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Background: Several studies have examined the enhanced efficacy of mesenchymal stem cells (MSCs) using neurotrophic factor transfection in ischemic rat models. However, gene therapy, e.g., the application of MSCs transfected with neurotrophic factors, is not feasible in clinical practice for ethical reasons. Therefore, we evaluated cultivation with specific trophic factors in an attempt to enhance the efficacy of human MSCs (hMSCs) in ischemic stroke., Methods: Using quantitative sandwich enzyme-linked immunosorbent assay (ELISA), we analyzed the levels of trophic factors released from hMSCs after treatment with ischemic brain extract. Trophic factors were pretreated under ex vivo culture conditions. The concentrations of each trophic factor produced by the trophic factor-pretreated and non-pretreated hMSCs were then measured and compared., Results: hMSCs cultured with ischemic rat brain extract showed increased production of BDNF (brain-derived neurotrophic factor), VEGF (vascular endothelial growth factor) and HGF (hepatocyte growth factor). Ex vivo treatment with trophic factors led to a further increase in the production of the trophic factor by hMSC, suggesting autocrine regulation of hMSCs. The morphology and expression of surface markers of hMSCs were not changed, but the cell viability and cell proliferation ability increased after treatment with trophic factors., Conclusions: Our data indicate that hMSCs provide trophic support to the ischemic brain, which can be enhanced by ex vivo treatment of trophic factors during cultivation of hMSCs., (Copyright © 2010 Elsevier B.V. All rights reserved.)

HyperIgEemia and atopy have recently been reported to be related to various neurological diseases such as Hirayama disease and idiopathic myelitis. The aims of this study are to determine frequency of atopy or hyperIgEemia in idiopathic myelitis and to characterize the clinical and laboratory profiles of atopic myelitis (AM). From January 2006 to August 2008, 29 consecutive patients with idiopathic myelitis were recruited. We compared demographic data, laboratory results and radiologic findings between patients with atopic diathesis and those without. Allergic or atopic history was found in only 4 patients (13%), but hyperIgEemia and mite antigen-specific IgE were observed in 17 (58%) and 19 (65%) of idiopathic myelitis patients, respectively. Patients with AM (n=14, 48%) showed the following distinctive features: (1) younger age at onset, (2) non-acute onset and long duration of symptoms at admission, (3) predominant sensory symptoms with mild weakness, (4) low EDSS score, (5) low frequency of abnormal SEP findings, and (6) increased eosinophils in peripheral blood. Common MR findings of AM included eccentric lesions occupying more than two-thirds of spinal cord with focal peripheral enhancement on axial image. These lesions were usually extended over more than 3 to 5 vertebral segments with cord swelling. HyperIgEemia and mite antigen-specific IgE are fairly common in idiopathic myelitis patients. The AM patients show relatively homogenous clinicolaboratory and radiological features. It is noteworthy that none of these patients showed brain abnormalities suggestive of multiple sclerosis or neuromyelitis optica (NMO).

Background: Mesenchymal stem cells (MSCs) have the potential to promote brain repair and improve recovery following stroke. We investigated changes in free fatty acids (FFAs) following intravenous human MSC (hMSC) transplantation into rats that had undergone transient middle cerebral artery occlusion (MCAo)., Methods: Rats were subjected to 2-hours MCAo, followed by intravenous transplantation of hMSC or phosphate-buffered saline (PBS) at one day after MCAo. All rats were sacrificed 5 days after MCAo. Metabolic profiling of free fatty acids (FFAs) level was assessed in plasma and brain from control rats (n=8), PBS-treated MCAo rats (n=6), and hMSC-treated MCAo rats (MCAo+hMSC, n=6)., Results: The levels of some FFAs in plasma and brain samples of the MCAo and MCAo+hMSC groups were significantly different from those of the control group. The percentage composition of myristic acid in plasma and those of myristic acid, linoleic acid, and eicosenoic acid in brain tissues of the MCAo+hMSC group were significantly reduced compared to those in the untransplanted MCAo group., Conclusion: Our metabolic approach has provided insights into understanding the complexity of biochemical and physiological events that occur in ischemic brain injury and the transplantation effects of MSCs in stroke.

Objective: Diffusion-weighted imaging (DWI) infarct patterns can play a useful role in the management of ischemic stroke patients, particularly in identifying index stroke mechanisms. Novel vascular risk factors like high sensitivity C-reactive protein (hs-CRP) and the metabolic syndrome have recently been shown to be of prognostic importance following ischemic stroke. We aimed to determine the relationship between these novel factors and infarct patterns noted on DWI., Methods: A total of 886 patients with acute cerebral infarcts within the MCA territory were prospectively studied. Using the DWI data the patients were divided into four groups: cortical, small (<1cm) superficial, border-zone, and deep infarcts patterns. The independent associations of various infarct DWI patterns vs. hs-CRP and presence of the metabolic syndrome were evaluated after adjusting for the confounders., Results: hs-CRP was highest among patients with cortical infarcts, while the metabolic syndrome was most frequent in patients with border-zone infarcts. Compared to the lowest quartile of hs-CRP level, those in the highest quartile were more likely to have the cortical pattern (OR, 3.55; 95% CI, 1.92-6.56; P<0.001), and less likely to have the deep infarct pattern (OR, 0.49; 95% CI, 0.29-0.81; P=0.006) in logistic regression analyses. There was an independent association between presence of the metabolic syndrome and the border-zone pattern (OR, 1.75; 95% CI, 1.12-2.73; P=0.013)., Conclusions: hs-CRP levels and metabolic derangements are independently associated with infarct pattern in acute ischemic stroke, and may be the potential targets for lessening the clinical impact of certain infarct patterns.