An investigation into the cerebral autoregulatory upper limit: Normal control mechanisms and changes associated with ageing

Thompson, Emma Louise (2018). An investigation into the cerebral autoregulatory upper limit: Normal control mechanisms and changes associated with ageing. University of Birmingham. Ph.D.

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Abstract

Cerebral autoregulation (CA) is the process by which cerebral arterial vessels constrict or dilate, in order to maintain cerebral blood flow (CBF) in the face of changes in arterial blood pressure. This thesis aimed to investigate the mechanisms that normally control CA, with specific reference to the upper limit (UL ); the point at which autoregulatory vasoconstriction is overcome. The UL is associated with an increase in CBF, which can potentially cause damaging cerebrovascular hyperperfusion. Ageing is associated with a general decrease in regulatory mechanisms, and an increased risk of stroke. Therefore we sought to assess whether changes in CA at the UL may predispose older rats to haemorrhagic stroke. We assessed CA by infusion of phenylephrine to increase ABP in an anaesthetised rat model, whilst measuring CBF to enable identification of the UL. This protocol was repeated in young (6-8 weeks) and old (12-15 months) rats in control conditions, or during removal of regulatory inputs. The UL in young, control rats was 168±4mmHg. Removal of nitric oxide-mediated dilatation and sympathetically-mediated vasoconstriction increased the UL. In old rats, the increase in UL was even greater. Thus we propose a new working hypothesis to explain the control of CA and the UL.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):