A Kv1.3 channel-specific blocker alleviates neurological impairment through inhibiting T-cell activation in experimental autoimmune encephalomyelitis.

AIM: Multiple sclerosis (MS) is a neurological autoimmune disorder characterized by mistaken attacks of inflammatory cells against the central nervous system (CNS), resulting in demyelination and axonal damage. Kv1.3 channel blockers can inhibit T-cell activation and have been designed for MS therapy. However, little is known about the effects of Kv1.3 blockers on protecting myelin sheaths/axons in MS. This study aimed at investigating the neuroprotection efficacy of a selective Kv1.3 channel blocker ImKTx88 (ImK) in MS animal model. METHODS: Experimental autoimmune encephalomyelitis (EAE) rat model was established. The neuroprotective effect of ImK was assessed by immunohistochemistry and transmission electron microscopy (TEM). In addition, the antiinflammatory effect of ImK by suppressing T-cell activation was assessed by flow cytometry and ELISA in vitro. RESULTS: Our results demonstrated that ImK administration ameliorated EAE clinical severity. Moreover, ImK increased oligodendrocytes survival, preserved axons, and myelin integrity and reduced the infiltration of activated T cells into the CNS. This protective effect of the peptide may be related to its suppression of autoantigen-specific T-cell activation via calcium influx inhibition. CONCLUSION: ImK prevents neurological damage by suppressing T-cell activation, suggesting the applicability of this peptide in MS therapy.

[Anti-hepatofibrosis effect of fasudil hydrochloride on Schistosoma japonicum-infected mice].

OBJECTIVE: To investigate the anti-fibrotic effect of fasudil hydrochloride on Schistosoma japonicum-infected mice, and the effect of fasudil hydrochloride on hepatic stellate cells (HSCs). METHODS: Thirty female BALB/c mice were randomly divided into 3 groups viz, normal control group (NC group), infection group, and experiment group. Mice in both infection group and experiment group were infected with (14:2) cercariae of S japonicum. At 6 weeks post infection, mice in experiment group were intraperitoneally injected with fasudil hydrochloride (10 mg/kg) twice a day for 7 d, while mice in NC group and infection group received the same volume of physiological saline. All mice were sacrificed 12 h after the last injection. Livers from NC group and infection group were used to prepare tissue sections for hematoxylin and eosin (HE) staining, or sirius red staining, and observed under light microscope. Livers from all three groups were used to detect content of hydroxyproline (Hyp) and the mRNA expressions of alpha-smooth muscle actin (alpha-SMA), type I collagen alpha1 (Col1alpha1) and epithelial cell transforming sequence 2 (Ect2). HSCs from mice in all three groups were isolated to detect the mRNA levels of alpha-SMA, Col1alpha1, and Ect2, respectively. RESULTS: Pathological sections showed that in livers from mice in infection group, inflammatory cells infiltrated and collagenous fibre proliferated around portal areas and egg granulomas. The content of Hyp in liver from mice of NC group, infection group, and experiment group was (279.7 +/- 21.2) microg, (528.0 +/- 15.0) microg, and (355.4 +/- 22.6) microg, respectively. The content of Hyp in livers from mice of experiment group was significantly reduced compared to infection group (P < 0.01). The mRNA expression of alpha-SMA, Col1alpha1 and Ect2 in livers and HSCs from mice in experiment group were significantly down-regulated compared to infection group (P < 0.05). CONCLUSION: Fasudil hydrochloride can depress hepatofibrosis in Schistosoma japonicum-infected mice.