011 - Early turning behavior in a preclinical rodent model as an indicator of neonatal hypoxic-ischemic encephalopathy

Publication Number: 11.5012

Bertta M.. Korhonen, University of Turku, Turku, Varsinais-Suomi, Finland; Paula Lehtinen, University of Turku, Turku, Varsinais-Suomi, Finland; Vilhelmiina Parikka, University of Turku, Turku, Varsinais-Suomi, Finland

Background: Hypoxic-ischemic encephalopathy (HIE) is the result of inadequate oxygen delivery to brain tissue during birth and is a major contributor to neonatal mortality and long-term complications. Experimental animal models have been extensively used to elucidate pathophysiological mechanisms and to test novel therapies for HIE. However, there are no established methods for early recognition of affected animals. Early detection of functional impairment following hypoxic-ischemic injury has also remained a challenge.

Objective: We aimed to investigate differences in early motor performance between injured and uninjured animals in a preclinical model of neonatal HIE.

Design/Methods: Neonatal hypoxic-ischemic brain injury was induced in 9-day-old Sprague–Dawley rat pups by permanent litigation of the left common carotid artery followed by hypoxia (8% oxygen) for 120 minutes. Sham controls underwent a reveal of the common carotid artery without arterial ligation and exposure to hypoxia. Early motor assessment was performed 24 hours after the injury by placing the pup on a flat surface and measuring its movement at 30 seconds. The assessment was videorecorded and subsequently analyzed. Measurements included time and angle of turn, forward movement (time and distance), time at rest and head lifts (number and duration).

Results: Early movement assessment revealed a difference in turning behavior between HIE and control animals. Rats with hypoxic-ischemic brain injury presented more ipsiversive turning (median [IQR] angle 1103 [877] vs 425 [437] degrees; p< 0.050) during the 30-s recording period. The assessment also revealed less turning to the contralateral (uninjured) side, as measured by both in median [IQR] angle (45 [184] vs 383 [428] degrees; p=0.006) and median time (1 [3.25] vs 6 [11] seconds; p=0.007) in 30 seconds. Forward movement, time at rest and head lifts did not show significant differences between the groups.

Conclusion(s): This study focusing on early motor performance, revealed ipsiversive turning behavior in neonatal rats following unilateral hypoxic-ischemic brain injury. Our results not only provide new insights into understanding the pathophysiology of the HIE rat model, but also suggest that turning behavior may be a promising tool to distinguish injured from uninjured animals at an early stage. Further studies are needed to investigate the correlation between motor performance and the severity of the brain injury.