Skip to main content
SpringerLink
Log in

Time- and pressure-dependent changes in blood-brain barrier permeability after temporary middle cerebral artery occlusion in rats

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

After 180 min of temporary middle cerebral artery occlusion in rats, the affect of phenylephrine-induced hypertension on blood-brain barrier permeability was assessed. One of the following blood-pressure regimens was maintained during either a 30- or 120-min period of reperfusion: (a) 30/Norm, 30 min of normotensive reperfusion was allowed; (b) 30/HTN, mean arterial blood pressure was increased by 35 mm Hg during 30 min of reperfusion; (c) 120/Norm, 120 min of normotensive reperfusion was allowed; or (d) 120/HTN, mean arterial blood pressure was increased by 35 mm Hg during 120 min of reperfusion. Evans blue (30 mg/kg) was given, and brains were analyzed for Evans blue by spectrophotometry. Evans blue (μg/g brain tissue, mean ± SD) was greater (P<0.05) in both hypertensive groups versus their time matched normotensive groups (30/HTN: 80±16 versus 18±6 in the 30/Norm group; 120/HTN: 17±6 versus 8±3 in the 120/Norm group). In addition, Evans blue was greater (P<0.05) in both 30-min groups versus their pressure matched 120-min groups (30/Norm: 18±6 versus 8±3 in the 120/Norm group; 30/HTN: 80±16 versus 17±6 in the 120/HTN group). The data are consistent with previous studies which have demonstrated an opening of the blood-brain barrier at the onset of reperfusion. In addition, the data support a hypothesis that changes in blood-brain barrier permeability are more sensitive to hypertension in the early period of reperfusion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aspey BS, Ehteshami S, Hurst CM, McCoy AL, Harrison MJG (1987) The effect of increased blood pressure on hemispheric lactate and water content during acute cerebral ischaemia in the rat and gerbil. J Neurol Neurosurg Psychiatry 50:1493–1498

    Google Scholar 

  2. Auer L (1977) The role of cerebral perfusion pressure as origin of brain edema in acute arterial hypertension. Eur Neurol 15:153–156

    Google Scholar 

  3. Bell BA, Symon L, Branston NM (1985) CBF and time thresholds for the formation of ischemic cerebral edema and effect of reperfusion in baboons. J Neurosurg 62:31–41

    Google Scholar 

  4. Betz AL, Goldstein GW (1986) Specialized properties and solute transport in brain capillaries. Annu Rev Physiol 48:241–250

    Google Scholar 

  5. Chikovani O, Corkill G, McLeish I, Ong S, Beilin D (1978) Effect on canine cerebral blood flow of two common pressor agents during prolonged halothane anesthesia. Surg Neurol 9:211–213

    Google Scholar 

  6. Clasen RA, Pandolfi S (1970) Vital staining, serum albumin and the blood-brain barrier. J Neuropathol Exp Neurol 29:266–284

    Google Scholar 

  7. Cole DJ, Drummond JC, Shapiro HM, Hertzog RE, Brauer FS (1989) The effect of hypervolemic hemodilution with and without hypertension on cerebral blood flow following middle cerebral artery occlusion in rats anesthetized with isoflurane. Anesthesiology 71:580–585

    Google Scholar 

  8. Cole DJ, Drummond JC, Marcantonio S, Matsumura JS, Chi-Lum BI (1990) Hemodilution and hypertension during middle cerebral artery occlusion in rats: the effect on blood-brain barrier permeability. Can J Neurol Sci 17:372–377

    Google Scholar 

  9. Cole DJ, Drummond JC, Osborne T, Matsumura J (1990) Hypertension and hemodilution during cerebral ischemia reduce brain injury and edema. Am J Physiol 259:H211-H217

    Google Scholar 

  10. Cole DJ, Drummond JC, Ruta TS, Peckham NA (1990) Hemodilution and hypertension effects on cerebral hemorrhage in cerebral ischemia in rats. Stroke 21:1333–1339

    Google Scholar 

  11. Cole DJ, Matsumura JS, Drummond JC, Schell RM, Hertzog RS (1990) The effect of hypertension on reperfusion cerebral blood flow following temporary middle cerebral artery occlusion. J Neurosurg Anesthesiol 2:211

    Google Scholar 

  12. Del Zoppo GJ (1988) Thrombolytic therapy in cerebrovascular disease. Stroke 19:1174–1179

    Google Scholar 

  13. Drummond JC, Oh Y-S, Cole DJ, Shapiro HM (1989) Phenylephrine-induced hypertension reduces ischemia following middle cerebral artery occlusion in rats. Stroke 20:1538–1544

    Google Scholar 

  14. Durward QJ, Del Maestra FD, Amacher AL, Farrar JK (1983) The influence of systemic arterial pressure and intracranial pressure on the development of cerebral vasogenic edema. J Neurosurg 59:803–809

    Google Scholar 

  15. Hansson H, Johansson BB, Blomstrand C (1975) Ultrastructural studies on cerebrovascular permeability in acute hypertension. Acta Neuropathol (Berl) 32:187–198

    Google Scholar 

  16. Hatashita S, Hoff JT (1986) Role of a hydrostatic pressure gradient in the formation of early ischemic brain edema. J Cereb Blood Flow Metab 6:546–552

    Google Scholar 

  17. Klatzo I (1987) Pathophysiological aspects of brain edema. Acta Neuropathol (Berl) 72:236–239

    Google Scholar 

  18. Kogure K, Busto R, Scheinberg P (1981) The role of hydrostatic pressure in ischemic brain edema. Ann Neurol 9:273–282

    Google Scholar 

  19. Kuroiwa T, Ting P, Martinez H, Klatzo I (1985) The biphasic opening of the blood-brain barrier to proteins following temporary middle cerebral artery occlusion. Acta Neuropathol (Berl) 68:122–129

    Google Scholar 

  20. Kuroiwa T, Shibutani M, Okeda R (1988) Blood-brain barrier disruption and exacerbation of ischemic brain edema after restoration of blood flow in experimental focal cerebral ischemia. Acta Neuropathol 76:62–70

    Google Scholar 

  21. Lowe RE, Gilboe DD (1971) Demonstration of alpha and beta adrenergic receptors in canine cerebral vasculature. Stroke 2:193–200

    Google Scholar 

  22. Masaoka H, Klatzo I, Tomida S, Vass K, Wagner HG, Nowak TS (1988) Role of circulatory disturbances in the development of post-ischemic brain edema. Neurochem Pathol 9:21–29

    Google Scholar 

  23. Mayhan WG, Heistad DD (1986) Role of veins and cerebral venous pressure in disruption of the blood-brain barrier. Circ Res 95:216–220

    Google Scholar 

  24. Murphy VA, Johanson CE (1985) Adrenergic-induced enhancement of brain barrier system permeability to small nonelectrolytes: choroid plexus versus cerebral capillaries. J Cereb Blood Flow Metab 5:401–412

    Google Scholar 

  25. Nag S, Robertson DM, Dinsdale HB (1977) Cerebral cortical changes in acute experimental hypertension. An ultrastructural study. Lab Invest 36:150–161

    Google Scholar 

  26. Petterson CAV, Sharma SH, Olsson Y (1990) Vascular permeability of spinal nerve roots. Acta Neuropathol 81:148–154

    Google Scholar 

  27. Raichle ME, Hartman BK, Eichling JO, Sharpe LG (1975) Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc Nat Acad Sci USA 72:3726–3730

    Google Scholar 

  28. Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L (1978) Measurement of local cerebral blood flow with iodo-C-14-antipyrine. Am J Physiol 234:H59-H66

    Google Scholar 

  29. Schultz RL, Willey TJ (1973) Extracellular space and membrane changes in brain owing to different alkali metal buffers. J Neurocytol 2:289–303

    Google Scholar 

  30. Shigeno T, Teasdale GM, McCulloch J, Graham GI (1985) Recirculation model following MCA occlusion in rats. Cerebral blood flow, cerebrovascular permeability, and brain edema. J Neurosurg 63:272–277

    Google Scholar 

  31. Simonescu M, Simonescu N (1986) Functiions of the endothelial cell surface. Ann u Rev Physiol 48:279–293

    Google Scholar 

  32. Simonescu M, Simonescu N, Palade GE (1982) Biochemically differentiated microdomains of the cell surface of capillary endothelium. Ann NY Acad Sci 401:9–24

    Google Scholar 

  33. Simonescu M, Simonescu M, Palade GE (1975) Permeability of muscle capillaries to small hemepeptides. Evidence for the existence of patent transendothelial channels. J Cell Biol 64:586–607

    Google Scholar 

  34. Stewart PA, Farrell CR, Coomber BL (1988) Blood-brain barrier ultrastructure: beyond tight junctions. Ann NY Acad Sci 529:295–297

    Google Scholar 

  35. Strangaard S, Paulson OB (1984) Cerebral autoregulation. Stroke 15:413–416

    Google Scholar 

  36. Suzuki R, Yamaguchi T, Kirino T, Orzi F, Klatzo I (1983) The effects of 5-minute ischemia in Mongolian gerbils. I. Blood-brain barrier, cerebral blood flow and local cerebral glucose utilization changes. Acta Neuropathol (Berl) 60:207–216

    Google Scholar 

  37. Symon L, Branston NM, Strong AJ (1976) Autoregulation in acute focal ischemia. An experimental study. Stroke 7:547–554

    Google Scholar 

  38. Ulrich K, Kuschinsky W (1985) In vivo effects of alpha-adrenoceptor agonists and antagonists on pial veins of cats. Stroke 16:880–884

    Google Scholar 

  39. Westgaard E, Deurs B, Bronsted HE (1977) Increased vesicular transfer of horsearadish peroxidase across cerebral endothelium, evoked by hypertension. Acta Neuropathol (Berl) 37:141–152

    Google Scholar 

  40. Wilkinson L (1987) Multivariate general linear hypothesis. In: SYSTAT: the system for statistics. SYSTAT, Inc., Evanston, pp 22–30

    Google Scholar 

  41. Wise G, Sutter R, Burkholder J (1972) The treatment of brain ischemia with vasopressor drugs. Stroke 3:135–140

    Google Scholar 

  42. Yamaguchi S, Kobayashi S, Yamashita K, Kitani M (1989) Pial arterial pressure contribution to early ischemic brain edema. J Cereb Blood Flow Metab 9:597–602

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Loma Linda University, 92354, Loma Lind, CA, USA

    D. J. Cole, J. S. Matsumura & M. H. Wong

  2. Department of Anatomy, Loma Linda University, 92354, Loma Lind, CA, USA

    R. L. Schultz

  3. Department of Anesthesiology, VA Medical Center, San Diego, CA

    J. C. Drummond

  4. Department of Anesthesiology, University of California at San Diego, La Jolla, CA

    J. C. Drummond

Authors
  1. D. J. Cole
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. S. Matsumura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. C. Drummond
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. L. Schultz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. H. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cole, D.J., Matsumura, J.S., Drummond, J.C. et al. Time- and pressure-dependent changes in blood-brain barrier permeability after temporary middle cerebral artery occlusion in rats. Acta Neuropathol 82, 266–273 (1991). https://doi.org/10.1007/BF00308811

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00308811

Key words

Search

Navigation