Abstract
Ischaemia, whether focal or global in nature, produces a sequence of intracellular events leading to increased cell permeability to water and ions including Ca++. There is a loss of cellular integrity and function, with increased production of prostaglandins, free radicals, andacidosis with lactate accumulation. These events may be exacerbated by glucose administration. Pharmacological agents aimed at alleviating ischaemic injury could be directed at decreasing cerebral metabolic requirements for oxygen, improving flow to ischaemic areas, preventing Ca++-induced injury, inhibition of free radical formation, lactate removal, inhibition of prostaglandin synthesis, and prevention of complement-mediated leukocyte aggregation. Part 1 of this paper describes some of the pathophysiological events leading to ischaemic brain injury. Part 2 of this paper will consider the current agents available for brain protection.
Résumé
L’ ischémie, qu’elle soil globale ou non, entraîne une cascade de modifications intracellulaires amenant une augmentation de la perméabilité cellulaire à l’eau et aux ions dont le Ca++. Intégrité et fonction cellulaires sont compromises avec une augmentation de la production des prostaglandines, des radicaux libres et de l’acidose avec accumulation de lactate, le tout pouvant être exacerbé par la perfusion de glucose. Afin de limiter les dommages induits par l’ischémie cérébrale, les agents thérapeutiques peuvent emprunter plusieurs avenues : diminution des besoins métaboliques en oxygène, amélioration du flot sanguin dans les zones ischémiques, prévention des dommages dus au Ca++, inhibition de la synthèse des radicaux libres et/ou des prostaglandines, élimination des lactates et prévention de l’agrégation leucocytaire induite par le complément. Dans un premier temps, nous décrivons la cascade pathophysiologique entraînant la lésion cérébrale ischémique. Dans la deuxième partie de notre travail, nous nous attarderons aux modes de protection cérébrale.
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Part II: “The pharmacology of brain protection” will be published in the October issue of the journal.
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Murdoch, J., Hall, R. Brain protection: physiological and pharmacological considerations. Part I: The physiology of brain injury. Can J Anaesth 37, 663–671 (1990). https://doi.org/10.1007/BF03006487
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DOI: https://doi.org/10.1007/BF03006487