Kyung-Il Park

Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia

Ischemic stroke is caused by the interruption of cerebral blood flow that leads to brain damage with long-term sensorimotor deficits. Stem cell transplantation may recover functional deficit by replacing damaged brain. In this study, we attempted to test whether the human neural stem cells (NSCs) can improve the outcome in the rat brain with intravenous injection and also determine the migration, differentiation and the long-term viabilities of human NSCs in the rat brain. Focal cerebral ischemia was induced by intraluminal thread occlusion of middle cerebral artery (MCA). One day after surgery, the rats were randomly divided into two groups: NSCs-ischemia vs. Ischemia-only. Human NSCs infected with retroviral vector encoding beta galactosidase were intravenously injected in NSCs-ischemia group (5 x 10(6) cells) and the same amount of saline was injected in Ischemia-only group for control. The animals were evaluated for 4 weeks using turning in an alley (TIA) test, modified limb placing test (MLPT) and rotarod test. Transplanted cells were detected by X gal cytohistochemistry or beta gal immunohistochemistry with double labeling of other cell markers. The NSCs-ischemia group showed better performance on TIA test at 2 weeks, and MLPT and rotarod test from 3 weeks after ischemia compared with the Ischemia-only group. Human NSCs were detected in the lesion side and labeled with marker for neurons or astrocytes. Postischemic hemispheric atrophy was noted but reduced in NSCs-ischemia group. X gal+ cells were detected in the rat brain as long as 540 days after transplantation. Our data suggest intravenously transplanted human NSCs can migrate and differentiate in the rat brain with focal ischemia and improve functional recovery.

Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans

Aims/hypothesisResistin is thought to be an important link between obesity and insulin resistance. It has been suggested that genetic polymorphism in the promoter of resistin gene is a determinant of resistin mRNA expression and possibly associated with obesity and insulin resistance. In this study, we investigated the association between the genotype of resistin promoter and its plasma concentrations.MethodsWe examined g.-537A>C and g.-420C>G polymorphisms in the resistin promoter and measured plasma resistin concentrations in Korean subjects with or without Type 2 diabetes. We also did haplotype-based promoter activity assays and the gel electrophoretic mobility shift assay.ResultsThe −420G and the −537A alleles, which were in linkage disequilibrium, were associated with higher plasma resistin concentrations. Individuals with haplotype A-G (−537A and −420G) had significantly higher plasma resistin concentrations than the others. Haplotype A-G had modestly increased promoter activity compared to the other haplotypes. Electrophoretic mobility shift assay showed that the −420G allele is specific for binding of nuclear proteins from adipocytes and monocytes. However, none of the two polymorphisms were associated with Type 2 diabetes or obesity in our study subjects.Conclusions/interpretationPolymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans.

Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia

Recent studies have indicated the beneficial effects of vascular endothelial growth factor (VEGF), and transplanted neural stem cells (NSCs) in cerebral ischemia. We investigated the effects of the combined administration of NSCs and VEGF on focal cerebral ischemia in adult rats. Four groups (n = 12, respectively)--group 1 (ischemia-only), group 2 (ischemia + VEGF), group 3 (ischemia + NSCs) and group 4 (ischemia + NSCs + VEGF)--were compared. Human NSCs (HB1.F3), labeled with Lac Z+ or PKH26, were given intravenously 24h after surgery (5 x 10(6) cells). At 48 h after surgery, recombinant human VEGF (50 microg/kg) was infused intravenously (1 microg/(kg min)). Behavioral tests using the modified limb placing and rotarod tests were performed every week following ischemia. Immunohistochemistry for endothelial barrier antigen (EBA), VEGF and Nissl staining were performed at day 35 after ischemia. Group 4 showed better behavioral recovery at 7, 14 and 28 days than group 3 (p = 0.020, 0.005 and 0.043, respectively). These functional recoveries were correlated with enhanced EBA immunoreactivities at day 35 after ischemia, especially in the ipsilesional striatum. Group 4 showed lesser degree of brain atrophy in cortex and striatum, when compared with other groups. The distribution of VEGF was not co-localized with NSCs. Our results suggest that VEGF may act synergistically on NSC-transplanted, ischemic brain via a pro-angiogenic effect.

Spontaneous intracranial hypotension Efficacy of radiologic targeting vs blind blood patch

Objective: The aim of this study was to evaluate the efficacies and compare the outcomes of targeted and blind epidural blood patch (EBP) treatments of spontaneous intracranial hypotension (SIH). Methods: Between January 1999 and December 2009, 56 patients who were diagnosed with SIH received either a targeted or blind EBP. The efficacies of targeted and blind EBPs were evaluated based on degree and duration of symptom relief and on the need for repeat EBP. Results: Fifty-six patients (23 men and 33 women; mean age, 39.6 years; age range, 22–69 years) were included in this study. Thirty-one patients received EBP that targeted CSF leak segments, and 25 received a blind EBP because primary CSF leak sites were not identified (19 patients via a lumbar epidural route, mainly the L 3–4 level, regardless of primary CSF leak site, and 6 patients via upper thoracic epidural spaces, mainly the T4–6 level). In the 31 patients who received a targeted EBP, 27 (87.1%) exhibited clinical improvement after first administration. In contrast, 13 of the 25 patients (52%) who received a blind EBP via a lumbar or upper thoracic epidural route achieved complete recovery. Targeted EBPs were more effective than blind EBPs for the treatment of SIH (p < 0.05). Conclusions: EBPs targeting CSF leaks can be safely placed under fluoroscopic guidance in patients with SIH and are more likely to be effective than blindly placed EBPs.

Frontal lobe epilepsy: Clinical characteristics, surgical outcomes and diagnostic modalities

OBJECTIVE To identify surgical prognostic factors and to characterize clinical features according to the location of the intracranial ictal onset zone of frontal lobe epilepsy (FLE) in order to assess the role of various diagnostic modalities, including concordances with presurgical evaluations. METHODS We studied 71 FLE patients who underwent epilepsy surgery and whose outcomes were followed for more than 2 years. Diagnoses were established by standard presurgical evaluation. RESULTS Clinical manifestations could be categorized into six types: initial focal motor (9 patients), initial versive seizure (15), frontal lobe complex partial seizure (14), complex partial seizure mimicking temporal lobe epilepsy (18), initial tonic elevation of arms (11), and sudden secondary generalized tonic-clonic seizure (4). Thirty-seven patients became seizure-free after surgery. Five patients were deleted in the analysis because of incomplete resection of ictal onset zones. The positive predictive value of interictal EEG, ictal EEG, MRI, PET, and ictal SPECT, respectively were 62.5%, 56.4%, 73.9%, 63.2%, and 63.6%, and the negative predictive value were 46.0%, 44.4%, 53.5%, 44.7%, and 51.7%. No significant relationship was found between the diagnostic accuracy of these modalities and surgical outcome, with the exception of MRI (p=0.029). Significant concordance of two or more modalities was observed in patients who became seizure-free (p=0.011). We could not find any clinical characteristic related to surgical outcome besides seizure frequency. No definite relationship was found between the location of intracranial ictal onset zone and clinical semiology. CONCLUSION Although various diagnostic methods can be useful in the diagnosis of FLE, only MRI can predict surgical outcome. Concordance between presurgical evaluations indicates a better surgical outcome.

Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population.

Aims  Kir6.2 is found in the pancreatic B‐cell, cardiac and skeletal muscle and non‐vascular smooth muscle. KCNJ11, encoding Kir6.2, has been shown to be associated with both Type 2 diabetes mellitus and cardiovascular disease in several populations. In this study, we investigated whether polymorphisms in KCNJ11 are associated with Type 2 diabetes and other metabolic phenotypes in the Korean population.

The prevalence of the mitochondrial DNA 16189 variant in non-diabetic Korean adults and its association with higher fasting glucose and body mass index.

Aims To evaluate the prevalence of the 16189 variant of mitochondrial DNA in Korean adults and its association with insulin resistance.

A multicenter, randomized, placebo-controlled, double-blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15-0444 in patients with type 2 diabetes

Aim: The objective of this study was to evaluate the optimal dose, efficacy and safety of a novel dipeptidyl peptidase‐4 (DPP‐IV) inhibitor, LC15‐0444, in Korean subjects with type 2 diabetes mellitus treated by diet and exercise.

Anti‐LGI1 Encephalitis is Associated with Unique HLA Subtypes

Autoimmune encephalitis (AE), represented by anti–leucine‐rich glioma‐inactivated 1 (anti‐LGI1) and anti–N‐methyl‐D‐aspartate receptor (anti‐NMDAR) encephalitis, has increasing clinical significance based on recent discoveries of neuronal autoantibodies. However, its immunopathogenesis is not fully understood. Here, we investigated whether AE is associated with the human leukocyte antigen (HLA) subtypes.

Altered Expression of the Long Noncoding RNA NEAT1 in Huntington’s Disease

Huntington’s disease (HD) is a devastating neurodegenerative disease caused by cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin gene. Growing evidence supports the regulatory functions of long noncoding RNAs (lncRNAs) in the disease process, but little is known about the association between lncRNAs and neuronal death in HD. Here, we evaluated the altered expression profiles of lncRNA in HD by using microarrays. Among dysregulated lncRNAs, we focused on the upregulation of nuclear paraspeckle assembly transcript 1 (NEAT1). Quantitative PCR analysis validated increased NEAT1 levels in the R6/2 mouse brain as well as the human HD postmortem brain. To determine the biological effects of NEAT1 on neuronal survival, neuro2A cells were transfected with the NEAT1 short isoform vector and were subjected to H2O2-induced injury. Subsequently, NEAT1-transfected cells showed increased viability under oxidative stress. Our observations support the notion that NEAT1 upregulation in HD contributes to the neuroprotective mechanism against neuronal injury rather than the pathological process underlying neurodegeneration in HD.