The pathogenetic and prognostic significance of blood-brain barrier damage at the acute stage of aneurysmal subarachnoid haemorrhage. Clinical and experimental studies
- 114 Downloads
- 82 Citations
Summary
In a retrospective study, pathological tissue enhancement was found in nearly two fifths of patients with acute SAH on contrastenhanced cranial computed tomography. By means of absorption measurements with the region of interest technique over the basal ganglia, it was proved indirectly that pathological tissue enhancement should be brought about not only by hyperaemia,i.e., a blood volume increase, but also by extravasation of the contrast material,i.e., blood-brain barrier (BBB) disruption. A similar conclusion was drawn from the retrospective isotope brain scintigraphy study. It was further established that, although the pathological contrast enhancement was most obvious in the cortex, and particularly in the neighbourhood of the subarachnoid spaces, the phenomenon is probably widespread throughout the brain. Patients with abnormal enhancement are likely to be in less favourable clinical grades, have a high incidence of marked or diffuse spasm, have a poorer outcome independent of surgical or conservative treatment, and develop cerebral infarction more frequently. Systemic arterial hypertension was associated with an increased incidence of abnormal enhancement. Pathological tissue contrast enhancement or isotope accumulation in the first few days of SAH may serve as prognostic signs indicative of the late development of vasospasm and ischaemia. As ischaemic disruption of the capillary system is not prominent in the initial days following any stroke, vasoactive substances arising from the breakdown of the blood clot should play important part in the BBB damage in the acute stage of SAH. The “cortical SAH” model developed in the animal experiments ensured a constant subarachnoid blood volume with minimal local brain damage. The intracranial pressure and mean arterial blood pressure did not change significantly, and perfusion defects did not arise. Thus, this model proved suitable for studying the influence on the BBB of vasoactive blood breakdown products (responsible for arterial spasm) without the accompanying effects of pathological conditions such as raised intracranial pressure, systemic hypertension, non-reflow phenomena, which also disrupt the BBB. Measurements on the water, electrolyte, albumin contents of brain tissue, as well as the immunohistochemical localization af albumin, clearly indicated that the brain oedema developing at the acute stage of experimental SAH could be classified as having a primary vasogenic component in addition to the cytotoxic component. This increased capillary permeability was found to be brought about by opening of tight junctions and pinocytosis in the endothelial cells. The pathological capillary permeability was uninfluenced by dexamethasone, antihistamines and calcium-blocking treatment, but decreased by the adenyl cyclase blocking agent. These findings may have implications in the clinical treatment of SAH, as the integrity of the BBB is essential for maintaining a constant environment for the nervous tissue.
Keywords
Aneurysm blood-brain barrier CT scans experimental subarachnoid haemorrhage isotope brain scintigraphyPreview
Unable to display preview. Download preview PDF.
References
- 1.Agnoli, A. L., Schoch, P., Bayindir, S.,et al., Komputertomographische Befunde bei Gefäßmißbildungen der Hirnarterien. Röntgenblätter34 (1981), 55–60.Google Scholar
- 2.Ambrose, J., Computerized X-ray scanning of the brain. J. Neurosurg.40 (1974), 679–685.Google Scholar
- 3.Asano, T., Sano, K., Pathogenic role of no-reflow phenomenon in experimental subarachnoid hemorrhage in dogs. J. Neurosurg.46 (1977), 454–466.Google Scholar
- 4.Auer, L., Brain edema in acute arterial hypertension. I. Macroscopic findings. Acta Neuropathol.38 (1977), 67–72.Google Scholar
- 5.Barry, K. J., Gogjian, M. A., Stein, B. M., Small animal model for investigation of subarachnoid hemorrhage and cerebral vasospasm. Stroke10 (1979), 538–541.Google Scholar
- 6.Bell, B. A., Kendall, B. E., Symon, L., Computed tomography in aneurysmal subarachnoid haemorrhage. J. Neurol. Neurosurg. Psych.43 (1980), 522–524.Google Scholar
- 7.Boullin, D. J., Model systems for investigation of cerebral vasopasm. In: Cerbral Vasospasm (Boullin, D. J., ed.), pp. 241–293. Chichester-New York-Brisbane-Toronto: J. Wiley and Sons. 1980.Google Scholar
- 8.Boullin, D. J., Mohan, J., Grahame-Smith, D. G., Evidence for the presence of vasoactive substance (possibly involved in the aetiology of cerebral arterial spasm) in cerebro-spinal fluid from patients with subarachnoid haemorrhage. J. Neurol. Neurosurg. Psych.39 (1976), 756–766.Google Scholar
- 9.Bradbury, M. W. B., The Concept of Blood Brain-Barrier, pp. 369–374. Chichester-New York-Brisbane-London: J. Wiley and Sons, 1979.Google Scholar
- 10.Burch, H. Ch., Histologische Technik, pp. 105–106. Stuttgart: G. Thieme. 1969.Google Scholar
- 11.Caille, J. M., Guibert, F., Bidabe, A. M.,et al., Enhancement of cerebral infarcts with CT. J. Comput. Assist. Tomogr.4 (1980), 73–77.Google Scholar
- 12.Clasen, R. A., Huckman, M. S., von Roenn, K. A.,et al., A correlative study of computed tomography and histology in human and experimental vasogenic cerebral oedema. J. Comput. Assist. Tomogr.5 (1981), 313–327.Google Scholar
- 13.Crompton, M. R., The pathogenesis of cerebral infarction following rupture of cerebral aneurysms. Brain87 (1964), 491–510.Google Scholar
- 14.Cserr, H. F., Relationship between cerebrospinal fluid and intestinal fluid of brain. Fed. Proc.33 (1974), 2075–2078.Google Scholar
- 15.Davis, K. R., New, P. F. J., Ojemann, R. F.,et al., Computerized tomographic evaluation of haemorrhage secondary to intracranial aneurysm. Am. J. Roentgenol.127 (1976), 143–153.Google Scholar
- 16.Davis, J. M., Davis, K. R., Crowell, R. M., Subarachnoid haemorrhage secondary to ruptured intracranial aneurysm. Am. J. Neuroradiol.1 (1980), 17–21.Google Scholar
- 17.Dóczi, T., Huszka, E., Blood-brain barrier in SAH (Letters). J. Neurosurg.59 (1983), 1109–1110.Google Scholar
- 18.Dóczi, T., O'Laoire, S. A., Ambrose, J., The significance of contrast enhancement in cranial computed tomography following subarachnoid hemorrhage. J. Neurosurg.60 (1984), 335–343.Google Scholar
- 19.Dóczi, T., László, F. A., Szerdahelyi, P., Joó, F., Involvement of vasopressin in brain edema formation: further evidence obtained from the Brattleboro Diabetes Insipidus Rat with experimental subarachnoid hemorrhage. Neurosurgery14 (1984), 436–440.Google Scholar
- 20.DuBulay, G. N., Cerebral blood flow in man and animals. In: Cerebral Vasospasm (Boullin, D. J., ed.), pp. 91–111. Chichester-New York-Brisbane-Toronto: J. Wiley and Sons. 1980.Google Scholar
- 21.Fein, J. M., Cerebral energy metabolism after subarachnoid hemorrhage. Stroke6 (1975), 1–8.Google Scholar
- 22.Fisher, C. M., Kistler, J. P., Davis, J. M., Relation of cerebral vasospasm to subarachnoid haemorrhage visualized by computed tomography. Neurosurgery6 (1980), 1–9.Google Scholar
- 23.Fox, J. L., Ko, J. P., Cerebral vasospasm: A clinical observation. Surg. Neurol.10 (1978), 269–275.Google Scholar
- 24.Fraser, R. A., Cerebral Vasospasm, After 15 Years in the Laboratory. In: Cerebral Arterial Spasm (Wilkins, R. N., ed.), pp. 287–291. Baltimore-London: Williams and Wilkins. 1980.Google Scholar
- 25.Gado, M. H., Phelps, M. E., Coleman, R. E., An extravascular component of contrast enhancement in cranial computed tomography. Part I: The tissue blood ratio of contrast enhancement. Radiology117 (1975), 589–593.Google Scholar
- 26.Gado, M. H., Phelps, M. E., Coleman, R. E., An extravascular component of contrast enhancement in cranial computed tomography. Part II: Contrast enhancement and the blood tissue barrier. Radiology117 (1975), 595–597.Google Scholar
- 27.Grubb, R. L., Raichle, M. E., Eichung, J. O.,et al., Effects of subarachnoid haemorrhage on cerebral blood volume, blood flow, and oxygen utilization in humans. J. Neurosurg.46 (1977), 446–453.Google Scholar
- 28.Hashi, K., Meyer, J. S., Shinmaru, S., Changes in cerebral motor reactivity to CO2 and autoregulation following experimental subarachnoid hemorrhage. J. Neurol. Sci.17 (1972), 15–22.Google Scholar
- 29.Hopkins, L. N., Long, D. M., (eds.), Clinical Management of Intracranial Aneurysm (Seminars in Neurological Surgery). New York: Raven Press. 1982.Google Scholar
- 30.Hayward, R. D., O'Reilly, G. V. A., Inracerebral haemorrhage. Accuracy of computerized transverse axial scanning in predicting the underlying aetiology. Lancet1 (1976), 1–4.Google Scholar
- 31.Hirata, Y., Matsukado, Y., Fukumura, A., Subarachnoid enhancement secondary to subarachnoid haemorrhage with special reference to the clinical significance and pathogenesis. Neurosurgery11 (1982), 367–371.Google Scholar
- 32.Hossmann, K. A., Olsson, Y., The effect of transient cerebral ischemia on the vascular permeability to protein tracers. Acta Neuropathol.18 (1971), 103–112.Google Scholar
- 33.Hunt, W. E., Hess, W. H., Surgical risk as related to time of intervention in the repair of intracranial aneurysm. J. Neurosurg.28 (1968), 14–19.Google Scholar
- 34.Inoue, Y., Saiwai, S., Miyamoto, T.,et al., Post-contrast computed tomography in subarachnoid haemorrhage from ruptured aneurysm. J. Comput. Assist. Tomogr.5 (1981), 341–344.Google Scholar
- 35.Johansson, B. B., Effect of an acute increase of the intravascular pressure on the blood-brain barrier. Stroke9 (1978), 588–590.Google Scholar
- 36.Johansson, B. B., Strangaard, S., Lassen, N. A., On the pathogenesis of hypertensive encephalopathy: the hypertensive break-through of autoregulation of cerebral blood flow with forced vasodilatation, flow increase and blood-brain barrier damage. Circ. Res.34/35 (Suppl. I) (1974), 167–171.Google Scholar
- 37.Joó, F., Rakonczay, Z., Wollemann, M., cAMP-mediated regulation of the permeability in the brain capillaries. Experimentia31 (1975), 582–583.Google Scholar
- 38.Kamiya, K., Kuyama, L., Symon, L., An experimental study of the acute stage of subarachnoid haemorrhage. J. Neurosurg.59 (1983), 917–924.Google Scholar
- 39.Katzman, R., Pappius, H. M., Brain Electrolytes and Fluid Metabolism, pp. 519–524. Baltimore: Waverley Press. 1973.Google Scholar
- 40.Klatzo, I., Neuropathological aspects of brain edema. J. Neuropathol. Exp. Neurol.26 (1967), 1–14.Google Scholar
- 41.Kendall, B. E., Lee, B. C. P., Claveria, E., Computerized tomography and angiography in subarachnoid haemorrhage. Br. J. Radiol.49 (1976), 483–501.Google Scholar
- 42.Kendall, B. E., Pullicino, P., Intravascular contrast injection of ischaemic lesions. Part II: Effect on prognosis. Neuroradiology19 (1980), 241–243.Google Scholar
- 43.Kendall, B. E., Neuroradiology. In: Brain Tumours (Thomas, D. G. T., Graham, D. I., eds.), pp. 233–234. London-Boston-Sidney-Wellington-Durban-Toronto: Butterworths. 1980.Google Scholar
- 44.Kingsley, D. P. E., Kendall, B. E., Greitz, T.,et al., Extravasation of contrast enhanced blood into the subarachnoid space during CT. Neuroradiology18 (1979), 259–262.Google Scholar
- 45.König, T. F. R., Klippel, R. A., The Rat Brain. New York: Krieger. 1967.Google Scholar
- 46.Lacy, P. S., Earle, A. M., A small animal model for ECG abnormalities observed after an experimental subarachnoid hemorrhage. Stroke14 (1983), 371–377.Google Scholar
- 47.Levin, E., Are the terms blood brain barrier and brain capillary permeability synonymous? In: The Ocular and Cerebrospinal Fluids, (Bito, L. Z., Davson, H., Fenstermacher, J. D., eds.), pp. 191–199. London-New York-San Francisco: Academic Press. 1977.Google Scholar
- 48.Liliequist, B., Lindquist, M., Valdimarsson, E., Computed tomography and subarachnoid haemorrhage. Neuroradiology14 (1977), 21–26.Google Scholar
- 49.Moran, C. V., Naidich, T. P., Gado, M. H.,et al., Leptomeningeal findings in CT of subarachnoid haemorrhages. J. Comput. Assist. Tomogr.2 (1978), 520–521.Google Scholar
- 50.Nagata, I., Handa, N., Hashimoto, N., Hazama, F., Experimentally induced cerebral aneurysms in rats. Part VII. Surg. Neurol.16 (1981), 291–296.Google Scholar
- 51.Naidich, T. P., Pudlowski, R. M., Leeds, N. E.,et al., The normal contrast enhanced computed axial tomogram of the brain. J. Comput. Assist. Tomogr.1 (1977), 16–29.Google Scholar
- 52.Nagy, Z., Mathieson, G., Hüttner, L, Blood-brain barrier opening to horseradish peroxydase in acute arterial hypertension. Acta Neuropathol.48 (1979), 45–53.Google Scholar
- 53.Neuwelt, E. A., Maravilla, K. R., Frenkel, E. P.,et al., Use of enhanced computed tomography to evaluate osmotic bloodbrain barrier disruption. Neurosurgery6 (1980), 49–56.Google Scholar
- 54.Nornes, H., Magnaes, B., Intracranial pressure in patients with ruptured saccular aneurysm. J. Neurosurg.36 (1972), 537–547.Google Scholar
- 55.Nornes, H., The role of intracracranial pressure in the arrest of haemorrhage in patients with ruptured intracranial aneurysm. J. Neurosurg.39 (1973), 226–234.Google Scholar
- 56.Nornes, H., Knutzen, H. B., Wikeby, P., Cerebral arterial blood flow and aneurysm surgery. J. Neurosurg.47 (1977), 819–827.Google Scholar
- 57.Pappius, H. M., Evolution of edema in experimental cerebral infarction. In: Cerebrovascular Diseases. Eleventh Princton Conference (Price, T. R., Nelson, E., eds.), pp. 131–141. New York: Raven Press. 1979.Google Scholar
- 58.Pertuiset, B., Management of subarachnoid haemorrhage. Postgraduate Course of the European Neurosurgical Societies. Bratislava, Sept. 1–7, 1982.Google Scholar
- 59.Peterson, E. W., Cardoso, E. R., The blood-brain barrier following experimental subarachnoid hemorrhage. J. Neurosurg.58 (1983), 338–344.Google Scholar
- 60.Peterson, E. W., Cardoso, E. R., The blood-brain barrier following experimental subarachnoid hemorrhage. Response to mercuric chloride infusion. J. Neurosurg.58 (1983), 345–351.Google Scholar
- 61.Pia, H. W., Aneurysm surgery-grading and timing. Neurosurg. Rev.1 (1982), 89–104.Google Scholar
- 62.Pia, H. W., Grading of cerebral aneurysms and timing of operation. Neurosurg. Rev.4 (1981), 143–150.Google Scholar
- 63.Rapaport, S. I., Blood-Brain Barrier in Physiology and Medicine, pp. 25–37. New York: Raven Press. 1976.Google Scholar
- 64.Rothberg, C., Weir, B., Overton, T.,et al., Response to experimental subarachnoid hemorrhage in the spontaneously breathing primate. J. Neurosurg.52 (1980), 302–308.Google Scholar
- 65.Rössner, W., Tempel, K., Quantitative Bestimmung der Permeabilität der sogenannten Blut-Hirnschranke für Evans-Blau. Med. Pharmacol. exp.14 (1966), 169–182.Google Scholar
- 66.Scotti, G., Ethier, R., Melancon, D.,et al., Computed tomography in the evaluation of intracranial aneurysms and subarachnoid haemorrhage. Radiology123 (1977), 85–90.Google Scholar
- 67.Shibata, S., Hodge, C. P., Pappius, H. M., Effect of experimental ischemia on cerebral water and electrolytes. J. Neurosurg.41 (1974), 146–159.Google Scholar
- 68.Shigeno, T., Fritschka, E., Shigeno, S.,et al., Cerebral oedema following experimental subarachnoid haemorrhage. J. Cerebr. Blood Flow Metab. Suppl.1 (1981), 558–559.Google Scholar
- 69.Sicuteri, F., Fanciulacci, M., Bavazzano, A.,et al., Kinins and intracranial haemorrhages. Angiology21 (1970), 139–145.Google Scholar
- 70.Simeone, F. A., Vinall, P. E., Evaluation of animal models of cerebral vasospasm. In: Cerebral Arterial Spasm (Wilkins, R. H., ed.), pp. 284–287. Baltimore-London: Williams and Wilkins. 1980.Google Scholar
- 71.Skriver, E. B., Olsen, T. S., Transient disappearance of cerebral infarcts on CT scan, the so called fogging effect. Neuroradiology22 (1981), 61–65.Google Scholar
- 72.Skriver, E. B., Olsen, T. S., Contrast enhancement of cerebral infarcts. Incidence and clinical value in different states of cerebral infarction. Neuroradiology23 (1982), 259–265.Google Scholar
- 73.Starling, L. M., Boullin, D. J., Grahame-Smith, D. G.,et al., Responses of isolated human basilar arteries to 5 HT, NA, serum platelets and erythrocytes. J. Neurol. Neurosurg. Psych.38 (1975), 650–656.Google Scholar
- 74.Sternberger, L. A., Immunocytochemistry. Englewood Cliffs, New Jersey: Prentice Hall. 1980.Google Scholar
- 75.Strangaard, S., Olesen, J., Skinhoj, E.,et al., Autoregulation of brain circulation in severe arterial hypertension. Brit. Med. J.1 (1973), 507–510.Google Scholar
- 76.Symon, L., Pásztor, E., Summary of session E: Subarachnoid haemorrhage. In: Proceedings of the 3rd International Conference on Intracranial Pressure—Intracranial Pressure III (Beck J. F., Bosch, D. A., Brock, M., eds.), pp. 168–169. Berlin-Heidelberg-New York: Springer. 1976.Google Scholar
- 77.Symon, L., Disordered cerebro-vascular physiology in aneurysmal subarachnoid haemorrhage. Acta Neurochir. (Wien)41 (1978), 7–22.Google Scholar
- 78.Suzuki, J., Komatsu, S., Sato, T.,et al., Correlation between CT findings and subsequent development of cerebral infarction due to vasospasm in subarachnoid haemorrhage. Acta Neurochir. (Wien)55 (1980), 63–70.Google Scholar
- 79.Tazawa, T., Mizukami, M., Kawase, T.,et al., Relationship between contrast enhancement on CT and cerebral vasospasm in patients with SAH. Neurosurgery12 (1983), 643–648.Google Scholar
- 80.Trojanowski, T., Blood-brain barrier changes after experimental subarachnoid haemorrhage. Acta Neurochir. (Wien)60 (1982), 45–54.Google Scholar
- 81.Yock, D. H., Marshall, W. H., Recent ischaemic brain infarcts at computed tomography: Appearances pre- and post-contrast infusion. Radiology117 (1975), 599–608.Google Scholar
- 82.Yock, D. H., Jr., Larson, D. A., Computed tomography of haemorrhage from anterior communicating artery aneurysm with angiographic correlation. Radiology134 (1980), 399–407.Google Scholar
- 83.Weir, B. K. A., The incidence and onset vasospasm after SAH from ruptured aneurysm. In: Cerebral Arterial Spasm (Wilkins, R. H., ed.), pp. 397–408. Baltimore/London: Williams and Wilkins. 1980.Google Scholar
- 84.Westergaard, E., Enhanced vesicular transport of exogenous peroxidase across cerebral vessels, induced by serotonin. Acta Neuropathol.32 (1975), 27–42.Google Scholar
- 85.Wilkins, R. H., Cerebral Arterial Spasm. Part B. Biochemistry, pp. 144–229. Baltimore-London: Williams and Wilkins. 1980.Google Scholar
- 86.Wilmes, F., Hossmann, K. A., A specific immunofluorescence technique for the demonstration of vasogenic brain oedema in paraffin embedded material. Acta Neuropathol. (Berl.)45 (1979), 47–51.Google Scholar