Plasticity of Neurons and Glia Following Neonatal Hypoxic-Ischemic Brain Injury in Rats

Abstract

Periventricular white matter injury in premature infants is linked to chronic neurological dysfunction. Periventricular white matter injury is caused by many mechanisms including hypoxia-ischemia (HI). Animal models of HI in the neonatal rodent brain can replicate some important features of periventricular white matter injury. Most rodent studies have focused upon early cellular and tissue events following unilateral neonatal HI that is elicited by unilateral carotid artery ligation and followed by timed exposure to moderate hypoxia. Milder hypoxic-ischemic insults elicit preferential white matter injury. Little information is available about long-term cellular effects of unilateral HI. One month after unilateral neonatal hypoxia ischemia, we show that all the components for structural reorganization of the brain are present in moderately injured rats. These components in the injured side include extensive influx of neurites, axonal and dendritic growth cones, abundant immature synapses, and myelination of many small axons. Surprisingly, this neural recovery is often found in and adjacent to cysts that have the ultrastructural features of bone extracellular matrix. In contrast, brains with severe hypoxia ischemia one month after injury still undergo massive neuronal degeneration. While massive destruction of neurons and glia are striking events shortly after brain HI, neural cells re-express their intrinsic properties and attempt an anatomical recovery long after injury.

Hypothermia and erythropoietin for neuroprotection after neonatal brain damage

“…This has been described previously and may be considered a result of plasticity of the brain (33). Plasticity is one of the most prominent features of the central nervous system, especially in the developing brain (34), and EPO has been reported to promote brain plasticity in both newborn and adult animal models of brain injury (29,35).…”

Adding 5 h delayed xenon to delayed hypothermia treatment improves long-term function in neonatal rats surviving to adulthood

“…In this study, we did not find improved brain volume by adding xenon to hypothermia as compared to hypothermia alone, however, we found a significant long-term functional improvement in the hypothermia-xenon group. The research group of F. Silverstein have demonstrated ongoing long lasting neuronal and glial degeneration and recovery in an ultrastructual study (29). Combining delayed HT and delayed xenon improved long-term functional outcome even without a corresponding increase in brain volume.…”

Short and Long-Term Analysis and Comparison of Neurodegeneration and Inflammatory Cell Response in the Ipsilateral and Contralateral Hemisphere of the Neonatal Mouse Brain after Hypoxia/Ischemia

“…Following H/I in the P9 mouse, several authors have reported decreased expression levels of myelin basic protein (MBP) and proteolipid protein (PLP), decreased neurofilament expression, and the presence of apoptotic cells in the corpus callosum within 24 to 72 hours after injury [66, 67]. White matter damage has been related to the loss of immature oligodendrocytes in the tracts as well as the loss of subventricular zone (SVZ) progenitors after H/I, inducing a depletion of oligodendrocyte precursors [68, 69]. …”