Brain interstitial fluid TNF-α after subarachnoid hemorrhage

Abstract 

Objective

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

Interpretation

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

Keywords: Tumor necrosis factor-α, Intraventricular hemorrhage, Cerebral inflammatory response, Cerebral microdialysis, Brain interstitial fluid