Delayed neural network degeneration after neonatal hypoxia‐ischemia
- 1 November 2008
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 64 (5), 535-546
- https://doi.org/10.1002/ana.21517
Abstract
Objective Clinical magnetic resonance studies show delayed and ongoing neurodegeneration after neonatal hypoxia‐ischemia (HI), but the mechanisms and timing of this neurodegeneration remain unclear. We used ex vivo diffusion tensor imaging (DTI) and brain neuropathology to determine whether selective injury to white matter tracts occurs after neonatal HI in mice resulting in neural system–associated attrition in remote regions and at delayed times. Methods The Rice–Vannucci model (unilateral carotid ligation + 45 minutes of hypoxia FiO2 = 0.08) was used to cause brain injury in postnatal day 7 (p7) C57BL6 mice, and ex vivo DTI and correlative neuropathology were performed at p8, p11, p15, p21, p28, and p42. Results DTI provides excellent contrast visualization of unmyelinated white matter in the immature mouse brain. Severe ipsilateral injury to the hippocampus is seen with both histopathology and diffusion‐weighted magnetic resonance imaging 24 hours after injury. Injury to axons is evident 24 hours after HI in the hippocampal alveus. By p11 and continuing until p28, the ipsilateral fimbria fornix degenerates. At p15, there is injury and loss of axons entering the ipsilateral septal nucleus followed by ipsilateral septal atrophy. Volume loss in the hippocampus is rapid and severe, but is subacute and significantly slower in the ipsilateral septum. Neonatal HI also interrupts the normal developmental increase in fractional anisotropy in the ipsilateral fimbria but not in the contralateral fimbria from p8 to p42. Interpretation In neonatal brain, there is progressive systems‐preferential injury after HI. DTI allows unparalleled visualization of this neural network–associated attrition so that it can be followed longitudinally in developing brain. Ann Neurol 2008;64:535–546Keywords
This publication has 44 references indexed in Scilit:
- Quantified Corticospinal Tract Diffusion Restriction Predicts Neonatal Stroke OutcomeStroke, 2007
- Differential sensitivity of in vivo and ex vivo diffusion tensor imaging to evolving optic nerve injury in mice with retinal ischemiaNeuroImage, 2006
- Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neuronsBrain Research, 2005
- Analysis of noise effects on DTI‐based tractography using the brute‐force and multi‐ROI approachMagnetic Resonance in Medicine, 2004
- Apoptosis Induced by Differentiation or Serum Deprivation in an Immortalized Central Nervous System Neuronal Cell LineJournal of Neurochemistry, 2002
- MRI Evaluation and Functional Assessment of Brain Injury After Hypoxic Ischemia in Neonatal MiceStroke, 2002
- Involvement of Specific Caspases in Motoneuron Cell Deathin Vivoandin VitroFollowing Trophic Factor DeprivationMolecular and Cellular Neuroscience, 1998
- Nitric oxide synthase 1 and nitric oxide synthase 3 protein expression is regionally and temporally regulated in fetal brainDevelopmental Brain Research, 1996
- The connections of the septal region in the ratJournal of Comparative Neurology, 1979
- THE CONNEXIONS OF THE SEPTUMBrain, 1966