Blood–brain barrier leakage and hemorrhagic transformation: The Reperfusion Injury in Ischemic StroKe (RISK) study

Abstract

Background and purpose: In patients with acute ischemic stroke treated with reperfusion therapy we aimed to evaluate whether pretreatment blood-brain barrier (BBB) leakage is associated with subsequent hemorrhagic transformation (HT). Methods:We prospectively screened patients with acute ischemic stroke treated with intravenous thrombolysis and/or endovascular treatment. Before treatment, each patient received computed tomography (CT), CT angiography, and CT perfusion. We assessed pretreatment BBB leakage within the ischemic area using the volume transfer constant (K trans ) value. Our primary outcome was relevant HT, defined as hemorrhagic infarction type 2 or parenchymal hemorrhage type 1 or 2. We evaluated independent associations between BBB leakage and HT using logistic regression, adjusting for age, sex, baseline stroke severity, Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6, treatment type, and onset-to-treatment time. Results:We enrolled 171 patients with available assessment of BBB leakage. The patients' mean (±SD) age was 75.5 (±11.8) years, 86 (50%) were men, and the median (interquartile range) National Institutes of Health Stroke Scale score was 18 (12-23). A total of 32 patients (18%) received intravenous thrombolysis, 102 (60%) underwent direct endovascular treatment, and 37 (22%) underwent both. Patients with relevant HT (N = 31;18%) had greater mean BBB leakage (K trans 0.77 vs. 0.60; p = 0.027). After adjustment in the logistic regression model, we found that BBB leakage was associated both with a more than twofold risk of relevant HT (odds ratio [OR] 2.50; 95% confidence interval [CI] 1.03-6.03 per K trans point increase; OR 2.34; 95% CI 1.06-5.17 for K trans values > 0.63 [mean BBB leakage value]) and with symptomatic intracerebral hemorrhage (OR 4.30; 95% CI 1.13-13.77 per K trans point increase). Conclusion:Pretreatment BBB leakage before reperfusion therapy was associated with HT, and may help to identify patients at risk of HT.

Neuroinflammation, Stroke, Blood-Brain Barrier Dysfunction, and Imaging Modalities

“…77,78 A prospective study has recently demonstrated a significant correlation between pretreatment BBB permeability and posttreatment hemorrhagic transformation in patients with acute ischemic stroke who underwent perfusion CT before intravenous thrombolysis or endovascular thrombectomy. 79 On the contrary, the absence of an association between (reversible) BBB permeability before thrombolysis and unfavorable clinical outcome after 90 days has also been reported. 80…”

“…77,78 A prospective study has recently demonstrated a significant correlation between pretreatment BBB permeability and posttreatment hemorrhagic transformation in patients with acute ischemic stroke who underwent perfusion CT before intravenous thrombolysis or endovascular thrombectomy. 79 On the contrary, the absence of an association between (reversible) BBB permeability before thrombolysis and unfavorable clinical outcome after 90 days has also been reported. 80 Postprocedural hemorrhage and worse functional outcomes have also been associated with late contrast enhancement of cerebrospinal fluid space on follow-up T 2 -weighted fluid-attenuated inversion recovery MRIs of patients with acute ischemic stroke.…”

TPPU Downregulates Oxidative Stress Damage and Induces BDNF Expression in PC-12 Cells

“…The main symptoms of stroke may include pain, depression, cognitive function, fatigue, and disability [ 3 ]. Most strokes are of an ischemic type [ 4 ], and the reestablishment of blood flow may induce ischemia-reperfusion injury [ 5 ]. One of the main damage of ischemia-reperfusion is oxidative stress, which may destroy the respiration chain and phosphorylation, causing cell apoptosis and pathological damage, ultimately impairing the neurological function and inducing neuronal death [ 6 ].…”

Risk Factors and Clinical Outcomes of Brain Reperfusion Injury after Mechanical Thrombectomy for Ischemic Stroke

“…본 연구에서 조사한 일반적 특성과 임상적 특성 [4][5][6]12]. 치료적 특성 [8,9,[13][14][15], 임상결과 [20][21][22] www.bionursingjournal.or.kr 은 67명(39.9%)이었다. 뇌재관류 손상은 연령(Z = -3.84, p < .001), 음주 력(χ 2 = 9.43, p = .002)에서 통계적으로 유의한 차이가 있었다.…”

“…기계적 혈전제거술 후 발생하는 뇌재관류 손상은 혈관-뇌장벽 붕괴(disruption)로 뇌출혈성변환, 뇌부종, 뇌경색의 악화 [20]와 신경 학적 회복지연 [21]과 관련이 있다. 또한 기계적 혈전제거술 후 혈압 조절이 지연되면 유증상성 출혈(symptomatic hemorrhage) 비율과 사망률이 높아지고, 기능적 독립성(functional independence)이 낮아 지는 등 임상결과에 부정적인 영향을 미친다 [22].…”