To establish developmental correlates among perinatal neocortical damage, its impact on the infant developing brain, and its possible role in the pathogenesis of ensuing neurologic sequelae, the neuropathology of acute, subacute (healing), and chronic (repaired) stages of periventricular and layer I (subpial) hemorrhagic lesions have been studied. Thirty-three cases of infants who survived brain damage for hours, days, weeks, months, and/or years and have been studied with the rapid Golgi and other methods. In periventricular hemorrhagic injury: (a) the local destruction of radial glia stop all cellular migration above the lesion; (b) precursor cells already traveling in damaged radial glia also stop their migration, miss their target, and form acquired heterotopias; and, (c) the cytoarchitecture of the overlying and differentiating gray matter may be secondarily altered. In layer I (subpial) hemorrhagic injury: (a) the neocortex external glial limiting membrane is disrupted and must be repaired; (b) its reparation often causes superficial leptomeningeal heterotopias; (c) the cytoarchitecture and intrinsic circuitry of layer I and underlying gray matter are secondarily altered; and, (d) partially damaged (pruning) and/or displaced gray matter neurons undergo post-injury morphologic transformations, atrophy, hypertrophy, and reestablished new “abnormal” connections. These post-injury gray matter cytoarchitectural alterations could eventually play a role in cortical dysfunction and, hence, in the pathogenesis of neurologic sequelae.

Author notes

This work has been supported by a Jacob Javits Neuroscientist Investigator Award, from the NINCDS, grant NS-22897, NIH.