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Updated: Oct 1, 2026
Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
MRI evaluation and functional assessment of brain injury after hypoxic ischemia in neonatal mice
Ulrika Adén1, Viktoria Dahlberg, Bertil B Fredholm
1Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. ulrika.aden@fyfa.ki.se
Background And Purpose:
Severe perinatal asphyxia is an important cause of brain injury in the newborn infant. We examined early events after hypoxic ischemia (HI) in the 7-day-old mouse brain by MRI and related them to long-term functional effects and histopathology in the same animals at 4 to 5 weeks of age.
Methods:
HI was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated in vivo by MRI (T2 maps and apparent diffusion coefficient maps) at 3, 6, and 24 hours and 5 days after hypoxia. Locomotion and sensorimotor function were analyzed after 3 weeks. Four weeks after HI, the mice were killed, and cresyl violet-stained brain sections were examined morphologically.
Results:
A decrease in apparent diffusion coefficient values in cortex on the affected side was found at 3 hours after HI. T2 values were significantly increased after 6 hours and remained so for 5 days. Maximal size of the lesion was attained at 3 to 6 hours after HI and declined thereafter. Animals with MRI-detected lesions had decreased forward locomotion, performed worse than controls in the beam-walking test, and showed a unilateral hypotrophy in the cresyl violet-stained brain sections 4 weeks later.
Conclusions:
The temporal progression of the damage after HI in 7-day-old mice differs from that of the adult brain as judged by MRI. The early lesions detected by MRI were related to functional impairments for these mice in near-adult life.
Insights
Early brain injury from hypoxic ischemia (HI) in newborn mice, detected by MRI, correlates with long-term motor and sensory deficits. These findings in neonatal mice differ from adult patterns.
Area of Science:
- Neuroscience
- Developmental Biology
- Medical Imaging
Background:
- Severe perinatal asphyxia is a major cause of newborn brain injury.
- Hypoxic-ischemic (HI) brain injury in neonates requires early detection and understanding.
Purpose of the Study:
- To examine early MRI-detectable events following hypoxic ischemia (HI) in 7-day-old mouse brains.
- To correlate these early MRI findings with long-term functional outcomes and histopathology.
Main Methods:
- HI induced in 7-day-old mice via 8% oxygen exposure and carotid artery occlusion.
- In vivo MRI (T2 maps, ADC maps) assessed lesions at 3, 6, 24 hours, and 5 days post-HI.
- Locomotion, sensorimotor function, and brain morphology assessed at 3-5 weeks post-HI.
Main Results:
- Decreased apparent diffusion coefficient (ADC) at 3 hours post-HI; increased T2 values from 6 hours to 5 days.
- Maximal lesion size observed at 3-6 hours, followed by a decline.
- MRI-detected lesions correlated with reduced locomotion, impaired beam-walking, and unilateral brain atrophy.
Conclusions:
- The temporal progression of HI brain damage in neonatal mice, visualized by MRI, differs from that in adult brains.
- Early MRI-detected lesions accurately predict long-term functional impairments in young mice.
