scholarly journals Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream

2021 ◽  
Vol 12 ◽  
Author(s):  
Pasquale Cepparulo ◽  
Ornella Cuomo ◽  
Antonio Vinciguerra ◽  
Monica Torelli ◽  
Lucio Annunziato ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Hemorrhagic Stroke ◽  
Time Window ◽  
Recombinant Tissue Plasminogen Activator ◽  
Artery Occlusion ◽  
Blood Levels ◽  
Time Intervals ◽  
Transient Focal Ischemia ◽  
Preclinical Animal Models ◽  
Cerebral Artery Occlusion

To date, the only effective pharmacological treatment for ischemic stroke is limited to the clinical use of recombinant tissue plasminogen activator (rtPA), although endovascular therapy has also emerged as an effective treatment for acute ischemic stroke. Unfortunately, the benefit of this treatment is limited to a 4.5-h time window. Most importantly, the use of rtPA is contraindicated in the case of hemorrhagic stroke. Therefore, the identification of a reliable biomarker to distinguish hemorrhagic from ischemic stroke could provide several advantages, including an earlier diagnosis, a better treatment, and a faster decision on ruling out hemorrhage so that tPA may be administered earlier. microRNAs (miRNAs) are stable non-coding RNAs crucially involved in the downregulation of gene expression via mRNA cleavage or translational repression. In the present paper, taking advantage of three preclinical animal models of stroke, we compared the miRNA blood levels of animals subjected to permanent or transient middle cerebral artery occlusion (MCAO) or to collagenase-induced hemorrhagic stroke. Preliminarily, we examined the rat miRNome in the brain tissue of ischemic and sham-operated rats; then, we selected those miRNAs whose expression was significantly modulated after stroke to create a list of miRNAs potentially involved in stroke damage. These selected miRNAs were then evaluated at different time intervals in the blood of rats subjected to permanent or transient focal ischemia or to hemorrhagic stroke. We found that four miRNAs—miR-16-5p, miR-101a-3p, miR-218-5p, and miR-27b-3p—were significantly upregulated in the plasma of rats 3 h after permanent MCAO, whereas four other different miRNAs—miR-150-5p, let-7b-5p, let-7c-5p, and miR-181b-5p—were selectively upregulated by collagenase-induced hemorrhagic stroke. Collectively, our study identified some selective miRNAs expressed in the plasma of hemorrhagic rats and pointed out the importance of a precise time point measurement to render more reliable the use of miRNAs as stroke biomarkers.

Abstract 109: Depletion of Microglia Does Not Improve Functional Outcomes in Aged Mice After Transient Focal Ischemia

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Shirley Marino Lee ◽  
Jacob Hudobenko ◽  
Juneyoung Lee ◽  
Louise McCullough ◽  
Anjali Chauhan
Keyword(s):  
Ischemic Stroke ◽  
Immune Cell ◽  
Neuronal Degeneration ◽  
Artery Occlusion ◽  
Chow Diet ◽  
Early Recovery ◽  
Aged Mice ◽  
Transient Focal Ischemia ◽  
Cerebral Artery Occlusion ◽  
Oxidative Species

Introduction: With aging, microglia acquire a dysfunctional phenotype characterized by dystrophic morphology, impaired phagocytosis, reduced motility, and an exaggerated response to injury. Microglia become pathologically activated with aging and play a detrimental role in age-associated cognitive decline and neurodegenerative diseases. Older mice exhibit a differential response to stroke and have worse outcomes despite smaller infarcts compared to young mice. Microglia from aged mice produce higher levels of reactive oxidative species and have an exaggerated inflammatory response after ischemic stroke. Hypothesis: We hypothesized that ablation of microglia would reduce the exaggerated neuroinflammatory responses in aged mice and loss of microglia would improve early recovery after ischemic stroke. Aged (18-19 months) male mice were fed a control chow diet (CD) or PLX5622 chow diet (PLXD) for 21 days. On day 22, 60-minute middle cerebral artery occlusion (MCAo) or sham surgery was performed. Twenty-four hours after MCAo, neurological deficit scores (NDS) and immunohistochemistry assessments, as well as flow cytometry, were performed. Results: There was a significant reduction in Iba1 + cells in striatum and cortex of the aged mice with PLX treatment: day 7 (p<0.05), day 14 (p<0.001), and day 21 (p<0.001) vs day 0. Twenty-four hours after MCAo, the NDS were not different between CD (3.0±0.18) and PLXD (2.92±0.21). However, an increase in infarct size was seen in the aged PLXD group compared to the aged CD group (p<0.05). After MCAo, there was an increase in infiltrating monocytes and neutrophils in both diet groups compared to their respective shams (p<0.05). However, an increase in infiltrating monocytes was observed in the PLXD MCAo vs. CD MCAo (p<0.0001) reflecting a differential monocyte response in animals without microglia. Additionally, a decrease in NeuN immunoreactivity was seen in the PLXD MCAo group compared to PLXD sham (p<0.01). GFAP + cells increased in PLXD sham group as compared to CD sham (p<0.05). Conclusions: Our results suggest that microglia are essential immune cells that surprisingly limit immune cell infiltration, decrease neuronal degeneration, and reduce neuroinflammation after ischemic stroke in aged mice.

THE RELATIONSHIP BETWEEN TIMING OF RECANALIZATION AND CLINICAL OUTCOME OF ISCHEMIC STROKE DUE TO ACUTE MIDDLE CEREBRAL ARTERY OCCLUSION AFTER ULTRASOUND-ENHANCED THROMBOLYSIS

2017 ◽  
pp. 38-43
Author(s):  
Quang Thang Tran ◽  
Dat Anh Nguyen ◽  
Van Chi Nguyen ◽  
Duy Ton Mai ◽  
Van Thinh Le
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Recombinant Tissue Plasminogen Activator ◽  
Artery Occlusion ◽  
Stroke Patients ◽  
Tissue Plasminogen ◽  
Cerebral Artery Occlusion ◽  
The Relationship

Purpose: The relationship between arterial recanalization after use of intravenous recombinant tissue plasminogen activator (rtPA) and outcome is still uncertain. The aim of our study was to evaluate the association between the timing and impact of recanalization on functional outcomes in ischemic stroke patients due to acute middle cerebral artery occlusion. Subjects and methods: Nonrandomized 40 stroke patients with proximal middle arterial occlusion on a prebolus TCD receiving intravenously 0.6 mg/kg rtPA within 4.5 hours after stroke onset were monitored with portable diagnostic TCD equipment and a standard headframe. Complete recanalization was defined as thrombolysis in brain ischemia (TIBI) flow grades 4-5. Results: 40 patients (mean age 67±14 years, NIH Stroke Scale [NIHSS] 16.15±8.6 points) were treated at 180±80 minutes from symptom onset. TCD was monitored continously for 120 minutes. Complete recanalization on TCD within 2 hours after bolus was found in 13 patients (32.5%). In this group, NIHSS decreased quickly at 2 hours and 24 hours. Modified Rankins 0-1point was seen in 92.3% of patients with complete recanalization compared to 37.0% of patients with uncomplete recanalization at 90 days. Non-symptomatic intracranial hemorrhage was seen in 1 patient in the group of complete recanalization. Conclusions: Complete recanalization of middle cerebral arteries within 2 hours after IV rtPA treatment plays a role in predicting the good functional and clinical outcomes after ultrasound-enhanced thrombolysis in acute ischemic stroke patients due to acute middle cerebral artery occlusion. Key words: stroke, recombinant tissue plasminogen activator, transcranial Doppler sonography

scholarly journals Alteplase Treatment does not Increase Brain Injury After Mechanical Middle Cerebral Artery Occlusion in the Rat

2013 ◽  
Vol 33 (11) ◽  
pp. e1-e7 ◽  
Author(s):  
Brad A Sutherland ◽  
Alastair M Buchan
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Infarct Volume ◽  
Recombinant Tissue Plasminogen Activator ◽  
Artery Occlusion ◽  
Carrier Solution ◽  
Tissue Plasminogen ◽  
Cerebral Artery Occlusion

Recanalization of an occluded vessel with recombinant tissue plasminogen activator is an effective strategy for treating acute ischemic stroke. Recombinant tissue plasminogen activator is administered as alteplase, a formulation containing many excipients including L-arginine, the substrate for nitric oxide production. Most studies fail to compare the effects of alteplase on brain injury to its L-arginine carrier solution. This study aimed to verify the previously reported detrimental effects of alteplase after cerebral ischemia and delineate the contribution of L-arginine. Male Wistar rats, subjected to 90 minutes of intraluminal middle cerebral artery occlusion (MCAO), were administered alteplase, the carrier solution or saline upon reperfusion. Neither alteplase nor the carrier affected cerebral blood flow (CBF) restoration throughout the first 60 minutes of reperfusion. Alteplase treatment was associated with increased mortality after MCAO. Twenty-four hours after MCAO, neurologic function and infarct volume did not differ between rats treated with alteplase, the carrier solution, or saline. Irrespective of treatment group, infarct volume was correlated with CBF during reperfusion, neuroscore, and peri-infarct depolarizations. These results suggest that alteplase treatment, independent of thrombolysis, does not cause increased ischemic injury compared with its appropriate carrier solution, supporting the continued use of alteplase in eligible ischemic stroke patients.

scholarly journals Fatal recurrent ischemic stroke caused by vertebral artery stump syndrome

2021 ◽  
Vol 12 ◽  
pp. 445
Author(s):  
Akinari Yamano ◽  
Yasunobu Nakai ◽  
Kazuki Akutagawa ◽  
Haruki Igarashi ◽  
Kazuaki Tsukada ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Vertebral Artery ◽  
Mechanical Thrombectomy ◽  
Recurrent Stroke ◽  
Recombinant Tissue Plasminogen Activator ◽  
Artery Occlusion ◽  
Basilar Artery Occlusion ◽  
Tissue Plasminogen ◽  
The Right ◽  
Cerebral Artery Occlusion

Background: Vertebral artery stump syndrome (VASS) develops into recurrent posterior circulation ischemic stroke after ipsilateral vertebral artery (VA) occlusion at its origin. Case Description: The patient was a 46-year-old man with the right posterior cerebral artery occlusion. We used a recombinant tissue plasminogen activator (rt-PA) and then performed mechanical thrombectomy using a stent retriever. Angiography revealed left VA occlusion and stagnant flow to the left VA from the right deep cervical artery; therefore, we diagnosed VASS. Within 24 h of the rt-PA injection, the symptoms had dramatically improved, and so we avoided additional antithrombotic agents. Only 13 h later, the patient developed a basilar artery occlusion and died in spite of a repeated mechanical thrombectomy. Conclusion: Vigilance against early (and sometimes fatal) recurrent stroke induced by VASS is required.

Energy-Sensing Pathways in Ischemia: The Counterbalance Between AMPK and mTORC

2020 ◽  
Vol 25 (45) ◽  
pp. 4763-4770
Author(s):  
Angel Cespedes ◽  
Mario Villa ◽  
Irene Benito-Cuesta ◽  
Maria J. Perez-Alvarez ◽  
Lara Ordoñez ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cause Of Death ◽  
Artery Occlusion ◽  
Brain Pathology ◽  
Common Cause ◽  
Specific Analysis ◽  
Energy Sensing ◽  
Cerebral Artery Occlusion

: Stroke is an important cause of death and disability, and it is the second leading cause of death worldwide. In humans, middle cerebral artery occlusion (MCAO) is the most common cause of ischemic stroke. The damage occurs due to the lack of nutrients and oxygen contributed by the blood flow. : The present review aims to analyze to what extent the lack of each of the elements of the system leads to damage and which mechanisms are unaffected by this deficiency. We believe that the specific analysis of the effect of lack of each component could lead to the emergence of new therapeutic targets for this important brain pathology.

Dl-3-n-Butylphthalide (NBP): A Promising Therapeutic Agent for Ischemic Stroke

2018 ◽  
Vol 17 (5) ◽  
pp. 338-347 ◽  
Author(s):  
Shan Wang ◽  
Fei Ma ◽  
Longjian Huang ◽  
Yong Zhang ◽  
Yuchen Peng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Complex Disease ◽  
Time Window ◽  
Recombinant Tissue Plasminogen Activator ◽  
Research Progress ◽  
Apium Graveolens ◽  
Synthetic Compound ◽  
Stroke Treatment ◽  
Single Target ◽  
Anti Oxidant

Background and Objective: Stroke is a leading cause of morbidity and mortality in both developed and developing countries all over the world. The only drug for ischemic stroke approved by FDA is recombinant tissue plasminogen activator (rtPA). However, only 2-5% stroke patients receive rtPAs treatment due to its strict therapeutic time window. As ischemic stroke is a complex disease involving multiple mechanisms, medications with multi-targets may be more powerful compared with single-target drugs. Dl-3-n-Butylphthalide (NBP) is a synthetic compound based on l-3-n- Butylphthalide that is isolated from seeds of Apium graveolens. The racemic 3-n-butylphthalide (dl- NBP) was approved by Food and Drug Administration of China for the treatment of ischemic stroke in 2002. A number of clinical studies indicated that NBP not only improved the symptoms of ischemic stroke, but also contributed to the long-term recovery. The potential mechanisms of NBP for ischemic stroke treatment may target different pathophysiological processes, including anti-oxidant, antiinflammation, anti-apoptosis, anti-thrombosis, and protection of mitochondria et al. Conclusion: In this review, we have summarized the research progress of NBP for the treatment of ischemic stroke during the past two decades.

Cerebrolysin and Aquaporin 4 Inhibition Improve Pathological and Motor Recovery after Ischemic Stroke

2018 ◽  
Vol 17 (4) ◽  
pp. 299-308 ◽  
Author(s):  
Bogdan Catalin ◽  
Otilia-Constantina Rogoveanu ◽  
Ionica Pirici ◽  
Tudor Adrian Balseanu ◽  
Adina Stan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Vasogenic Edema ◽  
Artery Occlusion ◽  
Aquaporin 4 ◽  
Hypertonic Solution ◽  
Water Metabolism ◽  
Scar Region ◽  
Function Preservation ◽  
Neurotropic Factor ◽  
Cerebral Artery Occlusion

Background: Edema represents one of the earliest negative markers of survival and consecutive neurological deficit following stroke. The mixture of cellular and vasogenic edema makes treating this condition complicated, and to date, there is no pathogenically oriented drug treatment for edema, which leaves parenteral administration of a hypertonic solution as the only non-surgical alternative. Objective: New insights into water metabolism in the brain have opened the way for molecular targeted treatment, with aquaporin 4 channels (AQP4) taking center stage. We aimed here to assess the effect of inhibiting AQP4 together with the administration of a neurotropic factor (Cerebrolysin) in ischemic stroke. Methods: Using a permanent medial cerebral artery occlusion rat model, we administrated a single dose of the AQP4 inhibitor TGN-020 (100 mg/kg) at 15 minutes after ischemia followed by daily Cerebrolysin dosing (5ml/kg) for seven days. Rotarod motor testing and neuropathology examinations were next performed. Results: We showed first that the combination treatment animals have a better motor function preservation at seven days after permanent ischemia. We have also identified distinct cellular contributions that represent the bases of behavior testing, such as less astrocyte scarring and a larger neuronalsurvival phenotype rate in animals treated with both compounds than in animals treated with Cerebrolysin alone or untreated animals. Conclusion: Our data show that water diffusion inhibition and Cerebrolysin administration after focal ischemic stroke reduces infarct size, leading to a higher neuronal survival in the peri-core glial scar region.

scholarly journals The Key Regulator of Necroptosis, RIP1 Kinase, Contributes to the Formation of Astrogliosis and Glial Scar in Ischemic Stroke

2021 ◽  
Author(s):  
Yong-Ming Zhu ◽  
Liang Lin ◽  
Chao Wei ◽  
Yi Guo ◽  
Yuan Qin ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Glial Scar ◽  
Scar Formation ◽  
Reactive Astrocytes ◽  
Interacting Protein ◽  
Protein Levels ◽  
Endothelial Growth Factor ◽  
Cerebral Artery Occlusion

AbstractNecroptosis initiation relies on the receptor-interacting protein 1 kinase (RIP1K). We recently reported that genetic and pharmacological inhibition of RIP1K produces protection against ischemic stroke-induced astrocytic injury. However, the role of RIP1K in ischemic stroke-induced formation of astrogliosis and glial scar remains unknown. Here, in a transient middle cerebral artery occlusion (tMCAO) rat model and an oxygen and glucose deprivation and reoxygenation (OGD/Re)-induced astrocytic injury model, we show that RIP1K was significantly elevated in the reactive astrocytes. Knockdown of RIP1K or delayed administration of RIP1K inhibitor Nec-1 down-regulated the glial scar markers, improved ischemic stroke-induced necrotic morphology and neurologic deficits, and reduced the volume of brain atrophy. Moreover, knockdown of RIP1K attenuated astrocytic cell death and proliferation and promoted neuronal axonal generation in a neuron and astrocyte co-culture system. Both vascular endothelial growth factor D (VEGF-D) and its receptor VEGFR-3 were elevated in the reactive astrocytes; simultaneously, VEGF-D was increased in the medium of astrocytes exposed to OGD/Re. Knockdown of RIP1K down-regulated VEGF-D gene and protein levels in the reactive astrocytes. Treatment with 400 ng/ml recombinant VEGF-D induced the formation of glial scar; conversely, the inhibitor of VEGFR-3 suppressed OGD/Re-induced glial scar formation. RIP3K and MLKL may be involved in glial scar formation. Taken together, these results suggest that RIP1K participates in the formation of astrogliosis and glial scar via impairment of normal astrocyte responses and enhancing the astrocytic VEGF-D/VEGFR-3 signaling pathways. Inhibition of RIP1K promotes the brain functional recovery partially via suppressing the formation of astrogliosis and glial scar. Graphical Abstract

Abstract 166: Endothelial Overexpression of LOX-1 Increases Stroke Size in vivo

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Alexander Akhmedov ◽  
Remo D Spescha ◽  
Francesco Paneni ◽  
Giovani G Camici ◽  
Thomas F Luescher
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Endothelial Dysfunction ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Oxidized Ldl ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion ◽  
The Brain

Background— Stroke is one of the most common causes of death and long term disability worldwide primarily affecting the elderly population. Lectin-like oxidized LDL receptor 1 (LOX-1) is the receptor for oxidized LDL identified in endothelial cells. Binding of OxLDL to LOX-1 induces several cellular events in endothelial cells, such as activation of transcription factor NF-kB, upregulation of MCP-1, and reduction in intracellular NO. Accumulating evidence suggests that LOX-1 is involved in endothelial dysfunction, inflammation, atherogenesis, myocardial infarction, and intimal thickening after balloon catheter injury. Interestingly, a recent study demonstrated that acetylsalicylic acid (aspirin), which could prevent ischemic stroke, inhibited Ox-LDL-mediated LOX-1 expression in human coronary endothelial cells. The expression of LOX-1 was increased at a transient ischemic core site in the rat middle cerebral artery occlusion model. These data suggest that LOX-1 expression induces atherosclerosis in the brain and is the precipitating cause of ischemic stroke. Therefore, the goal of the present study was to investigate the role of endothelial LOX-1 in stroke using experimental mouse model. Methods and Results— 12-week-old male LOX-1TG generated recently in our group and wild-type (WT) mice were applied for a transient middle cerebral artery occlusion (MCAO) model to induce ischemia/reperfusion (I/R) brain injury. LOX-1TG mice developed 24h post-MCAO significantly larger infarcts in the brain compared to WT (81.51±8.84 vs. 46.41±10.13, n=7, p < 0.05) as assessed morphologically using Triphenyltetrazolium chloride (TTC) staining. Moreover, LOX-1TG showed higher neurological deficit in RotaRod (35.57±8.92 vs. 66.14±10.63, n=7, p < 0.05) and Bederson tests (2.22±0.14 vs. 1.25±0.30, n=9-12, p < 0.05) - two experimental physiological tests for neurological function. Conclusions— Thus, our data suggest that LOX-1 plays a critical role in the ischemic stroke when expressed at unphysiological levels. Such LOX-1 -associated phenotype could be due to the endothelial dysfunction. Therefore, LOX-1 may represent novel therapeutic targets for preventing ischemic stroke.

Sign in / Sign up

Export Citation Format

Share Document