Advertisement

Hypoxia and Inflammation-Induced Disruptions of the Blood-Brain and Blood-Cerebrospinal Fluid Barriers Assessed Using a Novel T1-Based MRI Method

  • Nabeela Nathoo
  • Hamza Jalal
  • Sirajedin S. Natah
  • Qiong Zhang
  • Ying Wu
  • Jeff F. Dunn
Part of the Acta Neurochirurgica Supplement book series (NEUROCHIRURGICA, volume 121)

Abstract

Subtle blood-brain barrier (BBB) disruption is involved in numerous neurological conditions. This disruption is found diffusely in the brain and requires quantitative methods for assessment. We propose a statistical method to identify individual voxels where the BBB is disrupted using T1-weighted MRI. We used models of severe and focal vs. mild and generalized disruption of the BBB to show proof of principle with the cold injury model, hypoxia, and a model of inflammation using low- and high-dose lipopolysaccharide (LPS) treatment. Using voxel-based analysis, we found that mild hypoxia resulted in diffuse disruption of the BBB, whereas more severe hypoxia and high-dose LPS treatment resulted in prominent leakage, particularly in the periventricular area, suggestive of blood-cerebrospinal fluid (CSF) barrier disruption. Our data suggest that the periventricular area may be compromised first in conditions of inflammation and hypoxia. Voxel-based analysis could be used in future studies assessing subtle blood-CSF or BBB disruption.

Keywords

Blood-brain barrier Blood-cerebrospinal fluid barrier Hypoxia Inflammation Lipopolysaccharide MRI Periventricular Sodium fluorescein 

Notes

Acknowledgments

This work was supported by Alberta-Innovates Health Solutions and the National Science and Engineering Research Council Canada.

Conflict of Interest

None.

References

  1. 1.
    Chen B et al (2009) Severe blood-brain barrier disruption and surrounding tissue injury. Stroke 40(12):e666–e674PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Hom J et al (2011) Blood-brain barrier permeability assessed by perfusion CT predicts symptomatic hemorrhagic transformation and malignant edema in acute ischemic stroke. AJNR Am J Neuroradiol 32(1):41–48PubMedGoogle Scholar
  3. 3.
    Oby E, Janigro D (2006) The blood-brain barrier and epilepsy. Epilepsia 47(11):1761–1774CrossRefPubMedGoogle Scholar
  4. 4.
    Seiffert E et al (2004) Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci 24(36):7829–7836CrossRefPubMedGoogle Scholar
  5. 5.
    Kumar AJ et al (2000) Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 217(2):377–384CrossRefPubMedGoogle Scholar
  6. 6.
    Broadwell RD, Sofroniew MV (1993) Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system. Exp Neurol 120(2):245–263CrossRefPubMedGoogle Scholar
  7. 7.
    Fujioka M et al (1999) Novel brain ischemic change on MRI. Delayed ischemic hyperintensity on T1-weighted images and selective neuronal death in the caudoputamen of rats after brief focal ischemia. Stroke 30(5):1043–1046CrossRefPubMedGoogle Scholar
  8. 8.
    Moseley ME et al (1990) Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy. Magn Reson Med 14(2):330–346CrossRefPubMedGoogle Scholar
  9. 9.
    Habgood MD et al (2007) Changes in blood-brain barrier permeability to large and small molecules following traumatic brain injury in mice. Eur J Neurosci 25(1):231–238CrossRefPubMedGoogle Scholar
  10. 10.
    Schneider G et al (2002) Pathophysiological changes after traumatic brain injury: comparison of two experimental animal models by means of MRI. MAGMA 14(3):233–241CrossRefPubMedGoogle Scholar
  11. 11.
    Provenzale JM, Mukundan S, Dewhirst M (2005) The role of blood-brain barrier permeability in brain tumor imaging and therapeutics. AJR Am J Roentgenol 185(3):763–767CrossRefPubMedGoogle Scholar
  12. 12.
    Kaya M, Ahishali B (2011) Assessment of permeability in barrier type of endothelium in brain using tracers: Evans blue, sodium fluorescein, and horseradish peroxidase. Methods Mol Biol 763:369–382CrossRefPubMedGoogle Scholar
  13. 13.
    Soon D et al (2007) Quantification of subtle blood-brain barrier disruption in non-enhancing lesions in multiple sclerosis: a study of disease and lesion subtypes. Mult Scler 13(7):884–894CrossRefPubMedGoogle Scholar
  14. 14.
    Natah SS et al (2009) Effects of acute hypoxia and hyperthermia on the permeability of the blood-brain barrier in adult rats. J Appl Physiol 107(4):1348–1356PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Nag S, Picard P, Stewart DJ (2001) Expression of nitric oxide synthases and nitrotyrosine during blood-brain barrier breakdown and repair after cold injury. Lab Invest 81(1):41–49CrossRefPubMedGoogle Scholar
  16. 16.
    Singh AK, Jiang Y (2004) How does peripheral lipopolysaccharide induce gene expression in the brain of rats? Toxicology 201(1–3):197–207CrossRefPubMedGoogle Scholar
  17. 17.
    Mikulis DJ, Roberts TP (2007) Neuro MR: protocols. J Magn Reson Imaging 26(4):838–847CrossRefPubMedGoogle Scholar
  18. 18.
    Redzic Z (2011) Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences. Fluids Barriers CNS 8(1):3PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Nabeela Nathoo
    • 1
    • 2
  • Hamza Jalal
    • 1
    • 2
  • Sirajedin S. Natah
    • 3
  • Qiong Zhang
    • 4
  • Ying Wu
    • 1
  • Jeff F. Dunn
    • 2
    • 5
    • 1
  1. 1.Department of RadiologyUniversity of CalgaryCalgaryCanada
  2. 2.Hotchkiss Brain InstituteUniversity of CalgaryCalgaryCanada
  3. 3.Department of PhysiologyUmm-Alqura UniversityMakkahSaudi Arabia
  4. 4.General ElectricBeijingChina
  5. 5.Experimental Imaging CentreUniversity of CalgaryCalgaryCanada

Personalised recommendations