Selective adenosine A2A receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young rats
Cellular elements of maturing brain are vulnerable to insults, which lead to neurodevelopmental defects. There are no established treatments at present. Here we examined the efficacy of selective adenosine A2A receptor inhibitor SCH58261 to combat brain injury, particularly oligodendrocyte (OL) line...
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doaj-6608606947234e8f9dd73a5696faa22d2020-12-27T04:28:54ZengElsevierSaudi Journal of Biological Sciences1319-562X2021-01-01281310316Selective adenosine A2A receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young ratsMohamed A. Al-Griw0Rabia O. Alghazeer1Nuri Awayn2Ghalia Shamlan3Areej A. Eskandrani4Afnan M. Alnajeebi5Nouf A. Babteen6Wafa S. Alansari7Department of Histology and Genetics, Faculty of Medicine, University of Tripoli, Tripoli 13203, Libya; Corresponding author at: Department of Histology and Genetics, Faculty of Medicine, University of Tripoli, P.O. Box: 13203, Tripoli, Libya.Department of Chemistry, Faculty of Sciences, University of Tripoli, Tripoli 50676, LibyaDepartment of Chemistry, Faculty of Sciences, University of Tripoli, Tripoli 50676, LibyaDepartment of Food Science and Nutrition, College of Food and agriculture Sciences, King Saud University, Riyadh 11362, Saudi ArabiaChemistry Department, Faculty of Science, Taibah University, Medina 30002, Saudi ArabiaBiochemistry Department, Faculty of Science, University of Jeddah, Jeddah 21577, Saudi ArabiaBiochemistry Department, Faculty of Science, University of Jeddah, Jeddah 21577, Saudi ArabiaBiochemistry Department, Faculty of Science, University of Jeddah, Jeddah 21577, Saudi ArabiaCellular elements of maturing brain are vulnerable to insults, which lead to neurodevelopmental defects. There are no established treatments at present. Here we examined the efficacy of selective adenosine A2A receptor inhibitor SCH58261 to combat brain injury, particularly oligodendrocyte (OL) lineage cells, in young rats. Wistar rats (n = 24, 6.5 days old) were randomly divided into equal groups of four. The sham (SHAM) group received no treatment, the vehicle (VEHICLE) group received 0.1% dimethylsufoxide, the injury (INJ) group was exposed to oxygen-glucose deprivation insult, and the injury+SCH58261 (INJ+SCH58261) group was exposed to the insult and received 1 μM SCH58261. Immunocytochemical experiments revealed that there was a significant reduction in the populations of mature OL (MBP+ OLs) and immature OL precursors (NG2+ OPCs) in the INJ group compared to SHAM group. Furthermore, there was also a significant increase in the percent of apoptotic MBP+ OL and NG2+ OPC populations as evidenced by TUNEL assay. In addition, there was a significant reduction in the proliferation rate among NG2+ OPCs, which was confirmed by BrdU immunostaining. On the other hand, treatment with SCH58261 significantly enhanced survival, evidenced by the reduction in apoptotic indices for both cell types, and it is preserved the NG2+ OPC proliferation. Activation of adenosine A2A receptors may contribute to OL lineage cell loss in association with decreased mitotic behavior of OPCs in neonatal brains upon injury. Future investigations assessing ability of SCH58261 to regenerate myelin will provide insights into its wider clinical relevance.http://www.sciencedirect.com/science/article/pii/S1319562X20304861Adenosine A2A receptorSCH58261NeuroprotectionOligodendrocyteApoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mohamed A. Al-Griw Rabia O. Alghazeer Nuri Awayn Ghalia Shamlan Areej A. Eskandrani Afnan M. Alnajeebi Nouf A. Babteen Wafa S. Alansari |
spellingShingle |
Mohamed A. Al-Griw Rabia O. Alghazeer Nuri Awayn Ghalia Shamlan Areej A. Eskandrani Afnan M. Alnajeebi Nouf A. Babteen Wafa S. Alansari Selective adenosine A2A receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young rats Saudi Journal of Biological Sciences Adenosine A2A receptor SCH58261 Neuroprotection Oligodendrocyte Apoptosis |
author_facet |
Mohamed A. Al-Griw Rabia O. Alghazeer Nuri Awayn Ghalia Shamlan Areej A. Eskandrani Afnan M. Alnajeebi Nouf A. Babteen Wafa S. Alansari |
author_sort |
Mohamed A. Al-Griw |
title |
Selective adenosine A2A receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young rats |
title_short |
Selective adenosine A2A receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young rats |
title_full |
Selective adenosine A2A receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young rats |
title_fullStr |
Selective adenosine A2A receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young rats |
title_full_unstemmed |
Selective adenosine A2A receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young rats |
title_sort |
selective adenosine a2a receptor inhibitor sch58261 reduces oligodendrocyte loss upon brain injury in young rats |
publisher |
Elsevier |
series |
Saudi Journal of Biological Sciences |
issn |
1319-562X |
publishDate |
2021-01-01 |
description |
Cellular elements of maturing brain are vulnerable to insults, which lead to neurodevelopmental defects. There are no established treatments at present. Here we examined the efficacy of selective adenosine A2A receptor inhibitor SCH58261 to combat brain injury, particularly oligodendrocyte (OL) lineage cells, in young rats. Wistar rats (n = 24, 6.5 days old) were randomly divided into equal groups of four. The sham (SHAM) group received no treatment, the vehicle (VEHICLE) group received 0.1% dimethylsufoxide, the injury (INJ) group was exposed to oxygen-glucose deprivation insult, and the injury+SCH58261 (INJ+SCH58261) group was exposed to the insult and received 1 μM SCH58261. Immunocytochemical experiments revealed that there was a significant reduction in the populations of mature OL (MBP+ OLs) and immature OL precursors (NG2+ OPCs) in the INJ group compared to SHAM group. Furthermore, there was also a significant increase in the percent of apoptotic MBP+ OL and NG2+ OPC populations as evidenced by TUNEL assay. In addition, there was a significant reduction in the proliferation rate among NG2+ OPCs, which was confirmed by BrdU immunostaining. On the other hand, treatment with SCH58261 significantly enhanced survival, evidenced by the reduction in apoptotic indices for both cell types, and it is preserved the NG2+ OPC proliferation. Activation of adenosine A2A receptors may contribute to OL lineage cell loss in association with decreased mitotic behavior of OPCs in neonatal brains upon injury. Future investigations assessing ability of SCH58261 to regenerate myelin will provide insights into its wider clinical relevance. |
topic |
Adenosine A2A receptor SCH58261 Neuroprotection Oligodendrocyte Apoptosis |
url |
http://www.sciencedirect.com/science/article/pii/S1319562X20304861 |
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