Neuroprotective properties of levosimendan in an in vitro model of traumatic brain injury

Röhl, Anna Bettina; Hein, Marc; Loetscher, Philipp D; Rossaint, Jan; Weis, Joachim; Rossaint, Rolf; Coburn, Mark

doi:10.1186/1471-2377-10-97

Cited by 37 publications

(40 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The fact that levosimendan improved perfusion via increased CI and vasodilatation could contribute to reduced neuronal injury in the hippocampal formation. In an in vitro model of traumatic brain injury, levosimendan showed direct neuroprotective properties (47). However, findings in dogs indicated that levosimendan does not substantially penetrate the bloodbrain barrier in the healthy brain (48).…”

Section: Discussionmentioning

confidence: 98%

Effects of Levosimendan on Hemodynamics, Local Cerebral Blood Flow, Neuronal Injury, and Neuroinflammation After Asphyctic Cardiac Arrest in Rats

Kelm

Wagenführer

Bauer

et al. 2014

Critical Care Medicine

View full text Add to dashboard Cite

Levosimendan increased cerebral blood flow after experimental cardiac arrest/cardiopulmonary resuscitation. This effect coincided with reduced neuronal injury and improved neurologic outcome. Findings seem to be independent of inflammatory effects because no effects by levosimendan on cerebral or systemic inflammation could be detected. In summary, levosimendan is a promising agent to improve neurological outcome after cardiac arrest/cardiopulmonary resuscitation.

show abstract

Section: Discussionmentioning

confidence: 98%

Effects of Levosimendan on Hemodynamics, Local Cerebral Blood Flow, Neuronal Injury, and Neuroinflammation After Asphyctic Cardiac Arrest in Rats

Kelm

Wagenführer

Bauer

et al. 2014

Critical Care Medicine

View full text Add to dashboard Cite

show abstract

“…In fact, levosimendan has been shown to reduce cell death and inflammatory responses and improve function after transient ischemia of the spinal cord in rabbits [7,8]. While a dose-dependent protective effect in an in vitro model of traumatic brain injury could be demonstrated [9], levosimendan failed to improve brain metabolism or reduce glutamate release, inflammation and dysfunction of autoregulation in the initial phase after experimental global ischemic/hypoxic cerebral injury [10]. Its effect on focal transient ischemia has not been investigated in vivo in the brain as it has been in the heart [11].…”

Section: Introductionmentioning

confidence: 99%

Levosimendan limits reperfusion injury in a rat middle cerebral artery occlusion (MCAO) model

et al. 2013

Self Cite

View full text Add to dashboard Cite

BackgroundNeuroprotective strategies in ischemic stroke are an important challenge in clinical and experimental research as an adjunct to reperfusion therapy that may reduce neurologic injury and improve outcome. The neuroprotective properties of levosimendan in traumatic brain injury in vitro, transient global brain ischemia and focal spinal cord ischemia suggest the potential for similar effects in transient brain ischemia.MethodsTransient brain ischemia was induced for 60 min by intraluminal occlusion of the middle cerebral artery in 40 male Wistar rats under general anesthesia with s-ketamine and xylazine and with continuous monitoring of their blood pressure and cerebral perfusion. Five minutes before inducing reperfusion, a levosimendan bolus (24 μg kg -1) was administered over a 20 minute period. Infarct size, brain swelling, neurological function and the expression of inflammatory markers were quantified 24 hours after reperfusion.ResultsAlthough levosimendan limited the infarct size and brain swelling by 40% and 53%, respectively, no effect on neurological outcome or mortality could be demonstrated. Upregulation of tumor necrosis factor α and intercellular adhesion molecule 1 was significantly impeded. Cerebral blood flow during reperfusion was significantly reduced as a consequence of sustained autoregulation.ConclusionsLevosimendan demonstrated significant neuroprotective properties in a rat model of transient brain ischemia by reducing reperfusion injury.

show abstract

“…A histogram of the red channel was generated for each image, showing the sum of all pixels sharing the same gray scale value from 0 to 255. As previous studies have shown, values below a threshold of 100 are caused by background fluorescence 62122. That is why only the values of pixels above this threshold were summed up to evaluate the extent of cell injury.…”

Section: Methodsmentioning

confidence: 99%

Argon attenuates the emergence of secondary injury after traumatic brain injury within a 2-hour incubation period compared to desflurane: an in vitro study

et al. 2017

Self Cite

View full text Add to dashboard Cite

Despite years of research, treatment of traumatic brain injury (TBI) remains challenging. Considerable data exists that some volatile anesthetics might be neuroprotective. However, several studies have also revealed a rather neurotoxic profile of anesthetics. In this study, we investigated the effects of argon 50%, desflurane 6% and their combination in an in vitro TBI model with incubation times similar to narcotic time slots in a daily clinical routine. Organotypic hippocampal brain slices of 5- to 7-day-old mice were cultivated for 14 days before TBI was performed. Slices were eventually incubated for 2 hours in an atmosphere containing no anesthetic gas, argon 50% or desflurane 6% or both. Trauma intensity was evaluated via fluorescent imagery. Our results show that neither argon 50% nor desflurane 6% nor their combination could significantly reduce the trauma intensity in comparison to the standard atmosphere. However, in comparison to desflurane 6%, argon 50% displayed a rather neuroprotective profile within the first 2 hours after a focal mechanical trauma (P = 0.015). A 2-hour incubation in an atmosphere containing both gases, argon 50% and desflurane 6%, did not result in significant effects in comparison to the argon 50% group or the desflurane 6% group. Our findings demonstrate that within a 2-hour incubation time neither argon nor desflurane could affect propidium iodide-detectable cell death in an in vitro TBI model in comparison to the standard atmosphere, although cell death was less with argon 50% than with desflurane 6%. The results show that within this short time period processes concerning the development of secondary injury are already taking place and may be manipulated by argon.

show abstract

Neuroprotective properties of levosimendan in an in vitro model of traumatic brain injury

Cited by 37 publications

References 11 publications

Effects of Levosimendan on Hemodynamics, Local Cerebral Blood Flow, Neuronal Injury, and Neuroinflammation After Asphyctic Cardiac Arrest in Rats

Effects of Levosimendan on Hemodynamics, Local Cerebral Blood Flow, Neuronal Injury, and Neuroinflammation After Asphyctic Cardiac Arrest in Rats

Levosimendan limits reperfusion injury in a rat middle cerebral artery occlusion (MCAO) model

Argon attenuates the emergence of secondary injury after traumatic brain injury within a 2-hour incubation period compared to desflurane: an in vitro study

Contact Info

Product

Resources

About