A new method for superselective middle cerebral artery infusion in the rat

2007 ◽  
Vol 106 (5) ◽  
pp. 872-878 ◽  
Author(s):  
Johannes Woitzik ◽  
Lothar Schilling
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Autologous Blood ◽  
Extended Period ◽  
Drug Uptake ◽  
Doppler Flowmetry ◽  
Flow Through ◽  
Intravascular Occlusion

Object Selective intraarterial drug delivery is used to achieve enhanced local uptake with reduced systemic side effects. In the present paper the authors describe and characterize a new microcatheter-based model of superselective perfusion of the middle cerebral artery (MCA) in rats combined with blockade of blood flow through the MCA. Methods Selectivity of administration was shown by infusion of Evans blue which diffusely stained the MCA territory, indicating an increased permeability of the blood–brain barrier during the blockade of blood flow to the MCA. Perfusion of autologous blood through the microcatheter resulted in a flow rate–related increase in the cerebral blood flow measured by laser Doppler flowmetry. Similarly, infusion of an artificial O2 carrier, Oxycyte, was accompanied by an increase in tissue oxygenation as measured using a Licox sensor. Blockade of blood flow to the MCA with the new microcatheter for an extended period of time resulted in the development of ischemia, which was comparable to that induced by intravascular occlusion using a silicone-coated thread. In a 24-hour MCA occlusion model, selective administration of a low dose of MK-801 (0.3 mg/kg body weight) resulted in a significantly smaller infarct volume than systemic application (339 ± 53 mm3 compared with 508 ± 26 mm3, p < 0.001). Conclusions This new model of superselective MCA infusion is a valuable tool for investigating the effect of selective delivery and enhanced drug uptake into cerebral ischemic tissue. Without constant blockade of blood flow through the MCA it may also be useful for enhanced drug uptake, gene transfer, or application of stem cells in other neuro-pathological conditions.

Studies of collateral perfusion to canine middle cerebral artery territory

1990 ◽  
Vol 259 (2) ◽  
pp. H560-H566 ◽  
Author(s):  
C. M. Loftus ◽  
G. M. Greene ◽  
K. N. Detwiler ◽  
G. L. Baumbach ◽  
D. D. Heistad
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Autologous Blood ◽  
Base Line ◽  
Collateral Flow ◽  
Area At Risk ◽  
Risk Area ◽  
Anatomical Basis

Previous studies of intracranial collateral circulation have not distinguished between true "collateral" blood flow (flow to a region that occurs only when a primary artery is occluded) and "overlap" flow (flow to a region that is present under both normal and demand conditions). These experiments had three purposes: 1) to identify tissues that were truly collateral dependent, 2) to determine potential for true collateral flow in the absence of overlap flow, and 3) to determine whether an anatomical basis for overlap flow could be demonstrated. Branches (700-900 microns) of the dog middle cerebral artery (MCA) were perfused with autologous blood. The perfused region, which was the area at risk, was identified by intravenous injection of neutral red dye. Microspheres were used to measure regional cerebral blood flow (rCBF). Overlap flow was determined by perfusion of the artery with microsphere-free blood. True collateral flow (total rCBF minus overlap flow) was determined by analysis of rCBF to the risk area after cessation of vessel perfusion. Most of the risk area had substantial levels of overlap flow (about one-third of base line). In the center of the area at risk, the true collateral-dependent area was identified [mean overlap flow 4 +/- 1 (mean +/- SE) ml.min-1.100 g-1], which had high levels of perfusion from collateral vessels (102 +/- 14) within 30 s of vascular occlusion. Microfil injection into two adjacent MCA branches showed discrete borders between vascular territories, with no overlapping vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Modeling of the Human Cerebral Collateral Circulation: Evaluation of the Impact on the Cerebral Perfusion in Case of Ischemic Stroke

2019 ◽  
Vol 5 (1) ◽  
pp. 533-536
Author(s):  
Lorena Krames ◽  
Rosa Daschner ◽  
Yannick Lutz ◽  
Axel Loewe ◽  
Olaf Dössel ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Collateral Circulation ◽  
Treatment Method ◽  
Developed Countries ◽  
Extended Model ◽  
Flow Through ◽  
The Impact

AbstractStroke is the third-most cause of death in developed countries. A new promising treatment method in case of an ischemic stroke is selective intracarotid blood cooling combined with mechanical artery recanalization. However, the control of the treatment requires invasive or MRI-assisted measurement of cerebral temperature. An auspicious alternative is the use of computational modeling. In this work, we extended an existing 1D hemodynamics model including the characteristics of the anterior, middle and posterior cerebral artery. Furthermore, seven ipsilateral anastomoses were additionally integrated for each hemisphere. A potential stenosis was placed into the M1 segment of the middle cerebral artery, due to the highest risk of occlusion there. The extended model was evaluated for various degrees of collateralization (“poor”, “partial” and “good”) and degrees of stenosis (0%, 50%, 75% and 99.9%). Moreover, cerebral autoregulation was considered in the model. The higher the degree of collateralization and the degree of stenosis, the higher was the blood flow through the collaterals. Hence, a patient with a good collateralization could compensate a higher degree of occlusion and potentially has a better outcome after an ischemic stroke. For a 99.9% stenosis, an increased summed mean blood flow through the collaterals of +97.7% was predicted in case of good collateralization. Consequently, the blood supply via the terminal branches of the middle cerebral artery could be compensated up to 44.4% to the physiological blood flow. In combination with a temperature model, our model of the cerebral collateral circulation can be used for tailored temperature prediction for patients to be treated with selective therapeutic hypothermia.

scholarly journals Cortical Negative DC Deflections following Middle Cerebral Artery Occlusion and KCl-Induced Spreading Depression: Effect on Blood Flow, Tissue Oxygenation, and Electroencephalogram

1994 ◽  
Vol 14 (1) ◽  
pp. 12-19 ◽  
Author(s):  
T. Back ◽  
K. Kohno ◽  
K.-A. Hossmann
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Spreading Depression ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Flow Response ◽  
Eeg Power ◽  
Oxygen Requirements ◽  
Cerebral Artery Occlusion

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 ∼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. The resulting episodes of relative hypoxia could explain the previously documented relationship between the number of depolarizations and infarct volume.

scholarly journals Effect of 20-HETE Inhibition on Infarct Volume and Cerebral Blood Flow after Transient Middle Cerebral Artery Occlusion

2008 ◽  
Vol 29 (3) ◽  
pp. 629-639 ◽  
Author(s):  
Marija Renic ◽  
Judith A Klaus ◽  
Tomohiro Omura ◽  
Naoya Kawashima ◽  
Michihito Onishi ◽  
...  
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Dienoic Acid ◽  
Artery Occlusion ◽  
Area At Risk

This study examined the effects of an inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis, N-(3-chloro-4-morpholin-4-yl)phenyl- N'-hydroxyimido formamide (TS-011), on infarct volume, volume at risk, cerebral blood flow (CBF), and levels of cytochrome P450 (CYP450) eicosanoids in the brain after transient occlusion of the middle cerebral artery (t-MCAO) in rats. TS-011 (0.1 mg/kg, iv) reduced cortical infarct volume by approximately 70% and total infarct volume by 55%. TS-011 had no effect on the volume at risk or CBF during or up to 30 mins after the ischemic period. TS-011 reduced the delayed fall in CBF seen 2 h after reperfusion. The levels of CYP450 eicosanoids were similar in the ischemic and contralateral hemispheres after t-MCAO. TS-011 reduced 20-HETE levels in cerebral tissue by 80% but had no effect on the levels of EETs. Administration of another 20-HETE inhibitor, HET0016 (0.01 to 1.0 mg/kg, iv) or a 20-HETE antagonist 20-hydroxyeicosa-6( Z),15( Z)-dienoic acid (10 mg/kg, iv) also reduced infarct size. These results indicate that inhibitors of the synthesis or vasoconstrictor effects of 20-HETE reduce infarct size in rats after cerebral ischemia. The effects of TS-011 are not associated with changes in the area at risk or CBF and may be because of a potential protective effect in neurons subjected to ischemic stress.

Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage

1995 ◽  
Vol 268 (1) ◽  
pp. R286-R292 ◽  
Author(s):  
C. Iadecola ◽  
F. Zhang ◽  
X. Xu
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Doppler Flowmetry ◽  
Spontaneously Hypertensive ◽  
Oxide Synthase

We sought to determine whether expression of the inducible, calcium-independent isoform of nitric oxide synthase (iNOS) contributes to the tissue damage produced by focal cerebral ischemia. The middle cerebral artery was occluded in halothane-anesthetized spontaneously hypertensive rats. Twenty-four hours later rats received intraperitoneal injections of the iNOS inhibitor aminoguanidine (100 mg/kg twice per day; n = 10) or of aminoguanidine + L-arginine (300 mg/kg four times per day; n = 7), aminoguanidine + D-arginine (n = 7), arginine alone (n = 6), or vehicle (n = 9). Drugs were administered for 3 consecutive days. Infarct volume was determined by image analysis in thionin-stained brain sections 4 days after induction of ischemia. Administration of aminoguanidine reduced infarct volume by 33 +/- 4% (P < 0.05 from vehicle; analysis of variance and Tukey's test), a reduction that was antagonized by coadministration of L- but not D-arginine. Administration of L-arginine alone did not affect infarct size (P > 0.05 vs. vehicle). In separate rats (n = 10), aminoguanidine attenuated calcium-independent NOS activity in the infarct (P < 0.05 vs. vehicle) without affecting calcium-dependent activity (P > 0.05). Aminoguanidine did not affect resting cerebral blood flow or the cerebrovascular vasodilation elicited by hypercapnia, as determined by laser-Doppler flowmetry (n = 4). We conclude that aminoguanidine selectively inhibits iNOS activity in the area of infarction and reduces the volume of the infarct produced by middle cerebral artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of early Sanguinate (PEGylated carboxyhemoglobin bovine) infusion on cerebral blood flow to the ischemic core in experimental middle cerebral artery occlusion

2021 ◽  
pp. neurintsurg-2021-018239
Author(s):  
Gregory A Christoforidis ◽  
Niloufar Saadat ◽  
Mira Liu ◽  
Yong Ik Jeong ◽  
Steven Roth ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Bolus Administration ◽  
Ischemic Core ◽  
Cerebral Artery Occlusion

BackgroundSanguinate, a bovine PEGylated carboxyhemoglobin-based oxygen carrier with vasodilatory, oncotic and anti-inflammatory properties designed to release oxygen in hypoxic tissue, was tested to determine if it improves infarct volume, collateral recruitment and blood flow to the ischemic core in hyperacute middle cerebral artery occlusion (MCAO).MethodsUnder an IACUC approved protocol, 14 mongrel dogs underwent endovascular permanent MCAO. Seven received Sanguinate (8 mL/kg) intravenously over 10 min starting 30 min following MCAO and seven received a similar volume of normal saline. Relative cerebral blood flow (rCBF) was assessed using neutron-activated microspheres prior to MCAO, 30 min following MCAO and 30 min following intervention. Pial collateral recruitment was scored and measured by arterial arrival time (AAT) immediately prior to post-MCAO microsphere injection. Diffusion-weighted 3T MRI was used to assess infarct volume approximately 2 hours after MCAO.ResultsMean infarct volumes for control and Sanguinate-treated subjects were 4739 mm3 and 2585 mm3 (p=0.0443; r2=0.687), respectively. Following intervention, rCBF values were 0.340 for controls and 0.715 in the Sanguinate group (r2=0.536; p=0.0064). Pial collateral scores improved only in Sanguinate-treated subjects and AAT decreased by a mean of 0.314 s in treated subjects and increased by a mean of 0.438 s in controls (p<0.0276).ConclusionPreliminary results indicate that topload bolus administration of Sanguinate in hyperacute ischemic stroke significantly improves infarct volume, pial collateral recruitment and CBF in experimental MCAO immediately following its administration.

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