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Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia.

ABSTRACT: We tested whether significant leukocyte infiltration occurs in a mouse model of permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or 24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral artery occlusion (MCAO). Using flow cytometry, we observed ∼15,000 leukocytes (CD45(+high) cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising ∼40% lymphoid cells and ∼60% myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to ∼5,000 as early as 3 hours after pMCAO. Several cell types (monocytes, macrophages, B lymphocytes, CD8(+) T lymphocytes, and natural killer cells) were also increased at 3 hours to levels sustained for 24 hours, whereas others (CD4(+) T cells, natural killer T cells, and dendritic cells) were unchanged at 3 hours, but were increased by 24 hours after pMCAO. Immunohistochemical analysis revealed that leukocytes typically had entered and widely dispersed throughout the parenchyma of the infarct within 3 hours. Moreover, compared with pMCAO, there were ∼50% fewer infiltrating leukocytes at 24 hours after transient MCAO (tMCAO), independent of infarct size. Microglial cell numbers were bilaterally increased in both models. These findings indicate that a profound infiltration of inflammatory cells occurs in the brain early after focal ischemia, especially without reperfusion.

SUBMITTER: Chu HX

PROVIDER: S-EPMC3948121 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia.

Chu Hannah X HX Kim Hyun Ah HA Lee Seyoung S Moore Jeffrey P JP Chan Christopher T CT Vinh Antony A Gelderblom Mathias M Arumugam Thiruma V TV Broughton Brad R S BR Drummond Grant R GR Sobey Christopher G CG

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20131211 3

We tested whether significant leukocyte infiltration occurs in a mouse model of permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or 24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral artery occlusion (MCAO). Using flow cytometry, we observed ∼15,000 leukocytes (CD45(+high) cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising ∼40% lymphoid cells and ∼60% myeloid cells. Neutrophils were the predomi ...[more]

PMID: 24326388

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Project description:BackgroundMalignant middle cerebral artery infarction (MMI) is associated with a high incidence of severe disability and mortality. Decompressive hemicraniectomy has become a recognized treatment that can improve the prognosis for patients if performed within a certain time window. Nevertheless, despite this intervention, a mortality rate of approximately 20-40% persists following the surgery. The trends and clinical implications of intracranial pressure (ICP) in these situations remain unclear. We aimed to investigate whether intracranial pressure (ICP) trends are associated with clinical outcomes in patients undergoing decompressive hemicraniectomy for MMI.MethodsThis retrospective cohort study included consecutive patients with MMI who underwent decompressive craniectomy and received ICP monitoring after surgery. Using a linear mixed model, we categorized the patients into ICP increase and decrease groups based on the ICP values obtained over 192 h. We then compared the proportion of 3-month favorable outcomes (modified Rankin Scale of 0-4) and mortality rates between these groups.ResultsOf 112 MMI patients who underwent decompressive hemicraniectomy, 66 (58.9%) received invasive ICP monitoring. ICP monitoring was performed for a median of 146.5 h (IQR 72.5-181.8). Among the 66 patients, 37 (56.1%) were in the ICP increase group, and 29 (43.9%) were in the ICP decrease group. During the monitoring period, the initial monitored ICP and peak ICP did not significantly differ between the ICP increase and decrease groups. However, the ICP trend was significantly different between the two groups (P < 0.001). In multivariable logistic regression analyses, the ICP increase group had a significantly lower proportion of 3-month favorable outcomes compared to the ICP decrease group (adjusted OR 0.11; 95% CI, 0.01-0.59; P = 0.019), and significantly higher mortality in the intensive care unit (adjusted OR 6.98; 95% CI, 1.37-54.6; P = 0.031).ConclusionsIn MMI patients, continuous ICP monitoring could be useful for detecting those with an increasing ICP trend that may be associated with unfavorable clinical outcomes.

Project description:A disrupted blood-brain barrier (BBB) with extravasation of macromolecules plays a critical role in the development of malignant middle cerebral artery infarction (MMI). Proteinuria is considered a marker of generalized endothelial dysfunction, including BBB disruption. This study aimed to clarify whether proteinuria identified in the acute stage of stroke is associated with MMI development. Patients with infarctions involving the middle cerebral artery territory were reviewed. Urine samples collected within 8 hours after stroke were analyzed using urine dipsticks. Patients were divided into proteinuria (urine dipstick reading of 1 + to 4+) and nonproteinuria groups. MMI was present if either signs of uncal herniation or a progressive conscious disturbance were recorded along with a midline shift > 5 mm identified on follow-up computed tomography (CT). Among the 1261 patients identified between January 2010 and June 2019, 138 were eligible for final analyses. Patients in the MMI group had lower Alberta Stroke Program Early CT Scores (ASPECTS), higher National Institutes of Health Stroke Scale scores, and a greater proportion of proteinuria than those in the non-MMI group. Four multivariate logistic regression models were used to clarify the role of proteinuria in MMI development. In model 1, proteinuria was significantly associated with MMI after adjusting for age, sex, dyslipidemia and ASPECTS (OR = 2.987, 95% CI = 1.329-6.716, P = .0081). The risk of developing MMI in patients with proteinuria remained significant in model 2 (OR = 3.066, 95% CI = 1.349-6.968, P = .0075) after adjusting for estimated glomerular filtrate rate (eGFR) < 60ml/min/1.73 m2 in addition to variables in model 1. In model 3, proteinuria was still significantly associated with MMI after adjusting for age, sex, dyslipidemia, ASPECTS, hypertension, diabetes, and atrial fibrillation (OR = 2.521, 95% CI = 1.075-5.912, P = .0335). In model 4, the risk of developing MMI in patients with proteinuria remained significant (OR = 2.579, 95% CI = 1.094-6.079, P = .0304) after adjusting for eGFR < 60ml/min/1.73 m2 in addition to variables in model 3. Proteinuria is independently associated with MMI development. Proteinuria may be a clinically accessible predictor of MMI development.

Project description:BackgroundMalignant middle cerebral artery infarction is a potentially life-threatening disease. Decompressive hemicraniectomy constitutes an evidence-based treatment practice, especially in patients under 60 years of age; however, recommendations with respect to postoperative management and particularly duration of postoperative sedation lack standardization.ObjectiveThis survey study aimed to analyze the current situation of patients with malignant middle cerebral artery infarction following hemicraniectomy in the neurointensive care setting.Material and methodsFrom 20 September 2021 to 31 October 2021, 43 members of the initiative of German neurointensive trial engagement (IGNITE) network were invited to participate in a standardized anonymous online survey. Descriptive data analysis was performed.ResultsOut of 43 centers 29 (67.4%) participated in the survey, including 24 university hospitals. Of the hospitals 21 have their own neurological intensive care unit. While 23.1% favored a standardized approach regarding postoperative sedation, the majority utilized individual criteria (e.g., intracranial pressure increase, weaning parameters, complications) to assess the need and duration. The timing of targeted extubation varied widely between hospitals (≤ 24 h 19.2%, ≤ 3 days in 30.8%, ≤ 5 days in 19.2%, > 5 days in 15.4%). Early tracheotomy (≤ 7 days) is performed in 19.2% and 80.8% of the centers aim for tracheotomy within 14 days. Hyperosmolar treatment is used on a regular basis in 53.9% and 22 centers (84.6%) agreed to participate in a clinical trial addressing the duration of postoperative sedation and ventilation.ConclusionThe results of this nationwide survey among neurointensive care units in Germany reflect a remarkable heterogeneity in the treatment practices of patients with malignant middle cerebral artery infarction undergoing hemicraniectomy, especially with respect to the duration of postoperative sedation and ventilation. A randomized trial in this matter seems warranted.

Dataset Information

Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia.

Publications

Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia.

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