Advances and Technical Standards in Neurosurgery Vol. 30

Depolarisation Phenomena in Traumatic and Ischaemic Brain Injury (p. 3)

A. J. Strong and R. Dardis
History, Definitions and Introduction

In 1944 a young Brazilian physiologist, Aristides Lea˜o, was studying for his doctorate in Harvard University. According to Somjen [1], he was attempting to study propagation of epileptic activity in the cerebral cortex, and he approached the problem by applying electrical stimulation to the frontal convexity cortex of anaesthetised rabbits, and recording from an array of corticography electrodes posterior to this (Fig. 1).

Instead of seeing propagating epileptic activity, he observed a period of electrical silence, which was first seen adjacent to the stimulating electrodes, and did indeed propagate from the site of stimulation backwards along the cere- bral hemisphere – at a rate of some 3 millimetres per minute.

The phenomenon resolved after 5–15 minutes, with – apparently – full resumption of cortical electrical activity. He reported his .ndings in a landmark paper entitled ‘‘Spreading depression of activity in the cerebral cortex’’ [2].

The event which he described became known as ‘‘spreading depression’’ or ‘‘cortical spreading depression’’ [of Lea˜o] (CSD), and has remained a subject of intense interest to neurophysiologists. Although the electrophysiological and haemodynamic features have become very well characterised, with mass focal depolarisation of neurones and glia as the defining event, its most enigmatic challenges have remained its uncertain physiological role in grey matter, and its relevance – if any – to human disease states.

Since 1977–1978, stroke research laboratories have become aware of a feature of cerebral cortex in the ischaemic penumbra which shares certain characteristics with CSD, but also di¤ers from it in critical aspects. ‘‘Periinfarct depolarisations’’ (PIDs) arise spontaneously in cortex at the edge of the core ischaemic territory and propagate in the penumbra, but unlike CSD, they are harmful in that they cause progressive recruitment of the penumbra into the core territory, thus enlarging the infarct [3].

Somjen refers to such events as hypoxic spreading depression-like depolarisations (HSD) [1]. The evolution of this concept, and increasing awareness among some clinicians of its existence, has prompted increasing speculation as to whether CSD or PIDs occur in the injured human brain. Demonstrations of CSD-like events in models of traumatic brain injury, the imaging in the laboratory of propagation of PIDs across the cerebral cortex in models of focal cerebral ischaemia, the knowledge that not only cerebral cortex but also deep nuclei and the hippocampus may be subject to CSD, and particularly the recent confirmation that such events do indeed occur in patients with serious head injury [4], seem likely to open a fresh chapter in clinical brain injury research. This is an area of research to which neurosurgeons are uniquely placed to contribute.

The features of cortical spreading depression as it is observed in the experimental laboratory have been the subject of a number of authoritative reviews extending over many years, and the reader seeking the most detailed information is directed to them [1, 5–7]. We have relied extensively on these reviews as well as on the original sources.