This study investigates the developmental stages of oligodendrocyte (OL) lineage cells in the human brain during the perinatal period, focusing on the developmental window of vulnerability for periventricular leukomalacia (PVL). PVL is a common cause of cerebral palsy and cognitive impairment in premature infants, characterized by hypoxic-ischemic injury to the periventricular cerebral white matter. The study used immunohistochemical techniques to analyze OL lineage stages in 26 normal human brains at various postconceptional ages (18-41 weeks). Key findings include: 1. **OL Lineage Stages**: Three successive stages were identified: late OL progenitor (NG2+ O4+), immature OL (O4+ O1+), and mature OL (MBP+). Late OL progenitors were the predominant stage throughout the latter half of gestation. 2. **Developmental Window of Vulnerability**: The high-risk period for PVL coincides with the presence of late OL progenitors, which are more susceptible to ischemic injury than mature OLs. 3. **Myelination and PVL Incidence**: The onset of myelination in the periventricular white matter, marked by an increase in MBP+ myelin sheaths, occurred around 30-32 weeks. This coincides with a decline in PVL incidence, suggesting that the risk for PVL is related to the presence of late OL progenitors in the periventricular white matter. The study highlights the importance of understanding the cellular and molecular events during OL lineage progression to better understand and potentially prevent PVL.This study investigates the developmental stages of oligodendrocyte (OL) lineage cells in the human brain during the perinatal period, focusing on the developmental window of vulnerability for periventricular leukomalacia (PVL). PVL is a common cause of cerebral palsy and cognitive impairment in premature infants, characterized by hypoxic-ischemic injury to the periventricular cerebral white matter. The study used immunohistochemical techniques to analyze OL lineage stages in 26 normal human brains at various postconceptional ages (18-41 weeks). Key findings include: 1. **OL Lineage Stages**: Three successive stages were identified: late OL progenitor (NG2+ O4+), immature OL (O4+ O1+), and mature OL (MBP+). Late OL progenitors were the predominant stage throughout the latter half of gestation. 2. **Developmental Window of Vulnerability**: The high-risk period for PVL coincides with the presence of late OL progenitors, which are more susceptible to ischemic injury than mature OLs. 3. **Myelination and PVL Incidence**: The onset of myelination in the periventricular white matter, marked by an increase in MBP+ myelin sheaths, occurred around 30-32 weeks. This coincides with a decline in PVL incidence, suggesting that the risk for PVL is related to the presence of late OL progenitors in the periventricular white matter. The study highlights the importance of understanding the cellular and molecular events during OL lineage progression to better understand and potentially prevent PVL.