|dc.description.abstract||Brain trauma occurs frequently in children and its consequences cause significant
health and financial burden to the patients, their carers and society. This thesis
assessed the modulating effects of physiological, genetic, and biochemical factors on
the sequelae of childhood brain trauma.
Primary brain injury from the mechanical forces of trauma and secondary brain
insults consequent on the primary injury are determinants of brain trauma outcome.
The most important secondary insults recognised are reduced cerebral perfusion
pressure (CPP) and raised intracranial pressure (ICP). CPP is governed by the mean
arterial blood pressure and the ICP. During childhood these physiological measures
change with age. With continuous physiological recordings, ‘critical’ age-related
minimum CPP thresholds for children aged 2-6, 7-10 and 11-15 years were defined
as 48, 54 and 58mmHg respectively. Utilising these thresholds and a novel
cumulative pressure-time index (PTIc), we have demonstrated that CPP insult still
remains a feature in 80% of the severe brain trauma patients and significantly relates
to global outcome.
Brain trauma and cerebral ischaemia are stimuli to the inflammatory cascade leading
to further brain damage. Serum adhesion molecule levels after brain trauma indicate
injury severity and predict outcome better than brain specific proteins. Predictability
is improved using more than one serum biomarker level. Neuro-inflammatory
pathways involving adhesion molecules may have a strong modulating effect on
brain trauma outcome but warrants further investigations in relation to CPP insult.
Genetic factors such as Apolipoprotein E (APO E) genetic polymorphisms may
additionally influence outcome, but it was not known whether genetic factors lessen
the quantity of CPP insult or the cellular response to it. We demonstrated that the e4
carriers who had unfavourable outcome had 22 times less CPP insult than the non-e4
carriers, while the e3 homozygous who had good recovery had 26 times more CPP
insult than the non-e3 homozygous. This suggests that APO E polymorphisms may
affect the patient’s cerebral ischaemic tolerance differently, indicating especially the
need to prevent CPP insult among e4 carriers.
Cerebral ischaemia may, therefore, be a common pathway through which
physiological and genetic factors modulate outcome after brain trauma.||en