Abstract
BackgroundTreatment options for spontaneous intracerebral hemorrhage (ICH) are limited. A possible inflammatory response in the brain tissue surrounding an ICH may exacerbate the initial injury and could be a target for treatment of subsequent secondary brain injury. The study objective was to compare levels of inflammatory mediators in the interstitial fluid of the perihemorrhagic zone (PHZ) and in seemingly normal cortex (SNX) in the acute phase after surgical evacuation of ICH, with the hypothesis being that a difference could be demonstrated between the PHZ and the SNX.MethodsIn this observational study, ten patients needing surgical evacuation of supratentorial ICH received two cerebral microdialysis catheters: one in the PHZ and one in the SNX that is remote from the ICH. The microdialysate was analyzed for energy metabolites (including lactate pyruvate ratio and glucose) and for inflammatory mediators by using a multiplex immunoassay of 27 cytokines and chemokines at 6–10 h, 20–26 h, and 44–50 h after surgery.ResultsA metabolic crisis, indicated by altered energy metabolic markers, that persisted throughout the observation period was observed in the PHZ when compared with the SNX. Proinflammatory cytokines interleukin (IL) 8, tumor necrosis factor α, IL-2, IL-1β, IL-6 and interferon γ, anti-inflammatory cytokine IL-13, IL-4, and vascular endothelial growth factor A were significantly higher in PHZ compared with SNX and were most prominent at 20–26 h following ICH evacuation.ConclusionsHigher levels of both proinflammatory and anti-inflammatory cytokines in the perihemorrhagic brain tissue implies a complex role for inflammatory mediators in the secondary injury cascades following ICH surgery, suggesting a need for targeted pharmacological interventions.
Highlights
Spontaneous supratentorial intracerebral hemorrhage (ICH) represents the most severe form of stroke [1]
Univariate Analysis Univariate analysis of cytokines and chemokines revealed a significantly higher level of IL-2, IL-8, and IL-1α at 20–26 h post surgery, whereas IL-6 and IL-4 levels were increased at 44–50 h in the perihemorrhagic zone (PHZ) when compared with the seemingly normal cortex (SNX) (Fig. 3; p < 0.05)
Increased proinflammatory cytokine expression in perihemorrhagic tissue including expression of IL-1β, tumor necrosis factor (TNF)-α, and macrophage inflammatory protein (MIP)-1α has previously been observed in animal models [18, 44,45,46,47], there are no previous studies of cytokine expression in brain tissue of patients with ICH
Summary
Spontaneous supratentorial intracerebral hemorrhage (ICH) represents the most severe form of stroke [1]. The ICH causes an initial primary injury to the brain by direct tissue destruction and a possibly increased intracranial pressure (ICP). The blood break-down products and/or the increased ICP cause an additional secondary brain injury by initiating reactive cellular, metabolic, and neurotoxic cascades. The tissue surrounding an ICH, the perihemorrhagic zone (PHZ), shows an acute hypometabolic and hypoperfusion state [8,9,10], including mitochondrial dysfunction and metabolic failure [11, 12], and this region may be vulnerable to secondary injury. Treatment options for spontaneous intracerebral hemorrhage (ICH) are limited. A possible inflammatory response in the brain tissue surrounding an ICH may exacerbate the initial injury and could be a target for treatment of subsequent secondary brain injury. The study objective was to compare levels of inflammatory mediators in the interstitial fluid of the perihemorrhagic zone (PHZ) and in seemingly normal cortex (SNX) in the acute phase after surgical evacuation of ICH, with the hypothesis being that a difference could be demonstrated between the PHZ and the SNX
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