This review explains how low oxygen levels in the brain damage nerve cells and their connection points (dendritic spines) through a cascade of molecular changes. The brain normally has protective mechanisms, but severe or prolonged hypoxia overwhelms these defenses, leading to memory loss and cognitive problems. Several molecular pathways and supporting cells called astrocytes and microglia can help protect neurons. Understanding these protective mechanisms may lead to new treatments for brain conditions caused by low oxygen, such as stroke.