Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra
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Abstract We prospectively tested the hypothesis that early recovery after ischemic stroke depends on the ultimate survival of functionally impaired, critically ischemic (i.e., “penumbral”) tissue. From a series of 26 consecutive patients studied with positron emission tomography within 18 hours of first‐ever stroke in the middle cerebral artery territory, all 11 survivors to the 2‐month end point who exhibited increased oxygen extraction fraction were declared eligible. The positron emission tomographic images were compared to ultimate infarction defined by computed tomography performed during the chronic stage. The penumbra (operationally defined by increased oxygen extraction fraction and divided outcome despite uniformly reduced cerebral blood flow) was individually detected in 10 of the 11 patients; cerebral blood flow ranged from 7 to 17 ml/100 gm·min, consistent with that found in monkey studies. The volume of the penumbra that escaped infarction was highly correlated with neurological recovery ( p <0.04 to p <0.0001, depending on the scale used). This longitudinal study is the first to characterize the penumbra in humans and to document one mechanism strongly influencing recovery; the surviving penumbra may offer opportunities for secondary perifocal neuronal reorganization. Therapeutic measures to prevent infarction of the penumbra (up to 16 hours in this series) may have reduced residual neurological impairment. Mapping the extent of the penumbra, according to prospective criteria, may allow one to predict each patient's potential for recovery, and to select the most appropriate candidates for therapeutic trials.Keywords:
Penumbra
Stroke
Objective To explore the relationship of local cerebral glucose metabolism decrease and local cerebral blood flow, decrease with cerebral infarction. Methods The results of cerebral (superscript 18)F-FDG PET images and (superscript 99m)Tc-ECD cerebral blood flow images in 30 patients with multiple cerebral infarction were analyzed retrospectively. Results Local cerebral glucose metabolism decrease was positively related to clinical manifestations, and also to infarction position and local cerebral blood flow decrease. Conclusions (superscript 18)F-FDG PET images can provide the evidence for the diagnosis and treatment of ischemic cerebrovascular diseases.
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Objective: To investigate whether quantitative apparent diffusion coefficient(ADC) measurements can be employed to predict the prognosis of infarction in acute ischemic stroke without intravenous contrast material.Methods: Thirty-three patients having acute stroke symptoms with verified infarction in magnetic resonance imaging(MRI) were included in this study.Their MRI studies were performed between 6 and 12 h after the onset of their symptoms and were repeated.The infarction volumes were calculated by using DWI and the patients were divided into two groups as the ones having an expansion in the infarction area(group I,n=22) and the others having no expansion in the infarction area(group II,n=11).The groups were compared in terms of the ADC values and areas obtained from DWI,referring to three points: the core of the infarction,ischemic penumbra and the contralateral nonischemic parenchymal tissue.Quantitative ADC values and the infarction area were estimated.P 0.05 were accepted to be statistically significant.Results: The internal mean infarction area during the times between 6 and 12 h and in the fourth day was calculated by DWI.A significant statistical result was demonstrated on the DWI between the two groups(P0.001) and there was no difference between the core of the infarction and parenchymal tissue(P0.05).The ADC values of ischemic penumbra between the groups were found to be highly significant(P0.001).Conclusion: We believe that ADC results obtained from the core and the penumbra of the infarction area without intravenous contrast material will be a feasible and practical in the estimation of the infarction prognosis and in the planning of a treatment protocol.
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Brain infarction
Stroke
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Objective To study the expression of VEGF during reperfusion after focal cerebral ischemia in rats.Methods The left middle cerebral arteries were transiently occluded by inserting a nylon thread into the carotid artery, used neurological scale, TTC stain, Pathohistology method to evaluate the model. On the basis of this, we used immunohistochemistry method to observe ischemic core and penumbra after 3?h of ischemia and at 3, 6, 24, 72?h of reperfusion after 3?h of ischemia.Results The expression of VEGF is slightly positive in control and sham operated group. The expression of VEGF increases obviously in ischemic core and penumbra after 3?h of ischemia and at 3, 6?h of reperfusion after 3?h of ischemia. It has great difference compared with the sham operated group. With the elongation of the time of reperfusion after ischemia in ischemic core expression of VEGF is nearly normal. While the expression of VEGF increases gradually. It reaches peak at 24?h, while it decreases at 72?h of reperfusion.Conclusion The expression of VEGF is at low levels in normal brain tissue with the elongation of ischemic time, the expression of VEGF increase gradually in penumbra. The nerve cells in ischemic core become necrotic with the elongation of reperfusion time after ischemia and the ischemia of neurons in penumbra become more apparent. Indicating that VEGF can protect and repair the nerve cells that have damaged after focal erebral ischemic and reperfusion in rats.
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Gerbil
Neuronal damage
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Interventional treatment regimens have increased the demand for accurate understanding of the progression of injury in acute ischemic stroke. However, conventional animal models severely inhibit collateral blood flow and mimic the malignant infarction profile not suitable for treatment. The aim of this study was to provide a clinically relevant profile of the emergence and course of ischemic injury in cases suitable for acute intervention, and was achieved by employing a M2 occlusion model (M2CAO) that more accurately simulates middle cerebral artery (MCA) occlusion in humans. Twenty-five Sprague-Dawley rats were subjected to Short (90 min), Intermediate (180 min) or Extended (600 min) transient M2CAO and examined longitudinally with interleaved diffusion-, T2- and arterial spin labeling perfusion-weighted magnetic resonance imaging before and after reperfusion. We identified a rapid emergence of cytotoxic edema within tissue regions undergoing infarction, progressing in several distinct phases in the form of subsequent moderation and then reversal at 230 min (p < 0.0001). We identified also the early emergence of vasogenic edema, which increased consistently before and after reperfusion (p < 0.0001). The perfusion of the penumbra correlated more strongly to the perfusion of adjacent tissue regions than did the perfusion of regions undergoing infarction (p = 0.0088). This was interpreted as an effect of preserved collateral blood flow during M2CAO. Accordingly, we observed only limited recruitment of penumbra regions to the infarction core. However, a gradual increase in infarction size was still occurring as late as 10 hours after M2CAO. Our results indicate that patients suffering MCA branch occlusion stand to benefit from interventional therapy for an extended time period after the emergence of ischemic injury.
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Stroke
Collateral circulation
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The ischemic penumbra is both a concept in understanding the evolution of cerebral tissue injury outcome of focal ischemia and a potential therapeutic target for ischemic stroke. In this review, we examine the evidence that angiogenesis can contribute to beneficial outcomes following focal ischemia in model systems. Several studies have shown that, following cerebral ischemia, endothelial proliferation and subsequent angiogenesis can be detected beginning four days after cerebral ischemia in the border of the ischemic core, or in the ischemic periphery, in rodent and non-human primate models, although initial signals appear within hours of ischemia onset. Components of the neurovascular unit, its participation in new vessel formation, and the nature of the core and penumbra responses to experimental focal cerebral ischemia, are considered here. The potential co-localization of vascular remodeling and axonal outgrowth following focal cerebral ischemia based on the definition of tissue remodeling and the processes that follow ischemic stroke are also considered. The region of angiogenesis in the ischemic core and its surrounding tissue (ischemic periphery) may be a novel target for treatment. We summarize issues that are relevant to model studies of focal cerebral ischemia looking ahead to potential treatments.
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Neurovascular bundle
Stroke
Brain ischemia
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The temporal evolution of cerebral infarction was examined in rats subjected to transient occlusion of both common carotid arteries and the right middle cerebral artery. After severe (90-min) ischemia, substantial right-sided cortical infarction was evident within 6 h and fully developed after 1 day. After mild (30-min) ischemia, no cortical infarction was present after 1 day. However, infarction developed after 3 days; by 2 weeks, infarction volume was as large as that induced by 90-min ischemia. These data suggest that infarction after mild focal ischemia can develop in a surprisingly delayed fashion. Some evidence of neuronal apoptosis was present after severe ischemia, but only to a limited degree. However, 3 days after mild ischemia, neurons bordering the maturing infarction exhibited prominent TUNEL staining, and DNA prepared from the periinfarct area of ischemic cortex showed internucleosomal fragmentation. Furthermore, pretreatment with 1 mg/kg cycloheximide markedly reduced infarction volume 2 weeks after mild ischemia. These data raise the possibility that apoptosis, dependent on active protein synthesis, contributes to the delayed infarction observed in rats subjected to mild transient focal cerebral ischemia.
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Prediction of the regions of the ischemic penumbra that are likely to progress to infarction is of great clinical interest. Whether lowered apparent diffusion coefficient (ADC) values were present in the ischemic penumbra of patients presenting with acute ischemic stroke and were specific to regions of the penumbra that proceeded to infarction was investigated.Nineteen patients with hemispheric stroke of less than 6 hours' onset and with acute scans showing a perfusion lesion greater than a diffusion lesion (ischemic penumbra) were studied. Scans also were performed subacutely (days 3 to 5) and at outcome (day 90). The outcome scan was used to identify regions of the penumbra that proceeded to infarction.The ADC ratios were significantly reduced (P <.00001) in regions of the penumbra that progressed to infarction on the outcome scan compared with those that remained normal. In regions that showed transition to infarction, the mean ADC ratios were typically 0.75 to 0.90.Intermediate ADC values are present in the ischemic penumbra and are indicative of tissue at risk of infarction.
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Brain infarction
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