Young-Seo Kim

The immunomodulatory effects of human mesenchymal stem cells on peripheral blood mononuclear cells in ALS patients

In a previous study, we reported that intrathecal injection of mesenchymal stem cells (MSCs) slowed disease progression in G93A mutant superoxide dismutase1 transgenic mice. In this study, we found that intrathecal MSC administration vastly increased the infiltration of peripheral immune cells into the spinal cord of Amyotrophic lateral sclerosis (ALS) mice (G93A mutant superoxide dismutase1 transgenic). Thus, we investigated the immunomodulatory effect of MSCs on peripheral blood mononuclear cells (PBMCs) in ALS patients, focusing on regulatory T lymphocytes (Treg; CD4+/CD25high/FoxP3+) and the mRNA expression of several cytokines (IFN‐γ, TNF‐α, IL‐17, IL‐4, IL‐10, IL‐13, and TGF‐β). Peripheral blood samples were obtained from nine healthy controls (HC) and sixteen patients who were diagnosed with definite or probable ALS. Isolated PBMCs from the blood samples of all subjects were co‐cultured with MSCs for 24 or 72 h. Based on a fluorescence‐activated cell sorting analysis, we found that co‐culture with MSCs increased the Treg/total T‐lymphocyte ratio in the PBMCs from both groups according to the co‐culture duration. Co‐culture of PBMCs with MSCs for 24 h led to elevated mRNA levels of IFN‐γ and IL‐10 in the PBMCs from both groups. However, after co‐culturing for 72 h, although the IFN‐γ mRNA level had returned to the basal level in co‐cultured HC PBMCs, the IFN‐γ mRNA level in co‐cultured ALS PBMCs remained elevated. Additionally, the levels of IL‐4 and TGF‐β were markedly elevated, along with Gata3 mRNA, a Th2 transcription factor mRNA, in both HC and ALS PBMCs co‐cultured for 72 h. The elevated expression of these cytokines in the co‐culture supernatant was confirmed via ELISA. Furthermore, we found that the increased mRNA level of indoleamine 2,3‐dioxygenase (IDO) in the co‐cultured MSCs was correlated with the increase in Treg induction. These findings of Treg induction and increased anti‐inflammatory cytokine expression in co‐cultured ALS PBMCs provide indirect evidence that MSCs may play a role in the immunomodulation of inflammatory responses when MSC therapy is targeted to ALS patients.

Effect of Seasonal and Monthly Variation in Weather and Air Pollution Factors on Stroke Incidence in Seoul, Korea

Background and Purpose— The purpose of the present study was to determine whether seasonal and monthly variations in stroke incidence exist and whether they are related to meteorologic and air pollution parameters under similar weather and environmental conditions in selected areas of Seongdong district, Seoul, South Korea. Methods— From January 1, 2004, to December 31, 2013, 3001 consecutive stroke events were registered in residents of selected areas of Seongdong district, Seoul, South Korea. The authors calculated the stroke attack rate per 100 000 people per month and the relative risk of stroke incidence associated with meteorologic and air pollution parameters. We also analyzed odds ratios with a 95% confidence interval for seasonal and monthly stroke incidence. Results— The incidence of stroke in September was significantly higher (odds ratio, 1.233; 95% confidence interval, 1.042–1.468) compared with January. The seasonal ischemic stroke incidence in summer (odds ratio, 1.183; 95% confidence interval, 1.056–1.345) was significantly higher than in winter, whereas the seasonal incidence of intracerebral hemorrhage relative to winter was not significant. The mean temperature was positively correlated with ischemic stroke (relative risk, 1.006; P=0.003), and nitrogen dioxide (relative risk, 1.262; P=0.001) showed a strong positive correlation with intracerebral hemorrhage incidence among the older age group. Conclusions— We demonstrated distinct patterns of seasonal and monthly variation in the incidence of stroke and its subtypes through consideration of the meteorologic and air pollution parameters. We therefore expect that these findings may enhance our understanding of the relationships between stroke and weather and pollutants.

Activation of the phosphatidylinositol 3-kinase pathway plays important roles in reduction of cerebral infarction by cilnidipine

Cerebral infarction causes permanent neuronal loss inducing severe morbidity and mortality. Because hypertension is the main risk factor for cerebral infarction and most patients with hypertension take antihypertensive drugs daily, the neuroprotective effects and mechanisms of anti‐hypertensive drugs need to be investigated. Cilnidipine, a long‐acting, new generation 1,4‐dihydropyridine inhibitor of both L‐ and N‐type calcium channels, was reported to reduce oxidative stress. In this study, we investigated whether cilnidipine has therapeutic effects in an animal model of cerebral infarction. After determination of the most effective dose of cilnidipine, a total of 128 rats were subjected to middle cerebral artery occlusion. Neurobehavioral function test and brain MRI were performed, and rats with similar sized infarcts were randomized to either the cilnidipine group or the control group. Cilnidipine treatment was performed with reperfusion after 2‐h occlusion. Western blots and immunohistochemistry were also performed after 24‐h occlusion. Initial infarct volume on diffusion‐weighted MRI was not different between the cilnidipine group and the control group; however, fluid‐attenuated inversion recovery MRI at 24 h showed significantly reduced infarct volume in the cilnidipine group compared with the control group. Cilnidipine treatment significantly decreased the number of triphosphate nick end labeling‐positive cells compared to the control group. Western blot and immunohistochemistry showed increased expression of phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase‐3β, and Bcl‐2 and decreased expression of Bax and cleaved caspase‐3. These results suggest that cilnidipine, which is used for the treatment of hypertension, has neuroprotective effects in the ischemic brain through activation of the PI3K pathway.

Spontaneous Anterior Cerebral Artery Dissection Presenting with Simultaneous Subarachnoid Hemorrhage and Cerebral Infarction in a Patient with Multiple Extracranial Arterial Dissections

Simultaneous subarachnoid hemorrhage and infarction is a quite rare presentation in a patient with a spontaneous dissecting aneurysm of the anterior cerebral artery. Identifying relevant radiographic features and serial angiographic surveillance as well as mode of clinical manifestation, either hemorrhage or infarction, could sufficiently determine appropriate treatment. Enlargement of ruptured aneurysm and progressing arterial stenosis around the aneurysm indicates impending risk of subsequent stroke. In this setting, prompt treatment with stent-assisted endovascular embolization can be a reliable alternative to direct surgery. When multiple arterial dissections are coexistent, management strategy often became complicated. However, satisfactory clinical results can be obtained by acknowledging responsible arterial site with careful radiographic inspection and antiplatelet medication.

Delayed-onset pineal abscess following transsphenoidal surgery for pituitary adenoma: a case report.

A 41-year-old woman suffered fever, speech disturbance and confusion four months after transsphenoidal surgery for pituitary macroadenoma. Meanwhile, the patient had been well except for transient asymptomatic postoperative pneumocephalus without cerebrospinal fluid (CSF) rhinorrhoea. Brain computed tomographic scan revealed a peripherally enhancing pineal abscess which superimposed on a preexisting pineal cyst. CSF findings showed elevated leukocyte count and positive bacterial culture. Three weeks of intensive antibiotic therapy and surgical evacuation of the pineal abscess ensued. The patient showed restricted postoperative recovery with moderate hypothalamic dysfunction. A unique case of delayed-onset postoperative pineal abscess which complicates the preexisting asymptomatic pineal cyst is presented and the possible explanation for this is speculated with review of the available literatures.

Association between Diurnal Variation of Ozone Concentration and Stroke Occurrence: 24-Hour Time Series Study.

Background and Purpose Increasing ozone concentrations have been known to damage human health and ecosystems. Although ozone tends to display diurnal variation, most studies have reported only on the association between daily ozone concentrations and ischemic stroke occurrence on the same day, or with a 1-day lag. We investigated the effect of the diurnal variation of ozone on ischemic stroke occurrence during the same day. Methods We included a consecutive series of 1,734 patients from January 1, 2008, to December 31, 2014, at a single tertiary hospital in Seoul, South Korea. We evaluated differences between temperature and pollutants at the time of stroke onset for each time interval and averaged those parameters across the 7-year study period. Results During the interval from 13:00 to 16:59, we found a positive association between ischemic stroke occurrence and ozone concentration relative to other time periods. Upper median ozone levels from 13:00 to 16:59 were positively correlated with ischemic stroke (odds ratio, 1.550; 95% confidence intervals, 1.220 to 1.970; P = <0.001) when compared with lower median levels. Conclusions The results show diurnal patterns of ischemic stroke occurrence based on upper and lower median ozone levels for a 24-hour period, which extends understanding of the association between stroke occurrence and environmental influences.