Cellular Neuroinflammation in Acute Brain Injury

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Conditions that cause acute brain injury, such as trauma and brain haemorrhage are common causes of death and disability. Previous research has shown that much of the brain damage caused by these conditions occurs in the hours and days after the acute insult. This secondary damage is caused by inflammation that is triggered off by the primary insult. It is our belief that by understanding how this secondary inflammation occurs we will be able to identify targets for drug development. Drugs that control this secondary inflammation can potentially limit the brain damage resulting from these conditions. To date almost all brain injury research involving live tissue has focused on animal models, and unfortunately, little of what was learnt has been found to be directly relevant in humans; to date no effective treatments have emerged from these efforts. The need for research based on live human brain has long been recognised but until recently accessing such tissue was nearly impossible. In our hospital we have overcome this problem by establishing an ethically approved procedure to capture the tiny fragments of brain tissue that in the past where inevitably sacrificed and discarded during brain surgery. In acute brain injury severely affected patients have been shown to benefit from invasive monitoring using a small probe inserted into the brain itself. The insertion, and removal, of this probe involves the unavoidable loss of tiny fragments of brain. We are now able to capture this tissue for scientific research rather than it being thrown away. In this research, we will combine the analysis of this live human brain tissue with the results from the standard monitoring that we use in patients with significant brain injury. This technique, which we have pioneered, measures specialised signalling molecules called cytokines. These are proteins that immune cells use to communicate with each other. The levels of cytokines in the brain reflect the activity of the various parts of the immune system. The brain tissue we will collect will be processed into individual cells and characterised using a technique called single cell mRNA sequencing. This analysis will thus allow us to establish which cells are present after injury and which cells are making or responding to the cytokines we measure. Because we will take two brain tissue samples from each subject we will be able to measure how the cells change over time during brain injury. In total we will collect samples from 20 patients with severe brain injury: we will also collect samples from patients undergoing planned neurosurgery, either without any brain injury (10 patients) or more than 3 months after a brain injury (10 patients). We believe that the increased understanding of human brain inflammation that our work will provide will transform the prospects for developing safe and effective immune based treatments.