Albumin therapy enhances collateral perfusion after laser-induced middle cerebral artery branch occlusion: a laser speckle contrast flow study

Laser speckle contrast (LSC) was used to compare the extent of cortical ischemia in two inbred mouse strains that differed in their degree of collateral circulation, after laser occlusion of the distal middle cerebral artery, and after treatment with 25% albumin (ALB) or saline (control). Sequential LSC images acquired over ∼90 minutes were coaligned, converted to relative flow, and normalized to baseline. After 3-day survival, infarction was quantified by triphenyl tetrazolium chloride or magnetic resonance imaging. In the sparsely collateralized BALB/c strain, mean flow fell to 13% to 14% and 33% to 34% of baseline in central (core) and peripheral (penumbral) regions of interest, and ALB treatment at 30 minutes enhanced perfusion in both regions by ∼2-fold relative to saline, restoring flow to the benign-oligemic range centrally, and to the hyperemic range peripherally. The ALB-induced increment in parenchymal perfusion was disproportionate to the subtle flow increase in the occluded artery itself, suggesting that ALB improved collateral circulation. Cortical infarction in BALB/c mice was reduced 45% by ALB treatment. In contrast to BALB/c mice, the better-collateralized CD-1 strain developed milder ischemia, had smaller infarcts, and showed no differential benefit of ALB. We conclude that where native collateralization is insufficient (BALB/c strain), ALB treatment exerts a significant therapeutic effect after ischemia by augmenting collateral perfusion.     

颈内动脉急性闭塞致大面积脑梗死侧支循环建立及影响因素

目的评估颈内动脉急性闭塞致大面积脑梗死侧枝循环建立情况及影响因素。方法纳入29例经诊断为颈内动脉急性闭塞致大面积脑梗死的患者,所有患者均行颈动脉超声、经颅多普勒超声(TCD)、头颅CT、头颅磁共振血管造影(MRA)、心电图检查,同时收集患者基本信息。结果一级侧枝循环建立与糖尿病显著相关(P 0. 05),与房颤、高血压、吸烟、NIHSS评分无关(P 0. 05)。二级侧枝循环建立与房颤、高血压、糖尿病、吸烟、NIHSS评分均无关(P 0. 05)。心源性脑栓塞导致的急性大面积脑梗死与脑疝显著相关(P 0. 05)。TCD评估一级侧枝循环的建立与MRA具有高度一致性(Kappa值=0. 656,P 0. 05)。结论糖尿病可促进颈内动脉急性闭塞导致的大面积脑梗死一级侧枝开放。心源性脑栓塞导致的大面积脑梗死易发生脑疝。TCD可以较好评估颈内动脉急性闭塞导致的大面积脑梗死的一级侧枝循环建立。     

慢性颈内动脉闭塞导致认知功能障碍的研究进展

慢性颈内动脉闭塞(CICAO)是认知功能障碍的独立危险因素,可通过多种机制影响脑部结构及血流动力学情况(包括淀粉样蛋白沉积、炎症介质形成、脑灌注不足等),导致非心脑血管事件风险增加。颈动脉系统重度狭窄或闭塞部位不同所致认知功能减退的表现形式可能存在差异,控制高血压等高危因素可降低其发生风险。临床上对于CICAO患者脑血流动力学情况常用的评估手段为CT灌注成像检查(CTP),其可能通过间接评估侧支循环及其他血流动力学指标来预测患者出现认知功能减退的风险,但准确性仍有争议。目前临床上常用药物可在一定程度上改善患者的认知功能,尚无根治药物,血管内介入治疗可能通过降低脑梗死再发及改善脑灌注而改善认知功能,但对于纳入患者的标准仍需严格评估,其安全性及有效性仍需进一步探索。该文基于该类疾病的研究现状,对其发病机制、影响因素、评估手段及治疗方案进行综述,以期为临床诊疗及后续研究提供参考。     

Clinical implications of collateral middle cerebral artery flow in acute ischaemic stroke with internal carotid artery occlusion

Background and purpose: The presence of collateral middle cerebral artery (MCA) flow via the primary collateral pathway is thought to protect against the progression of cerebral ischaemia. However, there have been few reports on early clinical outcomes according to the presence of collateral MCA flow in acute ischaemic stroke (AIS) with internal carotid artery (ICA) occlusion. Therefore, we sought to investigate the early clinical outcomes and lesion patterns according to the presence of collateral MCA flows in AIS with ICA occlusion. Methods: This is a retrospective study of patients with AIS with ICA occlusion consecutively admitted to our stroke center between October 2008 and March 2010. Patients were included if they were admitted within 12 h of symptom onset with AIS and symptomatic ICA occlusion. Collateral MCA flow was defined as the presence of MCA signals from proximal M1 to distal MCA branches ipsilateral to the ICA occlusion by magnetic resonance angiography. Early neurological deterioration (END) was defined as a 4‐point increase in the National Institutes of Health Stroke Scale (NIHSS) score and persistent neurological deterioration for at least 24 h or newly developed neurological symptoms within 7 days. Results: Sixty‐five patients (42 men, 23 women) were finally included. Initial NIHSS scores were significantly lower, and favorable outcomes at 3 months were better in patients with collateral MCA flow than in those without (P < 0.001). Initial lesion patterns were different according to the collateral MCA flow. However, patients with mild AIS might more frequently deteriorate than those with moderate to severe AIS. Conclusions: In our study, collateral MCA flow reduced initial stroke severity and was associated with favorable outcomes at 3 months but did not seem to protect against END in mild AIS patients with ICA occlusion. Therefore, the results of this study suggest that mild AIS patients with ICA occlusion should be carefully managed because their conditions may deteriorate.     

Augmenting collateral blood flow during ischemic stroke via transient aortic occlusion

Collateral circulation provides an alternative route for blood flow to reach ischemic tissue during a stroke. Blood flow through the cerebral collaterals is a critical predictor of clinical prognosis after stroke and response to recanalization, but data on collateral dynamics and collateral therapeutics are lacking. Here, we investigate the efficacy of a novel approach to collateral blood flow augmentation to increase collateral circulation by optically recording blood flow in leptomeningeal collaterals in a clinically relevant model of ischemic stroke. Using high-resolution laser speckle contrast imaging (LSCI) during thromboembolic middle cerebral artery occlusion (MCAo), we demonstrate that transiently diverting blood flow from peripheral circulation towards the brain via intra-aortic catheter and balloon induces persistent increases in blood flow through anastomoses between the anterior and middle cerebral arteries. Increased collateral flow restores blood flow in the distal middle cerebral artery segments to baseline levels during aortic occlusion and persists for over 1 hour after removal of the aortic balloon. Given the importance of collateral circulation in predicting stroke outcome and response to treatment, and the potential of collateral flow augmentation as an adjuvant or stand-alone therapy for acute ischemic stroke, this data provide support for further development and translation of collateral therapeutics including transient aortic occlusion.     

颈内动脉狭窄相关性脑缺血病变的临床分析

目的 探讨颈内动脉狭窄致脑缺血病变的临床特点及发生机制,为临床指导治疗及判断预后提供依据.方法 回顾分析111 例经CT 血管造影(CTA)证实的颈内动脉狭窄患者的颅内Willis 环形态、TCD 资料及临床表现.结果 颈内动脉轻、中、重度狭窄组脑梗死发生率分别为14.7% 、30.6% 、46.3%,三组间差异具有显...     

No evidence that severity of stroke in internal carotid occlusion is related to collateral arteries

Background/Aim

The neurological effects of internal carotid artery (ICA) occlusion vary between patients. The authors investigated whether the severity of symptoms in a large group of patients with ipsilateral or/and contralateral ICA occlusion at presentation with ocular or cerebral ischaemic symptoms could be explained by patency of other extra or intracranial arteries to act as collateral pathways.

Methods

The authors prospectively identified all patients (n = 2881) with stroke, cerebral transient ischaemic attack (TIA), retinal artery occlusion (RAO), and amaurosis fugax (AFx) presenting to our hospital over five years, obtained detailed history and examination, and examined the intra and extracranial arteries with carotid and colour‐power transcranial Doppler ultrasound. For this analysis, all those with intracranial haemorrhage on brain imaging and cerebral events without brain imaging were excluded.

Results

Among 2228/2397 patients with brain imaging (1713 ischaemic strokes, 401 cerebral TIAs, 193 AFx, and 90 RAO) who underwent carotid Doppler, 195 (9%) had ICA occlusion. Among those patients with cortical events, disease in potential collateral arteries (contralateral ICA, external carotid, ipsilateral or contralateral vertebral or intracranial arteries) was equally distributed among patients with severe and mild ischaemic presenting symptoms.

Conclusion

The authors found no evidence that the clinical presentation associated with an ICA occlusion was related to patency of other extra or intracranial arteries to act as collateral pathways. Further work is required to investigate what determines the clinical effects of ICA occlusion.     

Brain BDNF levels elevation induced by physical training is reduced after unilateral common carotid artery occlusion in rats

We investigated the contribution of blood flow elevation in the cerebrovasculature to physical training-induced brain-derived neurotrophic factor (BDNF) levels elevation in the brain. Brain-derived neurotrophic factor protein levels were measured in the motor cortex 24 h after the last session of a forced treadmill walking (30 minutes a day, 18 m/minute for 7 consecutive days). Unilateral common carotid artery occlusion and modulation of exercise intensity (0 versus −10% inclination of the treadmill) were used as strategies to reduce the (normal) elevation of flow in the cerebrovasculature occurring during exercise. Administration of N-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg before each exercise sessions) and genetic hypertension (spontaneously hypertensive rats) were used as approaches to reduce stimulation of nitric oxide production in response to shear stress elevation. Vascular occlusion totally and partially abolished the effect of physical training on BDNF levels in the hemisphere ipsilateral and contralateral to occlusion, respectively. BDNF levels were higher after high than low exercise intensity. In addition, both genetic hypertension and L-NAME treatment blunted the effects of physical training on BDNF. From these results, we propose that elevation of brain BDNF levels elicited by physical training involves changes in cerebral hemodynamics.     

Leptin augments cerebral hemodynamic reserve after three-vessel occlusion: distinct effects on cerebrovascular tone and proliferation in a nonlethal model of hypoperfused rat brain

The adipocytokine leptin has distinct functions regulating vascular tone, inflammation, and collateral artery growth. Arteriogenesis is an inflammatory process and provides a mechanism to overcome the effects of vascular obstruction. We, therefore, tested the effects of leptin in hypoperfused rat brain (three-vessel occlusion). Systemic leptin administration for 1 week after occlusion surgery increased cerebral hemodynamic reserve similar to granulocyte–macrophage colony-stimulating factor (GM-CSF), as indicated by improved CO₂ reactivity (vehicle 0.53%±0.26% versus leptin 1.05%±0.6% per mm Hg arterial pCO₂, P<0.05). Infusion of microspheres under maximal vasodilation failed to show a positive effect of leptin on cerebral perfusion (vehicle 64.9%±4.5% versus leptin 66.3%±7.0%, occluded/nonoccluded hemisphere). Acute treatment with GM-CSF led to a significant increased CO₂ reactivity and cerebral perfusion (79.2%±8.1% versus 64.9%±4.5%, P<0.05). Vasoconstrictive response of isolated rat carotid artery rings, after phenylephrine was attenuated at 24 hours following preincubation with leptin, was unaffected by removal of endothelium but abrogated by coculture with N-(omega)-nitro--arginine methylester, pointing toward an inducible nitric oxide synthase-mediated mechanism. In chronic cerebral hypoperfusion, acute leptin treatment restored the hemodynamic reserve of the cerebral vasculature through its effects on vascular tone, while leaving vascular outward remodeling unaffected. Our results, for the first time, reveal a protective role of leptin on vascular function in hemodynamically compromised brain tissue.     

DSA对单侧颈内动脉系统大动脉狭窄或闭塞后侧支循环建立的应用价值

目的 探讨DSA对单侧颈内动脉系统大动脉狭窄或闭塞后侧支循环建立的应用价值,探讨三级侧支循环在单侧颈内动脉开口部位狭窄或闭塞及大脑中动脉M1段狭窄或闭塞中的特点.方法 分别对56例颈内动脉开口处狭窄或闭塞及94例大脑中动脉M1段狭窄或闭塞的患者进行脑血管造影检查,根据其狭窄程度分析其侧支循环建立的情况.结果 颈内动脉开口部位闭塞组大脑动脉环开放率约38.5%,颅内外沟通开放率30.8%,软脑膜吻合支开放率约30.8%;重度狭窄组大脑动脉环开放率35.1%,软脑膜吻合支开放率16.2%,颅内外沟通开放率约5.4%;中轻度狭窄组无侧支循环建立.大脑中动脉M1段闭塞组大脑动脉环开放率5%,软脑膜吻合支开放率95%;重度狭窄组仅软脑膜吻合支开放,开放率约61%;轻中度狭窄组无侧支形成.结论 在颈内动脉开口部位重度狭窄或闭塞的病例中,一级侧支循环的开放代偿最为重要,二级侧支循环起着重要的辅助作用.在大脑中动脉M1段重度狭窄或闭塞的病例中,二级和三级侧支循环的开放起主要的代偿作用.     

Early microglial reaction following mild forebrain ischemia induced by common carotid artery occlusion in rats

Early microglial reaction following mild ischemic injury caused by bilateral common carotid artery occlusion has been investigated in rats. The ischemic insults lasted for 10, 15 and 20 min without recirculation, and with several reperfusion intervals from 1 h to 3 days. The resting and activated microglial cells were visualized with immunohistochemistry using monoclonal antibodies raised against the CR3 complement receptor, the MHC class I and class II antigens, the macrophage common antigen and with Bandeiiraea simplicifolia lectin-histochemistry. The neuroprotective effect of hypothermia on the early microglial activation was also studied. Ten minutes bilateral common carotid artery occlusion in hypothermic rats without reperfusion caused a mild microglial reaction in the hippocampus. Strong reaction was seen following 20 min insult without reperfusion. Ischemia followed by recirculation caused milder reaction than without reperfusion. Our results suggest that the microglial cells are very sensitive indicators of a mild, transient ischemic insult that does not result in neuronal cell death.     

Rat middle cerebral artery occlusion by an intraluminal thread compromises collateral blood flow

We compared in Wistar rats collateral blood flow through leptomeningeal anastomoses after middle cerebral artery occlusion using craniotomy (‘extravasal occlusion'), which results in a small volume of cerebral infarction, and after intraluminal thread occlusion (‘intravasal occlusion'), which produces a large volume of cerebral infarction. Simultaneous laser–Doppler flowmetry with two probes placed on the cerebral cortex was used to measure and compare collateral blood flow. Extravasal occlusion caused a cortical blood flow reduction along a gradient in lateral direction, whereas blood flow reduction after intravasal occlusion was more uniformly distributed. It is concluded that permanent intravasal occlusion compromises collateral blood flow and therefore may not be a suitable model for measuring the ability of pharmacotherapeutic agents, if any, to improve collateral blood flow acutely after middle cerebral artery occlusion. The two models can be useful for testing drugs on parenchymal neuroprotective properties. Thereby, the intraluminal technique is preferred because of the possibility to study reperfusion damage when transient occlusion is applied.     

Preoperative brain temperature imaging on proton magnetic resonance spectroscopy predicts hemispheric ischemia during carotid endarterectomy for unilateral carotid stenosis with inadequate collateral blood flow

Objective Preoperative magnetic resonance (MR) angiography sometimes shows the absence of collateral flow via the circle of Willis. This study examined whether brain temperature (BT) imaging on multi-voxel proton MR spectroscopy after this finding increases the accuracy of predicting hemispheric ischemia during internal carotid artery (ICA) clamping during endarterectomy for patients with symptomatic unilateral carotid stenosis.

Methods In 52 patients with ICA stenosis (≥70%) and absence of collateral blood flow via the circle of Willis on preoperative MR angiography, BT imaging was displayed using proton multi-voxel MR spectroscopy. The difference between BTs in the affected and contralateral hemispheres (BT_{affected hemisphere} ? BT_{contralateral hemisphere}) in the deep white matter of the centrum semiovale was calculated and defined as hemispheric ΔBT. Development of cerebral hemispheric ischemia during ICA clamping was determined from intraoperative electroencephalography (EEG).

Results Multivariate analysis revealed that high preoperative hemispheric ΔBT was significantly associated with development of EEG-defined hemispheric ischemia (95% confidence intervals [CIs], 5.376–15.452; p = 0.006). The positive-predictive value for development of EEG-defined hemispheric ischemia was significantly greater for preoperative hemispheric ΔBT following preoperative MR angiography (95%CI, 42–87%) than for preoperative MR angiography alone (95%CI, 13–37%).

Conclusions For patients without collateral flow via the circle of Willis, BT imaging increases the predictive accuracy for development of hemispheric ischemia during ICA clamping during CEA.     

侧支循环对颈内动脉重度狭窄或闭塞患者脑血管反应性和注意网络的影响

目的探讨侧支循环开放的类型对颈内动脉(internal carotid artery,ICA)重度狭窄或闭塞患者脑血管反应性和注意网络的影响。方法将有侧支循环形成的患者分为前交通动脉(anterior communicating artery,Aco A)开放组、后交通动脉(posterior communicating artery,Pco A)开放组和眼动脉(ophthalmic artery,OA)开放组,分别检测各组的屏气指数(breath-holding index,BHI)和注意网络测试(attention network test,ANT)指标。结果 Aco A开放组患侧BHI、总平均反应时间(reaction time,RT)和执行功能优于其它两组,OA开放组的定向和执行功能较其它两组减退(P0.05)。Aco A和Pco A开放组患侧的BHI与相应的ANT总平均RT呈负相关(P0.01)。结论 Aco A开放患者脑血管反应性和注意网络损害的程度较Pco A和OA开放者较轻,Aco A是对于注意功能最有效的侧支循环。     

Regional cerebral blood flow after occlusion of the middle cerebral artery

Occlusions of the middle cerebral artery (MCA) are mostly of embolic origin (appr. 80%) and give rise to about one third of all ischemic strokes, most of these being major strokes. MCA occlusions lasting for less than 1/2 h are tolerated without occurrence of permanent tissue damage. Occlusions lasting between 1/2 h to 4-8 h lead to permanent tissue damage and neurological deficits that are proportional to the duration of occlusion. Maximal tissue damage is obtained after 4-8 h occlusion. A cerebral blood flow of 8-23 ml/100 gr/min is sufficient for cellular viability but insufficient for normal tissue function ("ischemic penumbra"). Cellular function is completely abolished in the interval 8-16 ml/100 gr/min and flow at that level is tolerated only for 1-3 h before neuronal death ensues. In the interval 18-23 ml/100 gr/min there is some functional activity although it is reduced. Experimental and clinical evidence suggests that flow in this interval may be tolerated for several days, months or even longer ("chronic ischemic penumbra"). After MCA occlusion the blood flow falls below 8 ml/100 gr/min in most cases and permanent MCA occlusion always leads to relatively large areas of frank infarction. The ischemic infarcts may be surrounded by collaterally perfused areas where the blood flow is pressure-dependent (impaired autoregulation) and quite commonly insufficient for normal neuronal function (below 23 ml/100 gr/min). Such collaterally perfused areas may include a "chronic ischemic penumbra". Emboli causing MCA occlusions commonly disintegrate and/or migrate more peripherally within the first few weeks post stroke. This leads to reperfusion and changes of ischemic infarcts into hyperemic infarcts where flow is severely increased. The vascular reactivity is completely abolished in hyperemic infarcts and the hyperemic state lasts for about two weeks. Probably, anemic infarcts are equivalent to ischemic infarcts while the hemorrhagic variety is equivalent to hyperemic infarcts. The "partial infarct" with selective neuronal necrosis occurs in experimental animals after MCA occlusions of less than four h but not after permanent MCA occlusion. The significance of partial infarction in human stroke is not clarified. The extent of irreversible tissue damage can be reduced only if therapy sets in within 4-8 h after the occlusion. If a "chronic penumbra" exists the extension of reversible tissue damage can be reduced if therapy aimed at increasing the blood flow in the penumbra sets in within weeks or even months after the stroke.(ABSTRACT TRUNCATED AT 400 WORDS)