Related Experiment Video
Updated: Jun 27, 2026
08:47
The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia
Published on: November 19, 2008
Delayed neural network degeneration after neonatal hypoxia-ischemia
Brian S Stone1, Jiangyang Zhang, Devin W Mack
1Department of Pediatrics, Eudowood Neonatal Pulmonary Division, Neonatal Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Annals of Neurology
|December 11, 2008
Summary
Neonatal hypoxia-ischemia (HI) causes progressive, system-preferential white matter injury in the developing brain. Diffusion tensor imaging (DTI) effectively visualizes this neural network attrition over time.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Medical Imaging
Background:
- Neonatal hypoxia-ischemia (HI) is a significant cause of brain injury with delayed neurodegeneration.
- The precise mechanisms and timing of post-HI neurodegeneration, particularly in white matter tracts, remain incompletely understood.
- Understanding these processes is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the timing and extent of white matter tract injury following neonatal HI using ex vivo diffusion tensor imaging (DTI) and neuropathology.
- To determine if HI leads to selective injury in white matter, resulting in remote neural system attrition.
- To characterize the longitudinal changes in white matter integrity and associated brain regions.
Main Methods:
- The Rice-Vannucci model was employed to induce unilateral HI in postnatal day 7 (p7) C57BL6 mouse pups.
- Ex vivo DTI and correlative neuropathology were performed at multiple time points (p8, p11, p15, p21, p28, and p42) post-injury.
- DTI was utilized for its ability to visualize unmyelinated white matter in the immature brain.
Main Results:
- DTI provided excellent visualization of immature white matter, complementing histopathology.
- Severe ipsilateral hippocampal injury and axonal damage in the alveus were observed within 24 hours post-HI.
- Progressive degeneration of the ipsilateral fimbria fornix and injury to the septal nucleus were noted from p11 to p15, leading to septal atrophy.
- Neonatal HI disrupted the normal developmental increase in fractional anisotropy in the ipsilateral fimbria, indicating white matter damage.
Conclusions:
- Neonatal HI results in progressive, systems-preferential injury within the developing brain.
- DTI offers unparalleled visualization of neural network attrition, enabling longitudinal tracking of injury progression in the developing brain.
- These findings highlight the vulnerability of white matter tracts to HI and provide a framework for studying neurodevelopmental consequences.
Related Concept Videos
01:15Neurogenesis and Regeneration of Nervous Tissue
In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
01:25Secondary Spinal Cord Injury llI: Pathophysiology
Early Ischemia and Ionic ImbalanceWithin minutes of spinal cord injury, a secondary cascade begins, progressing over hours to weeks. Vascular damage reduces blood flow, causing ischemia and mitochondrial dysfunction. ATP depletion leads to ion pump failure, membrane depolarization, sodium influx, potassium efflux, and water accumulation, resulting in cellular swelling. Increased intracellular calcium further disrupts mitochondria and accelerates cellular injury.Excitotoxicity and Neuronal...