Abstracts

Rationale: Hypoxic ischemic encephalopathy (HIE) affects 1-8 out of every 1000 full term newborns and accounts for significant perinatal mortality and childhood disabilities such as seizures, spasticity as well as visual and hearing impairments. The pathogenesis of HIE consists of an initial hypoxic insult followed by a cascade of oxidative injury, apoptosis, inflammation and altered growth and protein synthesis. Experimental studies denote that micro RNA (mi RNA) dysregulation may form a transformative role in HIE. This study aimed to compare mi RNA expression in the post-mortem brain tissue of infants with HIE to control infants who died of other causes. Methods: Autopsy database at our institute was reviewed to identify infants who succumbed to HIE during the study period. Age, sex and race matched infants who died from other causes were identified as a control group. Formalin fixed paraffin embedded (FFPE) curls of brain cortex were obtained. Microarray analysis for mi RNA expression was completed on these specimens. Results: The 4 newborns in the study group had severe HIE, whereas the control group was constituted of 3 with complex congenital heart diseases and 1 with congenital diaphragmatic hernia. Stringent criteria were used to select mi RNAs significantly different between the two groups: 1) q-values <=0.05 (5% FDR); and 2) minimum 1.5-fold change between HIE and control. The 2 mi RNAs found to be differentially expressed were miR- 4483 miR-302c-5p. The list of 15 genes targeted by either miR - 4483 or miR-302c-5p were involved in key pathways of brain development and epileptogenesis - 1) Ubiquitin Proteasome system 2) c-Jun N-terminal kinase or JNK signaling pathway 3) Ion Channels 4) Neurotransmitter release 5) Neuronal migration. Conclusions: Micro RNA dysregulation is observed in brain tissue of newborns with HIE and possibly influences epilepsy genes. Studies with larger sample size may help in developing diagnostic, prognostic and therapeutic targets in neonatal brain injury in the future. Funding: Ashok and Ingrid Sarnaik Resident Research Funding