Abstract
Distinctive cerebral lesions with disruptions to the developing white matter are found in very low birth weight (VLBW) infants. Although hypoxia-ischemia (HI) is a causal pathway, the pathogenesis of cerebral white matter injury in the VLBW infant is not fully understood. Pertinent murine models would facilitate the investigation of the processes leading to these cerebral lesions and enable the evaluation of therapeutic strategies. Postnatal d 3 (P3) rats are at a stage of cortical oligodendroglial maturation and axonal outgrowth similar to very preterm infants. Our aim was to characterize the effects of a focal hypoxic-ischemic injury at P3 on subsequent cerebral development. Three groups of P3 Wistar rats were investigated: group I underwent right carotid ligation followed by 6% hypoxia for 30 min (HI), group 2 had carotid ligation only, and group 3 had no intervention. At P21, in the HI group, the right cortical area was reduced compared with controls (p < 0.01). There were no significant alterations in the size of the dorsal hippocampus, striatum, and thalamus. The cortical myelinated area was reduced in the HI animals compared with controls (p < 0.01). There was a corresponding loss of myelinated axons extending up into the cortex, with deep cortical neuronal and axonal architecture markedly disrupted. Glial fibrillary acidic protein immunohistology showed a reactive gliosis in the deep parietal cortex (p < 0.01). Moderate HI injury in the immature rat brain compromised cortical growth and led to a selective alteration of cortical myelinated axons with persistent gliosis. These alterations induced at P3 by unilateral HI share neuropathological similarities with the diffuse white matter lesions found in VLBW infants.
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Abbreviations
- HI:
-
hypoxia-ischemia
- WM:
-
white matter
- PVL:
-
periventricular leukomalacia
- MBP:
-
myelin basic protein
- GFAP:
-
glial fibrillary acidic protein
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Supported by grants from the Health Research Council of New Zealand and from New Zealand Lotteries Board.
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Sizonenko, S., Sirimanne, E., Mayall, Y. et al. Selective Cortical Alteration after Hypoxic-Ischemic Injury in the Very Immature Rat Brain. Pediatr Res 54, 263–269 (2003). https://doi.org/10.1203/01.PDR.0000072517.01207.87
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DOI: https://doi.org/10.1203/01.PDR.0000072517.01207.87
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