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The pathogenetic and prognostic significance of blood-brain barrier damage at the acute stage of aneurysmal subarachnoid haemorrhage. Clinical and experimental studies

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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.

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  1. T. Dóczi

    Present address: Department of Neurosurgery, University Medical School, Szeged, Hungary

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    The autor has been awarded the 1984 Upjohn Prize of the European Association of Neurosurgical Societies for this scientific work.

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    Dóczi, T. The pathogenetic and prognostic significance of blood-brain barrier damage at the acute stage of aneurysmal subarachnoid haemorrhage. Clinical and experimental studies. Acta neurochir 77, 110–132 (1985). https://doi.org/10.1007/BF01476215

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