Selective, Delayed Increase in Transfer Constants for Cerebrovascular Permeation of Blood-Borne 3H-Sucrose Following Forebrain Ischaemia in the Rat

  • E. Preston
  • J. Saunders
  • N. Haas
  • M. Rydzy
  • P. Kozlowski
Conference paper
Part of the Acta Neurochirurgica book series (NEUROCHIRURGICA, volume 51)


Experiments were conducted to explore the time course of changes in blood-brain barrier (BBB) permeability that may occur in the 2-vessel occlusion model of stroke in the rat. Anaesthetized Sprague-Dawley rats underwent 10 min of cerebral ischaemia produced by bilateral carotid occlusion plus haemorrhagic hypotension. After 6 min, or 3, 6, 18, 24, 48 h recovery and re-anaesthetization, an i.v. injection of 3H-sucrose was permitted to circulate for 30 min. Regional transfer constants (Ki) for BBB permeation of sucrose were calculated from the ratio of sucrose concentration in parenchyma relative to the time-integrated plasma concentration. In the 6-min group, all cerebral regions showed evidence of early BBB leakiness (increase in Ki above non-stroke baseline) which was maximal in forebrain cortex. This effect was diminished at subsequent time points, except in striatum and hippocampus which exhibited delayed intensification of opening, maximal in the 6 h group. Ki values had largely normalized by 24 h. Ki values were also determined 6 min, 6 h and 24 h after a 20-min stroke procedure. Early and regionally selective, delayed BBB openings were also seen, but recovery was not evident in cerebral regions at 24 h. Cortex exhibited a large increase in Ki indicating that a delayed, marked deterioration of BBB integrity had developed between the 6 h and 24 h time points. It is concluded that the combination of transfer constant measurements and the 2-vessel occlusion model could provide a sensitive means for investigating the cerebrovascular consequences and therapy of stroke.


Forebrain Ischaemia Marked Deterioration Transfer Constant Carotid Occlusion Cerebral Region 
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  1. 1.
    Kuroiwa T, Ting P, Martinez H, and Klatzo I (1985) The bi-phasic opening of the blood-brain barrier to proteins following temporary middle cerebral artery occlusion. Acta Neuropathol (Berl) 68: 122–129CrossRefGoogle Scholar
  2. 2.
    Ohno K, Pettigrew KD, Rapoport SI (1978) Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. Am J Physiol 235: H 299-H 307Google Scholar
  3. 3.
    Preston E, Allen M, Haas N (1983) A modified method for measurement of radiotracer permeation across the rat blood-brain barrier: The problem of correcting brain uptake for intravascular tracer. J Neurosci Methods 9: 45–55PubMedCrossRefGoogle Scholar
  4. 4.
    Preston E, and Haas N (1986) Defining the lower limits of blood-brain barrier permeability: factors affecting the magnitude and interpretation of permeability area products. J Neurosci Res 16: 709–719PubMedCrossRefGoogle Scholar
  5. 5.
    Saunders JK, Smith ICP, MacTavish JC, Rydzy M, Peeling J, Sutherland E, Lesiuk H, and Sutherland GR (1989) Forebrain ischaemia studied using magnetic resonance imaging and spectroscopy. NMR in Biomedicine 2: 312–3166PubMedCrossRefGoogle Scholar
  6. 6.
    Smith ML, Auer RN, Siesjo BK (1984) The density and distribution of ischaemic brain injury in the rat following 2–10 min of forebrain ischaemia. Acta Neuropathol (Berl) 64: 319–332CrossRefGoogle Scholar
  7. 7.
    Sutherland G, Peeling J, Lesiuk H, Saunders J (1990) Experimental cerebral ischaemia studied using nuclear magnetic resonance imaging and spectroscopy. J Can Assoc Radiol 41: 24–31Google Scholar
  8. 8.
    Suzuki R, Yamaguchi T, Kirino T, Orzi F, Klatzo I (1983) The effects of 5 minute ischaemia in mongolian gerbils: I. Blood-brain barrier, cerebral blood flow and local cerebral glucose utilization changes. Acta Neuropathol (Berl) 60: 207–216CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • E. Preston
    • 1
  • J. Saunders
  • N. Haas
  • M. Rydzy
  • P. Kozlowski
  1. 1.Division of Biological SciencesNational Research Council of CanadaOttawaCanada

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