Abstract T P83: Strain Differences In Leptomeningeal Collateral Flow Dynamics Correlate With Differences In Stroke Outcome

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Yasuo Nishijima ◽  
Yosuke Akamtsu ◽  
Chih Cheng Lee ◽  
Jialing Liu

Introduction: Emerging evidences suggest that the collateral circulation plays a key role in the risk of stroke and the severity of infarction. The current study aimed to investigate the effect of the brain collateral circulation in acute phase of stroke and outcome in two inbred mouse strains that differ markedly in anatomical collateralization. Methods: Male C57BL/6 and Balb/C mice were subjected to permanent unilateral common carotid artery occlusion (CCAO) or temporary distal middle cerebral artery occlusion (dMCAo). Regional cerebral blood flow (rCBF) was assessed by laser doppler flowmetry. In vivo imaging of collateral blood flow and flow velocity was evaluated by doppler optical coherence tomography (DOCT). Infarct size and motor function was assessed at 24 hours and 1 week after dMCAo, respectively. DiI-labeling was used to reveal anastomoses and to determine vessel diameter. Results: The diameters of the ICA and ACA on the ischemic side in both strains markedly decreased at 24 hours after CCAO but recovered at 7 days, although the diameters of ICA, MCA and ACA are larger in the Balb/C compared to the C57BL/6 strain before and after CCAO. Balb/C mice exhibited significantly less leptomeningeal connecting collateral arteries compared to C57BL/6 (0.6±0.3 vs 11.3±0.4, p<0.001), coincided with a larger infarction and worse neurological outcomes after dMCAo compared to C57BL/6. During the acute phase of occlusion of the CCA or MCA, C57BL/6 mice also demonstrated a much more robust retrograde filling of several distal branches of the MCA from ACA compared to Balb/C mice. Conclusion: Our results demonstrate that anatomical insufficiency of the leptomeningeal collateralization is associated with an impaired collateral flow dynamics, resulting in reduced rCBF during the acute phase of MCA stroke, which might in part, contribute to the larger infarction observed in the Balb/C strain.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Yosuke Akamatsu ◽  
Chih C Lee ◽  
Ruikang K Wang ◽  
Jialing Liu

Introduction: Type 2 diabetes mellitus (T2DM) is a major risk factor for stroke, yet it is unclear whether T2DM associated-poor outcome after stroke is related to unfavorable cerebral blood flow dynamics. The current study aimed to investigate the effect of T2DM on acute blood flow dynamics and stroke outcome. Methood: Adult male db/db and db/+ mice (8-9 weeks of age) were subjected to permanent distal middle cerebral artery occlusion (pMCAo). Neurologic deficit was assessed with a 5-point scoring system (0 to 4) and infarction volume was determined at 48 hours after pMCAo by TTC staining. Hemodynamics was evaluated by laser doppler flowmetry. The number of connecting collateral vessels, functional microvascular network morphology, and vessel area density of the ischemic hemisphere were determined by DiI-labeling, and optical coherence tomography (OCT), respectively. Results: db/db mice had a higher baseline blood glucose level (341±39.7 vs. 172±26.5 mg/dl, p <0.01) and a larger infarct volume after pMCAO compared to db/+ mice (69.5±5.4 vs. 51.0±3.1 mm 3 , p <0.01). Neurologic deficit did not differ between groups at 2 hours after pMCAO, but was significantly worse in the db/db at 24 hours after pMCAo compared to db/+ mice (1.9±0.1 vs. 1.4±0.2, p <0.05), correlated with lower rCBF in the core of the MCA territory at 24 and 48 hours (10.9%±1.1 vs. 14.4%±0.8, p <0.05 and 9.5%±1.0 vs. 14.1%±1.2, p =0.01). Ipsilateral functional microvascular density as detected by OCT did not differ between groups at one hour after occlusion but was significantly lower in the db/db mice at 24 hr after pMCAo ( p <0.05). However, we did not observe a significant difference in the number of connecting collateral arteries between groups at 48 hours after pMCAo in this age group. Conclusion: Our results demonstrate that T2DM is associated with lower rCBF and lower density of functional blood vessels during the acute phase of pMCAo, which might in part, contribute to the observed worse outcome in the db/db mice. Ongoing experiments will investigate whether T2DM affects the flow dynamics in individual collateral following MCA occlusion and outward remodeling of the collateral vessels.


Author(s):  
Brian A Tong ◽  
Dan‐Victor Giurgiutiu

Introduction : Rationale: Bilateral vertebral artery occlusion with collateral reconstitution is a rare finding. Compared to patients with acute occlusion, symptom progression may be much slower [1]. Atherosclerotic risk factors lead to occlusion, including hypertension and hyperlipidemia, but it is unclear what leads to collateral reconstitution [2]. These patients may have collateral circulation from anterior and posterior circulation sources that are well developed [1] [2]. Sufficient collateral flow correlates with lower rates of hemorrhagic transformation following recanalization [3] [4]. However, given the risk of spontaneous hemorrhage from microvascular collaterals, the hemorrhagic risk associated with thrombolytic therapy in patients with moyamoya collaterals, due to the fragility of these vessels [5], must be balanced with the benefit of therapy in the presence of severe neurologic deficits along with the mortality and morbidity that may stem from the occlusion. Patient concerns: 67 year old Caucasian male with past medical history of coronary artery disease, abdominal aortic aneurysm, hypertension, history of tobacco use and type 2 diabetes mellitus presents with acute right‐sided weakness. Methods : Diagnoses: On admission, CTA Head and Neck suggested chronic total occlusion of bilateral V4 segments from their origin to the midportion with tandem bilateral high‐grade stenoses throughout the imaged distal V2 and V3 segments bilaterally. MRI could not be obtained because of old lumbar fusion spinal hardware. Cerebral angiography showed microvascular reconstitution, analogous to moyamoya, with slow mid basilar flow, which could be either due to occlusion or competitive flow from top of the basilar collaterals. Interventions: Patient received intra‐arterial integrilin and tPA thrombolysis with TICI 1 reperfusion. Results : Outcomes: Patient presented with NIHSS 18 notable for right sided weakness (2/5 strength in his right upper extremity and 1/5 strength in RLE), bilateral hemianopia, severe dysarthria and right gaze preference. Patient had significant improvement in his exam the next day following thrombolysis. Notably, patient had 5/5 strength in his right upper and right lower extremities compared to his strength on presentation. Repeat head CT on the following day after thrombolysis showed left pontine infarct. Repeat NIHSS was 3 at 24 hours for partial hemianopia, minor nasolabial flattening and mild dysarthria. Conclusions : Conclusion: Bilateral intracranial vertebral artery stenosis and occlusion commonly occurs distal to PICA and near the vertebrobasilar junction [2]. Proximal (specifically areas supplied by PICA) and distal territories within the posterior circulation are often infarcted [2], which can yield a unique exam upon presentation that can help accurately guide diagnosis and treatment when appropriately recognized. The involvement of collateral circulation can play a crucial role in patients undergoing endovascular revascularization therapy [6]. In the setting of bilateral vertebral occlusion with microvascular reconstitution, patients can still undergo catheter based thrombolysis, but not thrombectomy.


1995 ◽  
Vol 15 (6) ◽  
pp. 1075-1081 ◽  
Author(s):  
Michael G. Muhonen ◽  
Christopher M. Loftus ◽  
Donald D. Heistad

Adenosine is a potent cerebral vasodilator. We tested the hypothesis that dilatation of collateral vessels in cerebrum, in response to topical adenosine and 2-chloroadenosine (2-CAD), would increase blood flow to collateral-dependent cerebrum. In dogs anesthetized with halothane, a branch of the middle cerebral artery (MCA) was occluded proximally and cannulated distally. The collateral-dependent area at risk for infarction was perfused from a reservoir with microsphere-free blood, and blood flow to normal cerebrum and to cerebrum dependent on collateral flow was measured with radioactive microspheres injected into the left ventricle through a femoral artery catheter. Perfusion through the cannulated MCA branch was stopped, and flow to normal and collateral-dependent cerebrum was measured after adenosine (10−2 M) or 2-CAD (10−4 M) was added to the superfusate over the cerebrum. In normal cerebrum, topical application of adenosine increased flow to outer but not inner layers. Topical application of adenosine had little effect on flow to collateral-dependent tissue. In normal cerebrum, 2-CAD increased flow to outer layers, whereas flow to inner layers tended to increase. During 2-CAD, flow to outer cortical layers of collateral-dependent cerebrum increased from 140 ± 20 ml/100 g/min (mean ± SD) to 231 ± 68, whereas flow to the inner collateral-dependent tissue did not change. The findings indicate that, after occlusion of a cerebral artery, topical 2-CAD increases blood flow to outer layers of collateral-dependent and normal cerebrum. The findings suggest also that, after arterial occlusion, collateral circulation to cerebrum has dilator reserve, and flow to tissues that are dependent on collaterals may be augmented.


Author(s):  
Yang Liu ◽  
Lei Zhu ◽  
Bei Hou ◽  
Tuoyi Wang ◽  
Dechao Xu ◽  
...  

Abstract Background and purpose Bilateral carotid artery occlusion (CAO) is a rare condition and the collateral circulation is more complicated than in unilateral CAO. The circle of Willis (CoW) is the most important collateral circulation compensation pathway in CAO. However, the specific role of CoW in the collateral circulation compensation pathway of CAO has not been fully elucidated. The purpose of this study is to investigate the role of CoW in the collateral circulation compensation pathway of CAO. Materials and methods Clinical, imaging, and hemodynamic data of 30 patients with bilateral CAO were collected to analyze the collateral blood flow compensation pathway and its characteristics, and to examine the correlation between the structure of the CoW and the collateral circulation of bilateral CAO. Results This paper summarized 30 patients with bilateral CAO. There were 0 cases of the CoW complete type, 18 cases of the partially complete type (60%), and 12 cases of the incomplete type (40%). For the partially complete type cases, there were 14 complete anterior circulation cases (46.7%). The collateral circulation collateral circulation pathway included 14 cases with anterior communicating artery(ACoA), 7 cases with posterior cerebral artery (PCA)-middle cerebral artery (MCA) leptomeningeal anastomosis (LMA), 5 cases with ophthalmic artery(OA), 3 cases with lateral posterior communicating artery(PCoA), 1 case with internal carotid artery (ICA) stealing, 1 case with new Moyamoya vessels, and 4 cases of other types. There were four cases (13.3%) with complete posterior circulation, including four cases with bilateral PCoA, three cases with PCA-MCA LMA, and two cases with OA. There were 12 cases (40%) with incomplete CoW, including 8 cases with PCA-MCA LMA, 3 cases with lateral PCoA, 1 case with anterior cerebral artery (ACA)-MCA LMA, 4 cases with OA, and 1 other case. Conclusion The collateral circulation pathway differs among patients with different CoW structure types. When the CoW is partially complete, it mainly provides blood flow compensation to the ischemic area through primary collateral circulation. When the CoW is incomplete, it mainly provides blood flow compensation to the ischemic area through secondary collateral circulation.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Ethem Murat Arsava ◽  
Osman Melih Topcuoglu ◽  
Erhan Akpinar ◽  
Kader K Oguz ◽  
Mehmet Akif Topcuoglu

Background: Previous studies have shown reduced penumbral salvage in ischemic stroke patients with higher leukoaraisosis (LA) volume. Although unproven, decreased cerebral vessel density and diminished capacity of cerebral vessels to dilate in response to reduced blood flow in severe LA, are considered among the factors that might explain the association between LA burden and infarct growth in ischemic stroke. Both of these factors, in theory, might negatively affect the extent of collateral blood flow, an important predictor of tissue and clinical outcome in patients with acute ischemic stroke. In this study, we therefore analyzed whether extent of LA adversely affected the degree of collateral circulation in a cohort of patients presenting with middle cerebral artery occlusion. Methods: We retrospectively analyzed a consecutive series of patients admitted with a diagnosis of middle cerebral artery occlusion. Computed tomography angiography source images (CTA-SI) were used to assess the degree of collateral circulation, based on a previously validated scoring system which grades collateral vessels in the sylvian fissure and leptomeningeal convexity separately on a scale from 1 to 5, with 1 being the worst and 5 the best. The extent of LA was determined on FLAIR images by using the Fazekas scale. Multivariate analysis was used to explore the relationship between extent of LA and degree of collateral circulation, adjusted for other covariates like age, gender, vascular risk factors and time from symptom onset to CTA imaging. Results: A total of 51 patients (31 female, 20 male) were included into the study. LA severity was significantly and negatively correlated with the degree of collateral supply (r=-0.31, p=0.03). LA severity (OR 5.9, 95%CI 1.5-24.0) and history of prior stroke (OR 7.8, 95%CI 1.0-59.3) were the only significant variables associated with insufficient collaterals (defined as a combined sylvian and lepotmeningeal collateral score of 5 or less) in the multivariate logistic regression analysis. Conclusion: Patients with higher LA burden have a poor recruitment of collateral vessels after middle cerebral artery occlusion. This association might contribute to reduced penumbral salvage and increased susceptibility to infarct growth observed in patients with severe LA.


1998 ◽  
Vol 18 (5) ◽  
pp. 570-579 ◽  
Author(s):  
Kazuo Kitagawa ◽  
Masayasu Matsumoto ◽  
Gongming Yang ◽  
Takuma Mabuchi ◽  
Yoshiki Yagita ◽  
...  

Cerebral ischemia models using mice have drawn increasing attention, particularly because of the availability of transgenic animals. However, the variability of intracranial vasculature at the circle of Willis in mice can influence the degree of ischemia in both the bilateral common carotid artery (CCA) occlusion and intraluminal suture occlusion models. We have developed a method to predict the extent of the anastomosis between carotid and vertebrobasilar circulation in three mouse strains (C57BL/6, CBA, and DBA/2) by measuring cortical microperfusion with laser Doppler flowmetry during a 1-minute occlusion of both CCA. When animals showed residual cortical microperfusion of less than 12% during bilateral CCA occlusion, the mice showed absence of functional anastomosis, developed ATP depletion in the frontal cortex during occlusion, and had ischemic neuronal death in the hippocampus and caudoputamen after occlusion for 15 minutes and recirculation for 7 days. Furthermore, those mice exhibited decreased local cerebral blood flow and associated ischemic neuronal death in the hippocampus, within the territory supplied by the posterior cerebral artery, with the intraluminal suture occlusion model. The current study demonstrates the need for assessment of intracranial vasculature in each animal by measuring cortical microperfusion during temporary occlusion of both CCA, no matter whether cerebral ischemia is produced by bilateral CCA occlusion or intraluminal suture occlusion in transgenic mice.


1996 ◽  
Vol 271 (3) ◽  
pp. H914-H923 ◽  
Author(s):  
J. L. Unthank ◽  
J. C. Nixon ◽  
H. M. Burkhart ◽  
S. W. Fath ◽  
M. C. Dalsing

The technique to repeatedly observe exactly the same vessels in the rat intestine was used to investigate vascular compensation during the 1st wk after abrupt arterial ligation. A collateral-dependent tissue region was created by ligation of three to four sequential intestinal arteries. At the center of the collateral-dependent region, arterial pressure decreased from 96 +/- 3.7 to 29 +/- 2.5 mmHg, and intestinal blood flow fell approximately 80% during maximal dilation initially postligation. One week later, pressure and blood flow at the center had increased 31 and 250%, respectively. Relative to preligation values, the only compensatory adaptation was an enlargement (31 +/- 11%) of the collateral arteries located between normal tissue and the center; no increase was observed in the diameter or numbers of arterioles or collateral arteries at the center. Wall shear rate was increased 173 +/- 35% initially postligation at the site where luminal enlargement occurred. The selective enlargement of collateral arteries away from the center region is consistent with the hypothesis that collateral enlargement is induced by chronic increases in wall shear rate and can occur independently of tissue ischemia.


1987 ◽  
Vol 252 (6) ◽  
pp. H1105-H1111
Author(s):  
P. V. Hautamaa ◽  
X. Z. Dai ◽  
D. C. Homans ◽  
J. F. Robb ◽  
R. J. Bache

This study examined the ability of the immature coronary collateral circulation to undergo vasodilation in response to nitroglycerin and vasoconstriction in response to alpha-adrenoceptor stimulation. Studies were performed in 12 anesthetized dogs. Collateral flow was estimated from measurements of retrograde flow from the acutely ligated and cannulated anterior descending branch of the left coronary artery. Antegrade flow into the collateral-dependent myocardium was minimized by embolizing the anterior descending artery with 25-microns microspheres. Drugs to be tested were introduced into the left main coronary artery to reach collateral vessels arising from the left circumflex and septal arteries. Intracoronary administration of nitroglycerin (6 micrograms X kg-1 X min-1) resulted in a 33 +/- 7.7% increase in retrograde blood flow (P less than 0.01) and a 23 +/- 3.8% decrease in calculated collateral resistance (P less than 0.01). No significant change occurred in retrograde blood flow or calculated collateral resistance during cardiac sympathetic nerve stimulation after beta-adrenergic blockade with propranolol, selective alpha-adrenergic stimulation with phenylephrine (1 microgram X kg-1 X min-1), or selective alpha 2-stimulation with BHT 933 (2 micrograms X kg-1 X min-1). Thus, the immature coronary collateral circulation was capable of active vasomotion, as demonstrated by vasodilation in response to nitroglycerin, but did not undergo vasoconstriction in response to alpha-adrenoceptor stimulation.


1992 ◽  
Vol 12 (5) ◽  
pp. 727-733 ◽  
Author(s):  
T. Iijima ◽  
G. Mies ◽  
K.-A. Hossmann

Following permanent occlusion of the left middle cerebral artery (MCA) in rats, electrophysiological and hemodynamic characteristics of the periinfarct border zone were investigated in sham-operated (n = 6), untreated (n = 6), and MK-801-treated (3.0 mg/kg; n = 6) animals. For this purpose, direct current potential (DC), EEG, and blood flow (laser-Doppler flowmetry) were recorded from the cortex in the periphery of the MCA territory. In sham-operated rats, a single negative cortical DC deflection was observed after electrocoagulation of the cortex, whereas in untreated MCA-occluded animals, three to eight transient DC deflections were monitored during the initial 3 h of ischemia. The duration of these cortical DC shifts gradually increased from 1.2 ± 0.3 to 3.7 ± 2.7 min (mean ± SD; p < 0.05) during this time. In animals treated intraperitoneally with MK-801 (3.0 mg/kg) immediately after MCA occlusion, the number of cortical DC shifts significantly declined to one to three deflections (p < 0.005). The EEG of the treated animals revealed low-amplitude burst-suppression activity. In the untreated and treated experimental group, the reduction of cortical blood flow amounted to 69 ± 25 and 49 ± 13% of control, respectively. Despite the more pronounced cortical oligemia, MK-801 treatment resulted in a significant decrease of the volume of the ischemically injured tissue from 108 ± 38.5 (untreated group) to 58 ± 11.5 (p < 0.05) mm3. Our results suggest that repetitive cortical DC deflections in the periinfarct border zone contribute to the expansion of ischemic brain infarcts.


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