Intracerebral Haemorrhage and Inflammation

UoM administered thesis: Phd

  • Authors:
  • Oluwaseun Sobowale

Abstract

Intracerebral haemorrhage (ICH) is a significant healthcare concern worldwide. Following ICH, primary injury occurs due to physical injury to neurones and glia as a result of mass effect from the haematoma. Secondary mechanisms of injury include haematoma expansion, toxic effects of the products of coagulation and blood breakdown products and sterile inflammation. Perihaematomal oedema can exacerbate mass effect in the acute and sub-acute phase of ICH. At present, the pathophysiology behind the secondary mechanisms of injury following ICH is not fully understood and this has led to inability to translate new treatments from bench to bedside. Haematoma expansion is a significant contributor to neurological deterioration in the acute phase; however, understanding of the factors leading to a third of patients developing haematoma expansion is limited. This thesis presents the results of work aiming to develop a reproducible model of haematoma expansion in preclinical ICH. Using this model we found that a systemic inflammatory stimulus failed to induce haematoma expansion in spontaneously hypertensive rats or their healthy controls. We gained further insight into factors that may contribute to haematoma expansion in ICH by studying the proteomic profile of patients in clinical ICH. We demonstrate the feasibility of multi-modality brain imaging in sub-acute ICH, which we propose will be a useful tool to monitor neuro-inflammation in the acute stages if the disease. Finally, we investigated the association between peripheral markers of inflammation (white blood cell count and C-reactive protein) and perihaematomal oedema at baseline and clinical outcome (mortality at 30 days). Our findings suggest that acute inflammation may drive acute perihaematomal oedema and interestingly, we found a negative association between C-reactive protein at baseline and 30-day mortality. Our findings are significant in the field of clinical ICH, and suggest that the inflammatory response is important. We will take our findings forward in future work with the goal of understanding why haematoma expansion occurs, with the aim of developing a test to identify patients at highest risk and interventions to improve outcome after ICH.

Details

Original languageEnglish
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Award date1 Aug 2018