There is therefore a suggestion that neuronal apoptosis after TBI may be a protective response by the brain in order to buy SC79 remove injured tissue cells whilst having little effect on remaining brain tissue [27]. Apoptotic cells have been identified within contusions in the acute post-traumatic period, and in regions remote from the site of injury days and weeks after trauma. Pharmacological strategies to reduce apoptotic cell death have been investigated, [28] For example, rats treated with the caspase-3

inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (DEVD) demonstrate a 30% reduction in lesion volume measured 3 weeks after TBI when compared with vehicle-treated controls [19]. Long term pathophysiology Recent advances in the management of severe acute TBI has resulted in improved outcomes for patients who might previously CA4P datasheet have had poor outcomes. In particular the management of such patients in specialist units has had a significant impact, although the definitive factors contributing to improved outcomes remain elusive. [29]. In recent years there has been increasing

interest in elucidating the long term problems experienced by patients following TBI. Further, there have been reports of people Temsirolimus in vitro developing dementia-like symptoms following relatively minor head injuries (Brain injury with a GCS greater than 13 and without loss of consciousness, as well as an increased incidence of post traumatic stress disorders and depression [30]. TBI causes a generalised atrophy of brain which is proportional to the severity of the injury. [31]. The mechanisms for this are yet to be fully determined. In rats it has been shown that there are multiple antibodies to the amyloid precursor protein and amyloid precursor protein-like proteins for up to six months, which predisposes them to degeneration of the striatum and corpus callosum. This degeneration then leads to progressive brain atrophy and calcifications [32].

In moderate to severe TBI there is a high incidence of hippocampal atrophy which predisposes patients to cognitive decline. When anoxic brain damage was compared to TBI there was check details no overwhelming evidence of localised nerve damage. This supports the theory that the final mechanism for neurological injury is the same irrespective of the type of initial insult [33]. Surviving the ischaemic insult: the role of genes Surprisingly humans are made up of only 20,000 – 25,000 protein-coding genes, and these genes have profound implications on our survival [34]. The genetic constituents not only modify the risk of development of disease and its severity, but also the ability of an organ to repair, heal and function after an injury. In head injured patients the outcomes are variable and cannot easily be predicted. This variability cannot be fully explained by clinical features or by the character of the injury [35]. One of the mechanisms which could explain this is genetic polymorphism.