SCG2 mediates blood-brain barrier dysfunction and schizophrenia-like behaviors after traumatic brain injury.
Chao LinPengzhang ZhaoGuangchi SunNing LiuJing JiPublished in: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2024)
Traumatic brain injury (TBI), which is characterized by acute neurological dysfunction, is also one of the most widely recognized environmental risk factors for various neurological and psychiatric disorders. However, the role of TBI in neurological perturbation and the mechanisms underlying these disorders remain unknown. We evaluated transcriptional changes in cells of the frontal cortex after TBI by exploiting single-cell RNA sequencing (scRNA-Seq). We adopted the gene expression omnibus and scRNA-Seq to identify the mediation by secretogranin II (SCG2) of TBI-induced schizophrenia. Astrocytes are a principal source of SCG2 in the frontal cortex after TBI. Our analysis indicated that SCG2-triggered disruption of the blood-brain barrier (BBB) via the CypA-MMP-9 signaling pathway. Furthermore, astrocytic SCG2 knockout in the frontal cortex reduced BBB damage, mitigated inflammation, and inhibited schizophrenia after TBI. In conclusion, we identified the SCG2-CypA-MMP-9 signaling pathway in reactive astrocytes as a key switch in the protection of the BBB and provided a novel therapeutic avenue for treating psychiatric disorders after TBI.
Keyphrases
- extracorporeal membrane oxygenation
- traumatic brain injury
- blood brain barrier
- single cell
- acute respiratory distress syndrome
- functional connectivity
- severe traumatic brain injury
- gene expression
- signaling pathway
- cerebral ischemia
- bipolar disorder
- oxidative stress
- rna seq
- induced apoptosis
- mild traumatic brain injury
- working memory
- pi k akt
- liver failure
- cell cycle arrest
- epithelial mesenchymal transition
- high throughput
- drug induced
- cell proliferation
- intensive care unit
- transcription factor
- endothelial cells
- climate change
- depressive symptoms
- risk assessment
- brain injury
- cell migration
- heat stress
- social support