URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia–Ischemia and Enhances Neurogenesis in Females
The need for new and effective treatments for neonates suffering from hypoxia–ischemia is urgent, as the only implemented therapy in clinics is therapeutic hypothermia, only effective in 50% of cases. Cannabinoids may modulate neuronal development and brain plasticity, but further investigation is n...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1607 |
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| author | Gorane Beldarrain Marc Chillida Enrique Hilario Borja Herrero de la Parte Antonia Álvarez Daniel Alonso-Alconada |
| author_facet | Gorane Beldarrain Marc Chillida Enrique Hilario Borja Herrero de la Parte Antonia Álvarez Daniel Alonso-Alconada |
| author_sort | Gorane Beldarrain |
| collection | DOAJ |
| description | The need for new and effective treatments for neonates suffering from hypoxia–ischemia is urgent, as the only implemented therapy in clinics is therapeutic hypothermia, only effective in 50% of cases. Cannabinoids may modulate neuronal development and brain plasticity, but further investigation is needed to better describe their implication as a neurorestorative therapy after neonatal HI. The cannabinoid URB447, a CB1 antagonist/CB2 agonist, has previously been shown to reduce brain injury after HI, but it is not clear whether sex may affect its neuroprotective and/or neurorestorative effect. Here, URB447 strongly reduced brain infarct, improved neuropathological score, and augmented proliferative capacity and neurogenic response in the damaged hemisphere. When analyzing these effects by sex, URB447 ameliorated brain damage in both males and females, and enhanced cell proliferation and the number of neuroblasts only in females, thus suggesting a neuroprotective effect in males and a double neuroprotective/neurorestorative effect in females. |
| first_indexed | 2024-03-08T03:55:57Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:55:57Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c5b2c996f8464a00a7c3b1747b87585b2024-02-09T15:13:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01253160710.3390/ijms25031607URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia–Ischemia and Enhances Neurogenesis in FemalesGorane Beldarrain0Marc Chillida1Enrique Hilario2Borja Herrero de la Parte3Antonia Álvarez4Daniel Alonso-Alconada5Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainThe need for new and effective treatments for neonates suffering from hypoxia–ischemia is urgent, as the only implemented therapy in clinics is therapeutic hypothermia, only effective in 50% of cases. Cannabinoids may modulate neuronal development and brain plasticity, but further investigation is needed to better describe their implication as a neurorestorative therapy after neonatal HI. The cannabinoid URB447, a CB1 antagonist/CB2 agonist, has previously been shown to reduce brain injury after HI, but it is not clear whether sex may affect its neuroprotective and/or neurorestorative effect. Here, URB447 strongly reduced brain infarct, improved neuropathological score, and augmented proliferative capacity and neurogenic response in the damaged hemisphere. When analyzing these effects by sex, URB447 ameliorated brain damage in both males and females, and enhanced cell proliferation and the number of neuroblasts only in females, thus suggesting a neuroprotective effect in males and a double neuroprotective/neurorestorative effect in females.https://www.mdpi.com/1422-0067/25/3/1607neonatal hypoxia–ischemiaendocannabinoid systemneuroprotectionneurogenesis |
| spellingShingle | Gorane Beldarrain Marc Chillida Enrique Hilario Borja Herrero de la Parte Antonia Álvarez Daniel Alonso-Alconada URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia–Ischemia and Enhances Neurogenesis in Females International Journal of Molecular Sciences neonatal hypoxia–ischemia endocannabinoid system neuroprotection neurogenesis |
| title | URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia–Ischemia and Enhances Neurogenesis in Females |
| title_full | URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia–Ischemia and Enhances Neurogenesis in Females |
| title_fullStr | URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia–Ischemia and Enhances Neurogenesis in Females |
| title_full_unstemmed | URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia–Ischemia and Enhances Neurogenesis in Females |
| title_short | URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia–Ischemia and Enhances Neurogenesis in Females |
| title_sort | urb447 is neuroprotective in both male and female rats after neonatal hypoxia ischemia and enhances neurogenesis in females |
| topic | neonatal hypoxia–ischemia endocannabinoid system neuroprotection neurogenesis |
| url | https://www.mdpi.com/1422-0067/25/3/1607 |
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