Fig 6 - uploaded by Forough Sodaei
Content may be subject to copyright.
-MRI perfusion-diffusion mismatch. The small lesion on diffusion-weighted imaging (DWI) represents the infarct core, while the much larger area in the time to peak map calculated from perfusion imaging (PWI) identifies the area of critically hypoperfused tissue (prolonged TTP).
Source publication
Ischemic etiology of stroke is the most common health issue. Differentiating the ischemic core from the associated penumbra is tremendously important in tailoring an effective therapeutic strategy and potential intervention. Additionally, the degree of cell damage adjacent to the ischemic core may be either reversible or irreversible, which may als...
Contexts in source publication
Context 1
... depicts areas of brain tissue with reduced cerebral blood flow that occur with the onset of an acute occlusion, whereas lesions on DWI have long been thought to represent severely injured tissue. DWI in combination with PWI has shown great promise for the identification of brain tissue in patients with acute ischemic stroke ( Fig. 6 ) that is dysfunctional because of low blood flow but potentially salvageable on the restoration of blood flow [9] . The mismatch between DWI and PWI volumes represents the tissue at risk of an infraction and thus, the target tissue for reperfusion treatment. ...
Context 2
... depicts areas of brain tissue with reduced cerebral blood flow that occur with the onset of an acute occlusion, whereas lesions on DWI have long been thought to represent severely injured tissue. DWI in combination with PWI has shown great promise for the identification of brain tissue in patients with acute ischemic stroke ( Fig. 6 ) that is dysfunctional because of low blood flow but potentially salvageable on the restoration of blood flow [9] . The mismatch between DWI and PWI volumes represents the tissue at risk of an infraction and thus, the target tissue for reperfusion treatment. ...
Similar publications
Ischemic postconditioning (PostC) conventionally refers to a series of brief blood vessel occlusions and reperfusions, which can induce an endogenous neuroprotective effect and reduce cerebral ischemia/reperfusion (I/R) injury. Depending on the site of adaptive ischemic intervention, PostC can be classified as in situ ischemic postconditioning (ISP...
Citations
... The core receives nearly 10-25% of normal blood flow from the affected vessels resulting in irreversible necrosis. The penumbra, which is ischemic tissue surrounding the core, receives blood from collateral circulation, delaying the completion of the infarct [10]. These neurons are considered salvable if reperfused within a timely manner and are the target of treatment [11]. ...
... 5 Open access and alleviate neurotoxicity, specifically in the tissue surrounding the infarction core, known as the ischaemic penumbra. 6 Given the multifactorial nature of ischaemic brain tissue pathology, 7 previous attempts at clinical trials have been largely unsuccessful due to the interference of these treatments with vital physiological processes, as well as targeting pathological events. 8 9 Therefore, recognising these specific pathological and neuroprotective elements of the neurovascular unit can provide novel therapeutic approaches for ischaemic stroke. ...
Background
Stroke is a major cause of global mortality and disability. Currently, the treatment of acute ischaemic stroke through reperfusion has posed several challenges, raising the need for complementary options to protect the ischaemic penumbra. Recent investigations have indicated that certain epigenetic factors, specifically, histone deacetylases (HDACs) and sirtuins, can be promising for ischaemic stroke therapy, with recent studies suggesting that inhibitors of HDACs or sirtuins may provide neuronal protection after ischaemic stroke. However, the impact of specific HDAC/sirtuin isoforms on the survival of neuronal cells following stroke is still uncertain. This study aims to provide a comprehensive overview of the function of HDACs and their modulators in the treatment of acute ischaemic stroke.
Methods
This systematic review and meta-analysis will encompass animal intervention studies that explore the efficacy of modulation of HDACs and sirtuins in the acute phase of ischaemic stroke. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches will be conducted in PubMed, Web of Science and Scopus, with subsequent screening by independent reviewers based on the established eligibility criteria. Methodological quality will be evaluated using the SYRCLE risk of bias tool. The primary outcomes will be infarct volume and functional response, with the secondary outcomes established a priori. Data pertaining to infarct volume will be used for random-effects meta-analysis. Additionally, a descriptive summary will be conducted for the functional response and secondary outcomes.
Discussion
No systematic review and meta-analysis on the treatment of ischaemic stroke through HDAC modulation has been conducted to date. A comprehensive analysis of the available literature on the relevant preclinical investigations can yield invaluable insights in discerning the most effective trials and in further standardisation of preclinical studies.
Systematic review registration
This systematic review has been recorded in the International Prospective Register of Systematic Reviews (PROSPERO), with the assigned reference number: CRD42023381420
... However, failure to maintain or restore blood flow leads to the death of brain tissue, resulting in infarction. Another critical concept in understanding stroke is the ischemic penumbra, defined as the ischemic but reversibly dysfunctional tissue surrounding a core area of infarction (4). This area will progress to infarction if blood flow is not restored, making the preservation of the penumbra a crucial goal in vascularization therapies. ...
Background: Ischemic stroke is a leading cause of morbidity and mortality worldwide, prompting an urgent need for effective treatments outside the standard therapeutic window. With an estimated 6.5 million stroke-related deaths annually and a particular prevalence in the 18-49 age demographic, there is a substantial burden on healthcare systems. Intravenous thrombolysis and mechanical thrombectomy are time-sensitive treatments that are not universally accessible, highlighting the need for alternative strategies. Objective: The study aimed to evaluate the efficacy of induced hypertension as a therapeutic intervention for ischemic stroke patients who are beyond the window for conventional reperfusion therapies. Methods: This cross-sectional observational study was conducted at the Hyper Acute Stroke Unit (HASU) of PEMH, Rawalpindi. Over four months, 50 male patients who had suffered an ischemic stroke and were outside the therapeutic window for TPA and mechanical thrombectomy were recruited. Induced hypertension was achieved through intravenous administration of norepinephrine, titrated to maintain systolic blood pressure between 180-200 mmHg. Blood pressure was recorded at baseline, immediately before norepinephrine administration, and every 12 hours thereafter. Muscle power was assessed using the Medical Research Council (MRC) scale at 24-hour intervals over a 3-day observational period. Results: The mean systolic blood pressure was 140±5.07 mmHg, and the mean diastolic blood pressure was 94.16±4.71 mmHg, with a mean patient age of 55±4.4 years. Following induced hypertension, 30 out of the 50 patients (60%) showed improvement in muscle power. Specifically, in Group 1 (6 patients with leg muscle weakness), 3 patients improved from an MRC scale of 2 to 3, and 1 patient improved from an MRC scale of 3 to 4. In Group 2 (15 patients with upper and lower limb weakness), 7 patients improved from an MRC scale of 2 to 3, and 4 patients improved from an MRC scale of 3 to 4. Similar improvements were observed in other groups, with overall improvements ranging from 37.5% to 80% within individual subgroups. Conclusion: Induced hypertension via norepinephrine infusion appears to be a promising therapeutic strategy to improve muscle power in ischemic stroke patients who cannot receive standard reperfusion treatments. This intervention could potentially bridge the treatment gap for patients who present outside of the traditional therapeutic time frame.
... The larger the mismatch ratio, the larger the penumbra. In summary, an MR perfusion-diffusion mismatch is an effective diagnostic imaging marker of AIS [32]. However, while MRI can effectively quantify the volume of the penumbra, it remains costly, of long duration, and generally limited in availability worldwide. ...
Stroke is the second most common cause of death worldwide, with 50% of survivors experiencing long-term disability. For more than two decades, treatment with intravenous thrombolysis (IVT) and mechanical endovascular thrombectomy (MET), the only approved stroke reperfusion therapies, was restricted to patients within the 4.5-6 hour time window, respectively. Therefore, patients who presented with acute ischemic stroke (AIS) beyond the conventional time window were excluded from reperfusion treatment. This narrative review aims to review the scientific literature on the possibilities of reperfusion therapies for patients who present with an unknown time of stroke onset, and those with stroke onset beyond the conventional 4.5-6 hour time window. Beyond the conventional time window, the eligibility of patients for IVT or MET, the two main therapeutic procedures, is decided based on the concept of penumbral imaging. Penumbral imaging identifies patients with hypoperfused but viable brain tissue, who could benefit from reperfusion. On the other hand, clock-based DWI-fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can detect stroke that has occurred within 4.5 hours in patients with an unknown time of onset, including patients who awaken with stroke. The introduction of penumbral imaging and MRI-based tissue clocking as imaging biomarkers for stroke has revolutionized stroke therapy, potentially allowing for personalized treatment of eligible stroke patients.
... The inhibition of the main pathway of neuronal damage is an attractive target for stroke treatment, but many inhibitors of the excitotoxic cascade have not been successful in clinical trials. Following the occlusion of a vessel, the ischemic changes in brain tissue depend on the degree of hypoxia (Sodaei and Shahmaei, 2020). The site which suffers the most significant decrease in blood flow is the ischemic core, where neurons rapidly undergo cell death (Phan et al., 2002). ...
The primary mechanism for neuron death after an ischemic stroke is excitotoxic injury. Excessive depolarization leads to NMDA-mediated calcium entry to the neuron and, subsequently, cellular death. Therefore, the inhibition of the NMDA channel has been proposed as a neuroprotective measure in ischemic stroke. The high morbimortality associated with stroke warrants new therapies that can improve the functional prognosis of patients. Memantine is a non-competitive NMDA receptor antagonist which has gained attention as a potential drug for ischemic stroke. Here we analyze the available preclinical and clinical evidence concerning the use of memantine following an ischemic stroke. Preclinical evidence shows inhibition of the excitotoxic cascade, as well as improved outcomes in terms of motor and sensory function with the use of memantine. The available clinical trials of high-dose memantine in patients poststroke have found that it can improve patients’ NIHSS and Barthel index and help patients with poststroke aphasia and intracranial hemorrhage. These results suggest that memantine has a clinically relevant neuroprotective effect; however, small sample sizes and other study shortcomings limit the impact of these findings. Even so, current studies show promising results that should serve as a basis to promote future research to conclusively determine if memantine does improve the outcomes of patients’ post-ischemic stroke. We anticipate that future trials will fill current gaps in knowledge, and these latter results will broaden the therapeutic arsenal for clinicians looking to improve the prognosis of patients poststroke.
... Magnetic resonance imaging (MRI) has significantly higher sensitivity and specificity than computed tomography for the diagnosis of acute ischemic infarction in the first few hours following onset [10]. The earliest rescue of the penumbra, the reversibly injured brain tissue surrounding an ischemic core and target for the treatment of acute stroke, is key for effective treatment [11]. ...
... Chalela et al. described that ASL in acute stroke successfully depicted perfusion deficits, restored perfusion, hyperperfusion, perfusion/diffusion mismatches, and delayed arterial transit in addition to providing quantitative cerebral blood flow determination [13]. The mismatch between DWI and ASL represents the penumbra, or the tissue at risk of infarction [10]. ...
It is considered acceptable to conservatively manage coronary artery bypass grafting patients with carotid artery disease without the need for preoperative corrective carotid revascularization. However, in the present case, rapidly progressive stroke symptoms with penumbra suggested in the arterial spin labeling, carotid artery stenting was performed successfully.
... 9) Magnetic resonance imaging (MRI) has signi cantly higher sensitivity and speci city than computed tomography for the diagnosis of acute ischemic infarction in the rst few hours following onset. 10) The earliest rescue of the penumbra, the reversibly injured brain tissue surrounding an ischemic core and target for the treatment of acute stroke, is key for effective treatment. 11) Arterial spin labeling (ASL) is an alternative non-invasive perfusion method that does not require contrast, 12) through which the penumbra can be detected from the mismatch between diffusion-weighted image (DWI) and ASL in MRI images. ...
... 12) The mismatch between DWI and ASL represents the penumbra, or the tissue at risk of infarction. 10) Although the exact timing of the stroke was also unknown in this case, the decision to perform urgent revascularization was made because of neurologic ndings that rapidly progressed within the examination alone, the presence of penumbra on imaging, and the possibility of reversible recovery with revascularization. Although immediately post-surgical cardiac patients may not be amenable to transport for MRI imaging due to the placement of various infusion pumps and lines and the limitation of hemodynamics on prolonged imaging or movement, it is recommended that these issues be worked through so that non-invasive ASL may be performed in conjunction with head MRI imaging. ...
It is considered acceptable to conservatively manage coronary artery bypass grafting patients with carotid artery disease without the need for preoperative corrective carotid revascularization. However, in the present case, rapidly progressive stroke symptoms with penumbra shown in the arterial spin labeling, carotid artery stenting was performed successfully.
... MRI is a precise diagnostic tool for many cerebrovascular diseases [7]. Specifically, CE-MRA is becoming increasingly common, and with improvement of the spatial resolution of this technique, identifying pathology including lesions and abnormalities of the large vessels and vertebral arteries will become a popular method [8]. ...
Background: The vertebral arteries originate from the root of the neck as the first branches of the subclavian arteries. Variations of vertebral arteries are congenital anomalies occurring during embryonic development. Anatomic variations of the left vertebral artery are clinically symptomless and recognized incidentally during angiographic assessments or imaging techniques so the diagnosis of these anomalies is a serious challenge. Anomalous origin of vertebral arteries may lead to neurologic disorders. It is, thus, important to identify variations of the large vessels of the aortic arch when planning neck and cervical spine interventions and diagnostic radiology. For this reason, we would like to present this rare case of the left vertebral artery showing a different origin.
... MRI is a precise diagnostic tool for many cerebrovascular diseases [7]. Specifically, CE-MRA is becoming increasingly common, and with improvement of the spatial resolution of this technique, identifying pathology including lesions and abnormalities of the large vessels and vertebral arteries will become a popular method [8]. ...
Background: The vertebral arteries originate from the root of the neck as the first branches of the subclavian arteries. Variations of vertebral arteries are congenital anomalies occurring during embryonic development. Anatomic variations of the left vertebral artery are clinically symptomless and recognized incidentally during angiographic assessments or imaging techniques so the diagnosis of these anomalies is a serious challenge. Anomalous origin of vertebral arteries may lead to neurologic disorders. It is, thus, important to identify variations of the large vessels of the aortic arch when planning neck and cervical spine interventions and diagnostic radiology. For this reason, we would like to present this rare case of the left vertebral artery showing a different origin.
