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Traumatic brain injury is a major public health issue and represents the leading cause of disability and death among young adults and children in Europe. Repetitive mild TBI (rmTBI) is a particularly dangerous form of brain injury, due to both its prevalence and limited overt clinical signs. This is concerning as rmTBI can lead to cumulative injury and is an established risk factor for dementia. Despite this, little is known about the mechanisms driving the cumulative detrimental effects rmTBI, and there is a pressing need to develop novel interventional strategies. Inflammatory processes are closely linked to brain injury. It is now understood that nutrition and, in particular, n-3 PUFAs in the diet can prevent the harmful effects of brain inflammation and promote repair. Microglial are key mediators of brain inflammation but the way this inflammation resolves after mTBI, before a second injury, has received little attention. We hypothesise that unresolved inflammatory responses play a key role in the cumulative damage of rmTBI and these can be modulated by the administration of n-3 PUFAs, to reduce the harmful, cumulative effects of a second injury. To test these hypotheses, we will take a system’s biology approach in relevant mouse model of rmTBI and evaluate multiple parameters of microglia-mediated inflammation in the critical time period between two injuries. Genomic and lipidomic screens will provide new mechanistic insights for rmTBI treatments. We will then modulate these inflammatory processes through administration of n-3 PUFAs and evaluate behavioural outcomes and assess early signs of neurodegeneration to validate n-3 PUFAs as a clinical candidate for use in rmTBI.
I obtained my PhD with Prof. Dame Nancy Rothwell at the University of Manchester, working on the role cytokines in brain ischaemia and haemorrhage. My postdoctoral work was performed at McGill University, Canada, in the laboratory Dr Sam David. My fundamental research interests are focused the immune system’s role in central nervous system (CNS) injury and disease. More specifically, the role of inflammation after a physically traumatic event, such as a brain or spinal cord injury. My research has contributed to the preclinical development of anti-inflammatory molecules for the treatment of stroke and I am particularly interested in two cell-types involved in the immune response to CNS injury; microglia and macrophages. Microglia are the resident immune cell of the CNS, whereas macrophages infiltrate from the blood after CNS injury. Both cell types are thought to be to the recovery of brain and spinal cord tissue. My work is now focusing on the interconnected role of microglia and macrophages and how lipid derivatives and signaling could be crucial in their function.
Anderson WD, Greenhalgh AD, Takwale A, David S and Vadigepalli R, 2017. Novel Influences of IL-10 on CNS Inflammation Revealed by Integrated Analyses of Cytokine Networks and Microglial Morphology. Front. Cell. Neurosci. 11:233. Doi: 10.3389/fncel.2017.00233.
Greenhalgh AD, Passos dos Santos R, Zarruk JG, Salmon CK, Kroner A, David S, 2016. Arginase-1 is Expressed Exclusively by Infiltrating Myeloid Cells in CNS Injury and Disease. Brain Behav Immun., 56: 61-7.
Lewitus GM*, Konefal SC*, Greenhalgh AD, Pribiag H, Augereau K and Stellwagen D, 2016. Microglial TNFα suppresses cocaine-induced plasticity and behavioral sensitization. Neuron., 90(3):483-91 *contributed equally.
Kroner A, Greenhalgh AD, Zarruk JG, Passos Dos Santos R, Gaestel M, David S, 2014. TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. Neuron., 83(5):1098-116.
Greenhalgh AD, David S, 2014. Differences in the phagocytic response of microglia and peripheral macrophages after spinal cord injury and its effects on cell death. J Neurosci., 34(18):6316-22.
2013: Canadian Institute for Health Research (CIHR) Postdoctoral Fellowship – $135,000 / 3yrs.
2011: Neuroinflammation CIHR Strategic Training Program Award – $40,000 / 2yrs