Propofol: Neuroprotektion in einem In-vitro-Modell des traumatischen Hirnschadens

Introduction The anaesthetic agent propofol (2,6diisopropylphenol) has been shown to be an effective neuroprotective agent in different in vitro models of brain injury induced by oxygen and glucose deprivation. We examined its neuroprotective properties in an in vitro model of traumatic brain injury. Methods In this controlled laboratory study organotypic hippocampal brain-slice cultures were gained from sixto eightday-old mice pups. After 14 days in culture, hippocampal brain slices were subjected to a focal mechanical trauma and subsequently treated with different molar concentrations of propofol under both normoand hypothermic conditions. After 72 hours of incubation, tissue injury assessment was performed using propidium iodide (PI), a staining agent that becomes fluorescent only when it enters damaged cells via perforated cell membranes. Inside the cell, PI forms a fluorescent complex with nuclear DNA. Results A dose-dependent reduction of both total and secondary tissue injury could be observed in the presence of propofol under both normoand hypothermic conditions. This effect was further amplified when the slices were incubated at 32°C after trauma. Conclusions When used in combination, the dose-dependent neuroprotective effect of propofol is additive to the neuroprotective effect of hypothermia in an in vitro model of traumatic brain injury. Introduction Traumatic brain injury (TBI) is a common consequence of traffic-related accidents and incidents at work and at home. The annual incidence of TBI in the UK is estimated to be approximately 400 per 100,000 patients per year [1]. The treatment of patients with traumatic injury to the brain accounts for a considerable proportion of the budget spent annually on health care and the subsequent costs for rehabilitation, post-hospital long-term care and disability are a significant burden for the economy and society. It should be noted that all currently available therapy approaches for TBI are symptomatic in nature. To date, no clinically established therapy exists that specifically counteracts the actual pathological mechanisms leading to traumatic brain tissue injury. Propofol (2,6-diisopropylphenol) is a short-acting, intravenous hypnotic agent widely used for the induction and maintenance of general anaesthesia in the perioperative setting, for sedation in intensive care unit patients and for short-time interventional procedures. Propofol has been shown to be an effective neuroprotective agent in certain in vitro models of brain injury induced by oxygen-glucose deprivation. To this point, the effects of propofol on the outcome of mechanically induced brain injury have not been investigated. We demonstrate that the anaesthetic agent propofol (2,6diisopropylphenol) exerts a strong neuroprotective effect in an in vitro model of TBI and that this effect is further amplified when propofol is applied under hypothermic conditions. ANOVA: analysis of variance; DMSO: dimethyl sulfoxide; GABA: gamma-aminobutyric acid; HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; PI: propidium iodide; SEM: standard error of the mean; TBI: traumatic brain injury. Critical Care Vol 13 No 2 Rossaint et al.