Background: Intracerebral hemorrhage (ICH) causes severe sensorimotor dysfunction and cognitive decline which are aggravated by secondary brain injury, yet there are no effective management to alleviate these outcomes. Pyroptosis is strongly related to neuroinflammation, which plays a crucial role in the pathophysiological processes of secondary brain injury after ICH. OXT (oxytocin), as a pleiotropic neuropeptide, has multiple functions including anti-inflammation and antioxidation. This study aims to investigate the role of OXT in improving ICH outcomes and the underlying mechanisms. Methods: C57BL/6 mice were used to establish the ICH model by autologous blood injection. OXT was administered intranasally (0.2 μg/g) after ICH. Combing behavioral tests, Western blot, immunofluorescence staining, electron microscopy, and pharmacological approaches, we evaluated the effect of intranasal OXT application on neurological outcomes after ICH and explored the underlying mechanism. Results: Endogenous OXT level was decreased, whereas OXTR (oxytocin receptor) expression was increased after ICH. OXT treatment improved the short-term and long-term neurological functions and alleviated neuronal pyroptosis and neuroinflammation. In addition, OXT reduced excessive mitochondrial fission and mitochondrial-derived oxidative stress 3 days after ICH. OXT decreased the expression of pyroptotic and proinflammatory factors including NLRP3 (NOD-like receptor protein 3), ASC (apoptosis-associated speck-like protein containing a CARD), GSDMD (gasdermin D), caspase-1, IL (interleukin)-1β, and IL-18 and increased the expression of p-PKA (phospho-protein kinase A) and p-DRP1 (S637; DRP1 [dynamin-related protein 1] phosphorylation at Ser637). OXT-induced neuroprotective effects were blocked by either OXTR inhibitor or PKA inhibitor. Conclusions: Intranasal application of OXT can ameliorate neurological deficits and alleviate neural pyroptosis, inflammation, and excessive mitochondrial fission via OXTR/p-PKA/DRP1 signaling pathway after ICH. Thus, OXT administration may be a potential therapeutic strategy to improve the prognosis of ICH.

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Background Sepsis-associated encephalopathy (SAE) is a common and severe complication of sepsis. While several studies have reported the proteomic alteration in plasma, urine, heart, etc. of sepsis, few research focused on the brain tissue. This study aims at discovering the differentially abundant proteins in the brains of septic rats to identify biomarkers of SAE. Methods The Prague-Dawley rats were randomly divided into sepsis (n = 6) or sham (n = 6) groups, and then the whole brain tissue was dissected at 24 h after surgery for further protein identification by Quantitative iTRAQ LC-MS/MS Proteomics. Ingenuity pathway analysis, Gene ontology knowledgebase, and STRING database are used to explore the biological significance of proteins with altered concentration. Results Among the total of 3163 proteins identified in the brain tissue, 57 were increased while 38 were decreased in the sepsis group compared to the sham group. Bioinformatic analyses suggest that the differentially abundant proteins are highly related to cellular microtubule metabolism, energy production, nucleic acid metabolism, neurological disease, etc. Additionally, acute phase response signaling was possibly activated and PI3K/AKT signaling was suppressed during sepsis. An interaction network established by IPA revealed that Akt1, Gc-globulin, and ApoA1 were the core proteins. The increase of Gc-globulin and the decrease of Akt1 and ApoA1 were confirmed by Western blot. Conclusion Based on the multifunction of these proteins in several brain diseases, we first propose that Gc-globulin, ApoA1, PI3K/AKT pathway, and acute phase response proteins (hemopexin and cluster of alpha-2-macroglobulin) could be potential candidates for the diagnosis and treatment of SAE. These results may provide new insights into the pathologic mechanism of SAE, yet further research is required to explore the functional implications and clinical applications of the differentially abundant proteins in the brains of sepsis group.