scholarly journals Hyperglycemia primes NETosis, which exacerbates ischemic brain damage

2019 ◽  
Author(s):  
Jiangshan Deng ◽  
Fei Zhao ◽  
Yunlong Zhang ◽  
Yajun Zhou ◽  
Xiaofeng Xu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Brain Damage ◽  
Artery Occlusion ◽  
Wild Type ◽  
Stroke Patients ◽  
Acute Hyperglycemia ◽  
Ischemic Brain ◽  
Infarction Volume ◽  
Cerebral Artery Occlusion

Abstract Background：Hyperglycemia is common and associated with poor outcomes in acute ischemic stroke patients. It is not well understood how hyperglycemia exacerbates brain damage in ischemic stroke. Neutrophil extracellular traps (NETs) have shown an emerging role in noninfectious diseases. We aimed to determine the role of NETs in acute ischemic stroke with hyperglycemia. Methods: NETs were immunostained using NET markers (citrullinated histone H3 (H3Cit)) and quantified in thrombi retrieved from ischemic stroke patients undergoing endovascular treatment. BKS-db/db and wild-type mice were used to establish the permanent middle cerebral artery occlusion (pMCAO) model. Wild-type mice were injected with glucose to simulate acute hyperglycemia after middle cerebral artery occlusion. NETs were detected in the peri-ischemic brain tissue. After inhibition of NET formation, infarction volume, neurological function and inflammatory factors in pMCAO mice were evaluated. Results: H3Cit, a marker of NETs, was observed in almost all thrombi. H3Cit was much more abundant in thrombi from diagnosed diabetic patients and acute hyperglycemic patients compared with those in normglycemic patients. In pMCAO mice, NETs were induced by chronic diabetes and acute hyperglycemia. Inhibition of NET formation with the peptidylarginine deiminase 4 (PAD4) inhibitor Cl-amidine decreased the infarction volume both in db/db and wild-type mice with hyperglycemia. Neurological function deficits were alleviated by blocking NET formation, as shown in the grip strength and rotarod tests. The levels of TNF-α and IL-1β but not IL-6 coincided with NET formation. Conclusions: Hyperglycemia may exacerbate brain damage in ischemic stroke through NETs. The underlying mechanisms deserve to be further studied.

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 Early Reperfusion Following Ischemic Stroke Provides Beneficial Effects, Even After Lethal Ischemia with Mature Neural Cell Death

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1374 ◽  
Author(s):  
Yasue Tanaka ◽  
Nami Nakagomi ◽  
Nobutaka Doe ◽  
Akiko Nakano-Doi ◽  
Toshinori Sawano ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Neural Cells ◽  
Stroke Patients ◽  
Early Reperfusion ◽  
Beneficial Effects ◽  
Cerebral Artery Occlusion

Ischemic stroke is a critical disease caused by cerebral artery occlusion in the central nervous system (CNS). Recent therapeutic advances, such as neuroendovascular intervention and thrombolytic therapy, have allowed recanalization of occluded brain arteries in an increasing number of stroke patients. Although previous studies have focused on rescuing neural cells that still survive despite decreased blood flow, expanding the therapeutic time window may allow more patients to undergo reperfusion in the near future, even after lethal ischemia, which is characterized by death of mature neural cells, such as neurons and glia. However, it remains unclear whether early reperfusion following lethal ischemia results in positive outcomes. The present study used two ischemic mouse models—90-min transient middle cerebral artery occlusion (t-MCAO) paired with reperfusion to induce lethal ischemia and permanent middle cerebral artery occlusion (p-MCAO)—to investigate the effect of early reperfusion up to 8 w following MCAO. Although early reperfusion following 90-min t-MCAO did not rescue mature neural cells, it preserved the vascular cells within the ischemic areas at 1 d following 90-min t-MCAO compared to that following p-MCAO. In addition, early reperfusion facilitated the healing processes, including not only vascular but also neural repair, during acute and chronic periods and improved recovery. Furthermore, compared with p-MCAO, early reperfusion after t-MCAO prevented behavioral symptoms of neurological deficits without increasing negative complications, including hemorrhagic transformation and mortality. These results indicate that early reperfusion provides beneficial effects presumably via cytoprotective and regenerative mechanisms in the CNS, suggesting that it may be useful for stroke patients that experienced lethal ischemia.

scholarly journals No Role for Interleukin-18 in Acute Murine Stroke-Induced Brain Injury

2003 ◽  
Vol 23 (5) ◽  
pp. 531-535 ◽  
Author(s):  
Rachel D. Wheeler ◽  
Herve Boutin ◽  
Omar Touzani ◽  
Giamal N. Luheshi ◽  
Kiyoshi Takeda ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Brain Damage ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Interleukin 18 ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Cerebral Artery Occlusion

There is now extensive evidence to show that the cytokine interleukin-1 (IL-1) contributes directly to reversible and permanent ischemic brain damage in rodents. Because interleukin-18 (IL-18) shares many structural and functional similarities with IL-1, the authors tested the hypothesis that IL-18 contributes directly to ischemic brain damage in mice exposed to focal, reversible (15-minute or 30-minute) middle cerebral artery occlusion. IL-18 expression was not induced acutely by middle cerebral artery occlusion, and deletion of the IL-18 gene (IL-18 knockout mice) did not affect infarct volume. The present results suggest that IL-18 does not contribute to acute ischemic brain damage.

scholarly journals Deletion of the WNK3-SPAK kinase complex in mice improves radiographic and clinical outcomes in malignant cerebral edema after ischemic stroke

2016 ◽  
Vol 37 (2) ◽  
pp. 550-563 ◽  
Author(s):  
Hanshu Zhao ◽  
Rachel Nepomuceno ◽  
Xin Gao ◽  
Lesley M Foley ◽  
Shaoxia Wang ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Ischemic Stroke ◽  
Magnetic Resonance ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Cerebral Edema ◽  
Artery Occlusion ◽  
Wild Type ◽  
Resonance Imaging ◽  
Cerebral Artery Occlusion

The WNK-SPAK kinase signaling pathway controls renal NaCl reabsorption and systemic blood pressure by regulating ion transporters and channels. A WNK3-SPAK complex is highly expressed in brain, but its function in this organ remains unclear. Here, we investigated the role of this kinase complex in brain edema and white matter injury after ischemic stroke. Wild-type, WNK3 knockout, and SPAK heterozygous or knockout mice underwent transient middle cerebral artery occlusion. One cohort of mice underwent magnetic resonance imaging. Ex-vivo brains three days post-ischemia were imaged by slice-selective spin-echo diffusion tensor imaging magnetic resonance imaging, after which the same brain tissues were subjected to immunofluorescence staining. A second cohort of mice underwent neurological deficit analysis up to 14 days post-transient middle cerebral artery occlusion. Relative to wild-type mice, WNK3 knockout, SPAK heterozygous, and SPAK knockout mice each exhibited a >50% reduction in infarct size and associated cerebral edema, significantly less demyelination, and improved neurological outcomes. We conclude that WNK3-SPAK signaling regulates brain swelling, gray matter injury, and demyelination after ischemic stroke, and that WNK3-SPAK inhibition has therapeutic potential for treating malignant cerebral edema in the setting of middle cerebral artery stroke.

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