The presence APOE-ε4 is associated with a poor outcome in cognitive dysfunction and functionality following brain injury rehabilitation [47–49]. It is also associated with a rapid cognitive decline in Alzheimer’s

disease [50] and in autopsy studies has been demonstrated to incur a significantly increased risk of development of cerebral amyloid angiopathy [51]. In larger retrospective studies of outcome following TBI, the presence of APOE-ε4 correlates with a significantly worse outcome in young patiens (aged 0–15 years). This correlation reduces with age, with, neutralisation at 55 years HDAC inhibitor [45]. The P53 gene is important in the regulation of apoptosis; this gene exhibits a common polymorphism that results in either proline or arginine at amino acid 72. Arg/Arg genotype selleck kinase inhibitor of the Arg72Pro polymorphism in p53 is associated with an increased likelihood of a poor outcome at discharge from the surgical intensive care unit following TBI. [52] Genes regulating the catecholamines There are three isoforms of the enzyme catechol-o-methyltransferase (COMT) encoded by

3 genetic polymorphisms (COMT Val/Val, COMT Val/Met, and COMT Met/Met). This enzyme is associated with inactivation of dopamine and norepinephrine and is thought to functionally modulate dopamine neurons, thus influencing frontal-executive functioning. In a study Thalidomide by Lipsky et al (2005) in patients with TBI, polymorphism (Val/Val), and presumably lower cortical DA levels, resulted in worse performance on

the Wisconsin Card Sorting Test compared to patients with the low activity polymorphism (Met/Met) and presumably higher cortical DA levels [53]. Pharmacological therapies A variety of pharmacological agents have been trialed, all of which have shown promising results in animal models, but when translated into the clinical setting have universally failed to influence outcome following TBI. These agents include Selfotel, Cerestat, CP 101–606, D-CPP-ene, Steroids, tirilazad, PEG-SOD, IGF-1/growth hormone, Nimodipine, Bradycor, Dexanabinol, SNX-III, and anticonvulsants (such as Valproate and Magnesium Sulphate). The neuroprotective actions of these agents result from a variety of mechanisms of action, including antagonism of glutamate (Selfotel and CP 101–606), and free radical scavenging (PEG-SOD) [6]. Dexanabinol is a synthetic chemical analogue of the active component of marijuana. It is a non-competitive inhibitor of the NMDA receptor, a free radical scavenger and antioxidant, and an inhibitor of the pro-inflammatory cytokine TNF alpha [6]. Steroids are used with good effect in the treatment of brain oedema associated with brain tumours, and have been shown in laboratory studies to reduce free radical production and have a protective effect on the brain.