Brain interstitial fluid TNF-alpha after subarachnoid hemorrhage

Abstract

Objective: TNF-alpha is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. Recent studies have suggested that TNF-alpha may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (SAH).

Methods: We studied 14 comatose SAH patients who underwent multimodality neuromonitoring with intracranial pressure (ICP) and cerebral microdialysis as part of their clinical care. Continuous physiological variables were time-locked every 8h and recorded at the same point that brain interstitial fluid TNF-alpha was measured in brain microdialysis samples. Significant associations were determined using generalized estimation equations.

Results: Each patient had a mean of 9 brain tissue TNF-alpha measurements obtained over an average of 72h of monitoring. TNF-alpha levels rose progressively over time. Predictors of elevated brain interstitial TNF-alpha included higher brain interstitial fluid glucose levels (beta=0.066, p<0.02), intraventricular hemorrhage (beta=0.085, p<0.021), and aneurysm size >6mm (beta=0.14, p<0.001). There was no relationship between TNF-alpha levels and the burden of cisternal SAH; concurrent measurements of serum glucose, or lactate-pyruvate ratio.

Interpretation: Brain interstitial TNF-alpha levels are elevated after SAH, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels.

Figure 1

mean of log TNF-α between SAH days 4-6