Seminar: managing spreading depolarisations in the brain
11 December 2012
Professor Anthony Strong’s talk for the most recent of SRMRC’s seminar series provided an insight into an area of neurological research which could be the basis for new approaches to some kinds of brain injury.
Prof Strong is Emeritus Professor of Neurosurgery at King’s College London, and was discussing the work done by the Co-operative Study of Brain Injury Depolarisations (COSBID).
Spreading depolarisations, which can often behave as destructively in the partially injured brain as a tsunami does in a coastal area, can be thought of in simple terms as a wave of short-circuiting of all nerve cells and astrocytes (supporting cells) in the path of the wave. These cells can be thought of as a large network of batteries, each with its own charge, that must quickly be restored if the cell is to remain viable, and this represents the largest known challenge to the cerebral circulation and metabolism. To restore the natural charge requires a dramatic temporary increase in perfusion, and in the healthy brain, cerebral blood flow increases quickly, delivering the required transient but major increments in oxygen and glucose availability. These changes spread in the cerebral grey matter in the immediate wake of the wave of shortcircuiting.
The depolarisation leads to transient depression of the normal electrocorticogram, the aspect that led its discoverer (in animal experiments in 1944), Brazilian scientist Aristides de Azevedo Pacheco Leão, to term the phenomenon “spreading depression of cortical activity”. Its occurrence in the injured human brain was first demonstrated definitively by Prof Strong and colleagues in a seminal paper in 2002.
Further research by the COSBID group has confirmed that the condition occurs in a wide range of human patients, including those who have suffered strokes, aneurysms, subarachnoid haemorrhage, and traumatic brain injury when a focal brain contusion is present. Using a variety of sensors on the scalp and at various depths within the injured patient’s brain, Prof Strong and his colleagues have been able to demonstrate transient changes in electrical potential. Closely linked to these are the subsequent changes in blood flow and in the levels of extracellular metabolites such as glucose and potassium.
Importantly, in partially injured but still “salvageable” areas of cerebral cortex around a traumatic contusion or the core of a stroke lesion, instead of the normal vasodilator response of the cerebral circulation, there is very often a major vasoconstrictor response in the microcirculation – vasospasm. This further restricts blood flow precisely when an increase is vital, leading often to further depletion of tissue glucose, and soon afterwards to the death of the tissue affected by the wave, since the brain’s critical and vital store of adenosine triphosphate can no longer be maintained.
He also spoke about the importance of an appropriate duration for continuous monitoring, as patients often remain at risk of spreading depolarisations for up to perhaps two weeks after the initial injury or stroke. Short, intermittent spells of monitoring will often fail to detect the depressions in brain activity that accompany the depolarisations. These depressions can be remarkably periodic.
Very importantly, depolarisations in patients with traumatic brain injury have now been shown to be associated with poor outcome.
This means that safe methods to suppress the worst depolarisations need to be identified, but before adopting pharmacological strategies, we need first to minimize secondary insults to the injured brain that are known, either from clinical or from experimental work, to promote depolarisations, such as episodes of arterial hypotension or hypoxia, hypoglycaemia, or pyrexia.
He then discussed the potential of the COSBID research to lead to therapeutic measures or prognostic indicators. The research is promising but further work is needed to develop the knowledge into ways of saving and changing lives.