Evolution of Blood-brain-barrier Permeability After Acute Ischemic Stroke

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Feb 17

PMID 28207745

Citations 77

Authors

Zamir Merali

Kun Huang

David Mikulis

Frank Silver

Andrea Kassner

Affiliations

Soon will be listed here.

Abstract

The dynamics of BBB permeability after AIS in humans are not well understood. In the present study we measured the evolution of BBB permeability after AIS in humans using MRI. Patients presenting to our institution with a diagnosis of AIS underwent a single dynamic contrast-enhanced MRI (DCE-MRI) sequence to measure BBB permeability during their initial workup. Forty-two patients were included in the final analysis. The patient sample underwent DCE-MRI at a mean time of 23.8hrs after the onset of AIS symptoms (range: 1.3-90.7hrs). At all time-points the BBB permeability within the infarct region of the brain as defined on DWI/ADC was higher compared to the homologous region of the contralateral hemisphere (p<0.005). BBB permeability, expressed as a ratio of infarct permeability to contralateral permeability, was greatest at 6-48hrs after the onset of AIS. Although the data was not acquired longitudinally, these findings suggest that the permeability of the BBB is continually elevated following AIS, which contradicts previous assertions that BBB permeability after AIS follows a biphasic course. Knowledge of BBB dynamics following AIS may provide insight into future treatments for AIS, especially BBB stabilizing agents.

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References

Israeli D, Tanne D, Daniels D, Last D, Shneor R, Guez D . The application of MRI for depiction of subtle blood brain barrier disruption in stroke. Int J Biol Sci. 2011; 7(1):1-8. PMC: 3014550. DOI: 10.7150/ijbs.7.1. View

Rosell A, Cuadrado E, Ortega-Aznar A, Hernandez-Guillamon M, Lo E, Montaner J . MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke. Stroke. 2008; 39(4):1121-6. DOI: 10.1161/STROKEAHA.107.500868. View

Kwan J, Schulze C, Wang W, Leon H, Sariahmetoglu M, Sung M . Matrix metalloproteinase-2 (MMP-2) is present in the nucleus of cardiac myocytes and is capable of cleaving poly (ADP-ribose) polymerase (PARP) in vitro. FASEB J. 2004; 18(6):690-2. DOI: 10.1096/fj.02-1202fje. View

Huang Z, Xue D, Preston E, Karbalai H, Buchan A . Biphasic opening of the blood-brain barrier following transient focal ischemia: effects of hypothermia. Can J Neurol Sci. 1999; 26(4):298-304. DOI: 10.1017/s0317167100000421. View

Liu S, Zhen G, Meloni B, Campbell K, Winn H . RODENT STROKE MODEL GUIDELINES FOR PRECLINICAL STROKE TRIALS (1ST EDITION). J Exp Stroke Transl Med. 2010; 2(2):2-27. PMC: 2848489. DOI: 10.6030/1939-067x-2.2.2. View

Aoki T, Sumii T, Mori T, Wang X, Lo E . Blood-brain barrier disruption and matrix metalloproteinase-9 expression during reperfusion injury: mechanical versus embolic focal ischemia in spontaneously hypertensive rats. Stroke. 2002; 33(11):2711-7. DOI: 10.1161/01.str.0000033932.34467.97. View

PATLAK C, Blasberg R . Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J Cereb Blood Flow Metab. 1985; 5(4):584-90. DOI: 10.1038/jcbfm.1985.87. View

Kassner A, Roberts T, Moran B, Silver F, Mikulis D . Recombinant tissue plasminogen activator increases blood-brain barrier disruption in acute ischemic stroke: an MR imaging permeability study. AJNR Am J Neuroradiol. 2009; 30(10):1864-9. PMC: 7051295. DOI: 10.3174/ajnr.A1774. View

Kassner A, Roberts T, Taylor K, Silver F, Mikulis D . Prediction of hemorrhage in acute ischemic stroke using permeability MR imaging. AJNR Am J Neuroradiol. 2005; 26(9):2213-7. PMC: 7976167. View

10.

Rosenberg G, Estrada E, Dencoff J . Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke. 1998; 29(10):2189-95. DOI: 10.1161/01.str.29.10.2189. View

11.

Durukan A, Tatlisumak T . Acute ischemic stroke: overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia. Pharmacol Biochem Behav. 2007; 87(1):179-97. DOI: 10.1016/j.pbb.2007.04.015. View

12.

Lin T, Sun S, Cheung W, Li F, Chang C . Dynamic changes in cerebral blood flow and angiogenesis after transient focal cerebral ischemia in rats. Evaluation with serial magnetic resonance imaging. Stroke. 2002; 33(12):2985-91. DOI: 10.1161/01.str.0000037675.97888.9d. View

13.

Kastrup A, Groschel K, Ringer T, Redecker C, Cordesmeyer R, Witte O . Early disruption of the blood-brain barrier after thrombolytic therapy predicts hemorrhage in patients with acute stroke. Stroke. 2008; 39(8):2385-7. DOI: 10.1161/STROKEAHA.107.505420. View

14.

Nagel S, Wagner S, Koziol J, Kluge B, Heiland S . Volumetric evaluation of the ischemic lesion size with serial MRI in a transient MCAO model of the rat: comparison of DWI and T1WI. Brain Res Brain Res Protoc. 2004; 12(3):172-9. DOI: 10.1016/j.brainresprot.2003.11.004. View

15.

Veltkamp R, Siebing D, Sun L, Heiland S, Bieber K, Marti H . Hyperbaric oxygen reduces blood-brain barrier damage and edema after transient focal cerebral ischemia. Stroke. 2005; 36(8):1679-83. DOI: 10.1161/01.STR.0000173408.94728.79. View

16.

Kassner A, Thornhill R . Measuring the integrity of the human blood-brain barrier using magnetic resonance imaging. Methods Mol Biol. 2010; 686:229-45. DOI: 10.1007/978-1-60761-938-3_10. View

17.

Jin R, Yang G, Li G . Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010; 87(5):779-89. PMC: 2858674. DOI: 10.1189/jlb.1109766. View

18.

Wu X, Du L, Wu G, Cao X . Effects of electroacupuncture on blood-brain barrier after cerebral ischemia-reperfusion in rat. Acupunct Electrother Res. 2001; 26(1-2):1-9. DOI: 10.3727/036012901816356063. View

19.

Heye A, Thrippleton M, Armitage P, Valdes Hernandez M, Makin S, Glatz A . Tracer kinetic modelling for DCE-MRI quantification of subtle blood-brain barrier permeability. Neuroimage. 2015; 125:446-455. PMC: 4692516. DOI: 10.1016/j.neuroimage.2015.10.018. View

20.

Singh V, Edwards N . Advances in the critical care management of ischemic stroke. Stroke Res Treat. 2013; 2013:510481. PMC: 3671542. DOI: 10.1155/2013/510481. View