Ischaemic stroke, caused by blood clot blocking an artery to the brain, is a leading cause of death and disability. In around 10% of patients the stroke enlarges in the first 24-48 h (stroke-in-progression).

Typically, these are people who arrive with mild or rapidly improving stroke symptoms, but most end up with long-term disability. There is no effective treatment, in part because for the last few decades we have been wrong about the cause for stroke progression, so have been trying to treat the wrong mechanism. Recent advanced brain-imaging studies have shown that the cause of stroke progression is not related to increased blood clot, as was thought, but rather due to the ‘failure’ of bypass channels (collaterals) connecting the blocked artery to its neighbours. However there has been no good explanation of why collaterals fail. We have made an important discovery which provides the likely explanation. We found that 24 h after small stroke , there is a previously unsuspected dramatic, but transient, increase in pressure within the skull (intracranial pressure – ICP). This is predicted to cause collateral failure and our preliminary data suggests it does. Most importantly, we have an extremely promising treatment – 1-2 h of mild body cooling soon after stroke completely prevents the ICP rise.

These studies will use MRI to enable us to show change in the size of the stroke (infarct) over time. In the second part of the study we will capitalise on our world-leading acute stroke imaging database (including clinical outcomes) to gather evidence of the same mechanism occurring in stroke patients. We will use advanced imaging with computed tomography and magnetic resonance perfusion imaging and angiography to show that collateral flow drops before the stroke progression. This proposal will capitalise on our international lead in this rapidly evolving field, provide the necessary information for a clinical trial and also has broader implications for several other important disorders associated with increased ICP and disordered brain blood flow.


Professor Neil Spratt, Dr Damian McLeod

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