectiveness of adenosine using DWI in the MCA-occluded rats.

Abstracts of literature

Abstracts of literature

A Newin VivoMethod for Quantitative Analysis of Stroke Lesions Using Diffusion-Weighted Magnetic Resonance Microscopy

Using three-dimensional diffusion-weighted MR microscopy and a rat model of focal cerebral ischemia, we evaluated the statistical characteristics of two parameters:absolutestroke volumes andchangein stroke volumes over 6 h of middle cerebral artery (MCA) occlusion. In all rats, the absolute stroke volumes increased linearly over the 6-h MCA occlusion time period. On average, stroke volume growth rate was 2.1 ± 0.5%/h. Sample size power analysis of our data demonstrated that to demonstrate a 10% reduction of the 6-h volumes, sample size per group would require 29 animals (these calculations are based on α=0.05, β=0.20 using normal approximation). A similar 30% reduction of stroke volume at 6 h poststroke (from ≈200 to 140 mm3) would, in our “slope model,” translate into a reduction of stroke growth rate from the normal +11.25 mm3/h (150 to 200 mm3over 4 h) to 7 mm3/h (150 to 178 mm3over 4 h); power analysis in this case demonstrated that sample size is reduced to 15 animals per group (these calculations are based on α=0.05, β=0.20 using normal approximation). We conclude that from a statistical standpoint our study demonstrates that strokegrowth ratemight be a more suitable parameter for evaluating the effect of treatment in both clinical and experimental stroke trials.

Anti-ischaemic efficacy of a nitric oxide synthase inhibitor and a N-methyl-D-aspartate receptor antagonist in models of transient and permanent focal cerebral ischaemia.

1. We have recently developed a new model of transient focal ischaemia in the rat utilising topical application of endothelin-1 to the left middle cerebral artery (MCA). In order to validate this approach the present study assessed the neuroprotective efficacy of the NMDA receptor antagonist dizocilpine (MK-801) in the endothelin-1 model. The anti-ischaemic efficacy of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was subsequently evaluated, and contrasted with its efficacy against permanent focal ischaemia, to determine the utility of the endothelin-1 model for identification of novel pharmacoprotective agents. 2. MK-801 (0.12 mg kg-1 bolus, 108 micrograms kg-1 h-1 infusion i.v., either 1 or 2.5 h pre-transient MCA occlusion (MCAO)) induced hypotension that persisted for approximately 1.5 h so that mean arterial blood pressure (MABP) at the time of MCAO was significantly lower in the 1 h group compared with control (MABP: 86 +/- 11, 68 +/- 6 and 84 +/- 4 mmHg (mean +/- s.d.) for saline, 1 h MK-801 and 2.5 h MK-801 groups respectively). The 2.5 h pretreatment schedule resulted in significant reduction (71%) in the volume of hemispheric damage (assessed 4 h post onset of ischaemia) while the 1 h pretreatment schedule did not (volumes of hemispheric damage: 59 +/- 38, 51 +/- 51 and 17 +/- 28 mm3 for saline, 1 h and 2.5 h MK-801 groups). 3. Thus the considerable neuroprotective effect of MK-801 in the endothelin-1 model of transient focal cerebral ischaemia was highly sensitive to drug-induced hypotension. This result is in contrast to previous studies of permanent MCAO where MK-801-induced hypotension did not compromise its neuroprotective action.4. L-NAME (3 mg kg-1, i.v. 30 min pre-MCAO) moderately, but significantly, reduced (16%) the volume of ischaemic damage 4 h post-permanent MCA occlusion, whereas the 29% reduction in volume of damage achieved in the model of transient focal ischaemia did not attain significance due to the greater variability associated with this model. L-NAME did not significantly alter MABP in either model.5. The modest neuroprotection achieved with NO synthase inhibition suggests NO is of relatively minor importance as a mediator of neurotoxicity following permanent focal cerebral ischaemia. In addition the comparable efficacy of L-NAME against transient focal ischaemia suggests the presence of reperfusion does not enhance the contribution of NO to neuronal injury in the acute (4 h) phase following a focal ischaemic insult.

Treatment of Acute Focal Cerebral Ischemia with Concentrated Albumin

The object of the investigation was to study the effects of concentrated albumin upon the evolution of cerebral infarction. Twenty adult cats lightly anesthetized with ketamine hydrochloride underwent right middle cerebral artery (MCA) occlusion for 6 hours. Ten cats were not treated and 10 cats received concentrated (i.e., 25 g/100 ml) human serum albumin (5 ml/kg i.v.) at the time of MCA occlusion. The blood volume increased 30 to 40% in the cats receiving concentrated albumin. The hematocrit fell for 32 +/- 5% (SD) before occlusion to 23 +/- 6% at 2.5 hours after occlusion in treated cats, whereas the hematocrit in untreated cats remained stable at 35 +/- 5. Regional cerebral blood flow (rCBF) changes in the right sylvian region were similar in the untreated and treated groups. The mean rCBF before occlusion was 42 +/- 11 ml/100 g/minute in the untreated cats and 44 +/- 8 ml/100 g/minute in the treated cats. Untreated and treated cats had similar reductions of rCBF in the right sylvian region to less than or equal to 18 ml/100 g/minute at some point after occlusion. An index of erythrocyte flow and microcirculatory resistance was determined by measuring the transit of 99Tc-labeled erythrocytes in the right sylvian region. The erythrocyte transit time before occlusion was 10 +/- 2 seconds in the untreated group and 9 +/- 1 seconds in the treated group. After 6 hours, the erythrocyte transit was 19 +/- 3 seconds in the untreated group and 15 +/- 3 seconds in the treated group (p less than or equal to 0.1), suggesting that less microcirculatory impairment occurred in some treated cats. Electroencephalographic changes during the initial 3 hours of occlusion were less severe in the treated cats than in the untreated cats, suggesting that the collateral flow in the border zone of the MCA territory initially may have been improved by treatment. Impairment of carbon perfusion, ischemic edema, and neuronal alterations after 6 hours of occlusion were the same in both groups. Increased permeability of the blood-brain barrier to Evans blue dye, however, was more marked in the treated group. The findings of the study indicate that concentrated albumin does not substantially modify the evolution of cerebral infarction.

Treatment of acute focal cerebral ischemia with concentrated albumin

The object of the investigation was to study the effects of concentrated albumin upon the evolution of cerebral infarction. Twenty adult cats lightly anesthetized with ketamine hydrochloride underwent right middle cerebral artery (MCA) occlusion for 6 hours. Ten cats were not treated and 10 cats received concentrated (i.e., 25 g/100 ml) human serum albumin (5 ml/kg i.v.) at the time of MCA occlusion. The blood volume increased 30 to 40% in the cats receiving concentrated albumin. The hematocrit fell from 32 ± 5% (SD) before occlusion to 23 ± 6% at 2.5 hours after occlusion in treated cats, whereas the hematocrit in untreated cats remained stable at 35 ± 5%. Regional cerebral blood flow (rCBF) changes in the right sylvian region were similar in the untreated and treated groups. The mean rCBF before occlusion was 42 ± 11 ml/100 g/minute in the untreated cats and 44 ± 8 ml/100 g/minute in the treated cats. Untreated and treated cats had similar reductions of rCBF in the right sylvian region to ≤18 ml/100 g/minute at some point after occlusion. An index of erythrocyte flow and microcirculatory resistance was determined by measuring the transit of 99Tc-labeled erythrocytes in the right sylvian region. The erythrocyte transit time before occlusion was 10 ± 2 seconds in the untreated group and 9 ± 1 seconds in the treated group. After 6 hours, the erythrocyte transit was 19 ± 3 seconds in the untreated group and 15 ± 3 seconds in the treated group (p ≤ 0.1), suggesting that less microcirculatory impairment occurred in some treated cats. Electroencephalographic changes during the initial 3 hours of occlusion were less severe in the treated cats than in the untreated cats, suggesting that the collateral flow in the border zone of the MCA territory initially may have been improved by treatment. Impairment of carbon perfusion, ischemic edema, and neuronal alterations after 6 hours of occlusion were the same in both groups. Increased permeability of the blood-brain barrier to Evans blue dye. however, was more marked in the treated group. The findings of the study indicate that concentrated albumin does not substantially modify the evolution of cerebral infarction. (Neurosurgery 9:552-558, 1981)