Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in Rats
Background: In the United States, traumatic brain injury (TBI) contributes significantly to mortality and morbidity. Elovanoids (ELVs), a novel class of homeostatic lipid mediators we recently discovered and characterized, have demonstrated neuroprotection in experimental stroke models but have neve...
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2024-11-01
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| author | Nicolas G. Bazan Andre Obenaus Larissa Khoutorova Pranab K. Mukherjee Bokkyoo Jun Rostyslav Semikov Ludmila Belayev |
| author_facet | Nicolas G. Bazan Andre Obenaus Larissa Khoutorova Pranab K. Mukherjee Bokkyoo Jun Rostyslav Semikov Ludmila Belayev |
| author_sort | Nicolas G. Bazan |
| collection | DOAJ |
| description | Background: In the United States, traumatic brain injury (TBI) contributes significantly to mortality and morbidity. Elovanoids (ELVs), a novel class of homeostatic lipid mediators we recently discovered and characterized, have demonstrated neuroprotection in experimental stroke models but have never been tested after TBI. Methods: A moderate fluid-percussion injury (FPI) model was used on male rats that were treated with ELVs by intravenous (IV) or intranasal (IN) delivery. In addition, using liquid chromatography-mass spectrometry (LC-MS/MS), we examined whether ELVs could be detected in brain tissue after IN delivery. Results: ELVs administered intravenously 1 h after FPI improved behavior on days 2, 3, 7, and 14 by 20, 23, 31, and 34%, respectively, and preserved hippocampal CA3 and dentate gyrus (DG) volume loss compared to the vehicle. Whole-brain tractography revealed that ELV-IV treatment increased corpus callosum white matter fibers at the injury site. In comparison to treatment with saline on days 2, 3, 7, and 14, ELVs administered intranasally at 1 h and 24 h after FPI showed improved neurological scores by 37, 45, 41, and 41%. T2-weighted imaging (T2WI) abnormalities, such as enlarged ventricles and cortical thinning, were reduced in rats treated by ELV-IN delivery compared to the vehicle. On day 3, ELVs were detected in the striatum and ipsilateral cortex of ELV-IN-treated rats. Conclusion: We have demonstrated that both ELV-IN and ELV-IV administration offer high-grade neuroprotection that can be selectively supplied to the brain. This discovery may lead to innovative therapeutic targets for secondary injury cascade prevention following TBI. |
| format | Article |
| id | doaj-art-01fc51d5ea8644eba3905677b8c18984 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-01fc51d5ea8644eba3905677b8c189842024-11-26T17:53:12ZengMDPI AGBiomedicines2227-90592024-11-011211255510.3390/biomedicines12112555Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in RatsNicolas G. Bazan0Andre Obenaus1Larissa Khoutorova2Pranab K. Mukherjee3Bokkyoo Jun4Rostyslav Semikov5Ludmila Belayev6Neuroscience Center of Excellence, School of Medicine, LSU Health New Orleans, New Orleans, LA 70112, USADivision of Biomedical Sciences, University of California Riverside, Riverside, CA 92507, USANeuroscience Center of Excellence, School of Medicine, LSU Health New Orleans, New Orleans, LA 70112, USANeuroscience Center of Excellence, School of Medicine, LSU Health New Orleans, New Orleans, LA 70112, USANeuroscience Center of Excellence, School of Medicine, LSU Health New Orleans, New Orleans, LA 70112, USANeuroscience Center of Excellence, School of Medicine, LSU Health New Orleans, New Orleans, LA 70112, USANeuroscience Center of Excellence, School of Medicine, LSU Health New Orleans, New Orleans, LA 70112, USABackground: In the United States, traumatic brain injury (TBI) contributes significantly to mortality and morbidity. Elovanoids (ELVs), a novel class of homeostatic lipid mediators we recently discovered and characterized, have demonstrated neuroprotection in experimental stroke models but have never been tested after TBI. Methods: A moderate fluid-percussion injury (FPI) model was used on male rats that were treated with ELVs by intravenous (IV) or intranasal (IN) delivery. In addition, using liquid chromatography-mass spectrometry (LC-MS/MS), we examined whether ELVs could be detected in brain tissue after IN delivery. Results: ELVs administered intravenously 1 h after FPI improved behavior on days 2, 3, 7, and 14 by 20, 23, 31, and 34%, respectively, and preserved hippocampal CA3 and dentate gyrus (DG) volume loss compared to the vehicle. Whole-brain tractography revealed that ELV-IV treatment increased corpus callosum white matter fibers at the injury site. In comparison to treatment with saline on days 2, 3, 7, and 14, ELVs administered intranasally at 1 h and 24 h after FPI showed improved neurological scores by 37, 45, 41, and 41%. T2-weighted imaging (T2WI) abnormalities, such as enlarged ventricles and cortical thinning, were reduced in rats treated by ELV-IN delivery compared to the vehicle. On day 3, ELVs were detected in the striatum and ipsilateral cortex of ELV-IN-treated rats. Conclusion: We have demonstrated that both ELV-IN and ELV-IV administration offer high-grade neuroprotection that can be selectively supplied to the brain. This discovery may lead to innovative therapeutic targets for secondary injury cascade prevention following TBI.https://www.mdpi.com/2227-9059/12/11/2555omega-3 fatty acidsT2 mappingdiffusion tensor imagingwhite matterfluid-percussion injury |
| spellingShingle | Nicolas G. Bazan Andre Obenaus Larissa Khoutorova Pranab K. Mukherjee Bokkyoo Jun Rostyslav Semikov Ludmila Belayev Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in Rats Biomedicines omega-3 fatty acids T2 mapping diffusion tensor imaging white matter fluid-percussion injury |
| title | Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in Rats |
| title_full | Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in Rats |
| title_fullStr | Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in Rats |
| title_full_unstemmed | Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in Rats |
| title_short | Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in Rats |
| title_sort | elovanoids a novel class of lipid mediators are neuroprotective in a traumatic brain injury model in rats |
| topic | omega-3 fatty acids T2 mapping diffusion tensor imaging white matter fluid-percussion injury |
| url | https://www.mdpi.com/2227-9059/12/11/2555 |
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