Cerebral Artery Occlusion Research Articles

FoxO1 and Wnt/β-catenin signaling pathway: Molecular targets of human amniotic mesenchymal stem cells-derived conditioned medium (hAMSC-CM) in protection against cerebral ischemia/reperfusion injury

Ischemia-reperfusion (I/R) injury has weakened the effects of available treatment options for ischemic stroke. Although conditioned medium obtained from human amniotic mesenchymal stem cells (hAMSC-CM) has been reported to exert protective effect against stroke, detailed knowledge about its possible molecular mechanisms is not still completely available. The present study was designed to investigate whether hAMSC-CM can modulate FoxO1 and Wnt/β-catenin signaling pathway after ischemic stroke to create neuroprotective effects.Middle cerebral artery occlusion (MCAO) model with male Wistar rats was used to evaluate the effects of hAMSC-CM on activities of FoxO1, Wnt/β-catenin signaling pathway, and endogenous antioxidant system and apoptotic cell death. The results demonstrated that induction of MCAO significantly reduced activities of FoxO1, Wnt/β-catenin signaling pathway, and endogenous antioxidant system and enhanced apoptotic cell death (P < 0.05). In addition, treatment by hAMSC-CM immediately after cerebral reperfusion resulted in significantly reduced infarct size and increased activities of FoxO1, Wnt/β-catenin signaling pathway, and restoring endogenous antioxidant system and suppressing apoptotic cell death (P < 0.05). Likewise, increased activity of Wnt/β-catenin signaling pathway resulted in suppressing the neuroinflammation by inhibiting the expression of TNF-α and increasing the expression of IL-10. These findings demonstrate that hAMSC-CM can be considered as an excellent candidate in the treatment of acute ischemic stroke in clinical routine.

Aloe-emodin prevents nerve injury and neuroinflammation caused by ischemic stroke via the PI3K/AKT/mTOR and NF-κB pathway.

Ischemic stroke (IS) caused by cerebral arterial occlusion is the leading cause of global morbidity and mortality. Cellular oxidative stress and inflammation play a vital role in the pathological process of neural damage in IS. It is necessary to develop functional food or drugs, which target neuroinflammation and oxidation mechanisms against IS. The molecule compound aloe-emodin (AE) is derived from aloe and rhubarb. However, the exact mechanism of the pharmacological action of AE on IS remains unclear. Here, for aiming to demonstrate the mechanism of AE, our study explored the middle cerebral occlusion reperfusion (MCAO/R) rats in vivo, oxygen and glucose deprivation reperfusion (OGD/R), and lipopolysaccharide (LPS)-stimulated cells in vitro. We found that AE significantly improved the infarct size and behavioral score of MCAO/R rats, decreased the expression of TNF-α, MDA, LDH, Caspase 3, and increased the expression of SOD, Bcl-2/Bax. Liquid chromatography-mass spectrometry (LC/MS) results showed that AE could penetrate the blood-brain barrier in the sham group and MCAO/R group. In vitro, AE significantly protected SH-SY5Y cells from the insult of OGD/R and reduced the production of inflammatory cytokines in BV2 cells stimulated by LPS. In vivo and in vitro, western blot analysis results showed that AE significantly increased the expression of PI3K, AKT and mTOR proteins. In addition, AE significantly decreased NF-κB protein expression in BV2 cells. The use of AKT-specific inhibitor MK-2206 2HCL to inhibit AKT expression can block the protective effect of AE on SH-SY5Y cells subjected to OGD/R insults. Overall, our study suggests that AE protected against cerebral ischemia-reperfusion injury probably via the PI3K/AKT/mTOR and NF-κB signaling pathways. Thus, these results indicated that AE could be a promising first-line therapy for preventing and treating ischemic stroke and can be used as functional food.

Dilated cardiomyopathy-related stroke mimicking large-artery atherosclerosis-related stroke: report of two cases

The clinical characteristics and treatment of stroke caused by dilated cardiomyopathy (DCM) are not clear, especially in patients with large-artery atherosclerosis (LAA)-related stenosis, which commonly causes acute ischemic stroke (AIS); therefore, the diagnosis and treatment of such patients are challenging. Herein, we summarize the clinical characteristics and suggest clues to guide the diagnosis and treatment of two cases. Case 1: A 67-year-old woman with a history of DCM presented with sudden-onset slurred speech and left limb weakness (&gt;2 hours duration), which worsened after intravenous thrombolysis. Repeated brain computed tomography showed no hemorrhage; thus, cerebral artery occlusion or embolism was suspected. Emergency magnetic resonance imaging (MRI) and angiography (MRA) revealed acute multiple bilateral cerebral infarctions and severe left middle cerebral artery stenosis, respectively. We considered a DCM-related stroke and administered anticoagulation therapy. Subsequently, the patient’s symptoms improved significantly, and she was discharged on day 9, after showing no abnormal neurological signs. Case 2: A 49-year-old man with a history of DCM presented with acute headache and blurred vision for 4 days. MRI and MRA revealed multiple acute cerebral infarctions and left vertebral artery stenosis, respectively. We considered an LAA-related stroke and administered antiplatelet and cholesterol-lowering drugs. Eventually, the patient was discharged on day 13, after his right-sided hemianopia improved significantly. Both patients had LAA, which can be easily misdiagnosed as a stroke. LAA-related and DCM-related stroke need to be differentiated. DCM-related AIS lesions are often distributed in the areas supplied by the different cerebral arteries. It is necessary to carefully analyze the shape, location, and scope of the lesions, and identify the main causes of stroke. Anticoagulant therapy is preferred for DCM-related AIS.

Effect of Ultramicro Superparamagnetic Iron Oxide Nanoparticles on Cerebral Infarction in Mice.

To investigate the effect of Feraheme (ferumoxytol) intravenous injection on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion. We randomly divided 30 CS7BL6J mice into sham operated group, normal saline control group, and Feraheme group with 10 mice in each group. The model of permanent occlusion of right middle cerebral artery was made via the modified suture method in the normal saline control group and the Feraheme group. After 24 h of establishment the model, the tail vein was injected with 18 mg/kg Feraheme in the sham operation group and Feraheme group, and the normal saline control group was injected with an equal volume of normal saline. Neurobehavioral scores were obtained 24 h (before injection of Feraheme or normal saline) and 48 h (before MRI) after the model was established. The volume of cerebral infarction was calculated according to T2 weighted imaging. Orbital blood was collected after nodal scanning to detect serum TNF-α, IL-1β, and IL-6 levels. Then, the brain tissues of mice were killed for HE staining and IBAL immunohistochemical staining. No significant differences in cerebral infarction volume and neurological function were observed between the normal saline control group and Feraheme group. The levels of TNF-α, IL-1β and IL-6 in the normal saline control group and Feraheme group were significantly higher than those in the sham operation group (P < 0.05), but there were no significant differences between the normal saline control group and Feraheme group. We showed that intravenous injection of 18 mg/kg Feraheme 24 h after cerebral ischemia does not affect the infarct volume and inflammatory response, suggesting that the dose of Feraheme can be used for molecular imaging studies of inflammatory response after cerebral ischemia.

Peripheral arterial occlusion due to COVID-19: CT angiography findings of nine patients

BackgroundReports have indicated an association of large vessel peripheral arterial occlusion in the setting of Coronavirus Disease 2019 (COVID-19). While prior investigations have mostly focused on venous or cerebral arterial occlusions, we examined patients presenting exclusively with peripheral arterial extremity occlusions to investigate for any predisposing factors in this subset of COVID-19 patients. Materials and methodsThis is a retrospective study of COVID-19 patients with peripheral arterial occlusions presenting to a multi-hospital health care system in New York City between February 1st, 2020 and April 30th, 2020. Patient data and computed tomography angiography (CTA) exams in this subset were then collected and analyzed. ResultsFor the months of February, March, and April 2020, we identified 9 patients (ages 37–93 yrs) at our health care system who underwent extremity CTA for large vessel upper or lower extremity arterial occlusion and were diagnosed with COVID-19. Patient medical histories and clinical parameters were evaluated to identify common risk factors including obesity, hypertension, hyperlipidemia, and diabetes. Patients presented with increased inflammatory markers including ferritin, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as increased D-dimer. ConclusionOur findings suggest patients with COVID-19 and comorbidities presenting with elevated inflammatory markers and D-dimer may be at increased risk of large vessel peripheral arterial occlusion.

Long Non-Coding RNA SNHG7 Alleviates Oxygen and Glucose Deprivation/Reoxygenation-Induced Neuronal Injury by Modulating miR-9/SIRT1 Axis in PC12 Cells: Potential Role in Ischemic Stroke.

ObjectiveThe roles of long non-coding RNA (lncRNAs) in ischemic stroke (IS) have been widely illustrated. Here, we focused on the function and mechanism of lncRNA SNHG7 in IS.MethodsMiddle cerebral artery occlusion (MCAO) was used for inducing mice to establish IS models in vivo. Oxygen and glucose deprivation/reoxygenation (OGD/R) was used for treating PC12 cells to establish IS models in vitro. Relative expression of SNHG7 and miR-9 was determined by qRT-PCR. The neuronal injury was assessed by measuring relative activity of ROS, malondialdehyde (MDA) level and cell viability. Cell viability was determined by MTT assay. Dual-luciferase reporter (DLR) assay was employed to test the target of SNHG7 or miR-9. Western blot was used to determine the protein expression of SIRT1. Apoptosis rate was measured by flow cytometry.ResultsSNHG7 was down-regulated and miR-9 was up-regulated by MCAO treatment in brain tissues of mice and by OGD/R treatment in PC12 cells. Overexpression of SNHG7 or suppression of miR-9 decreased the relative activity of ROS and the MDA level as well as enhancing cell viability, and SNHG7 reduced apoptosis rate in OGD/R-induced PC12 cells (IS cells). MiR-9 was targeted by SNHG7 and SIRT1 was targeted by miR-9. The protein expression of SIRT1 was reduced by OGD/R treatment in PC12 cells. The suppressive effects of SNHG7 on the relative activity of ROS, the MDA level and apoptosis rate as well as the promotion effect of SNHG7 on cell viability were reversed by miR-9 mimics or sh-SIRT1 in IS cells.ConclusionLncRNA SNHG7 alleviated OGD/R-induced neuronal injury by mediating miR-9/SIRT1 axis in vitro.

Approaching the Boundaries of Endovascular Treatment in Acute Ischemic Stroke

Little is known about catheter-based endovascular treatment of vertebrobasilar artery branch occlusion (VEBABO) in acute ischemic stroke (AIS). Nonetheless, the experience of mechanical thrombectomy (MT) in distal small sized arteries of the anterior circulation seems promising in AIS. In this multicenter study, we report the feasibility, efficacy and safety of MT in VEBABO. Retrospective analysis of consecutive AIS patients treated with MT due to VEBABO including posterior and anterior inferior cerebellar artery (PICA, AICA) and superior cerebellar artery (SCA) occlusions at seven tertiary care centers between January 2013 and May 2020. Baseline demographics and angiographic outcomes including recanalization success of the affected cerebellar arteries and procedural complications were recorded. Clinical outcomes were evaluated by the modified Rankin scale (mRS) at discharge and 90days. Out of 668 endovascularly treated posterior circulation strokes we identified 16 (0.02%) cases with MT for VEBABO. Most frequently, MT of the SCA was done (13/16, 81%). Most VEBABOs occurred after MT of initial basilar/posterior cerebral artery occlusion (9/16, 56%). In 10/16 (63%) procedures, the affected VEBABO was successfully recanalized. Out of four patients three (75%) with isolated VEBABO had benefited from endovascular therapy. Subarachnoid hemorrhage was observed in 3/16 (19%) procedures. The rate of favorable outcome (mRS ≤2) was 40% at discharge and 47% at 90-day follow-up. Mortality was 13% (2/15). The use of MT for VEBABO is rare but appears to be feasible and effective; however, the comparatively high rate of procedure-related hemorrhage highlights that the indications for MT in these occlusion sites should be carefully weighed up.

Endovascular treatment results in patients with large cerebral artery occlusions in a metropolis. Moscow Stroke Registry data over 2019

Objective: to assess results from the Stroke Network created on the basis of the Infarction Network in the metropolis Moscow for endovascular treatment in patients with occlusion of the large cerebral artery (the internal carotid artery, the M1 and M2 segments of the middle cerebral artery, and the main artery).Patients and methods. A total of 742 thromboextractions were performed in patients with ischemic stroke in Moscow Stroke Network hospitals in 2019. The final analysis included 729 patients aged 25 to 97 years (mean age, 71 years); of them there were 370 (50.8%) men and 359 (49.2%) women. The selection criteria for endovascular treatment for ischemic stroke were consistent with those set out in the 2015 American Heart Association/American Stroke Association (AHA/ASA) guidelines, which included a pre-stroke modified Rankin Scale (MRS) score of 0–1; ≥18 years of age; a National Institutes of Health Stroke Scale (NIHSS) score of ≥6; and an Alberta Stroke Programme Early CT score (ASPECTS) ≥6. The angiographic results were assessed using the Thrombolysis in Cerebral Infarction (TICI) scale. The clinical outcomes were measured with the NIHSS and the MRS.Results and discussion. Successful recanalization (TICI 2b/3) was achieved in 547 (75%) patients. The predominant technique for thromboextraction was thromboaspiration that was used in 376 (51.6%) patients. Combined procedures (the co-use of an aspiration catheter and a stent retriever) were the second most commonly used – in 231 (31.7%) patients. By the end of the 20th day, good functional recovery (MSR 0–2 scores) was observed in 213 (29.2%) patients. The 20-day mortality rate was 31.8%.Conclusion. The successfully functioning Infarction Network in Moscow was used to create the Stroke Network for treatment in patients with ischemic stroke and large cerebral artery occlusion, the clinical results of which are comparable to large European registry studies.

Utility of Hounsfield unit in the diagnosis of tandem occlusion in acute ischemic stroke

BackgroundTandem occlusions can complicate medical and endovascular stroke treatment. To identify these occlusions, computed tomography angiography (CTA) represents the best imaging modality. However, CTA is still not initially performed in some patients not admitted directly to stroke centers. Early identification of an additional occlusion of the proximal extracranial internal carotid artery may improve the best suitable treatment strategy. The purpose of this study was to find a valuable threshold of thrombus attenuation in a non-contrast head CT (NCCT) scan to facilitate a safe diagnosis of tandem occlusions.Materials and methodsConsecutive patients with acute middle cerebral artery (MCA) occlusions who underwent endovascular treatment were identified from our registry of neuroendovascular interventions. Thrombus attenuations of the affected MCA and contralateral vessel were measured by NCCT. To compare individual baseline blood attenuations, the difference between the thrombus attenuation and the contralateral MCA attenuation (referred to as ΔTM) was calculated.ResultsThree hundred and twenty-five patients were included. There was a highly significant difference between mean thrombus attenuation with isolated MCA occlusion and additional extracranial internal carotid artery (ICA) occlusion (49.9 ± 8 vs. 56.2 ± 10 Hounsfield units (HU); P < 0.001). The area under the receiver operating characteristic curve of ΔTM was 0.72. The optimal threshold value was 13.5 HU, with a sensitivity of 67.5% and a specificity of 68.6%.ConclusionDespite a significant difference in thrombus attenuation in MCA occlusions with an additional extracranial ICA occlusion compared with isolated MCA occlusions, a relevant threshold of thrombus attenuation was not found.

Analysis of motor performance and histomorphometry of skeletal muscles of rats exercised after cerebral ischemia

Introduction Cerebral ischemia causes muscle atrophy and motor incoordination in animals, impairing motor performance. Objective Thus, the objective of the present study was to analyze the motor performance and histomorphometry of the biceps brachii, soleus, and anterior tibialis muscles of rats submitted to a treadmill training program after induction of cerebral ischemia by the transient occlusion of the middle cerebral artery (MCAO). Materials and Methods To do so, twenty-four 30-day-old Wistar rats were utilized. The exercises were performed for 6 weeks on a leveled treadmill, for 30 min/day, 5 days a week, at a controlled speed of 8 m/min, and the MCAO surgery took place for 60 min. The animals were divided into the following experimental groups: SC (n = 6): control animals that underwent false surgery (operation without the induction of cerebral ischemia) and did not exercise (sedentary); CEA (n = 6): control animals exercised on the treadmill after the false surgery; SI (n = 6): sedentary ischemic animals; IEA (n = 6): animals exercised on the treadmill after the induction of cerebral ischemia. Results The type-II fibers atrophy in muscle soleo was observed in groups CEA (5125.63 ± 158.83) and SI (4982.38 ± 248.16) when compared to the SC (5927.98 ± 106.17) and IEA (6526.73 ± 195.08) groups. Conclusion It is concluded that the low intensity physical exercise performed on the treadmill for six weeks after the induction of cerebral ischemia by OMCA, promoted a decrease in the atrophy of muscles important of the ischemic animals, benefiting their motor performance.

Acute progressive stroke with middle cerebral artery occlusion caused by idiopathic hypereosinophilic syndrome: a case report

BackgroundIdiopathic hypereosinophilic syndrome (IHES) is associated with various organ system dysfunctions. Neurologic abnormalities have been previously noted in this syndrome. Cerebral infarction secondary to occlusion of large cerebral artery is rarely reported. Here we described a patient with IHES presented progressive multiple cerebral infarctions caused by bilateral middle cerebral artery occlusion.Case presentationA 55-year-old Chinese woman presented to our hospital with acute onset of right limbs weakness and slurred speech. Laboratory tests showed a significant eosinophilia of 5.29 × 109/L (normal, < 0.5), 49.9% of leukocytes. Brain magnetic resonance imaging (MRI) revealed multiple acute cerebral ischemic lesions. Magnetic resonance angiography (MRA) demonstrated stenosis in horizontal segment of right middle cerebral artery. A pretibial skin biopsy revealed eosinophilic infiltration around the capillaries in deep dermis and adipose tissue. The patient was given oral dual anti platelet agents and intravenous methylprednisolone. However, one week later, the patient presented significant neurological deterioration with right-sided hemiparesis and totally motor aphasia. Brain MRI and computed tomography perfusion (CTP) demonstrated new acute cerebral ischemia in left hemisphere. Digital subtraction angiography (DSA) revealed left middle cerebral artery completely occluded. The patient received a high-dose of intravenous methylprednisolone 500 mg per day and the eosinophil count quickly fell to normal within 2 days. She was transferred to a rehabilitation center and her neurological symptoms improved with modified Ranking Scale from 4 to 2.ConclusionsIHES is one of the rare causes of acute ischemic stroke with large cerebral artery occlusion. An early high-dose of corticosteroids therapy should be considered in cases of IHES patients. Our case study is benefit to clinical diagnosis and treatment of cerebral infarction with IHES.

Prestroke statin use enhances collateralization in acute ischemic stroke patients

Statin therapy has been shown to be effective in the prevention of ischemic stroke. In addition, recent studies have suggested that prior statin therapy could lower the initial stroke severity and improve stroke functional outcomes in the event of stroke. It was speculated that prestroke statin use may enhance collateral circulation and result in favorable functional outcomes. The aim of the study was to investigate the association of prestroke statin use with leptomeningeal collaterals and to determine the association of prestroke statin use with stroke severity and functional outcome in acute ischemic stroke patients. We prospectively and consecutively enrolled 239 acute ischemic stroke patients with acute infarction due to occlusion of the middle cerebral artery within 24 h in the neurology department of West China Hospital from May 2011 to April 2017. Computed tomographic angiography (CTA) imaging was performed for all patients to detect middle cerebral artery thrombus; regional leptomeningeal collateral score (rLMCS) was used to assess the degree of collateral circulation; the National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity at admission; the modified Rankin scale (mRS) was used to measure outcome at 90 days; and premorbid medications were recorded. Univariate and multivariate analyses were performed. Overall, 239 patients met the inclusion criteria. Fifty-four patients used statins, and 185 did not use statins before stroke onset. Prestroke statin use was independently associated with good collateral circulation (rLMCS > 10) (odds ratio [OR], 4.786; 95% confidence interval [CI], 1.195-19.171; P = 0.027). Prestroke statin use was not independently associated with lower stroke severity (NIHSS score≤14) (OR, 1.955; 95% CI, 0.657-5.816; p = 0.228), but prestroke statin use was independently associated with favorable outcome (mRS score≤2) (OR, 3.868; 95% CI, 1.325-11.289; P = 0.013). Our findings suggest that prestroke statin use was associated with good leptomeningeal collaterals and clinical outcomes in acute ischemic stroke (AIS) patients presenting with occlusion of the middle cerebral artery. However, clinical studies should be conducted to verify this claim.

Plasma nitrite as an indicator of cerebral ischemia during extracranial/intracranial bypass surgery in moyamoya patients

Background and PurposeNitric oxide (NO) plays a key role in ischemia and shows potential as a biomarker for ischemia. We measured mixed venous nitrite (NO2-) as a proxy for NO, during controlled cerebral ischemia in patients with moyamoya disease (MMD) during direct extracranial/intracranial (EC/IC) bypass surgery with temporary occlusion of the M4 branch of the middle cerebral artery (MCA) to permit anastomosis with the superficial temporal artery (STA). This small, focal ischemic event is not reliably detected using cerebral oximetry, somatosensory evoked potentials (SSEPs) or electroencephalography (EEG). MethodsWe enrolled nine adult MMD patients (n=8 female, n=1 male) undergoing direct EC/IC bypass surgery. Nitrite was measured at least one hour prior to MCA occlusion, and before, during and after anastomosis. Cortical function was monitored using either multi-lead EEG and SSEPs, or frontal EEG activity. ResultsMixed venous NO2- was significantly elevated (p<0.05) within 12 min following arterial occlusion vs. baseline. An M4 branch of the MCA was cross clamped for a median duration of 18 (IQR = 5) minutes during anastomosis. One patient with elevated NO2- showed a transient neurologic deficit that resolved 3 days post-operatively. ConclusionsMixed venous NO2- was significantly elevated shortly following cerebral artery occlusion vs. baseline in a majority of the study subjects, suggesting that NO2- is a potential biomarker for ischemia. Since all patients received identical burst suppression anesthesia and vasopressors, the fact that NO2- was not elevated during cross-clamp in all patients supports the conclusion that the NO2- elevation is likely due to ischemia.

Исследование механизма нейропротективного действия пептидного препарата Семакс в мозге крыс в условиях ишемии-реперфузии

Синтетический пептид АКТГ(4-7)PGP ускоряет регресс неврологических нарушений при ишемическом инсульте, однако молекулярные механизмы его действия полностью не известны. На модели полуторачасовой окклюзии средней мозговой артерии крыс был проведен анализ влияния пептида на экспрессию ряда генов и белков, вовлеченных в сигнальные пути, приводящие к воспалению и гибели клеток в условиях ишемии-реперфузии. Показано, что пептид через 24 ч от начала окклюзии снижает повышенный при ишемии уровень экспрессии в ишемизированной ткани мозга крыс мРНК провоспалительных цитокинов и хемокинов IL-1α, IL-1β, IL-6, TNF-α, Cxcl2 и Ccl3. Пептид снижал повышенные при ишемии уровни экспрессии белков металлопротеиназы ММР-9, транскрипционного фактора c-Fos, активных JNK киназ и предотвращал ишемическое снижение уровня активного транскрипционного фактора CREB. The synthetic peptide ACTH (4-7) PGP accelerates the regression of neurological disorders in ischemic stroke, but the molecular mechanisms of its action are not completely known. On the model of an hour and a half occlusion of the rat middle cerebral artery, an analysis was made of the effect of the peptide on the expression of a number of genes and proteins involved in signaling pathways leading to inflammation and cell death under conditions of ischemia-reperfusion. It was shown that the peptide 24 hours after the onset of occlusion reduces the level of expression of mRNA of pro-inflammatory cytokines and chemokines IL-1α, IL-1β, IL-6, TNF-α, Cxcl2 and Ccl3 in ischemic brain tissue. The peptide decreased the levels of expression of proteins metalloproteinase MMP-9, transcription factor c-Fos, active JNK kinases wich were increased under ischemia, and prevented ischemic decrease in the level of active transcription factor CREB.

О влиянии нового производного пиримидина PIR-4 на концентрацию маркеров внешнего и внутреннего путей апоптоза в условиях экспериментальной церебральной ишемии

Исследовано антиапоптотическое действие нового производного пиримидина под шифром PIR-4 в условиях экспериментальной фокальной церебральной ишемии у крыс линии Вистар, разделенных на 5 групп (n = 10). В первую группу включены ложнооперированные особи, вторая группа — крысы негативного контроля, получавшие взвесь очищенной воды и твина-80. Третья и четвертая группы представлены животными, получавшими препараты сравнения кавинтон (3,2 мг/кг) и глиатилин (60 мг/кг), соответственно. Пятой группе крыс вводили соединение PIR-4. Все соединения вводили сразу после моделирования ишемии и в течение 3 сут ежедневно. Модель фокальной ишемии мозга — окклюзия левой средней мозговой артерии (наркоз — хлоралгидрат, 350 мг/кг). В ходе проведенного исследования установлено, что на фоне моделируемой патологии возрастает концентрация фактора некроза опухоли (TNF-α), фактора, индуцирующего апоптоз (AIF), p53-зависимого модулятора апоптоза (PUMA), снижается уровень Jun-N-концевой киназы (JNK). Препараты сравнения кавинтон и глиатилин корректировали возникшие изменения, препятствуя развитию внешнего и внутреннего путей апоптоза. На фоне получения крысами вещества PIR-4 также уменьшал концентрацию маркеров каспаза-зависимого и каспаза-независимого путей апоптоза, при этом по антиапоптотическому эффекту, превосходя кавинтон и не уступая глиатилину.

Stroke in the young’s: about a young woman case

According to epidemiological data, stroke’s incidence is clearly growing, especially in young people under 45. Ischemic stroke is the most common type (80%). Many risk factors have been identified, including hypertension, tobacco, dyslipidemia, diabetes, alcohol, and oestroprogestogenic contraceptive pill. The main mechanisms are atheroma of large arterial trunks, occlusion of small cerebral arteries unrelated to atherosclerosis, and cardio-embolic causes. The aim of our study is to present a clinical case of ischemic stroke in young subjects caused by heart disease at high embolic risk.

The experience of simultaneous endovascular occlusion of arteriovenous malformation and saccular aneurism in a parturient woman

The clinical case of simultaneous endovascular bloodstream exclusion of arteriovenous malformation and saccular aneurysm in parturient woman is presented. Onyx liquid adhesive composition and monospiral aneurysm occlusion technique were used. Patient X., 31, was hospitalized to the clinic on the 10th day of the postpartum period. From the anamnesis: twice (at 20th and 27th weeks of pregnancy) patient suffered intraventricular hemorrhage due to the rupture of arteriovenous malformation in the posterior third of the corpus callosum, left lateral ventricle and left parietal lobe of the brain. After the first hemorrhage a conservative treatment tactic was determined, given the high risk of complications associated with the surgical intervention for the mother and fetus. After the second hemorrhage endovascular embolization of malformation was suggested, however, the patient and her husband refused surgery, preferring conservative therapy with subsequent surgical treatment after delivery. In addition to the malformation, according to the data of selective cerebral subtraction angiography multiple cerebral saccular aneurysms of the left Anterior Cerebral – Anterior Communicating Artery and 2 Anterior Cerebral Artery aneurysms (A2-A2, A3-A4-segments) on the right side were diagnosed. Endovascular subtotal embolization of arteriovenous malformation and occlusion of the right Anterior Cerebral Artery (A2-A3-segment) saccular aneurysm were performed during the operation. A control angiographic examination after 3 months showed a complete exclusion of these arteriovenous malformation and saccular aneurysm and disappearance of all aneurysms of the left Anterior Cerebral Artery – Anterior Communicating Artery and right Anterior Cerebral Artery (A3-A4-segment).

Abstract TP280: A Bland-new Rat Model of Embolic Cerebral Ischemia Using Micro Catheter Under Fluoroscopic Guide

Background: The failure of clinical trials on neuroprotective treatment may be partially caused by unestablished animal models. To verify a trans-arterial regeneration therapy, our project is aimed at developing a brand-new focal stroke model using micro catheter. Methods: Using Sprague-Dawley rats (n=8), a micro catheter (ID 0.26mm, OD 0.35mm) was navigated from the caudal ventral artery to the middle cerebral artery in order to establish local occlusion under digital subtraction angiography apparatus. Results: We succeeded in brain angiography by percutaneous tail artery puncture and occlusion of the middle cerebral artery by a radiopaque micro bead with 6 rats (75%). Ischemic stroke lesion volume is 480.3 mm3±84.2 mm3 on sustained 1% TTC solution after 24 hours occlusion. Conclusion: We present a new rat model for focal stroke using micro catheter under fluoroscopic control. The model is capable of repeated super selective administration of therapeutics directly to cerebral artery, and practice the 3Rs principles in experimental animals because of minimal invasive.Figure Legend- A: A sheath is inserted through the ventral midline, approximately 5 cm from the root of the tail of the rat, with a sharp angle. B: Cerebral angiography of rats. Arrowhead pointe middle cerebral artery. C: Occlusion of the middle cerebral artery by a radiopaque micro bead (arrowhead). D: Brain is sliced and stained 1% TTC solution after 24 hours occlusion.

Abstract WP367: Effect of Early Blood Pressure Reduction on Infarct Size in Patients With Large Vessel Occlusion

Introduction: In patients with large vessel occlusion presenting with acute ischemic stroke, cerebral perfusion is a major determinant of stroke severity. However, limited data exists to guide hemodynamic management of these patients early after presentation. In this study, we aim to evaluate the effect of blood pressure reductions during the hyper-acute period on infarct size. Methods: From a clinical stroke registry at a single comprehensive stroke center, we reviewed patients with middle cerebral artery (M1) or internal carotid artery occlusion who underwent hyperacute magnetic resonance imaging (MRI) for endovascular treatment decision in 2018. Infarct volume was determined by area of reduced apparent diffusion coefficient using RAPID software. Collateral circulation was scored based on baseline CT angiogram (good collaterals constituted &gt;50% filling, poor collaterals ≤50% filling). Average mean arterial pressure (MAP) readings from the first hour of presentation were compared to average MAP readings from the hour prior to magnetic resonance imaging. For the purposes of our study, a drop of &gt; 20% in the average MAP was regarded as a significant decrease. We hypothesized that both significant drop in MAP and the presence of good collateral circulation were independent predictors of infarct volume expressed as a logarithmic value in multivariable regression model. Results: Of the 35 patients (mean age 67, mean NIHSS 16) meeting inclusion criteria, 11% of patients experienced an early significant drop in MAP prior to time of MRI. Among patients with a significant drop in MAP, the average decrease was 35 mm Hg ±3.3 among those with significant drop from a baseline mean MAP of 125 mm Hg. In the multivariable analysis adjusting for collateral status, a significant drop in average MAP was independently associated with an increase in infarct volume (β = -0.727, p=0.0306). Collateral status also independently predicted infarct size (β=0.775, p=0.0007). Conclusion: Among ischemic stroke patients with large vessel occlusion, a &gt;20% drop in MAP during the hyper-acute period is associated with larger infarct volumes. Further studies are needed to optimize early blood pressure management in these patients.

Abstract 56: Neuroimaging in Ischemic Stroke is Different Between Men and Women in the Defuse 3 Cohort

Introduction: Clinical deficits from ischemic stroke are more severe in women but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes were assessed in this sub-study of the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE)-3 clinical trial. Methods: DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6-16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on CT or MRI. Using univariate and adjusted regression models, the effect of sex was assessed on pre-randomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans. Results: All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline NIHSS, baseline modified Rankin score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (IQR) volumes for core were 8.0 mL (1.9-18.4) in women vs 12.6 mL (2.7-29.6) in men, for T max &gt;6 seconds 89.0 mL (63.8-131.7) vs 133.9 mL (87.0-175.4), and for mismatch 82.1 (53.8-112.8) vs 108.2 (64.1-149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15-0.46) vs. 0.39 (0.26-0.57), p = 0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group (p = 0.003). Conclusions: In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions.