Atorvastatin Rejuvenates Neural Stem Cells Injured by Oxygen-Glucose Deprivation and Induces Neuronal Differentiation Through Activating the PI3K/Akt and ERK Pathways.

Abstract

Oxygen and glucose (OGD) deprivation is one of the most important pathogenic mechanisms in cerebral infarction and is widely used as an in vitro model for ischemic stroke. OGD also damages neural stem cells (NSCs), which are important in brain recovery after cerebral infarction. To enhance recovery, there have been many studies aimed at determining methods to protect NSCs after stroke. Because atorvastatin has diverse protective effects on neural cells, we studied whether it could rejuvenate NSCs injured by OGD. Primary cultured NSCs were exposed to OGD for 8 h, and the main characteristics of stem cells, such as survival, proliferation, migration, and differentiation, were evaluated to confirm the effect of OGD on NSCs. Next, cells were treated with various concentrations of atorvastatin with exposure to OGD for 8 h to confirm whether it could rejuvenate NSCs. OGD significantly affected the survival, proliferation, migration, and differentiation of NSCs. However, treatment with atorvastatin meaningfully restored survival, proliferation, migration, and differentiation of NSCs. These beneficial effects of atorvastatin were blocked by treatment with either a PI3K inhibitor or an ERK inhibitor. In conclusion, OGD damages NSCs and causes them to lose the main characteristics of stem cells so that they cannot contribute to brain recovery after cerebral infarction. However, treatment with atorvastatin after cerebral infarction can effectively rejuvenate NSCs through activating the PI3K and ERK pathways to aid in brain regeneration.

• Authors: Na-Young Choi, Ji Young Kim, Mina Hwang, Eun-Hye Lee, Hojin Choi, Kyu-Yong Lee, Young Joo Lee, Seong-Ho Koh
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 56 Issue 4 Pg. 2964-2977 (Apr 2019) ISSN: 1559-1182 [Electronic] United States
• PMID: 30073508 (Publication Type: Journal Article)

Chemical References

• Atorvastatin
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Glucose
• Oxygen

Topics

• Animals
• Atorvastatin (pharmacology)
• Cell Death (drug effects)
• Cell Differentiation (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Enzyme Activation (drug effects)
• Glucose (deficiency)
• MAP Kinase Signaling System (drug effects)
• Neural Stem Cells (drug effects, metabolism, pathology)
• Neurogenesis (drug effects)
• Neuroglia (drug effects, metabolism, pathology)
• Neurons (drug effects, metabolism, pathology)
• Oxygen (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats, Sprague-Dawley