Brain-Skin Interactions

UoM administered thesis: Unknown

  • Authors:
  • Hamish Hunter

Abstract

Abstract of the thesis submitted by Hamish John Alexander Hunter for the degree of Doctor of Philosophy entitled 'Brain-Skin Interactions' September 2015Previous research has established a bidirectional interaction between the brain and the skin, the so-called 'brain-skin axis'; novel aspects of which were explored in human subjects in this thesis.Study 1 used positron emission tomography (PET) with the radioligand [11C]-(R)-PK11195 co-registered with magnetic resonance imaging (MRI) to investigate the relationship between systemic inflammation and neuroinflammation of the brain in psoriasis. Patients with chronic plaque psoriasis (n=12) and Healthy controls (n=12) underwent brain scanning and measurement of their peripheral inflammatory markers. Inflammatory markers were increased (significantly for interleukin-8) in psoriasis patients when compared with controls but brain neuroinflammation was not. There was heterogeneity in the degree of neuroinflammation in both groups which did not correlate with any measured variables. These findings suggest that in this population, the systemic inflammation associated with chronic plaque psoriasis does not induce brain neuroinflammation.Study 2 investigated the impact of psychosocial stress on cutaneous mast cell (MC) function. In sub-study 2.1, Healthy subjects were exposed to either the modified Trier paradigm (an acute, experimental psychosocial stressor, n=12) or sat quietly for an equivalent period of time (controls, n=12). The stressor did not affect MC density but significantly reduced MC degranulation, suggesting that acute psychosocial stress confers a degree of resilience to MC degranulation in heathy human skin. Sub-study 2.2 employed corticotropin-releasing hormone (CRH) as a surrogate 'chemical stressor' in an ex vivo full-thickness human skin organ culture model (n=5). Significant MC degranulation was induced by CRH, an effect replicated by Etanercept (tumour necrosis factor (TNF)-alpha inhibitor) supplementation of the culture medium. It is plausible that Etanercept triggers MC degranulation and TNF-alpha release which is subsequently neutralised by Etanercept binding; although this remains speculative.Both MC and Langerhans' cells (LC) are important in the cutaneous stress response. Study 3 investigated the effect of histamine, the prototypical granule-associated MC mediator on LC migration. Healthy human subjects (n=20) underwent skin prick testing (SPT) with histamine and normal saline (control). Two and four hours post-SPT biopsies were taken and analysed for the presence of LC. Histamine SPT had no impact on LC migration when compared to normal saline SPT. These findings suggest that histamine at this concentration does not directly influence LC migration.This thesis enhances our knowledge of brain-skin interactions which I hope will ultimately benefit patients with skin disease.

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Original languageEnglish
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Award date1 Aug 2016