Protective Efffects of Melatonin in Corpus Callosum Astrocytes during Ischemia in Transgenic Mice

Main Article Content

Badrah S. Alghamdi https://orcid.org/0000-0002-9411-3609

Keywords

Melatonin, Ischemia, Astrocyte

Abstract

Objective: Stroke is a leading cause of adult death and disability worldwide. Around 80% of all stroke cases are classed as ischemic stroke, which affects both gray and white matter brain regions. During ischemia, reactive oxygen species are generated and initiate multiple damaging processes such as lipid peroxidation, mitochondrial dysfunction, blood–brain barrier damage and brain edema. Melatonin is a potent antioxidant which can act as a direct oxygen species scavenger. Melatonin can also act at receptors (melatonin receptor 1 and 2), which are expressed in the nervous system cells including astrocytes.


Methods: Using live cell imaging of transgenic mice, the viability of astrocytes in the corpus callosum of adult brain sections was monitored during a standard 60 minutes period of modeled ischemia (oxygen-glucose deprivation) and 30 minutes of reperfusion in 8 groups; Control, artificial cerebrospinal fluid + Melatonin, oxygen-glucose deprivation, oxygen-glucose deprivation + Melatonin, oxygen-glucose deprivation + Melatonin + Luzindole (a nonselective melatonin receptor antagonist), oxygen-glucose deprivation + Luzindole, oxygen-glucose deprivation + Melatonin + propionamidotetralin (a selective melatonin receptor 2 antagonist), and oxygen-glucose deprivation + propionamidotetralin.


Results: Addition of melatonin significantly reduced the level of astrocyte death during oxygen-glucose deprivation from 71.94% ± 1.45 to 37.84% ± 1.9; p < 0.0001. This protective effect was blocked by luzindole or propionamidotetralin. Following known scoring categories for glial injury, ultrastructural morphology confirmed the protective effect of melatonin against acute ischemic injury in the white matter glial cells.


Conclusion: Melatonin is a promising neuroprotective agent during white matter ischemia.

Abstract 30 | PDF Downloads 18