miR-181b promotes angiogenesis and neurological function recovery after ischemic stroke.

Promotion of new blood vessel formation is a new strategy for treating ischemic stroke. Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke. miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model, while its effect on ischemic stroke remains elusive. In this study, we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell proliferation and enhanced angiogenesis. In rat models of focal cerebral ischemia, overexpression of miR-181b reduced infarction volume, promoted angiogenesis in ischemic penumbra, and improved neurological function. We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3'-UTR of phosphatase and tensin homolog (PTEN) mRNA to induce PTEN downregulation, leading to activation of the protein kinase B (Akt) pathway, upregulated expression of vascular endothelial growth factors, down-regulated expression of endostatin, and promoted angiogenesis. Taken together, these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stroke through activating the PTEN/Akt signal pathway and promoting angiogenesis.

Edaravone Attenuates the Proinflammatory Response in Amyloid-ß-Treated Microglia by Inhibiting NLRP3 Inflammasome-Mediated IL-1ß Secretion.

BACKGROUND/AIMS: Microglial activation is an important pathological feature in the brains of patients with Alzheimer's disease (AD), and amyloid-ß (Aß) peptides play a crucial role in microglial activation. In addition, edaravone (EDA) was recently shown to suppress oxidative stress and proinflammatory cytokine production in APPswePS1dE9 (APP/PS1) mice. However, the mechanism by which EDA inhibits the Aß-induced proinflammatory response in microglia is poorly understood. METHODS: The mitochondrial membrane potential (∆ψm) was evaluated using JC-1 staining. Intracellular reactive oxygen species (ROS) and mitochondrial ROS levels were detected using CM-H2DCFDA and MitoSOXTM Red, respectively. The levels of CD11b, NLRP3, pro-caspase-1 and manganese superoxide dismutase (SOD-2) were observed by western blotting, and the levels of interleukin-1beta (IL-1ß) in culture supernatants were quantified using an ELISA kit. RESULTS: Aß induced microglia activation and mitochondrial dysfunction. In addition, mitochondrial dysfunction was associated with ROS accumulation and activation of the NLRP3 inflammasome. Importantly, Aß induced activation of the NLRP3 inflammasome, leading to caspase-1 activation and IL-1ß release in microglia. Moreover, EDA obviously attenuated the depolarization of ∆ψm, reduced mitochondria-derived ROS production and increased SOD-2 activity, resulting in the suppression of NLRP3 inflammasome-mediated IL-1ß secretion in Aß-treated microglia. CONCLUSION: EDA is a mitochondria-targeted antioxidant and exhibits anti-inflammatory effects on Aß-treated microglia.

Guillain-Barré syndrome associated with Japanese encephalitis virus infection in China.

Abstract Guillain-Barré syndrome (GBS) is preceded by an infection in about two-thirds of patients. However, the infectious organism is often not identified. GBS secondary to Japanese encephalitis virus (JEV) infection has been reported only in India. Herein, we report a case of GBS preceded by JEV infection in China. A 23-year-old male had generalized weakness, numbness in the extremities, and bilateral facial nerve paralysis. One week prior, he had a high fever with headache, and several days later, he developed facial diplegia and sensory disturbances. Physical examination revealed facial diplegia and a weak gag reflex, quadriparesis more pronounced distally, generalized hyporeflexia, and no Babinski sign. JEV IgM and hepatitis B surface antibody (HbsAb) tests were positive. Other tests for hepatitis B infection were negative. Nerve electrophysiology suggested an acute demyelinating sensorimotor polyradiculoneuropathy. His cerebrospinal fluid was clear, the leukocyte count was 5 × 10(6)/L (normal range: 0-5 × 10(6)/L), protein 0.62 g/L (normal range: 0.15-0.45 g/L), and JEV IgM was weakly positive. He was diagnosed with GBS associated with a recent JEV infection. Intravenous (IV) immunoglobulins combined with IV methylprednisone was administered for 5 days, and at the 3-month follow-up, a complete neurological recovery was noted. GBS may be associated with JEV infection. GBS exhibits a good response to intravenous immunoglobulin or plasma exchange and has a good prognosis making prompt diagnosis important.

Clinicopathological features of Churg-Strauss syndrome with severe nerve degeneration: a case report.

Churg-Strauss syndrome (CSS) is a rare autoimmune vasculitis of unknown etiology that involves small- and medium-sized blood vessels. Its onset is thought to be associated with adult-onset asthma, and vasculitis typically involves vessels in the lungs. However, due to increased blood and tissue eosinophilia, vasculitis may result in the involvement multiple systems of (neurological, skin, etc.). We report a case of CSS with manifestations that included skin purpura and severe peripheral nerve degeneration in a 56-year-old woman with a recent history of asthma. After the treatment with methylprednisolone and standard immunosuppressive therapy, her rashes resolved, there were no acute asthma attacks, and the numbness in her lower limbs improved.