Lubeluzole protects hippocampal neurons from excitotoxicity in vitro and reduces brain damage caused by ischemia

European Journal of Pharmacology
C CulmseeJ Krieglstein

Abstract

Previously reported effects of lubeluzole, such as inhibition of glutamate release, inhibition of nitric oxide (NO) synthesis and blockage of voltage-gated Na+- and Ca2+-ion channels, suggest a neuroprotective action of this drug. Here we report about the effects of lubeluzole and its R-isomer on glutamate-induced neuronal cell death in mixed hippocampal cultures. In addition, we studied the effect of lubeluzole in focal cerebral ischemia models in mice and rats. In hippocampal cultures exposed to 500 nM glutamate for 1 h, lubeluzole (0.1-100 nM), but not the R-isomer (1-100 nM), reduced the percentage of damaged neurons from 42 +/- 8% to 18 +/- 7% (P < 0.01). In mice and rats, lubeluzole reduced ischemic brain damage, when administered immediately after middle cerebral artery occlusion. Interestingly, the protective effect (reduction of the infarct volume in rats to 77% of control; P < 0.01) was also found when the lubeluzole treatment (2.5 mg/kg) was started 3 h after ischemia. Especially this latter effect suggests that lubeluzole will be a useful drug for stroke therapy.

References

Mar 1, 1992·Journal of Pharmacological and Toxicological Methods·C BackhaussJ Krieglstein
Sep 1, 1989·Neurobiology of Aging·J T Greenamyre, A B Young
Jan 1, 1981·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·A TamuraG M Teasdale
Dec 1, 1993·Stroke; a Journal of Cerebral Circulation·M D LinnikM D Hatfield
Jan 1, 1993·Journal of Neurology, Neurosurgery, and Psychiatry·R S Marshall, J P Mohr
Jan 1, 1995·European Neurology·M O'NeillB E Leonard
Mar 1, 1996·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·C DuD W Choi
Jun 1, 1996·Neuropharmacology·J AronowskiJ C Grotta

❮ Previous
Next ❯

Citations

Jan 2, 2003·Annals of Neurology·Marc Fisher, Rajiv Ratan
Dec 21, 2000·Current Atherosclerosis Reports·S H AhmedC Y Hsu
Jun 25, 2002·European Journal of Pharmacology·Gordon Blackburn-MunroHelle K Erichsen
Nov 24, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·C CulmseeJ Krieglstein
Mar 1, 2008·Neuropharmacology·Myron D Ginsberg
Oct 2, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gang ZhaoGuanhua Du
Mar 8, 2006·Chirality·Claudio BrunoVincenzo Tortorella
Oct 25, 2003·Journal of Cardiovascular Pharmacology·Bruno Le GrandGareth W John
May 13, 1999·Biochimica Et Biophysica Acta·J P Bolaños, A Almeida
Sep 1, 2021·Clinical and Translational Science·Michael E ManiskasJustin F Fraser

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes in Repair & Regeneration

Astrocytes are glial cells found within the CNS and are able to regenerate new neurons. They become activated during CNS injury and disease. The activation leads to the transcription of new genes and the repair and regeneration of neurons. Discover the latest research on astrocytes in repair and regeneration here.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.