ARCADIC: AlteRed Circadian rhythm And immune Dysfunction In children with Cerebral palsy

Collaborators:
Dr. Lynne Kelly (Postdoc researcher), Prof Eleanor J Molloy (Neonatologist, Lab PI), Prof
Denise McDonald

Background: Cerebral palsy (CP) is associated with sleep disturbances, including obstructive sleep apnea (OSA), altered circadian rhythms, and melatonin regulation. Despite evidence of sleep fragmentation in children with CP, electroencephalogram and polysomnography studies suggest that these disturbances may not be solely linked to OSA. Persistent inflammation has been associated with sleep disturbance and altered circadian rhythm (CLOCK, CRY, BMAL & REVERBα). BMAL , in particular, is associated with an anti-inflammatory response. Melatonin may be effective in reducing the LPS response and may be beneficial
as an adjunctive therapy in children with CP.

Aim: We aim to examine sleep using questionnaires and correlate with circadian rhythm gene expression and inflammatory cytokines in children with CP.This study aims to better understand the molecular mechanisms underlying sleep disturbances in CP and explore the potential role of melatonin in managing these issues.

Methods: Whole blood will be analysed from children with CP and compared to healthy paediatric controls at baseline. Samples were bio banked following treatment with lipopolysaccharide (LPS) and Melatonin. Whole blood RNA was isolated following treatment. We will synthesize cDNA synthesized and analyse by quantitative PCR for the expression of CLOCK, CRY, BMAL & REVERBα. Erythropoietin and VEGF have been measured by ELISA. These will be correlated with circadian rhythm genes. In addition, clinical correlations with
sleep questionnaires and sleep studies for obstructive sleep apnoea will be analysed.