Identifying and utilizing the ischemic penumbra

Fisher, Marc; Baştan, Birgül

doi:10.1212/wnl.0b013e3182695814

Cited by 69 publications

(71 citation statements)

References 42 publications

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“…8 This potentially salvageable ischemic tissue is termed the ischemic penumbra and is the target of acute stroke therapy because saving all or part of the ischemic penumbra by initiating timely AIS treatment is the basis of acute stroke treatment. 9 Conversely, the ischemic region that has already progressed to irreversibility is called the ischemic core. Both regions can be identified and their extent approximated by advanced computed tomography (CT) and magnetic resonance imaging techniques that are clinically available.…”

mentioning

confidence: 99%

Acute Ischemic Stroke Therapy Overview

Catanese

Tarsia

Fisher

2017

Circulation Research

285

178

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A cute ischemic stroke (AIS) is a common disorder with almost 700 000 new or recurrent events per year in the United States. The risk of AIS varies by region, with the highest incidence occurring in the so-called stroke belt in the southern part of the country.1 The risk of AIS varies among African Americans, Latinos, and Caucasians, with the highest risk in African Americans. The risk of AIS increases with age, and the ageing of the US population portends an increase in AIS incidence and prevalence over the next several decades, despite increasingly effective efforts to treat stroke risk factors and the use of other preventive strategies.2 The incidence of AIS is also increasing in many other countries, largely related to potentially modifiable risk factors, especially in the developing world.3 The incidence of AIS is also greater among women beginning with an increased risk in the perimenopausal period and continuing into older age groups. Abstract: The treatment of acute ischemic stroke has undergone dramatic changes recently subsequent to the demonstrated efficacy of intra-arterial (IA) device-based therapy in multiple trials. The selection of patients for both intravenous and IA therapy is based on timely imaging with either computed tomography or magnetic resonance imaging, and if IA therapy is considered noninvasive, angiography with one of these modalities is necessary to document a large-vessel occlusion amenable for intervention. More advanced computed tomography and magnetic resonance imaging studies are available that can be used to identify a small ischemic core and ischemic penumbra, and this information will contribute increasingly in treatment decisions as the therapeutic time window is lengthened. Intravenous thrombolysis with tissue-type plasminogen activator remains the mainstay of acute stroke therapy within the initial 4.5 hours after stroke onset, despite the lack of Food and Drug Administration approval in the 3-to 4.5-hour time window. In patients with proximal, large-vessel occlusions, IA device-based treatment should be initiated in patients with small/moderate-sized ischemic cores who can be treated within 6 hours of stroke onset. The organization and implementation of regional stroke care systems will be needed to treat as many eligible patients as expeditiously as possible. Novel treatment paradigms can be envisioned combining neuroprotection with IA device treatment to potentially increase the number of patients who can be treated despite long transport times and to ameliorate the consequences of reperfusion injury. Acute stroke treatment has entered a golden age, and many additional advances can be anticipated. (Circ Res. 2017;120:541-558.

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mentioning

confidence: 99%

Acute Ischemic Stroke Therapy Overview

Catanese

Tarsia

Fisher

2017

Circulation Research

285

178

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“…19,20 In particular, assessment of the penumbra and cellular responses of the infarcted area is being conducted which would help to evaluate the effects of interventions with therapeutic drugs for stroke by visualizing hypoxia, neuronal integrity, apoptosis, and neuroinflammation. 21,22 The present findings indicate that mapping of mGlu1 with PET is a useful alternative tool for characterizing neuronal integrity and has potential to be used as a biomarker in future therapeutic regimens.…”

Section: Strokementioning

confidence: 99%

Monitoring Neuroprotective Effects Using Positron Emission Tomography With [ ¹¹ C]ITMM, a Radiotracer for Metabotropic Glutamate 1 Receptor

Yui¹,

Xie²,

Fujinaga³

et al. 2013

Stroke

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C]methoxy-N-methylbenzamide ([ 11 C]ITMM), a radiotracer for mGlu1. Methods-Rats were subjected to a 30-minute transient right middle cerebral artery occlusion. Saline or minocycline, a neuroprotective agent, was intravenously injected immediately after surgery and then daily during the subsequent 7 days. PET imaging with [ 11 C]ITMM was performed on the rats on days 1 to 7 after ischemia. In vitro autoradiography and histopathologic staining were conducted to confirm the results of in vivo PET. Results-PET with [11 C]ITMM demonstrated a gradual decrease of radioactivity in the ipsilateral sides of the ischemic brains. The radioactivity uptake ratio between the ipsilateral and contralateral sides also decreased with time. Minocycline treatment slowed down the decrease in the radioactivity level in the ipsilateral sides. Pretreatment with JNJ16259685, an mGlu1-selective ligand, significantly reduced brain radioactivity, confirming that the uptake of [ 11 C]ITMM primarily reflects mGlu1 levels in the brain regions, including the ischemic area. In vitro autoradiography and histopathology confirmed the changes in mGlu1 levels in the brains. Conclusions-[11 C]ITMM-PET may be a useful technique for characterizing the change in mGlu1 level during the occurrence and progression of neuronal damage and for evaluating the neuroprotective effects of drugs after ischemia.

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“…This tissue is ischemic penumbra. Ischemic penumbra is a main target of treatment for ischemic stroke [2,3] . One of the key methods to save the cells in ischemic penumbra is to improve angiogenesis or neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Inducible Factor-1α Promotes Neuroregeneration and Angiogenesis after Cerebral Ischemia

Xu²,

Wu³

2015

Ther Targets Neurol Dis

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To promote neuroregeneration and angiogenesis is a therapeutic target for the treatment of stroke. Hypoxia-inducible factor-1α (HIF-1α) has pleiotropic effects on neurogenesis, angiogenesis and neuroprotection in central nervous system. In this study we investigated whether HIF-1α treatment promotes the proliferation of ischemia induced neural stem cells (NSCs) and neuroregeneration in penumbra. The angiogenesis in penumbra was also investigated. Transient middle cerebral artery occlusion (tMCAO) rat model was used in this study. Rats were divided into 3 groups, Sham group, vehicle group and HIF-lα group. In this study, we found that rats with HIF-1α treatment had better behavioral recovery at day7, 14, 21 and 28 (p<0.05). HIF-lα treatment increased the number of ischemia induced endogenetic NSCs in penumbra obviously (p<0.01). HIF-1α also improved newborn neurons and glial cells in penumbra on the 28 d (p<0.01). HIF-1α treatment promoted expression of erythropoietin (EPO) in peri-ischemic area. Vascular endothelial growth factor (VEGF) expression in HIF-lα group was significantly higher than that in vehicle group (p<0.01). Number of CD 31 positive vascular in penumbra in HIF-lα treatment group was much more than that in vehicle group (p<0.01). In conclusion, our results indicate that modulate HIF-1α after ischemia may be a therapeutic target for the treatment of ischemic stroke through promoting neuroregeneration and angiogenesis.

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Identifying and utilizing the ischemic penumbra

Cited by 69 publications

References 42 publications

Acute Ischemic Stroke Therapy Overview

Acute Ischemic Stroke Therapy Overview

Monitoring Neuroprotective Effects Using Positron Emission Tomography With [ ¹¹ C]ITMM, a Radiotracer for Metabotropic Glutamate 1 Receptor

Hypoxia-Inducible Factor-1α Promotes Neuroregeneration and Angiogenesis after Cerebral Ischemia

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Identifying and utilizing the ischemic penumbra

Cited by 69 publications

References 42 publications

Acute Ischemic Stroke Therapy Overview

Acute Ischemic Stroke Therapy Overview

Monitoring Neuroprotective Effects Using Positron Emission Tomography With [ 11 C]ITMM, a Radiotracer for Metabotropic Glutamate 1 Receptor

Hypoxia-Inducible Factor-1α Promotes Neuroregeneration and Angiogenesis after Cerebral Ischemia

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Monitoring Neuroprotective Effects Using Positron Emission Tomography With [ ¹¹ C]ITMM, a Radiotracer for Metabotropic Glutamate 1 Receptor