Neuroprotective mechanisms of CB2 cannabinoid receptors and PPAR-α in hypoxia/ischemia-induced brain damage
In this thesis, we have developed a hypoxia-ischemia (HI) model in adult mice to study the neuroprotective mechanisms of CB2 cannabinoid receptors (CB2R), and the potential therapeutic effects of the new PPAR-α agonist, octadecylpropyl sulfamide (SUL). First, we determined the behavioural and cognit...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/664430 |
| Acceso en línea: | http://hdl.handle.net/10803/664430 |
| Access Level: | acceso abierto |
| Palabra clave: | Hypoxia-ischemia Neuroinflammation CB2 receptors Memory deficits Neurodegeneration Hipoxia-isquemia Neuroinflamación Receptores CB2 Déficits de memoria Neurodegeneración 616.8 |
| Sumario: | In this thesis, we have developed a hypoxia-ischemia (HI) model in adult mice to study the neuroprotective mechanisms of CB2 cannabinoid receptors (CB2R), and the potential therapeutic effects of the new PPAR-α agonist, octadecylpropyl sulfamide (SUL). First, we determined the behavioural and cognitive alterations induced by HI in CB2R knockout (KO) mice and wild-type (WT) littermates, as well as, the cellular and molecular alterations associated with brain injury. Second, we evaluated the effects of SUL on the behavioural and cognitive alterations induced by HI in C57BL/6J adult mice, and studied the associated neurodegeneration processes, and changes in gene expression related to the neuroinflammation/endocannabinoid signalling systems in the brain. Our findings suggest that CB2R confer neuroprotection following HI insult through the modulation of the microglial pro-inflammatory factors HIF-1α and TIM-3 acting as a defensive mechanism to reduce subsequent behavioural alterations. In addition, we demonstrated that the potent and stable PPAR-α agonist, SUL administered immediately after HI, exhibits neuroprotective properties, and could be a potential pharmacological treatment to prevent the impact of hypoxia on brain function in adults. |
|---|