No abstract

After acute brain injury there may be increased intracranial production of cytokines, with activation of inflammatory cascades. We have sought to determine if a transcranial cytokine gradient was demonstrable in paired sera of 32 patients requiring intensive care after acute brain injury. The difference between concentrations of IL-1 beta, IL-6, IL-8 and TNF alpha in jugular venous and arterial serum was measured on admission, and at 24, 48 and 96 h after the primary injury. There were no differences in IL-1 beta, IL-8 or TNF alpha, but median gradients of 6.7 and 11.5 pg ml-1 for IL-6 were demonstrated in the traumatic brain injury (n = 22) and subarachnoid haemorrhage (n = 10) groups, respectively (normal values in serum < 4.7 pg ml-1; P < 0.001 both groups). This suggests that there is significant production of IL-6 by intracranial cells after acute brain injury. Therapy directed towards combatting the negative effects of IL-6 may potentially benefit patients who have sustained an acute brain injury.

The apolipoprotein E (apoE) gene (APOE) is polymorphic with three alleles, e2, e3, and e4, which give rise to three isoforms, E2, E3 and E4. Many reports have now described a strong association between the e4 allele and risk of developing late onset Alzheimer's disease as the result of the E4 isoform binding to β-amyloid protein and accelerating the deposition of amyloid, which is the main constituent of senile plaques. 1 The APOE e4 allele also appears to be associated with deposition of β-amyloid after traumatic brain injury, which is also accompanied by increased APOE expression in the central and peripheral nervous systems.Neurological and cognitive decrements are well documented complications of coronary artery bypass grafting (CABG) surgery. Given that APOE e4 is associated with deposition of β-amyloid after traumatic brain injury, and poor neurological outcome after subarachnoid haemorrhage and stroke, it may also adversely influence neurocognitive outcome after CABG surgery. In a preliminary report, Tardiff and colleagues 2 found that the APOE e4 allele was associated with greater risk of cognitive impairment, especially in those patients with lower educational levels. More recently, Steed and colleagues 3 were unable to replicate the findings in a larger study. However, both of these studies had low incidences of APOE e4 allele, and thus its role remains equivocal.Previously, we have reported that palpable aortic atheroma and a preoperative neurological deficit are risk factors for a decline in cognition after CABG surgery. 4 Here we report the effect of the APOE e4 allele in 86 patients who formed a subgroup in that study.The day before and three months after CABG surgery, a battery of cognitive tests and a structured neurological examination were completed. Factor analysis of the cognitive test battery found that 52% of the test score variance before surgery on these six tests was explained by one component, validating the use of a General Cognitive Factor. The cognitive tests' z scores were summed to obtain an overall General Cognitive Score, which was shown to have a very high correlation (r=0.998) with the General Cognitive Factor.Blood (2.7 ml) was collected into potassium/EDTA (1.2 mg/ml) at the three month follow up appointment, and DNA was extracted for APOE genotyping.Fifty two patients were APOE e4 negative and 34 were APOE e4 positive. The allele frequencies for APOE e2, APOE e3, and APOE e4 were 0.07 (12/172), 0.72 (123/172), and 0.21 (37/172) respectively. The incidence of palpable aortic atheroma (χ 2 =0.536, p=0.464) and preoperative (χ 2 =0.124, p=0.724) and postoperative (χ 2 =2.44, p=0.118) neurological deficits were not significantly affected by the APOE e4 allele.We tested the hypothesis that people with one or more APOE e4 alleles would have a worse cognitive outcome after CABG surgery. Thus, using analysis of covariance, follow up cognitive score was the outcome variable, preoperative cognitive score was controlled by entering it as a covariate, and APOE e4 status was a between ...