Temporal Profile of Cerebrospinal Fluid,Plasma,and Brain Interleukin-6 After Normothermic Fluid-Percussion Brain Injury: Effect of Secondary Hypoxia

Abstract

Interleukin-6 (IL-6) is a proinflammatory cytokine that may play multiple roles in the pathogenesis of traumatic brain injury (TBI). The present study determined time-dependent changes in IL-6 concentrations in vulnerable brain regions, cerebrospinal fluid (CSF) samples, and plasma after normothermic TBI. Because secondary insults are common in head injured patients, we also assessed the consequences of a post-traumatic secondary hypoxic insult on this pleiotropic cytokine. Male Sprague-Dawley rats were intubated, anesthetized, and underwent a moderate parasagittal fluid-percussion brain injury (1.8–2.1 atm, 37°C) followed by either 30 minutes of normoxic or hypoxic (pO₂=30–40 mmHg) gas levels. Rats were sacrificed 3, 6, or 24 hours after TBI or sham-operated procedures. Brain samples, including the ipsilateral cerebral cortex and hippocampus were dissected and analyzed. Plasma and CSF samples were collected at similar times and stored at −80°C until analysis. IL-6 levels were significantly increased (p<0.05) at 3, 6, and 24 hours in the cerebral cortex and at 6 hours in the hippocampus after TBI. IL-6 levels in the TBI normoxic group for both structures returned to control levels by 24 hours. Plasma levels of IL-6 were elevated at all time points, while CSF levels were high at 3 and 6 hours, but normalized by 24 hours. Post-traumatic hypoxia led to significantly elevated (p<0.05) IL-6 protein levels in the cerebral cortex at 24 hours compared to sham-operated controls. These findings demonstrate that moderate TBI leads to an early increase in IL-6 brain, plasma, and CSF protein levels. Secondary post-traumatic hypoxia, a common secondary injury mechanism, led to prolonged elevations in plasma IL-6 levels that may participate in the pathophysiology of this complicated TBI model.