Enriched rehabilitation promotes motor recovery in rats exposed to neonatal hypoxia-ischemia

Clarissa Pedrini Schuch; Matthew Strider Jeffers; Sabina Antonescu; Carine Nguemeni; Mariana Gomez-Smith; Lenir Orlandi Pereira; Cindi M Morshead; Dale Corbett

doi:10.1016/j.bbr.2016.02.010

Enriched rehabilitation promotes motor recovery in rats exposed to neonatal hypoxia-ischemia

Behav Brain Res. 2016 May 1:304:42-50. doi: 10.1016/j.bbr.2016.02.010. Epub 2016 Feb 10.

Authors

Clarissa Pedrini Schuch¹, Matthew Strider Jeffers², Sabina Antonescu², Carine Nguemeni², Mariana Gomez-Smith², Lenir Orlandi Pereira³, Cindi M Morshead⁴, Dale Corbett⁵

Affiliations

¹ Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
² Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada.
³ Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
⁴ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
⁵ Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Faculty of Medicine, Memorial University, St. John's, NL, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada. Electronic address: dcorbett@uottawa.ca.

PMID: 26876139
DOI: 10.1016/j.bbr.2016.02.010

Abstract

Despite continuous improvement in neonatology there is no clinically effective treatment for perinatal hypoxia ischemia (HI). Therefore, development of a new therapeutic intervention to minimize the resulting neurological consequences is urgently needed. The immature brain is highly responsive to environmental stimuli, such as environmental enrichment but a more effective paradigm is enriched rehabilitation (ER), which combines environmental enrichment with daily reach training. Another neurorestorative strategy to promote tissue repair and functional recovery is cyclosporine A (CsA). However, potential benefits of CsA after neonatal HI have yet to be investigated. The aim of this study was to investigate the effects of a combinational therapy of CsA and ER in attempts to promote cognitive and motor recovery in a rat model of perinatal hypoxic-ischemic injury. Seven-day old rats were submitted to the HI procedure and divided into 4 groups: CsA+Rehabilitation; CsA+NoRehabilitation; Vehicle+Rehabilitation; Vehicle+NoRehabilitation. Behavioural parameters were evaluated pre (experiment 1) and post 4 weeks of combinational therapy (experiment 2). Results of experiment 1 demonstrated reduced open field activity of HI animals and increased foot faults relative to shams in the ladder rung walking test. In experiment 2, we showed that ER facilitated acquisition of a staircase skilled-reaching task, increased number of zone crosses in open-field exploration and enhanced coordinated limb use during locomotion on the ladder rung task. There were no evident deficits in novel object recognition testing. Delayed administration of CsA, had no effect on functional recovery after neonatal HI. There was a significant reduction of cortical and hemispherical volume and hippocampal area, ipsilateral to arterial occlusion in HI animals; combinational therapy had no effect on these morphological measurements. In conclusion, the present study demonstrated that ER, but not CsA was the main contributor to enhanced recovery of motor ability after neonatal HI.

Keywords: Cyclosporine animal models; Hypoxia-ischemia; Neonates; Perinatal asphyxia; Recovery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Animals
Animals, Newborn
Brain Infarction / drug therapy
Brain Infarction / etiology
Brain Infarction / rehabilitation
Cognition Disorders / drug therapy
Cognition Disorders / etiology
Cognition Disorders / rehabilitation
Cyclosporine / therapeutic use
Environment*
Exploratory Behavior / drug effects
Exploratory Behavior / physiology
Feeding Behavior / drug effects
Feeding Behavior / physiology
Female
Hypoxia-Ischemia, Brain / drug therapy
Hypoxia-Ischemia, Brain / physiopathology*
Hypoxia-Ischemia, Brain / rehabilitation*
Immunosuppressive Agents / therapeutic use
Male
Motor Activity / physiology*
Pregnancy
Psychomotor Performance / drug effects
Psychomotor Performance / physiology
Rats
Rats, Sprague-Dawley
Recognition, Psychology / drug effects
Recognition, Psychology / physiology
Recovery of Function / drug effects
Recovery of Function / physiology*

Substances

Immunosuppressive Agents
Cyclosporine