Development of Neural Stem Cell-Based Therapies for Parkinson’s Disease

Neural stem cell (NSC)-based therapies, such as cell transplantation, are an emerging strategy for restoring neuronal function in Parkinson’s disease (PD), which is characterized by a profound and selective loss of nigrostriatal dopaminergic (DA) neurons. Advanced researches on the microenvironment of grafted cells will promote clinical applications of NSCs for neurological disorders. A novel cell culture model of the neurovascular network was therefore devised to investigate autocrine, paracrine, and juxtacrine signaling in the neurovascular unit generated by NSCs and vascular endothelial cells. Preclinical studies using cutting-edge technologies, including cellular reprogramming, advancement in scaffolds for brain tissue engineering, image-guided injection, and noninvasive monitoring of tissue regeneration will pave the way for successful clinical trials of NSC-based therapies for PD. Once the implanted or regenerated DA neurons are integrated into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration

Amyloid-β peptide induces oligodendrocyte death by activating the neutral sphingomyelinase–ceramide pathway

Amyloid-β peptide (Aβ) accumulation in senile plaques, a pathological hallmark of Alzheimer's disease (AD), has been implicated in neuronal degeneration. We have recently demonstrated that Aβ induced oligodendrocyte (OLG) apoptosis, suggesting a role in white matter pathology in AD. Here, we explore the molecular mechanisms involved in Aβ-induced OLG death, examining the potential role of ceramide, a known apoptogenic mediator. Both Aβ and ceramide induced OLG death. In addition, Aβ activated neutral sphingomyelinase (nSMase), but not acidic sphingomyelinase, resulting in increased ceramide generation. Blocking ceramide degradation with N-oleoyl-ethanolamine exacerbated Aβ cytotoxicity; and addition of bacterial sphingomyelinase (mimicking cellular nSMase activity) induced OLG death. Furthermore, nSMase inhibition by 3-O-methyl-sphingomyelin or by gene knockdown using antisense oligonucleotides attenuated Aβ-induced OLG death. Glutathione (GSH) precursors inhibited Aβ activation of nSMase and prevented OLG death, whereas GSH depletors increased nSMase activity and Aβ-induced death. These results suggest that Aβ induces OLG death by activating the nSMase–ceramide cascade via an oxidative mechanism

Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

Tumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer

The potential impact of primary headache disorders on stroke risk

Distribution of PHDs. (DOC 55 kb

Association of Suicide Risk With Headache Frequency Among Migraine Patients With and Without Aura

Background: Migraines with aura have been associated with suicide in adolescents and young adults, but the association between suicide and migraine frequency has not been determined. This study investigated suicidal ideation and suicide attempts among patients with varying frequencies of migraines, with and without auras.Methods: This cross-sectional study analyzed 528 patients aged between 20 and 60 years from a headache outpatient clinic in Taiwan. All patients completed a set of questionnaires, including a demographic questionnaire, the Migraine Disability Assessment questionnaire, the Hospital Anxiety and Depression Scale, the Beck Depression Inventory, and the Pittsburgh Sleep Quality Index. Suicide risk was evaluated by self-reported lifetime suicidal ideation and attempts. Patients were divided into low-frequency (1–4 days/month), moderate-frequency (5–8 days/month), high-frequency (9–14 days/month), and chronic (≥15 days/month) migraine groups. The association between migraine frequency and suicidality was investigated using multivariable linear regression and logistic regression.Results: The rates of suicidal ideation and suicide attempts were the highest for chronic migraine with aura (ideation: 47.2%; attempts: 13.9%) and lowest in migraine-free controls (2.8%). Migraine frequency was an independent risk factor for suicidal ideation and attempts in patients with aura (both Ptrend < 0.001), but not in patients without auras. Migraine aura and depression were associated with higher risks of suicidal ideation and suicide attempts in patients with migraine.Conclusion: High migraine frequency has a correlation with high suicide risk in patients who experience an aura, but not in other patients with migraine

Ciprofloxacin-resistant Salmonella enterica Typhimurium and Choleraesuis from Pigs to Humans, Taiwan

We evaluated the disk susceptibility data of 671 nontyphoid Salmonella isolates collected from different parts of Taiwan from March 2001 to August 2001 and 1,261 nontyphoid Salmonella isolates from the National Taiwan University Hospital from 1996 to 2001. Overall, ciprofloxacn resistance was found in 2.7% (18/671) of all nontyphoid Salmonella isolates, in 1.4% (5/347) of Salmonella enterica serotype Typhimurium and in 7.5% (8/107) in S. enterica serotype Choleraesuis nationwide. MICs of six newer fluoroquinolones were determined for the following isolates: 37 isolates of ciprofloxacin-resistant (human) S. enterica Typhimurium (N = 26) and Choleraesuis (N = 11), 10 isolates of ciprofloxacin-susceptible (MIC <1 μg/mL) (human) isolates of these two serotypes, and 15 swine isolates from S. enterica Choleraesuis (N = 13) and Typhmurium (N = 2) with reduced susceptibility to ciprofloxacin (MIC >0.12 μg/mL). Sequence analysis of the gryA, gyrB, parC, parE, and acrR genes, ciprofloxacin accumulation; and genotypes generated by pulsed-field gel electrophoresis with three restriction enzymes (SpeI, XbaI, and BlnI) were performed. All 26 S. enterica Typhimurium isolates from humans and pigs belonged to genotype I. For S. enterica Choleraesuis isolates, 91% (10/11) of human isolates and 54% (7/13) of swine isolates belonged to genotype B. These two genotypes isolates from humans all exhibited a high-level of resistance to ciprofloxacin (MIC 16–64 μg/mL). They had two-base substitutions in the gyrA gene at codons 83 (Ser83Phe) and 87 (Asp87Gly or Asp87Asn) and in the parC gene at codon 80 (Ser80Arg, Ser80Ile, or Ser84Lys). Our investigation documented that not only did these two S. enterica isolates have a high prevalence of ciprofloxacin resistance nationwide but also that some closely related ciprofloxacin-resistant strains are disseminated from pigs to humans

Generalized chorea due to delayed encephalopathy after acute carbon monoxide intoxication

Movement disorder due to delayed encephalopathy after carbon monoxide (CO) intoxication is uncommon. Generalized chorea, presenting as an initial symptom of delayed encephalopathy, is extremely rare. We describe a 60-year-old woman, who had completely recovered from acute CO poisoning, developed mental and behavioral changes, urinary incontinence and generalized chorea 2 weeks thereafter. T2-weighted brain magnetic resonance imaging showed extensive hyperintensity of the bilateral periventricular and subcortical white matter and the globus pallidus. Brain single-photon emission computed tomography (SPECT) with technetium-99 ethylene cysteine dimer showed inhomogeneous perfusion in the cerebral cortex, with decreased uptake in bilateral frontal regions. Delayed encephalopathy after acute CO intoxication was diagnosed, and the symptoms gradually improved after hyperbaric oxygen therapy (HBOT). This case report demonstrates that generalized chorea may be one of the initial presenting symptoms of delayed encephalopathy after acute CO intoxication. We hypothesize that the generalized chorea in our patient may have been caused by the subcortical white matter lesions, which most likely interrupted the basal ganglia-thalamocortical circuits and that HBOT may be the treatment of choice for such patients

Increased One-Year Recurrent Ischemic Stroke after First-Ever Ischemic Stroke in Males with Benign Prostatic Hyperplasia

(1) Background: Patients with benign prostatic hyperplasia (BPH) were questioned about quality of life and sleep. Most BPH patients were treated with alpha-1 adrenergic receptor antagonists, which could improve cerebral blood flow for 1&ndash;2 months. Patients with ischemic stroke (IS) could experience cerebral autoregulation impairment for six months. The relationship between BPH and recurrent IS remains unclear. The aim of this study was to determine the risk of one-year recurrent IS conferred by BPH. (2) Methods: We used data from the Taiwanese National Health Insurance Database to identify newly diagnosed IS cases entered from 1 January 2008 to 31 December 2008. Patients were followed until the recurrent IS event or 365 days after the first hospitalization. The risk factors associated with one-year recurrent IS were assessed using Cox proportional hazards regression. (3) Results: Patients with BPH had a higher risk of recurrent IS (12.11% versus 8.15%) (adjusted hazard ratio (HR): 1.352; 95% confidence interval (CI): 1.028&ndash;1.78, p = 0.031). Other risk factors included hyperlipidemia (adjusted HR: 1.338; 95% CI: 1.022&ndash;1.751, p = 0.034), coronary artery disease (adjusted HR: 1.487; 95% CI: 1.128&ndash;1.961, p = 0.005), chronic obstructive pulmonary disease (adjusted HR: 1.499; 95% CI: 1.075&ndash;2.091, p = 0.017), and chronic kidney disease (adjusted HR: 1.523; 95% CI: 1.033&ndash;2.244, p = 0.033). (4) Conclusion: Patients with BPH who had these risk factors had an increased risk of one-year recurrent IS. The modification of risk factors may prevent recurrent IS