Jaylyn Waddell1, Nicholas C Rickman2, Min He3, Ningfeng Tang4, Cynthia F Bearer5. 1. Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. 2. Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA. 3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA. 4. Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. 5. Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA. Cynthia.bearer@UHhospitals.org.
Abstract
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a devastating disease with lifelong disabilities. Hypothermia is currently the only treatment. At term, the neonatal cerebellum may be particularly vulnerable to the effects of HIE. At this time, many developmental processes depend on lipid raft function. These microdomains of the plasma membrane are critical for cellular signaling and axon extension. We hypothesized that HIE alters the protein content of lipid rafts in the cerebellum. METHODS: Postnatal day (PN) 10 animals, considered human term equivalent, underwent hypoxic-ischemic (HI) injury by a right carotid artery ligation followed by hypoxia. For some animals, LPS was administered on PN7, and hypothermia (HT) was conducted for 4 h post-hypoxia. Lipid rafts were isolated from the right and left cerebella. The percent of total L1 cell adhesion molecule in lipid rafts was determined 4 and 72 h after hypoxia. RESULTS: No sex differences were found. HI alone caused significant increases in the percent of L1 in lipid rafts which persisted until 72 h in the right but not the left cerebellum. A small but significant effect of LPS was detected in the left cerebellum 72 h after HI. Hypothermia had no effect. CONCLUSIONS: Lipid rafts may be a new target for interventions of HIE. IMPACT: This article investigates the effect of neonatal exposure to hypoxic-ischemic encephalopathy (HIE) on the distribution of membrane proteins in the cerebellum. This article explores the effectiveness of hypothermia as a prevention for the harmful effects of HIE on membrane protein distribution. This article shows an area of potential detriment secondary to HIE that persists with current treatments, and explores ideas for new treatments.
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a devastating disease with lifelong disabilities. Hypothermia is currently the only treatment. At term, the neonatal cerebellum may be particularly vulnerable to the effects of HIE. At this time, many developmental processes depend on lipid raft function. These microdomains of the plasma membrane are critical for cellular signaling and axon extension. We hypothesized that HIE alters the protein content of lipid rafts in the cerebellum. METHODS: Postnatal day (PN) 10 animals, considered human term equivalent, underwent hypoxic-ischemic (HI) injury by a right carotid artery ligation followed by hypoxia. For some animals, LPS was administered on PN7, and hypothermia (HT) was conducted for 4 h post-hypoxia. Lipid rafts were isolated from the right and left cerebella. The percent of total L1 cell adhesion molecule in lipid rafts was determined 4 and 72 h after hypoxia. RESULTS: No sex differences were found. HI alone caused significant increases in the percent of L1 in lipid rafts which persisted until 72 h in the right but not the left cerebellum. A small but significant effect of LPS was detected in the left cerebellum 72 h after HI. Hypothermia had no effect. CONCLUSIONS: Lipid rafts may be a new target for interventions of HIE. IMPACT: This article investigates the effect of neonatal exposure to hypoxic-ischemic encephalopathy (HIE) on the distribution of membrane proteins in the cerebellum. This article explores the effectiveness of hypothermia as a prevention for the harmful effects of HIE on membrane protein distribution. This article shows an area of potential detriment secondary to HIE that persists with current treatments, and explores ideas for new treatments.
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