Midbrain FA initiates neuroinflammation and depression onset in both acute and chronic LPS-induced depressive model mice.

Both exogenous gaseous and liquid forms of formaldehyde (FA) can induce depressive-like behaviors in both animals and humans. Stress and neuronal excitation can elicit brain FA generation. However, whether endogenous FA participates in depression occurrence remains largely unknown. In this study, we report that midbrain FA derived from lipopolysaccharide (LPS) is a direct trigger of depression. Using an acute depressive model in mice, we found that one-week intraperitoneal injection (i.p.) of LPS activated semicarbazide-sensitive amine oxidase (SSAO) leading to FA production from the midbrain vascular endothelium. In both in vitro and in vivo experiments, FA stimulated the production of cytokines such as IL-1ß, IL-6, and TNF-α. Strikingly, one-week microinfusion of FA as well as LPS into the midbrain dorsal raphe nucleus (DRN, a 5-HT-nergic nucleus) induced depressive-like behaviors and concurrent neuroinflammation. Conversely, NaHSO3 (a FA scavenger), improved depressive symptoms associated with a reduction in the levels of midbrain FA and cytokines. Moreover, the chronic depressive model of mice injected with four-week i.p. LPS exhibited a marked elevation in the levels of midbrain LPS accompanied by a substantial increase in the levels of FA and cytokines. Notably, four-week i.p. injection of FA as well as LPS elicited cytokine storm in the midbrain and disrupted the blood-brain barrier (BBB) by activating microglia and reducing the expression of claudin 5 (CLDN5, a protein with tight junctions in the BBB). However, the administration of 30 nm nano-packed coenzyme-Q10 (Q10, an endogenous FA scavenger), phototherapy (PT) utilizing 630-nm red light to degrade FA, and the combination of PT and Q10, reduced FA accumulation and neuroinflammation in the midbrain. Moreover, the combined therapy exhibited superior therapeutic efficacy in attenuating depressive symptoms compared to individual treatments. Thus, LPS-derived FA directly initiates depression onset, thereby suggesting that scavenging FA represents a promising strategy for depression treatment.

[Assessment of hemodynamics in patients with Budd-Chiari syndrome after interventional treatment].

OBJECTIVE: To study the changes in morphology of liver and spleen and hemodynamics of the patients with Budd-Chiari syndrome (BCS) after interventional treatment. METHODS: The dimensions of liver and spleen were detected by routine ultrasonography in 30 normal control subjects and 256 BCS patients before and after inventional therapy. Color duplex sonography was employed to measure the hemodynamic changes. RESULTS: Compared with the control group, BCS patients before interventional therapy showed obvious liver and spleen enlargements (P<0.005), specially the caudate lobe of the liver (P<0.001), which were significantly reduced 7 days after interventional treatment (P<0.005), but the spleen was still larger than that of the control group (P<0.005) even till 6 months after the therapy. Color Doppler flow imaging (CDFI) revealed local high-speed blood flow in patients with stenosis of the inferior vena cave (IVC), but color flow was not detected in patients with IVC obstruction, who had hepatic vein dilation (P<0.005) with slowed blood flow and collateral formation of in the liver, as well as decreased velocity of blood flow in the portal vein. After interventional treatment, the diameter of the involved IVC increased with blood flow restoration and the size and shape of the stent were detected clearly. The velocity of blood flow was increased in both the hepatic and portal veins (P<0.005). CONCLUSION: Interventional therapy can relieve obstruction of blood flow in the liver and improve the hemodynamics of patients with BCS.