Vagus nerve stimulation is a potential treatment for ischemic stroke.

Microglia are the brain's primary innate immune cells, and they are activated and affect pro-inflammatory phenotype or regulatory phenotype after ischemic stroke. Vagus nerve stimulation was shown to activate microglial phenotypic changes and exhibit neuroprotective effects in ischemia/reperfusion injury. In this study, we established rat models of ischemic stroke by occlusion of the middle cerebral artery and performed vagus nerve stimulation 30 minutes after modeling. We found that vagus nerve stimulation caused a shift from a pro-inflammatory phenotype to a regulatory phenotype in microglia in the ischemic penumbra. Vagus nerve stimulation decreased the levels of pro-inflammatory phenotype markers inducible nitric oxide synthase and tumor necrosis factor α and increased the expression of regulatory phenotype markers arginase 1 and transforming growth factor ß through activating α7 nicotinic acetylcholine receptor expression. Additionally, α7 nicotinic acetylcholine receptor blockade reduced the inhibition of Toll-like receptor 4/nuclear factor kappa-B pathway-associated proteins, including Toll-like receptor 4, myeloid differentiation factor 88, I kappa B alpha, and phosphorylated-I kappa B alpha, and also weakened the neuroprotective effects of vagus nerve stimulation in ischemic stroke. Vagus nerve stimulation inhibited Toll-like receptor 4/nuclear factor kappa-B expression through activating α7 nicotinic acetylcholine receptor and regulated microglial polarization after ischemic stroke, thereby playing a role in the treatment of ischemic stroke. Findings from this study confirm the mechanism underlying vagus nerve stimulation against ischemic stroke.

Efficacy and safety of transcutaneous auricular vagus nerve stimulation combined with conventional rehabilitation training in acute stroke patients: a randomized controlled trial conducted for 1 year involving 60 patients.

Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a novel noninvasive treat-ment for stroke that directly stimulates the peripheral auricular branch of the vagus nerve. There have been recent reports that ta-VNS combined with conventional rehabilitation training promotes the recovery of neurological function of patients with acute stroke. However, these were small-sample-sized studies on the recovery of neurological function in patients after percutaneous vagus nerve stimulation in the subacute and chronic phases after stroke. This double-blinded randomized controlled trial involved 60 acute ischemic or hemorrhagic stroke patients aged 18-80 years who received treatment in the Second Affiliated Hospital of Chongqing Medical University. The subjects were randomly assigned to receive ta-VNS or sham ta-VNS combined with conventional rehabilitation training. The follow-up results over 1 year revealed that ta-VNS combined with conventional rehabilitation training greatly improved the recovery of motor and sensory functions and emotional responses compared with sham ta-VNS combined with conventional rehabilitation training. There were no obvious side effects. These findings suggest that ta-VNS combined with conventional rehabilitation training for the treatment of acute ischemic or hemorrhagic stroke patients is safe and effective.

Sema7A, a brain immune regulator, regulates seizure activity in PTZ-kindled epileptic rats.

AIMS: Semaphorin7A (Sema7A) plays an important role in the immunoregulation of the brain. In our study, we aimed to investigate the expression patterns of Sema7A in epilepsy and further explore the roles of Sema7A in the regulation of seizure activity and the inflammatory response in PTZ-kindled epileptic rats. METHODS: First, we measured the Sema7A expression levels in patients with temporal lobe epilepsy (TLE) and in rats of a PTZ-kindled epilepsy rat model. Second, to explore the role of Sema7A in the regulation of seizure activity, we conducted epilepsy-related behavioral experiments after knockdown and overexpression of Sema7A in the rat hippocampal dentate gyrus (DG). Possible Sema7A-related brain immune regulators (eg, ERK phosphorylation, IL-6, and TNF-α) were also investigated. Additionally, the growth of mossy fibers was visualized by anterograde tracing using injections of biotinylated dextran amine (BDA) into the DG region. RESULTS: Sema7A expression was markedly upregulated in the brain tissues of TLE patients and rats of the epileptic model after PTZ kindling. After knockdown of Sema7A, seizure activity was suppressed based on the latency to the first epileptic seizure, number of seizures, and duration of seizures. Conversely, overexpression of Sema7A promoted seizures. Overexpression of Sema7A increased the expression levels of the inflammatory cytokines, IL-6 and TNF-α, ERK phosphorylation, and growth of mossy fibers in PTZ-kindled epileptic rats. CONCLUSION: Sema7A is upregulated in the epileptic brain and plays a potential role in the regulation of seizure activity in PTZ-kindled epileptic rats, which may be related to neuroinflammation. Sema7A promotes the inflammatory cytokines TNF-α and IL-6 as well as the growth of mossy fibers through the ERK pathway, suggesting that Sema7A may promote seizures by increasing neuroinflammation and activating pathological neural circuits. Sema7A plays a critical role in epilepsy and could be a potential therapeutic target for this neurological disorder.

[Effects of electroacupuncture on expression of angiogenic growth factors and antiangiogenic growth factors in the brain tissue of the rat after focal cerebral ischemia reperfusion].

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in improving ischemic stroke. METHODS: A Wistar rat model of focal cerebral ischemia reperfusion was made by filament occlusion. The rats were randomly divided into a normal group, a model group, an EA group. EA was given at bilateral "Hegu" (LI 4) in the EA group. Vascular endothelial growth factor (VEGF) mRNA was detected with in situ hybridization and expression of angiogenin-1 (Ang-1) and endostatin proteins with immunohistochemical method. RESULTS: The expressions of angiogenic growth factors including VEGF and Ang-1 in the EA group were significantly increased, while the expressions of endostatin was significantly decreased as compared with those in the model group (both P<0.05). CONCLUSION: EA improving ischemic stroke is carried out possibly through up-regulating the expression of angiogenic growth factors and down-regulating the expression of antiangiogenic growth factors.