Brain injury and neurofunctional deficit in neonatal mice with hypoxic-ischemic encephalopathy

• Published in: Behavioural brain research 2003-10, Vol.145 (1), p.209-219
• Main Authors: Ten, Vadim S, Bradley-Moore, Maria, Gingrich, Jay A, Stark, Raymond I, Pinsky, David J
• Format: Article
• Language: English
• Subjects: Activity levels. Psychomotricity; Animals; Animals, Newborn - physiology; Behavior, Animal; Biological and medical sciences; Brain - anatomy & histology; Brain - pathology; Brain - physiopathology; Brain infarct; Brain Infarction; Brain Injuries - etiology; Brain Injuries - pathology; Correlation; Disease Models, Animal; Functional Laterality; Fundamental and applied biological sciences. Psychology; HIE; Hypoxia; Hypoxia-Ischemia, Brain - complications; Hypoxia-Ischemia, Brain - pathology; Ligation - methods; Maze Learning; Mice; Mice, Inbred C57BL; Neonatal mice; Organ Size; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychomotor activities; Reaction Time; Reference Standards; Reflex; Reproducibility of Results; Sensorimotor reflexes; Statistics as Topic; Time; Time Factors
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/S0166-4328(03)00146-3

Birth asphyxia accounts for the majority of developmental motor and cognitive deficits. Studies were undertaken to develop a reproducible murine model of perinatal hypoxic-ischemic encephalopathy (HIE) which would permit both anatomic and neurofunctional quantification of injury. Short-term neurofunctional outcomes consisted of three developmental reflexes (righting, cliff aversion and geotaxis) assessed in 7-day-old mouse pups 24 h after unilateral carotid artery ligation followed by inhalation of 8% oxygen. Cerebral infarct volume was dependent on duration of hypoxia, being ≈2.5-fold greater with longer (60 min) versus shorter (30 min) hypoxia exposure ( P=0.001). All three sensorimotor neonatal reflexes assessed at 24 h after HIE injury correlated significantly with long-term neurofunction evaluated using a water-maze test of navigational learning and memory assessed 8 weeks later in the same animals. Cerebral atrophy, a delayed consequence of HIE in this model, also correlated strongly with water-maze performance ( r=0.86, P=0.002). These data demonstrate for the first time that murine neonatal sensorimotor reflex performance can be rigorously quantified in the acute phase of perinatal HIE and has strong predictive value not only for anatomic extent of cerebral injury, but also for long-term neurofunctional outcome.