Penumbra in acute ischemic stroke

2021 ◽  
Vol 19 ◽  
Author(s):  
Yang Yi ◽  
Zijia Liu ◽  
Meng Wang ◽  
Mengting Sun ◽  
Xue Jiang ◽  
...  

Abstract: Acute ischemic stroke is one of the leading causes of disability and death worldwide. The brain tissue adjacent to the central necrotic core was first defined as ischemic penumbra characterized by reduced cerebral blood flow (CBF) with electrical failure but maintained ionic homeostasis and transmembrane electrical potentials. Since then, the evolving concepts of the ischemic penumbra have been proposed based on energy metabolism, CBF thresholds and protein synthesis, which provide insight for the diagnosis and treatment of acute ischemic stroke. This paper summarizes the recent advances in the understanding of ischemic penumbra, from its discovery to the diagnosis methods based on imaging techniques and biomarkers, finally some of the treatments developed. In addition, we discussed future perspectives on therapeutic targets beyond ischemic penumbra to develop a treatment for acute ischemic stroke.

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sungmin Hong ◽  
Anne-katrin Giese ◽  
Markus D Schirmer ◽  
Adrian V Dalca ◽  
Anna Bonkhoff ◽  
...  

Objective: Ability of the brain to recover after an acute ischemic stroke (AIS) is linked to the pre-stroke burden of white matter hyperintensity (WMH), a radiographic marker of brain health. We sought to determine the excessive WMH burden in an AIS population and investigate its association with 3-month stroke outcomes. Data: We used 2,435 subjects from the MRI-GENIE study. Three-month functional outcomes of 872 subjects among those subjects were measured by 90-day modified Ranking Scale (mRS). Methods: We automatically quantified WMH volume (WMHv) on FLAIR images and adjusted for a brain volume. We modeled a trend using the factor analysis (FA) log-linear regression using age, sex, atrial fibrillation, diabetes, hypertension, coronary artery disease and smoking as input variables. We categorized three WMH burden groups based on the conditional probability given by the model (LOW: lower 33%, MED: middle 34%, and HIGH: upper 33%). The subgroups were compared with respect to mRS (median and dichotomized odds ratio (OR) (good/poor: mRS 0-2/3-6)). Results: Five FA components out of seven with significant relationship to WMHv (p<0.001) were used for the regression modeling (R 2 =0.359). The HIGH group showed higher median (median=2, IQR=2) mRS score than LOW (median=1, IQR=1) and MED (median=1, IQR=1). The odds (OR) of good AIS outcome for LOW and MED were 1.8 (p=0.0001) and 1.6 (p=0.006) times higher than HIGH, respectively. Conclusion: Once accounted for clinical covariates, the excessive WMHv was associated with worse 3-month stroke outcomes. These data suggest that a life-time of injury to the white matter reflected in WMH is an important factor for stroke recovery and an indicator of the brain health.


2018 ◽  
Vol 27 (12) ◽  
pp. 1763-1777 ◽  
Author(s):  
Sheng-Wen Wang ◽  
Zhong Liu ◽  
Zhong-Song Shi

Non-coding RNAs (ncRNAs) are a class of functional RNAs that regulate gene expression in a post-transcriptional manner. NcRNAs include microRNAs, long non-coding RNAs and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes, including cerebral ischemic injury, neurodegeneration, neural development, and plasticity. Stroke is one of the leading causes of death and physical disability worldwide. Acute ischemic stroke (AIS) occurs when brain blood flow stops, and that stoppage results in reduced oxygen and glucose supply to cells in the brain. In this article, we review the latest progress on ncRNAs in relation to their implications in AIS, as well as their potential as diagnostic and prognostic biomarkers. We also review ncRNAs acting as possible therapeutic targets in future precision medicine. Finally, we conclude with a brief discussion of current challenges and future directions for ncRNAs studies in AIS, which may facilitate the translation of ncRNAs research into clinical practice to improve clinical outcome of AIS.


2016 ◽  
Vol 27 (5) ◽  
pp. 501-510 ◽  
Author(s):  
Jingrui Pan ◽  
Xiangpen Li ◽  
Ying Peng

AbstractStroke is a leading cause of disability with high morbidity and mortality worldwide. Of all strokes, 87% are ischemic. The only approved treatments for acute ischemic stroke are intravenous thrombolysis with alteplase within 4.5 h and thrombectomy within 8 h after symptom onset, which can be applied to just a few patients. During the past decades, ischemic preconditioning has been widely studied to confirm its neuroprotection against subsequent ischemia/reperfusion injury in the brain, including preconditioning in situ or in a remote organ (such as a limb) before onset of brain ischemia, the latter of which is termed as remote ischemic preconditioning. Because acute stroke is unpredicted, ischemic preconditioning is actually not suitable for clinical application. So remote ischemic conditioning performed during or after the ischemic duration of the brain was then designed to study its neuroprotection alone or in combination with alteplase in animals and patients, which is named as remote ischemic perconditioning or remote ischemic postconditioning. As expected, animal experiments and clinical trials both showed exciting results, indicating that an evolution in the treatment for acute ischemic stroke may not be far away. However, some problems or disputes still exist. This review summarizes the research progress and unresolved issues of remote ischemic conditioning (pre-, per-, and post-conditioning) in treating acute ischemic stroke, with the hope of advancing our understanding of this promising neuroprotective strategy for ischemic stroke in the near future.


2017 ◽  
Vol 10 (3) ◽  
pp. 279-284 ◽  
Author(s):  
Katsuharu Kameda ◽  
Junji Uno ◽  
Ryosuke Otsuji ◽  
Nice Ren ◽  
Shintaro Nagaoka ◽  
...  

Background and purposeOptimal thresholds for ischemic penumbra detected by CT perfusion (CTP) in patients with acute ischemic stroke (AIS) have not been elucidated. In this study we investigated optimal thresholds for salvageable ischemic penumbra and the risk of hemorrhagic transformation (HT).MethodsA total of 156 consecutive patients with AIS treated with mechanical thrombectomy (MT) at our hospital were enrolled. Absolute (a) and relative (r) CTP parameters including cerebral blood flow (aCBF and rCBF), cerebral blood volume (aCBV and rCBV), and mean transit time (aMTT and rMTT) were evaluated for their value in detecting ischemic penumbra in each of seven arbitrary regions of interest defined by the major supplying blood vessel. Optimal thresholds were calculated by performing receiver operating characteristic curve analysis in 47 patients who achieved Thrombolysis In Cerebral Infarction (TICI) grade 3 recanalization. The risk of HT after MT was evaluated in 101 patients who achieved TICI grade 2b–3 recanalization.ResultsAbsolute CTP parameters for distinguishing ischemic penumbra from ischemic core were as follows: aCBF, 27.8 mL/100 g/min (area under the curve 0.82); aCBV, 2.1 mL/100 g (0.75); and aMTT, 7.30 s (0.70). Relative CTP parameters were as follows: rCBF, 0.62 (0.81); rCBV, 0.83 (0.87); and rMTT, 1.61 (0.73). CBF was significantly lower in areas of HT than in areas of infarction (aCBF, p<0.01; rCBF, p<0.001).ConclusionsCTP may be able to predict treatable ischemic penumbra and the risk of HT after MT in patients with AIS.


2020 ◽  
Vol 7 (2) ◽  
pp. 55-60
Author(s):  
Hossein Aghamiri ◽  
Sepideh Paybast ◽  
Behnam Safarpour Lima ◽  
Behnam Mansoori

Cerebrovascular disease is the second cause of death and the sixth cause of morbidity worldwide, which will rise to fourth place by 2020. The treatment strategies for acute ischemic stroke (AIS) divided into two groups, including intravenous or intra-arterial thrombolysis and mechanical thrombectomy. Regarding growing development in the realm of diagnosis and treatment of stroke through state-of-the-art approaches, including emergent thrombectomy, there are new opportunities for investigation in this area. This is while a rough rate of 85% for strokes is occupied by, and the remained is hemorrhagic. Hence, the present study aimed to review recent advances in AIS with a focus on emergent thrombectomy. Here, we first provided the relevant history, and then the recent advances were discussed. The library data collection method was employed so that such databases as Web of Science, PubMed, and Science Direct used for data extraction. The evidence confirms the importance of emergent thrombectomy as all believe the famous statement "time is the brain." However, further investigations are required to find more strong evidence accordingly.


2000 ◽  
Vol XXXII (3-4) ◽  
pp. 76-76
Author(s):  
J. Yrjanheikki ◽  
T. Tikka ◽  
R. Keinanen ◽  
G. Goldsteins ◽  
P. H. Chan ◽  
...  

One of the reasons for the insufficient effectiveness of treatment of acute ischemic stroke may be secondary inflammation of the brain tissue, which, according to the results of modern studies, significantly worsens the consequences and outcome of the disease.


Author(s):  
Joseph Perosky ◽  
Adam Biddle ◽  
Kim DeGraaf ◽  
Whitney Hovan ◽  
Choi M. Li ◽  
...  

Ischemic stroke affects nearly 690,000 patients a year in the United States and is the leading cause of long-term disability and the third leading cause of death [1, 2]. Acute ischemic stroke occurs when a clot becomes lodged in a cerebral vessel, cutting off blood supply to areas of the brain. There are two treatment options for acute ischemic stroke: tissue plasminogen activator (beneficial within the first 4 hours of stroke onset), and mechanical removal (beneficial from 4 to 8 hours after stroke onset). The two FDA approved clot removal devices (MERCI and Penumbra) for ischemic stroke are capable of achieving revascularization rates between 48% and 80% [3, 4].


2017 ◽  
Vol 39 (3) ◽  
pp. 454-465 ◽  
Author(s):  
Alexander Seiler ◽  
Nicholas P Blockley ◽  
Ralf Deichmann ◽  
Ulrike Nöth ◽  
Oliver C Singer ◽  
...  

Oxygenation-sensitive spin relaxation time T2′ and relaxation rate R2′ (1/T2′) are presumed to be markers of the cerebral oxygen extraction fraction (OEF) in acute ischemic stroke. In this study, we investigate the relationship of T2′/R2′ with dynamic susceptibility contrast-based relative cerebral blood flow (rCBF) in acute ischemic stroke to assess their plausibility as surrogate markers of the ischemic penumbra. Twenty-one consecutive patients with internal carotid artery and/or middle cerebral artery occlusion were studied at 3.0 T. A physiological model of the cerebral vasculature (VM) was used to process PWI raw data in addition to a conventional deconvolution technique. T2′, R2′, and rCBF values were extracted from the ischemic core and hypoperfused areas. Within hypoperfused tissue, no correlation was found between deconvolved rCBF and T2′ ( r = −0.05, p = 0.788), or R2′ ( r = 0.039, p = 0.836). In contrast, we found a strong positive correlation with T2′ ( r = 0.444, p = 0.006) and negative correlation with R2′ ( r = −0.494, p = 0.0025) for rCBFVM, indicating increasing OEF with decreasing CBF and that rCBF based on the vascular model may be more closely related to metabolic disturbances. Further research to refine and validate these techniques may enable their use as MRI-based surrogate markers of the ischemic penumbra for selecting stroke patients for interventional treatment strategies.


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