Neonatal administration of erythropoietin attenuates cognitive deficits in adult rats following placental insufficiency. Issue 12 (20th February 2021)

• Record Type: Journal Article
• Authors: Robinson, Shenandoah; Winer, Jesse L.; Kitase, Yuma; Brigman, Jonathan L.; Jantzie, Lauren L.
• Other Names: Shi Zhongjie guestEditor.
• Is Part Of: Journal of neuroscience research. Volume 100:Issue 12(2022)
• Page Start: 2112
• Page End: 2126
• Publication Date: 2021-02-20
• Subjects: novel object recognition -- prematurity -- preterm -- reversal -- touchscreen operant chambers -- visual discrimination; Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.24815
• Languages: English
• ISSNs: 0360-4012

Abstract

Abstract: Preterm birth is a principal cause of neurological disability later in life, including cognitive and behavioral deficits. Notably, cognitive impairment has greater impact on quality of life than physical disability. Survivors of preterm birth commonly have deficits of executive function. Difficulties with tasks and planning complexity correlate positively with increasing disability. To overcome these barriers for children born preterm, preclinical and clinical studies have emphasized the importance of neurorestoration. Erythropoietin (EPO) is a endogenous cytokine with multiple beneficial mechanisms of action following perinatal brain injury. While most preclinical investigations have focused on pathology and molecular mechanisms, translational studies of repair using clinically viable biobehavioral biomarkers are still lacking. Here, using an established model of encephalopathy of prematurity secondary to placental insufficiency, we tested the hypothesis that administration of EPO in the neonatal period would attenuate deficits in recognition memory and cognitive flexibility in adult rats of both sexes. We assessed cognition and executive function in two ways. First, using the classic test of novel object recognition and second, using a touchscreen platform. Touchscreen testing allows for rigorous testing of cognition and executive function in preclinical and clinical scenarios. Data show that adult rats exhibit deficits in recognition memory and cognitive flexibility following in utero placental insufficiency. Notably, neonatal treatment of EPO attenuates these deficits in adulthood and facilitates functional repair. Together, these data validate EPO neurorestoration using a clinically relevant outcome measure and support the concept that postnatal treatment following in utero injury can improve cognition and executive function through adulthood. Abstract : In a transient systemic hypoxic‐ischemic model of placental insufficiency, erythropoietin is found to have lasting, mitigating effects on the diminished cognitive flexibility and increased perseveration which are associated with encephalopathy of prematurity. Highly translatable testing, including novel object recognition and touchscreen‐based visual discrimination and reversal learning, reveal significant differences post‐treatment.