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

Abstract

BackgroundThe 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.MethodsOrganotypic 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.ResultsDexmedetomidine 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.ConclusionIn this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.

Delirium in the Cardiac Intensive Care Unit

“…These properties may decrease delirium, both by avoiding deliriogenic opiates and sedatives but also by more direct neuroprotective mechanisms 60. This has led to several clinical studies involving dexmedetomidine in the ICU.…”

Combined Neuroprotective Effects of Propofol and Dexmedetomidine on Endoplasmic Reticulum Stress-mediated Apoptosis in SH-SY5Y Cells

“…Recent studies have indicated that dexmedetomidine also exhibits neuroprotective effects against ischemic injury 26 and promotes the survival of nervous tissue that has suffered traumatic injury 27 . However, a study in neutrophils reported that treatment with a high concentration of dexmedetomidine 100 ng / ml ; 499.3 nM accelerated apoptosis, whereas a clinically relevant concentration of dexmedetomidine 1 ng / ml ; 4.993 nM did not affect neutrophil apoptosis 28 .…”

Severe traumatic brain injury management and clinical outcome using the Lund concept

“…LC therefore advocates the use of anti-hypertensive treatment (beta-1 blockade, alpha-2 agonists, angiotensin II antagonist) (Asgeirsson et al, 1994, 1995, Grände, 2006. It has been shown that beta-blockade in sTBI patients is independently associated with improved survival (Cotton et al, 2007;Inaba et al, 2008) and that alpha-2 agonist effectively reduces blood pressure in sTBI patients (Kariya et al, 1999) and is neuroprotective in an in vitro model for traumatic brain injury (Schoeler et al, 2012). Beta-blockade has also a documented protective effect on the cardiovascular system after a sTBI (Cruickshank et al, 1987).…”