Skip to main content
Log in

Cerebrovascular permeability to horseradish peroxidase in hypertensive rats: effects of unilateral locus ceruleus lesion

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

Summary

Unilateral locus ceruleus lesion enhances leakage of radioiodinated human serum albumin into the ipsilateral cerebral cortex of rats with norepinephrine-induced hypertension. This ultrastructural study was undertaken, to determine the mechanism by which this permeability alteration occurs, using horseradish peroxidase (HRP) as a tracer. Unilateral locus ceruleus lesion was produced in male Wistar-Furth rats by stereotaxic microinfusion of 5 μg of 6-hydroxydopamine. Two weeks later, rats were injected with HRP intravenously and acute hypertension was induced in awake rats by an intravenous infusion of norepinephrine (6 μg), epinephrine (6 μg) or angiotensin amide (12 μg) given over a 2-min period. Thirty seconds later, the rats were perfused with fixative under deep anesthesia and their brains were sliced and processed for demonstration of HRP reaction product. Leakage of HRP occurred in both cerebral hemispheres in response to hypertension induced by the three pressor agents, but the leakage was greater on the lesioned side in response to epinephrine and norepinephrine, while in the case of angiotensin-induced hypertension side-to-side differences in permeability alterations were not observed. In both cerebral hemispheres increased permeability affected mainly arterioles, which showed enhanced pinocytosis as the principal mechanism of HRP extravasation.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ben-Menachem E, Johansson BB, Svensson TH (1982) Increased vulnerability of the blood-brain barrier to acute hypertension following depletion of brain noradrenaline. J Neural Transm 53:159–167

    Google Scholar 

  • Bruns RR, Palade GE (1968) Studies in blood capillaries. II. Transport of ferritin molecules across the wall of muscle capillaries. J Cell Biol 37:277–279

    Google Scholar 

  • Cervos-Navarro J, Artigas J, Mrsulja BJ (1983) Morphofunctional aspects of the normal and pathological blood-brain barrier. Acta Neuropathol (Berl) [Suppl] VIII:1–19

    Google Scholar 

  • Edvinsson L (1975) Neurogenic mechanisms in the cerebrovascular bed. Acta Physiol Scand [Suppl] 427:5–35

    Google Scholar 

  • Harik SI (1984) Locus ceruleus lesion by local 6-hydroxydopamine infusion causes marked and specific destruction of noradrenergic neurons, long-term depletion of norepinephrine and the enzymes that synthetize it, and enhanced dopaminergic mechanisms in the ipsilateral cerebral cortex. J Neurosci 4:699–707

    Google Scholar 

  • Harik SI, McGunigal TJ (1984) The protective influence of the locus ceruleus on the blood-brain barrier. Ann Neurol 15:568–574

    Google Scholar 

  • Harik SI, Duckrow RB, LaManna JC, Rosenthal M, Sharma VK, Banerjee SP (1981a) Cerebral compensation for chronic noradrenergic denervation induced by locus ceruleus lesion: recovery of receptor binding isoproterenol-induced adenylate cyclase activity and oxidative metabolism. J Neurosci 1:641–649

    Google Scholar 

  • Harik SI, Sharma VK, Wetherbee JR, Warren RH, Banerjee SP (1981b) Adrenergic and colinergic receptors of cerebral microvessels. J Cereb Blood Flow Metab 1:329–338

    Google Scholar 

  • Joó F, Rakonszay Z, Wollemann M (1975) cAMP-mediated regulation of the permeability in the brain capillaries. Experientia 31:582–584

    Google Scholar 

  • Nag S (1984) Cerebral endothelial surface charge in hypertension. Acta Neuropathol (Berl). 63:276–281

    Google Scholar 

  • Nag S (1985) Ultrastructural localisation of lectin receptors on cerebral endothelium. Acta Neuropathol (Berl) 66:105–110

    Google Scholar 

  • Nag S (1986) Cerebral endothelial plasma membrane alterations in acute hypertension. Acta Neuropathol (Berl) 70:38–43

    Google Scholar 

  • Nag S, Robertson DM, Dinsdale HB (1979) Quantitative estimate of pinocytosis in acute experimental hypertension. Acta Neuropathol (Berl) 46:107–116

    Google Scholar 

  • Nag S, Robertson DM, Dinsdale HB (1980) Morphological changes in spontaneously hypertensive rats. Acta Neuropathol (Berl) 52:27–34

    Google Scholar 

  • Nag S, Robertson DM, Dinsdale HB (1981) Cerebrovascular permeability in mechanically induced hypertension. Can J Neurol Sci 8:215–220

    Google Scholar 

  • Nitsch C, Goping G, Laursen H, Klatzo I (1986) The blood-brain barrier to horseradish peroxidase at the onset of bicuculline-induced seizures in hypothalamus, pallidum, hippocampus, and other selected regions of the rabbit. Acta Neuropathol (Berl) 69:1–16

    Google Scholar 

  • Palade GE, Simionescu M, Simionescu N (1979) Structural aspects of the permability of the microvascular endothelium. Acta Physiol Scand 463:11–32

    Google Scholar 

  • Petito C, Levy D (1980) The importance of cerebral arterioles in alterations of the blood-brain barrier. Lab Invest 43:262–268

    Google Scholar 

  • Sharma VK, Harik SI, Busto R, Banerjee S (1981) Effects of noradrenaline depletion on adrenergic and muscarinic cholinergic receptors in the cerebral cortex, hippocampus and cerebellum. Exp Neurol 72:179–194

    Google Scholar 

  • Shivers RR, Harris RJ (1984) Opening of the blood-brain barrier in Anolis carolinensis. A high voltage electron microscope protein tracer study. Neuropathol Appl Neurobiol 10:343–356

    Google Scholar 

  • Westergaard E (1977) The blood-brain barrier to horseradish peroxidase under normal and experimental conditions. Acta Neuropathol (Berl) 39:181–187

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by Heart and Stroke Foundation of Ontario Grant 2–6 (to S. N.) and by United States Public Health Service Grant NS-18150 (to S. I. H.)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nag, S., Harik, S.I. Cerebrovascular permeability to horseradish peroxidase in hypertensive rats: effects of unilateral locus ceruleus lesion. Acta Neuropathol 73, 247–253 (1987). https://doi.org/10.1007/BF00686618

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00686618

Key words

Navigation