Introduction: Ischemic stroke has high morbidity and mortality rates worldwide. Low oxygen (O2) levels detected in such conditions create a vulnerable environment for neural stem cells (NSC), altering neuronal function, and leading to neuronal injury or death. There are still no effective treatments for such consequences. This study investigates the molecular and functional effects of growth factors, namely, insulin-like growth factor 1 (IGF-I) and mechano growth factor (MGF), in NSC exposed to low O2 levels. 
Methods: An in vitro ischemia model was created by rat hippocampal NSC grown in culture that was exposed to varying oxygen levels, including 0%, 3%, and 20 % for the representation of anoxic, hypoxic, and normoxic conditions, respectively, during 24 h. NSC has investigated IGF-I, MGF, and HIF1-Alpha (HIF-1α) gene expressions by real-time reverse transcription polymerase chain reaction. The effects of external administration of growth factors (IGF-I and MGF) on NSC proliferation in such conditions were explored. 
Results: Increased IGF-I and MGF gene expressions were detected in the samples exposed to low O2. Anoxia was the highest stimulant for IGF-I and MGF gene expressions. Meanwhile, HIF1-α that encodes hypoxia-inducible factor-1α revealed downregulation in relative gene expression fold change with IGF-I application in all conditions, whereas MGF application upregulated its change in an anoxic environment. Furthermore, MGF-induced NSC had more proliferationmigration rate in all oxygen conditions. IGF-I induced significant NSC proliferation in 0% and 20% O2. 
Conclusion: These findings suggest that IGF-I and MGF expressions were increased to reduce the damage in NSC exposed to low oxygen, and exogenous MGF and IGF-I application increased NSC proliferation at the time of injury. The results might imply the role of exogenous MGF and IGF-I in the treatment of ischemia for relieving the effect of neuronal damage due to their neuroprotective and proliferative effects.