Injury to Oligodendroglial Cells in Diplegic Cerebral Palsy, 10/2005 

SUMMARY:
Cells destined to become neurons and those destined to become oligodendrocytes generate different isoprostanes when challenged by hypoxia/ischemia. In this autopsy study, the authors found that the oligodendrocyte isoprostane was elevated in the area of periventricular leucomalacia while the neuron isoprostane was not. In babies dying after perinatal hypoxia/ischemia the neuron isoprostane was expressed.

This Research Fact sheet is a bit technical so I will start with some explanations. It is well known that the most common form of cerebral palsy is spastic diplegia. Spastic diplegia occurs almost exclusively in premature children and is associated with a pathological change in the cerebral white matter called periventricular (around the ventricles) leucomalacia (white matter disease) abbreviated PVL.

The white matter of the brain consists of the long nerve cell processes called axons connecting one part of the brain with another and an insulating material called myelin which gives the white matter its distinctive color. Myelin is made by special cells called oligodendrocytes. Cells that will mature into oligodendrocytes are especially prevalent during the period of fetal life when PVL may develop. When oligodendrocyte precursors become hypoxic (shortage of oxygen) or ischemic (interruption of blood supply) they express a substance called F2-isoprostane while nerve cells precursors produce the closely related F4-isoprostane.

There is a great deal of interest in two related questions. Is PVL primarily the result of injury to developing nerve cells or to the cells destined to produce myelin? Is the injury primarily due to hypoxia/ischemia or is it the result of inflammation. Many would argue that both must be present to produce PVL.

This month we report on an autopsy study designed to address these questions¹ . The authors studied the isoprostanes expressed in the brains of 33 babies who had died of various causes and had come to autopsy at one of 2 medical centers in the United States. Of these infants, 10 had PVL. Five had hypoxic/ischemic injury at the time of birth but did not have PVL. Eighteen infants with neither condition served as controls.

They found that the F2-isoprostane was elevated in areas of PVL while F4-isoprostane was not. This elevation of F2-isoprostane was not found in the brains of the control babies or in the brains of those who suffered hypoxic/ischemic insults at birth.

They conclude that the occurrence of PVL in preterm infants is related to hypoxic injury to the cells that were destined to differentiate into oligodendrocytes. The role of inflammation was not addressed.

COMMENT:
These findings suggest that hypoxia/ischemia is important to the development of PVL and that oligodendrocytes are the principle target. Since the babies were not evaluated for possible inflammatory changes, their data does not exclude a critical role for this factor as well.