Neonatal Hypoxic-Ischemic Encephalopathy Yields Permanent Deficits in Learning Acquisition: A Preclinical Touchscreen Assessment

Frontiers in Pediatrics

article

Jessie R. Maxwell¹  Amber J. Zimmerman²  Nathaniel Pavlik¹  Jessie C. Newville²  Katherine Carlin³  Shenandoah Robinson⁴  Jonathan L. Brigman²  Frances J. Northington³  Lauren L. Jantzie³ 

[1] Department of Pediatrics, University of New Mexico, United States;Department of Neurosciences, University of New Mexico, United States;Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, United States;Department of Neurosurgery, Johns Hopkins University School of Medicine, United States;Department of Neurology, Johns Hopkins University School of Medicine, United States;Department of Neurology, Kennedy Krieger Institute, United States

关键词: biobehavioral biomarker;    HIE;    touchscreen;    learning acquisition;    cognitive flexibility;    reversal learning;   

DOI  :  10.3389/fped.2020.00289

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Neonatal hypoxic-ischemic encephalopathy (HIE) remains a common problem world-wide for infants born at term. The impact of HIE on long-term outcomes, especially into adulthood, is not well-described. To facilitate identification of biobehavioral biomarkers utilizing a translational platform, we sought to investigate the impact of HIE on executive function and cognitive outcomes into adulthood utilizing a murine model of HIE. HIE mice (unilateral common carotid artery occlusion to induce ischemia, followed by hypoxia with a FiO 2 of 0.08 for 45 min) and control mice were tested on discrimination and reversal touchscreen tasks (using their noses) shown to be sensitive to loss of basal ganglia or cortical function, respectively. We hypothesized that the HIE injury would result in deficits in reversal learning, revealing complex cognitive and executive functioning impairments. Following HIE, mice had a mild discrimination impairment as measured by incorrect responses but were able to learn the paradigm to similar levels as controls. During reversal, HIE mice required significantly more total trials, errors and correction trials across the paradigm. Analysis of specific stages showed that reversal impairments in HIE were driven by significant increases in all measured parameters during the late learning, striatal-mediated portion of the task. Together, these results support the concept that HIE occurring during the neonatal period results in abnormal neurodevelopment that persists into adulthood, which can impact efficient associated learning. Further, these data show that utilization of an established model of HIE coupled with touchscreen learning provides valuable information for screening therapeutic interventions that could mitigate these deficits to improve the long-term outcomes of this vulnerable population.

【 授权许可】

CC BY