Qishen Yiqi Dropping Pill facilitates post-stroke recovery of motion and memory loss by modulating ICAM-1-mediated neuroinflammation.

BACKGROUND: Promotion of functional recovery in patients is the primary goal of stroke management. However, its achievement is low due to the lack of full understanding of the complex pathological process of stroke and therefore limited therapeutic strategies. Qishen Yiqi Dropping Pill (QSYQ) is a component-based Chinese medicine that has been widely used in clinical treatment of ischemic cardiovascular diseases. Our previous studies indicated that QSYQ were protective for acute ischemic stroke in animal models and this study aimed to investigate the effect of QSYQ on brain function during stroke recovery. METHODS: The therapeutic effects of QSYQ were evaluated by neurological deficit score, dark avoidance test, gait analysis, Morris water maze and brain tissue atrophy volume in a rat model of middle cerebral artery occlusion (MCAO) with ischemia for 60 min. The underlying mechanisms of QSYQ accelerating the functional recovery of MCAO rats was then revealed using proteomic sequencing and validated by immunohistochemistry, qRT-PCR and ELISA assays. The active components in QSYQ were elucidated by molecular docking and verified biochemically in vitro. RESULTS: QSYQ treatment for 28 days significantly improved the neurological function, gait, spontaneous activity, spatial memory, and reduced brain atrophy in MCAO rats. Proteomic analysis of ischemic brain region and the following bioinformatics studies showed that QSYQ intervention markedly modulated neuroinflammatory responses post stroke, in which ICAM-1 played a dominant role. In particular, QSYQ reversed high cerebral expression of ICAM-1 in MCAO rats and decreased the content of TNF-α, IL-6 and IL1ß in brain tissue and serum. In vitro, it was found that the active component rosmarinic acid in QSYQ evidently inhibit the expression of ICAM-1 caused by oxygen glucose deprivation/reoxygenation injury via using immunofluorescence staining. CONCLUSION: QSYQ effectively accelerates the recovery of motor impairment and memory loss in rats after stroke via downregulation of ICAM-1-mediated neuroinflammation, and rosmarinic acid is one of its main active components.

[Clinical and molecular genetic analysis of a family with normokalemic periodic paralysis].

OBJECTIVE: Periodic paralysis (PP) is one type of skeletal muscle channelopathies characterized by episodic attacks of weakness. It is usually classified into hyperkalemic periodic paralysis (HyperPP), hypokalemic periodic paralysis (HypoPP) and normokalemic periodic paralysis (NormoPP) based on the blood potassium levels. HypoPP is the most common type of these three and NormoPP is the rarest one. The aim of this study was to explore the clinical and genetic features of a Chinese family with normokalemic periodic paralysis (NormoKPP). METHOD: Clinical features of all patients in the family with NormoKPP were analyzed. Genomic DNA was extracted from peripheral blood leukocytes and amplified with PCR. We screened all 24 exons of SCN4A gene and then sequence analysis was performed in those who showed heteroduplex as compared with unaffected controls. RESULT: (1) Fifteen members of the family were clinically diagnosed NormoKPP, and their common features are: onset within infacy, episodic attacks of weakness, the blood potassium levels were within normal ranges, high sodium diet or large dosage of normal saline could attenuate the symptom. One muscle biopsy was performed and examination of light and electronic microscopy showed occasionally degenerating myofibers. (2) Gene of 12 patients were screened and confirmed mutations of SCN4A genes--c. 2111 T > C/p. Thr704Met. CONCLUSION: The study further defined the clinical features of patients with NormoKPP, and molecular genetic analysis found SCN4A gene c. 2111 T > C/p. Thr704Met point mutation contributed to the disease. In line with the autosomal dominant inheritance laws, this family can be diagnosed with periodic paralysis, and be provided with genetic counseling. And the study may also help the clinical diagnosis, guide treatment and genetic counseling of this rare disease in China.