Synaptamide Ameliorates Hippocampal Neurodegeneration and Glial Activation in Mice with Traumatic Brain Injury

Traumatic brain injury (TBI) is a major concern for public health worldwide, affecting 55 million people and being the leading cause of death and disability. To improve the outcomes and effectiveness of treatment for these patients, we conducted a study on the potential therapeutic use of N-docosahexaenoylethanolamine (synaptamide) in mice using the weight-drop injury (WDI) TBI model. Our study focused on exploring synaptamide's effects on neurodegeneration processes and changes in neuronal and glial plasticity. Our findings showed that synaptamide could prevent TBI-associated working memory decline and neurodegenerative changes in the hippocampus, and it could alleviate decreased adult hippocampal neurogenesis. Furthermore, synaptamide regulated the production of astro- and microglial markers during TBI, promoting the anti-inflammatory transformation of the microglial phenotype. Additional effects of synaptamide in TBI include stimulating antioxidant and antiapoptotic defense, leading to the downregulation of the Bad pro-apoptotic marker. Our data suggest that synaptamide has promising potential as a therapeutic agent to prevent the long-term neurodegenerative consequences of TBI and improve the quality of life.

Automated summary

Traumatic brain injury (TBI) is a global public health concern, affecting 55 million people and being the leading cause of death and disability. Our study investigated the potential therapeutic use of synaptamide in a mouse model of TBI and found that it could prevent working memory decline, neurodegenerative changes, and decreased neurogenesis in the hippocampus. Synaptamide also regulated the production of astro- and microglial markers, promoting an anti-inflammatory microglial phenotype. Additionally, synaptamide stimulated antioxidant and antiapoptotic defense, leading to the downregulation of the pro-apoptotic marker Bad. These findings suggest that synaptamide has promising potential as a therapeutic agent for preventing long-term neurodegenerative consequences of TBI and improving quality of life.