Show simple item record

dc.contributor.authorTucker, Loreleien
dc.date.accessioned2019-07-03T16:14:58Zen
dc.date.available2019-07-03T16:14:58Zen
dc.date.issued2019-05en
dc.identifier.urihttp://hdl.handle.net/10675.2/622448en
dc.description.abstractNeonatal hypoxic ischemic encephalopathy (HIE), initiated by hypoxic-ischemic (HI) injury to the brain in the perinatal period, is a leading cause of infant mortality and disability. HI damage to the developing brain triggers a complex pathology, initiating with mitochondrial insult, which culminates in neuronal cell death. Photobiomodulation (PBM), the application of near-infrared light, is an experimental neuroprotective strategy targeting the activity of mitochondrial cytochrome c oxidase (CCO), but its effect on HIE is unknown. This work was designed to shed light on the effect of PBM on a neonatal rat HI injury model. Postnatal day 10 mixed-sex pups underwent HI insult followed by 7 daily PBM treatment sessions via a continuous wave diode laser (808 nm). HI pups suffered significant ipsilateral hemispheric brain shrinkage and substantial cell death in the cortex and hippocampal CA1 and CA3 subregions. PBM treatment reduced neuronal cell death in the cortex and hippocampal subregions and reduced hemispheric brain shrinkage. HI pups displayed impaired motor function and spatial learning and memory which was ameliorated by PBM. Blood-brain barrier integrity was compromised in HI animals, as evidenced by reduced extravasation of Evans blue, but was reversed by PBM. PBM also mitigated microglial activation and upregulation of pro-inflammatory cytokines in HI pups. PBM treatment induced robust reduction in oxidative damage markers and protein carbonyl production in the cortex and hippocampus. Investigation of mitochondrial function revealed that PBM markedly attenuated mitochondrial dysfunction and preserved ATP production in neonatal HI rats. Furthermore, PBM treatment profoundly suppressed HI-induced mitochondrial fragmentation. PBM administration reduced activation of pro-apoptotic caspase 3/9 and TUNEL-positive neurons in HI pups. Finally, we demonstrated that the neuroprotective action of PBM could be reversed in a primary hippocampal neuronal OGD model by application of low-dose KCN, a CCO inhibitor. Taken together, our findings demonstrated that PBM treatment contributed to a robust neuroprotection via attenuation of mitochondrial dysfunction, oxidative stress, and neuronal apoptosis in the neonatal HI brain. Additionally, we demonstrated that these effects are, in part, mediated by modulation of CCO activity. This suggests that PBM may offer a promising role as a potential treatment strategy for HIE.en
dc.publisherAugusta Universityen
dc.subjectNeurosciencesen
dc.subjectbehavior, mitochondria, Neonatal Hypoxic-ischemic encephalopathy, neuronal cell death, photobiomodulationen
dc.titlePHOTOBIOMODULATION AS A MITOCHONDRIAL TARGETED TREATMENT STRATEGY IN NEONATAL HYPOXIC ISCHEMIC ENCEPHALOPATHYen
dc.typedissertationen
dc.contributor.departmentDepartment of Neuroscience and Regenerative Medicineen
dc.language.rfc3066enen
dc.date.updated2019-07-03T16:14:58Zen
dc.description.advisorZhang, Quanguangen
dc.description.degreePh.D.en
dc.description.committeeBrann, Darrellen
dc.description.committeeMcCluskey, Lynetteen
dc.description.committeePillai, Anilkumaren
dc.description.committeeDhandapani, Krishnanen
refterms.dateFOA2019-08-05T18:15:01Zen
dc.description.embargo04/05/2020en


Files in this item

Thumbnail
Name:
Tucker_gru_1907E_10113.pdf
Size:
3.634Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record