Post-Stroke Blood-Brain Barrier Disruption and Poor Functional Outcome in Patients Receiving Thrombolytic Therapy

Abstract

Background and Purpose: The role played by post-stroke inflammation after an ischemic event in limiting functional recovery remains unclear. One component of post-stroke inflammation is disruption of the blood-brain barrier (BBB). This study examines the relationship between post-stroke BBB disruption and functional outcome. Methods: Acute stroke patients treated with thrombolysis underwent magnetic resonance imaging scanning 24 h and 5 days after their initial event. BBB permeability maps were generated from perfusion weighted imaging. Average permeability was calculated in the affected hemisphere. Good functional outcome, defined as a modified Rankin score of 0 or 1, was compared with average permeability using logistic regression. Results: Of the 131 patients enrolled, 76 patients had the necessary data to perform the analysis at 24 h, and 58 ­patients had data for the 5-day assessment. Higher BBB permeability measured at 24 h (OR 0.57; 95% CI 0.33–0.99, p = 0.045) and at 5 days (OR 0.24; 95% CI 0.09–0.66, p = 0.005) was associated with worse functional outcome 1–3 months after the acute ischemic stroke. For every percentage increase in BBB disruption at 5 days, there was a 76% decrease in the chance of achieving a good functional outcome after stroke. Multivariate analysis found this to be independent of age, stroke volume, or clinical stroke severity. Conclusions: Post-stroke BBB disruption appears to be predictive of functional outcome irrespective of stroke size.

CD36 deficiency reduces chronic BBB dysfunction and scar formation and improves activity, hedonic and memory deficits in ischemic stroke

“…BBB disruption is also predictive of outcome irrespective of lesion size. 39,40 BBB dysfunction, as evaluated by IgG staining in our study, was significantly attenuated in CD36 KO animals only in the chronic, but not acute, phase of stroke. Since the lesions were comparable in size between genotypes, reduced BBB disruption in the chronic stage indicates CD36 is an important mediator of its integrity.…”

Reduced perforin release from T cells as a mechanism underlying hypothermia‐mediated neuroprotection

“…17 In the present study, the rate of apoptosis was greater than that of necrosis in Pfntreated BMVECs. 26,27 Therefore, the present results further suggest that the blockage of Pfn-mediated apoptosis in BMVECs by therapeutic hypothermia might be important in reducing vascular permeability and the protection of the BBB with consequently improved clinical outcomes. [30][31][32] Injury and/or death of BMVECs, with a subsequent increase in vascular permeability and BBB disruption, 24,25 results in worse clinical outcomes in stroke patients.…”

Characterization of the Blood Brain Barrier Disruption in the Photothrombotic Stroke Model

“…Breakdown of the BBB and the risk of hemorrhagic transformation usually occurs within the first days in stroke patients ( Nadareishvili et al, 2019 ). Therefore, we first evaluated the BBB integrity 24 h following the induction of the stroke.…”

“…The spatiotemporal profile of the BBB opening following human stroke is complex and may also occur beyond the acute stage ( Merali et al, 2017 ; Nadareishvili et al, 2019 ). Re-openings of the BBB have been observed days to weeks following the initial ischemic injury in clinical and pre-clinical research ( Huang et al, 1999 ; Kassner and Merali, 2015 ; Merali et al, 2017 ).…”