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Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Behavioral and histological outcomes following neonatal HI injury in a preterm (P3) and term (P7) rodent model
M Alexander1, H Garbus1, A L Smith1
1University of Connecticut, Department of Psychology, 406 Babbidge Road, Unit 1020, Storrs, CT 06269, USA.
Insights
Neonatal brain hypoxia-ischemia (HI) timing impacts outcomes. Early HI (P3) caused attention deficits without brain volume loss, while later HI (P7) led to broader learning impairments and tissue damage.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatric Neurology
Background:
- Hypoxia-ischemia (HI) is a critical condition compromising brain oxygen and blood supply.
- Neonatal HI can affect both preterm and term infants, leading to long-term behavioral deficits.
- Rodent models replicate preterm and term HI neuropathologies based on injury timing.
Purpose of the Study:
- To compare outcomes of early (postnatal day 3) versus late (postnatal day 7) HI injury in a rat model.
- To elucidate the task-specific behavioral deficits and neuropathological differences based on HI timing.
- To correlate findings with human outcomes in premature versus term infants.
Main Methods:
- Neonatal male rats underwent HI injury on postnatal day 3 (P3) or postnatal day 7 (P7), or sham procedures.
- Animals were assessed using various behavioral tasks during juvenile and adult stages.
- Neuroanatomical analysis was performed to quantify brain volume changes.
Main Results:
- P7 HI rats exhibited deficits in motor learning, auditory processing, and other cognitive functions, accompanied by reduced brain volume.
- P3 HI rats showed transient deficits in auditory processing during juvenility but persistent deficits in visual attention in adulthood.
- No significant brain volume reduction was detected in P3 HI animals.
Conclusions:
- Behavioral deficits after neonatal HI are dependent on the timing of the injury.
- Later HI (P7) is associated with widespread deficits and significant brain tissue loss.
- Early HI (P3) may lead to attention deficits linked to neural connectivity issues rather than global brain volume loss.
Abstract:
Hypoxia-ischemia (HI) occurs when blood and/or oxygen delivery to the brain is compromised. HI injuries can occur in infants born prematurely (<37 weeks gestational age) or at very low birth weight (<1500 g), as well as in term infants with birth complications. In both preterm and term HI populations, brain injury is associated with subsequent behavioral deficits. Neonatal HI injury can be modeled in rodents (e.g., the Rice-Vannucci method, via cautery of right carotid followed by hypoxia). When this injury is induced early in life (between postnatal day (P)1-5), neuropathologies typical of human preterm HI are modeled. When injury is induced later (P7-12), neuropathologies typical of those seen in HI term infants are modeled. The current study sought to characterize the similarities/differences between outcomes following early (P3) and late (P7) HI injury in rats. Male rats with HI injury on P3 or P7, as well as sham controls, were tested on a variety of behavioral tasks in both juvenile and adult periods. Results showed that P7 HI rats displayed deficits on motor learning, rapid auditory processing (RAP), and other learning/memory tasks, as well as a reduction in volume in various neuroanatomical structures. P3 HI animals showed only transient deficits on RAP tasks in the juvenile period (but not in adulthood), yet robust deficits on a visual attention task in adulthood. P3 HI animals did not show any significant reductions in brain volume that we could detect. These data suggest that: (1) behavioral deficits following neonatal HI are task-specific depending on timing of injury; (2) P3 HI rats showed transient deficits on RAP tasks; (3) the more pervasive behavioral deficits seen following P7 HI injury were associated with substantial global tissue loss; and (4) persistent deficits in attention in P3 HI subjects might be linked to neural connectivity disturbances rather than a global loss of brain volume, given that no such pathology was found. These combined findings can be applied to our understanding of differing long-term outcomes following neonatal HI injury in premature versus term infants.
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