Fluoxetine reduces organ injury and improves motor function after traumatic brain injury in mice

Weaver, Jessica L.; Eliceiri, Brian P.; Costantini, Todd W.

doi:10.1097/ta.0000000000003646

Cited by 3 publications

(4 citation statements)

References 34 publications

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“…Clustering analysis showed that molecules involved in inflammatory responses, metabolic disorders, tissue repair, and bacterial defense were significantly dysregulated. These findings suggested similarities in physiopathological processes between the intestines and other organs in response to traumatic injury [ 27 , 28 ]. The landscape of protein reprogramming can reveal the molecular mechanisms of TCI progression and provide data support for subsequent research.…”

Section: Discussionmentioning

confidence: 99%

Melatonin supplementation protects against traumatic colon injury by regulating SERPINA3N protein expression

Cao,

Gao,

Zhang

et al. 2023

iMeta

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Traumatic colon injury (TCI) is a typical injury with high mortality. Prolongation of the intervention time window is a potentially useful approach to improving the outcomes of TCI casualties. This study aimed to identify the pathological mechanisms of TCI and to develop effective strategies to extend the survival time. A semicircular incision was made to prepare a TCI model using C57BL/6 mice. An overview of microbiota dysregulation was achieved by metagenome sequencing. Protein expression reprogramming in the intestinal epithelium was investigated using proteomics profiling. The mice that were subjected to TCI died within a short period of time when not treated. Gut symbiosis showed abrupt turbulence, and specific pathogenic bacteria rapidly proliferated. The protein expression in the intestinal epithelium was also reprogrammed. Among the differentially expressed proteins, SERPINA3N was overexpressed after TCI modeling. Deletion of Serpina3n prolonged the posttraumatic survival time of mice with TCI by improving gut homeostasis in vivo. To promote the translational application of this research, the effects of melatonin (MLT), an oral inhibitor of the SERPINA3N protein, were further investigated. MLT effectively downregulated SERPINA3N expression and mitigated TCI‐induced death by suppressing the NF‐κB signaling pathway. Our findings prove that preventive administration of MLT serves as an effective regimen to prolong the posttraumatic survival time by restoring gut homeostasis perturbed by TCI. It may become a novel strategy for improving the prognosis of patients suffering from TCI.

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Section: Discussionmentioning

confidence: 99%

Melatonin supplementation protects against traumatic colon injury by regulating SERPINA3N protein expression

Cao,

Gao,

Zhang

et al. 2023

iMeta

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“…cognitive impairment was demonstrated to be mediated by 5-HT in the hippocampus in a tryptophan depletion clinical trial [112]. Considering such evidence, the role of serotonin in treating or altering the outcomes of TBI is under study [66,116,117]. Data about the efficacy of selective serotonin reuptake inhibitors (SSRIs) in treating TBI patients comes from preclinical models.…”

Section: Serotoninmentioning

confidence: 99%

“…Created with www. Biore nder placebo [117]. Craine et al studied the role of chronic IP milnacipran treatment (30 mg/kg/day), a serotonin-norepinephrine reuptake inhibitor (SNRI), in improving cognition in male rats subjected to frontal lobe injury.…”

Section: Serotoninmentioning

confidence: 99%

Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

El Baassiri,

Raouf,

Badin

et al. 2024

J Neuroinflammation

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Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with a high risk of psychiatric and neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack of effective treatments underscore the urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as a crucial bidirectional pathway connecting the brain and the gastrointestinal (GI) system through an intricate network of neuronal, hormonal, and immunological pathways. Four main pathways are primarily implicated in this crosstalk, including the systemic immune system, autonomic and enteric nervous systems, neuroendocrine system, and microbiome. TBI induces profound changes in the gut, initiating an unrestrained vicious cycle that exacerbates brain injury through the brain-gut axis. Alterations in the gut include mucosal damage associated with the malabsorption of nutrients/electrolytes, disintegration of the intestinal barrier, increased infiltration of systemic immune cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction and disruption in the enteric nervous system (ENS) and autonomic nervous system (ANS). Collectively, these changes further contribute to brain neuroinflammation and neurodegeneration via the gut-brain axis. In this review article, we elucidate the roles of various anti-inflammatory pharmacotherapies capable of attenuating the dysregulated inflammatory response along the brain-gut axis in TBI. These agents include hormones such as serotonin, ghrelin, and progesterone, ANS regulators such as beta-blockers, lipid-lowering drugs like statins, and intestinal flora modulators such as probiotics and antibiotics. They attenuate neuroinflammation by targeting distinct inflammatory pathways in both the brain and the gut post-TBI. These therapeutic agents exhibit promising potential in mitigating inflammation along the brain-gut axis and enhancing neurocognitive outcomes for TBI patients.

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“…A pilot study suggested that the diversity of the microbial ecosystem in brain tumour patients was less than the healthy controls [ 14 ], while caecal content transfer experiments in mice revealed that cancer-associated alteration in caecal metabolites was involved in late-stage glioma progression [ 15 ]. In addition, there is clear evidence that TBI can cause gut microbiota dysbiosis [ 16 ], while disruption of the gut barrier and depletion of the gut microbiota are associated with neurologic outcomes following TBI [ 17 ]. With a growing understanding of BGA, people have a strong interest in studying the influences of BGA in neural recovery and neurorehabilitation after TBI.…”

Section: Introductionmentioning

confidence: 99%

The Potential Role of m6A in the Regulation of TBI-Induced BGA Dysfunction

et al. 2022

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The brain–gut axis (BGA) is an important bidirectional communication pathway for the development, progress and interaction of many diseases between the brain and gut, but the mechanisms remain unclear, especially the post-transcriptional regulation of BGA after traumatic brain injury (TBI). RNA methylation is one of the most important modifications in post-transcriptional regulation. N6-methyladenosine (m6A), as the most abundant post-transcriptional modification of mRNA in eukaryotes, has recently been identified and characterized in both the brain and gut. The purpose of this review is to describe the pathophysiological changes in BGA after TBI, and then investigate the post-transcriptional bidirectional regulation mechanisms of TBI-induced BGA dysfunction. Here, we mainly focus on the characteristics of m6A RNA methylation in the post-TBI BGA, highlight the possible regulatory mechanisms of m6A modification in TBI-induced BGA dysfunction, and finally discuss the outcome of considering m6A as a therapeutic target to improve the recovery of the brain and gut dysfunction caused by TBI.

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Fluoxetine reduces organ injury and improves motor function after traumatic brain injury in mice

Abstract: Fluoxetine reduces organ injury in a mouse model of traumatic brain injury

Cited by 3 publications

References 34 publications

Melatonin supplementation protects against traumatic colon injury by regulating SERPINA3N protein expression

Melatonin supplementation protects against traumatic colon injury by regulating SERPINA3N protein expression

Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

The Potential Role of m6A in the Regulation of TBI-Induced BGA Dysfunction

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