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Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Hypoxic postconditioning improves behavioural deficits at 6 weeks following hypoxic-ischemic brain injury in neonatal
Jonathan D Teo1, Margaret J Morris1, Nicole M Jones1
1Department of Pharmacology, School of Medical Sciences, UNSW Sydney, New South Wales, 2052, Australia.
Insights
Hypoxic-ischemic brain injury in newborns can cause long-term deficits. Mild hypoxic postconditioning (PostC) treatment improved both neurological function and reduced brain damage in neonatal rat models, showing clinical potential.
Area of Science:
- Neuroscience
- Neonatal Research
- Neuroprotection
Background:
- Hypoxic-ischemic (HI) brain injury in newborns leads to significant mortality and long-term neurological impairments.
- Previous studies demonstrated that immediate hypoxic postconditioning (PostC) offers short-term protection against HI in neonatal rats.
- The long-term functional and histological effects of PostC following neonatal HI brain injury remain largely unexamined.
Purpose of the Study:
- To investigate the efficacy of hypoxic postconditioning (PostC) in mitigating long-term functional deficits and histological brain damage after neonatal hypoxic-ischemic (HI) injury.
- To assess the sustained neuroprotective effects of PostC beyond the acute injury phase.
Main Methods:
- Neonatal Sprague-Dawley rats (postnatal day 7) were subjected to unilateral carotid artery occlusion followed by hypoxia (HI).
- Animals received either normoxic conditions or hypoxic postconditioning (8% oxygen, 1h/day for 5 days).
- Functional assessments included reflex tests (P8, P14) and motor/memory tasks (P42); histological scoring evaluated brain injury.
Main Results:
- PostC significantly improved righting reflex deficits by postnatal day 14 compared to HI alone.
- Long-term (6-week) behavioral deficits in grid walking and novel object recognition were ameliorated by PostC.
- Histological analysis revealed reduced brain injury in PostC-treated rats compared to the HI-only group.
Conclusions:
- Hypoxic postconditioning (PostC) provides significant long-term neuroprotection against functional deficits and histological damage following neonatal hypoxic-ischemic (HI) brain injury.
- These findings highlight the potential of mild hypoxia as a therapeutic strategy for neonatal HI brain injury.
- PostC demonstrates sustained efficacy, improving both neurological function and reducing brain pathology in a preclinical model.
Abstract:
Hypoxic-ischemic (HI) brain injury in newborns is associated with high morbidity and mortality, with many babies suffering neurological deficits. Recently, we showed that hypoxic postconditioning (PostC) immediately post injury can protect against HI up to one week in neonatal rats. Here, we aimed to examine whether long term functional deficits were also improved by PostC. Sprague-Dawley rats were assigned to control (C) or HI group on postnatal day 7 (P7). The HI group underwent unilateral carotid artery occlusion followed by hypoxia (7% oxygen, 3h). Half of each group were randomly assigned to the PostC group (8% oxygen, 1h/day for 5days post-injury), or normoxic group, where animals were kept under ambient conditions. Righting reflex and negative geotaxis tests were performed on P8 and P14. On P42, rats underwent further behavioural tests of motor function and memory (forelimb grip strength, grid walking and novel object recognition tasks). Brain injury was assessed using histological scoring of brain sections. At P14, PostC reduced the righting reflex deficit compared to HI alone. Long-term (6 weeks) behavioural deficits were observed in grid walking and novel object recognition tests after HI alone, with both functions improved following PostC. Following HI, there was an increase in brain injury assessed by histological scoring compared to control, and this damage was reduced by PostC. This novel finding of long-term histological neuroprotection accompanied by functional improvements by PostC further demonstrates the clinical potential of mild hypoxia for the treatment of HI brain injury.
