Argon: Neuroprotection in in Vitro Models of Cerebral Ischemia and Traumatic Brain Injury

Overview

Journal Crit Care

Specialty Critical Care

Date 2009 Dec 19

PMID 20017934

Citations 65

Authors

Philip D Loetscher

Jan Rossaint

Rolf Rossaint

Joachim Weis

Michael Fries

Astrid Fahlenkamp

Yu-Mi Ryang

Oliver Grottke

Mark Coburn

Affiliations

Soon will be listed here.

Abstract

Introduction: Recently, it has been shown in several experimental settings that the noble gases xenon and helium have neuroprotective properties. In this study we tested the hypothesis that the noble gas argon has a neuroprotective potential as well. Since traumatic brain injury and stroke are widespread and generate an enormous economic and social burden, we investigated the possible neuroprotective effect in in vitro models of traumatic brain injury and cerebral ischemia.

Methods: Organotypic hippocampal slice cultures from mice pups were subjected to either oxygen-glucose deprivation or to a focal mechanical trauma and subsequently treated with three different concentrations (25, 50 and 74%) of argon immediately after trauma or with a two-or-three-hour delay. After 72 hours of incubation tissue injury assessment was performed using propidium iodide, a staining agent that becomes fluorescent when it diffuses into damaged cells via disintegrated cell membranes.

Results: We could show argon's neuroprotective effects at different concentrations when applied directly after oxygen-glucose deprivation or trauma. Even three hours after application, argon was still neuroprotective.

Conclusions: Argon showed a neuroprotective effect in both in vitro models of oxygen-glucose deprivation and traumatic brain injury. Our promising results justify further in vivo animal research.

Citing Articles

Effects of Argon in the Acute Phase of Subarachnoid Hemorrhage in an Endovascular Perforation Model in Rats.

Krenzlin H, Wesp D, Korinek A, Ubbens H, Volland J, Masomi-Bornwasser J Neurocrit Care. 2024; .

PMID: 39174846 DOI: 10.1007/s12028-024-02090-3.

Are Protein Cavities and Pockets Commonly Used by Redox Active Signalling Molecules?.

Hancock J Plants (Basel). 2023; 12(14).

PMID: 37514209 PMC: 10383989. DOI: 10.3390/plants12142594.

Argon mitigates post-stroke neuroinflammation by regulating M1/M2 polarization and inhibiting NF-κB/NLRP3 inflammasome signaling.

Xue K, Qi M, She T, Jiang Z, Zhang Y, Wang X J Mol Cell Biol. 2022; 14(12).

PMID: 36574951 PMC: 10165685. DOI: 10.1093/jmcb/mjac077.

Noble gas and neuroprotection: From bench to bedside.

Yin H, Chen Z, Zhao H, Huang H, Liu W Front Pharmacol. 2022; 13:1028688.

PMID: 36532733 PMC: 9750501. DOI: 10.3389/fphar.2022.1028688.

Three-Hour Argon Inhalation Has No Neuroprotective Effect after Open Traumatic Brain Injury in Rats.

Antonova V, Silachev D, Ryzhkov I, Lapin K, Kalabushev S, Ostrova I Brain Sci. 2022; 12(7).

PMID: 35884727 PMC: 9313057. DOI: 10.3390/brainsci12070920.

References

Goldberg M, Strasser U, Dugan L . Techniques for assessing neuroprotective drugs in vitro. Int Rev Neurobiol. 1997; 40:69-93. DOI: 10.1016/s0074-7742(08)60716-3. View

Finley M, Fairman D, Liu D, Li P, Wood A, Cho S . Functional validation of adult hippocampal organotypic cultures as an in vitro model of brain injury. Brain Res. 2004; 1001(1-2):125-32. DOI: 10.1016/j.brainres.2003.12.009. View

Crain S . Development of specific synaptic network functions in organotypic central nervous system (CNS) cultures: implications for transplantation of CNS neural cells in vivo. Methods. 1999; 16(3):228-38. DOI: 10.1006/meth.1998.0681. View

Kennedy R, STOKES J, Downing P . Anaesthesia and the 'inert' gases with special reference to xenon. Anaesth Intensive Care. 1992; 20(1):66-70. DOI: 10.1177/0310057X9202000113. View

Wise-Faberowski L, Raizada M, Sumners C . Desflurane and sevoflurane attenuate oxygen and glucose deprivation-induced neuronal cell death. J Neurosurg Anesthesiol. 2003; 15(3):193-9. DOI: 10.1097/00008506-200307000-00006. View

Noraberg J, Poulsen F, Blaabjerg M, Kristensen B, Bonde C, Montero M . Organotypic hippocampal slice cultures for studies of brain damage, neuroprotection and neurorepair. Curr Drug Targets CNS Neurol Disord. 2005; 4(4):435-52. DOI: 10.2174/1568007054546108. View

Diemer N, Valente E, Bruhn T, Berg M, Jorgensen M, Johansen F . Glutamate receptor transmission and ischemic nerve cell damage: evidence for involvement of excitotoxic mechanisms. Prog Brain Res. 1993; 96:105-23. DOI: 10.1016/s0079-6123(08)63261-6. View

Rossaint J, Rossaint R, Weis J, Fries M, Rex S, Coburn M . Propofol: neuroprotection in an in vitro model of traumatic brain injury. Crit Care. 2009; 13(2):R61. PMC: 2689510. DOI: 10.1186/cc7795. View

Schmidt M, Marx T, Gloggl E, Reinelt H, Schirmer U . Xenon attenuates cerebral damage after ischemia in pigs. Anesthesiology. 2005; 102(5):929-36. DOI: 10.1097/00000542-200505000-00011. View

10.

Strasser U, Fischer G . Protection from neuronal damage induced by combined oxygen and glucose deprivation in organotypic hippocampal cultures by glutamate receptor antagonists. Brain Res. 1995; 687(1-2):167-74. DOI: 10.1016/0006-8993(95)00519-v. View

11.

Schwartz-Bloom R, Miller K, Evenson D, Crain B, Nadler J . Benzodiazepines protect hippocampal neurons from degeneration after transient cerebral ischemia: an ultrastructural study. Neuroscience. 2000; 98(3):471-84. DOI: 10.1016/s0306-4522(00)00144-5. View

12.

Adembri C, Bechi A, Meli E, Gramigni E, Venturi L, Moroni F . Erythropoietin attenuates post-traumatic injury in organotypic hippocampal slices. J Neurotrauma. 2004; 21(8):1103-12. DOI: 10.1089/0897715041651079. View

13.

Faden A . Neuroprotection and traumatic brain injury: theoretical option or realistic proposition. Curr Opin Neurol. 2002; 15(6):707-12. DOI: 10.1097/01.wco.0000044767.39452.bf. View

14.

Rekling J . Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation. Neurosci Lett. 2003; 335(3):167-70. DOI: 10.1016/s0304-3940(02)01193-x. View

15.

Petzelt C, Blom P, Schmehl W, Muller J, Kox W . Xenon prevents cellular damage in differentiated PC-12 cells exposed to hypoxia. BMC Neurosci. 2004; 5:55. PMC: 544856. DOI: 10.1186/1471-2202-5-55. View

16.

Coburn M, Maze M, Franks N . The neuroprotective effects of xenon and helium in an in vitro model of traumatic brain injury. Crit Care Med. 2008; 36(2):588-95. DOI: 10.1097/01.CCM.0B013E3181611F8A6. View

17.

Martin J, Ma D, Hossain M, Xu J, Sanders R, Franks N . Asynchronous administration of xenon and hypothermia significantly reduces brain infarction in the neonatal rat. Br J Anaesth. 2007; 98(2):236-40. DOI: 10.1093/bja/ael340. View

18.

Galeffi F, Sinnar S, Schwartz-Bloom R . Diazepam promotes ATP recovery and prevents cytochrome c release in hippocampal slices after in vitro ischemia. J Neurochem. 2000; 75(3):1242-9. DOI: 10.1046/j.1471-4159.2000.0751242.x. View

19.

Allen J, Knoblach S, Faden A . Combined mechanical trauma and metabolic impairment in vitro induces NMDA receptor-dependent neuronal cell death and caspase-3-dependent apoptosis. FASEB J. 1999; 13(13):1875-82. DOI: 10.1096/fasebj.13.13.1875. View

20.

Kristensen B, Noraberg J, Zimmer J . Comparison of excitotoxic profiles of ATPA, AMPA, KA and NMDA in organotypic hippocampal slice cultures. Brain Res. 2001; 917(1):21-44. DOI: 10.1016/s0006-8993(01)02900-6. View