There also is abundant evidence showing increased production of free radicals, like superoxides and H2O2 in response to reperfusion injury after hypoxic-ischemic events, as well as in response to infection and inflammation. These substances can cause cell damage and even death. And of course, cell death would cause release of glutamates producing yet more cell damage. The premature has deficient and immature mechanisms that would normally protect against free radicals, such as catalases and superoxide dysmutase. In addition, the premature has an absence of neuroprotective substances that would ordinarily be provided by the mother, across the placenta and which cannot be synthesized by the fetus.

Another potentially important factor, especially in the development of PVL, involves microglia. Glial or supporting cells actually outnumber neurons in the cerebral cortex and are overwhelmingly the predominant cell in white matter. There are 3 types of glia:

• astrocytes are important nutritively for neurons and are active glutamate scavengers
• oligodendrocytes are critical in the formation of myelin
• microglia are the primary immune cell of the CNS

Microglia are particularly concentrated in white matter of the premature brain. Infection and inflammation, as well as hypoxia and ischemia and reperfusion injury, not only damage neurons and glial cells but can activate these microglial cells. When activated, the microglia release cytokines, glutamate and reactive oxygen species that are further damaging to white matter, especially to oligodendrocytes which are especially sensitive.

While the available evidence is not as strong supporting a role for infection and inflammation in the production of IVH, there is no doubt that all of the mediators discussed above, released in response to infection and inflammation, can alter CBF with the potential to cause IVH.