Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury

Department of Anesthesiology, University Hospital of the RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
BMC Neurology (Impact Factor: 2.04). 04/2012; 12(1):20. DOI: 10.1186/1471-2377-12-20
Source: PubMed


The α2-adrenoreceptor agonist dexmedetomidine is known to provide neuroprotection under ischemic conditions. In this study we investigated whether dexmedetomidine has a protective effect in an in vitro model for traumatic brain injury.
Organotypic hippocampal slice cultures were subjected to a focal mechanical trauma and then exposed to varying concentrations of dexmedetomidine. After 72 h cell injury was assessed using propidium iodide. In addition, the effects of delayed dexmedetomidine application, of hypothermia and canonical signalling pathway inhibitors were examined.
Dexmedetomidine showed a protective effect on traumatically injured hippocampal cells with a maximum effect at a dosage of 1 μM. This effect was partially reversed by the simultaneous administration of the ERK inhibitor PD98059.
In this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.

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    • ", nonessential amino acids, and 10% fetal bovine serum) or growth medium alone (control) for 24 hours at 37 C. The Dex concentrations used in this study were based on those previously used in neuronal cell culture studies (Sanders et al., 2010) as well as concentrations previously demonstrated to be neuroprotective in an organotypic hippocampal slice culture model of traumatic brain injury (Schoeler et al., 2012). At the end of the exposure period, the media were removed by aspiration, and each well was rinsed twice with 1 mL of phosphate-buffered saline warmed to 37 C. "
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    • "Of all the JAK/STAT pathways, JAK2 signaling through STAT1 and STAT3 are the best studied in diseases affecting the kidney. An in vitro study has shown that dexmedetomidine may exert a significant neuroprotective effect by involving the activation of extracellular regulated protein kinases (ERK) [25]. Interference with ERK and STAT signaling pathways may also play a role in myocardial I/R injury [20]. "
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