1.Effect of Huazhuo Jiedu Huoxue Tongluo Prescription on Brain-gut Axis of Rats with Cerebral Ischemia-reperfusion Injury Based on 16S rRNA Sequencing of Intestinal Flora
Rui-qing HUO ; Min-han ZHAO ; Fang-zhao LI ; Yu-fan HAN ; Kuo SUN ; Jun-biao TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(1):121-130
ObjectiveTo study the effect of Huazhuo Jiedu Huoxue Tongluo (HJHT) prescription on the intestinal flora in rats with cerebral ischemia-reperfusion injury, and to explore the mechanism of Chinese medicinal prescription regulating intestinal flora to restore the balance of brain-gut axis. MethodFifty male SPF SD rats were randomly assigned into sham group, model group, high-dose HJHT group (25.0 g·kg-1), medium-dose HJHT group (12.5 g·kg-1), and low-dose HJHT group (6.25 g·kg-1), with 10 rats in each group. The rat model of permanent middle cerebral artery infarction was established according to Longa method and previous research experience, and reperfusion was performed 2 h after ischemia. The recovery of neurological function deficit and the percentage of cerebral infarction area were detected 72 h after administration. Real-time PCR was performed to detect the mRNA levels of Occludin and zonula occludens-1 (ZO-1) in rat colon. Hematoxylin-eosin (HE) staining was conducted to reveal the intestinal damage. The feces of 6 rats in each group were collected for 16S rRNA sequencing. The expression of Treg and Th17 in intestinal tissue, peripheral blood, and brain tissue were detected. ResultCompared with the sham group, the model group showed obvious neurological deficit (P<0.05) and large cerebral infarction area (P<0.05). High-dose and medium-doses HJHT alleviated the symptoms of neurological impairment (P<0.05) and reduce the cerebral infarction area (P<0.05) compared with the model group. Compared with the sham group, the model group showed destroyed structure of colonic mucosa and incomplete epithelial cells and goblet cells, while high-dose and medium-doses HJHT alleviated such changes. The mRNA levels of Occludin and ZO-1 in the model group were lower than those in the sham group (P<0.05),and the high-dose HJHT groups were higher than the model group (P<0.05). The intestinal flora structure was significantly different between the model group and the sham group while similar between the high-dose HJHT group and sham group. Compared with the sham group, the model group showed down-regulated expression of Treg and up-regulated expression of Th17 in the intestinal tissue, peripheral blood, and brain tissue, and high-dose and medium-dose HJHT alleviated the changes in the expression of Treg and Th17 in the model group (P<0.05). ConclusionHuazhuo Jiedu Huoxue Tongluo prescription may improve the permeability of intestinal wall by adjusting the abundance and diversity of intestinal microorganisms to reduce the migration of intestinal Th17 cells toward the ischemic lateral brain tissue, mitigate the inflammatory response, and thus alleviate the cerebral ischemia-reperfusion injury in rats.
2.Transcranial Direct Current Stimulation in ADHD: A Systematic Review of Efficacy, Safety, and Protocol-induced Electrical Field Modeling Results.
Mohammad Ali SALEHINEJAD ; Vahid NEJATI ; Mohsen MOSAYEBI-SAMANI ; Ali MOHAMMADI ; Miles WISCHNEWSKI ; Min-Fang KUO ; Alessio AVENANTI ; Carmelo M VICARIO ; Michael A NITSCHE
Neuroscience Bulletin 2020;36(10):1191-1212
Transcranial direct current stimulation (tDCS) is a promising method for altering cortical excitability with clinical implications. It has been increasingly used in neurodevelopmental disorders, especially attention-deficit hyperactivity disorder (ADHD), but its efficacy (based on effect size calculations), safety, and stimulation parameters have not been systematically examined. In this systematic review, we aimed to (1) explore the effectiveness of tDCS on the clinical symptoms and neuropsychological deficits of ADHD patients, (2) evaluate the safety of tDCS application, especially in children with ADHD, (3) model the electrical field intensity in the target regions based on the commonly-applied and effective versus less-effective protocols, and (4) discuss and propose advanced tDCS parameters. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach, a literature search identified 14 empirical experiments investigating tDCS effects in ADHD. Partial improving effects of tDCS on cognitive deficits (response inhibition, working memory, attention, and cognitive flexibility) or clinical symptoms (e.g., impulsivity and inattention) are reported in 10 studies. No serious adverse effects are reported in 747 sessions of tDCS. The left and right dorsolateral prefrontal cortex are the regions most often targeted, and anodal tDCS the protocol most often applied. An intensity of 2 mA induced stronger electrical fields than 1 mA in adults with ADHD and was associated with significant behavioral changes. In ADHD children, however, the electrical field induced by 1 mA, which is likely larger than the electrical field induced by 1 mA in adults due to the smaller head size of children, was sufficient to result in significant behavioral change. Overall, tDCS seems to be a promising method for improving ADHD deficits. However, the clinical utility of tDCS in ADHD cannot yet be concluded and requires further systematic investigation in larger sample sizes. Cortical regions involved in ADHD pathophysiology, stimulation parameters (e.g. intensity, duration, polarity, and electrode size), and types of symptom/deficit are potential determinants of tDCS efficacy in ADHD. Developmental aspects of tDCS in childhood ADHD should be considered as well.