Immediate postnatal central hypothyroidism caused by maternal Graves' disease: Importance of early screening.

This report illustrates a case of central hypothyroidism in a newborn immediately after birth caused by maternal Graves' disease. Infants from mothers with Graves' disease require careful examination without waiting for neonatal screening results, even though the mother's thyroid function is normal at birth or the newborn does not have goiter.

Transplantation of hematopoietic stem cells: intra-arterial versus intravenous administration impacts stroke outcomes in a murine model.

Based on results of hematopoietic stem cell transplantation in animal models of stroke, clinical trials with hematopoietic stem cells administered intra-arterially or intravenously have been initiated in patients. Although intra-arterial injection is expected to deliver transplanted cells more directly to the ischemic tissue, the optimal route for enhancing clinical outcomes has not been identified in the setting of stroke. In this study, we compared the therapeutic potential of intra-arterial versus intravenous injection of bone marrow derived-mononuclear cells (BM-MNCs) and CD133-positive (CD133(+)) cells in a murine stroke model.

Intravenous Autologous Bone Marrow Mononuclear Cell Transplantation for Stroke: Phase1/2a Clinical Trial in a Homogeneous Group of Stroke Patients.

The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke. Major inclusion criteria included patients with cerebral embolism, age 20-75 years, National Institute of Health Stroke Scale (NIHSS) score displaying improvement of ≤ 5 points during the first 7 days after stroke, and NIHSS score of ≥ 10 on day 7 after stroke. Bone marrow aspiration (25 or 50 mL; N = 6 patients in each case) was performed 7-10 days poststroke, and bone marrow mononuclear cells were administrated intravenously.

Improvement in PET/CT image quality in overweight patients with PSF and TOF.

Objective: The aim of this study was to evaluate the effect of the point spread function (PSF) and time of flight (TOF) on PET/CT images of overweight patients in relation to the iteration number and the acquisition time.

Methods: This study consisted of a phantom study and a clinical study. The NEMA IEC body phantom and a 40 cm diameter large phantom (LG phantom) simulating an overweight patient were used in this study.

Cilostazol add-on therapy in patients with mild dementia receiving donepezil: a retrospective study.

Goal: Combinatorial therapy directed at both vascular and neurodegenerative aspects of dementia may offer a promising strategy for treatment of dementia, which often has a multifactorial basis in the elderly. We investigated whether the phosphodiesterase III inhibitor cilostazol, which is often used in the prevention of stroke and peripheral artery disease, may delay cognitive decline in the elderly receiving donepezil.

Methods: Medical records were retrospectively surveyed to identify patients who had received donepezil for more than one year and had undergone Mini-Mental State Examination (MMSE) at least at two time points.

Cilostazol improves cognitive function in patients with mild cognitive impairment: a retrospective analysis.

Background And Purpose: Cerebral ischemia and accumulation of amyloid β (Aβ) are major risk factors for the development of dementia, including vascular dementia and Alzheimer's disease. Cilostazol, an antiplatelet drug, has been shown to improve cerebral circulation and reduce accumulation of Aβ. In this study, the long-term effect of cilostazol on cognitive function was investigated retrospectively.

Experimental evidence and early translational steps using bone marrow derived stem cells after human stroke.

Neurogenesis is principally restricted to the subventricular zone of the lateral ventricle wall and the subgranular zone of the hippocampal dentate gyrus in physiological situations. However, neuronal stem cells are known to be mobilized into the post- and peristroke area and we have demonstrated that appropriate support of these stem cells, achieved by therapeutic angiogenesis, enhances neuroregeneration followed by neuronal functional recovery in an experimental stroke model. We also found that neural stem cells are mobilized in patients after stroke, as well as in animal models.

A novel reproducible model of neonatal stroke in mice: comparison with a hypoxia-ischemia model.

Neonatal stroke occurs in 1/4000 live births and leaves life-long neurological impairments, such as cerebral palsy and epilepsy. Currently, the rodent models of neonatal stroke that are available exhibit significant inter-animal variability, which makes it difficult to accurately assess the mechanisms of brain injury and the efficacy of candidate treatments. We aimed to introduce a novel, highly reproducible model of stroke, middle cerebral artery occlusion (MCAO), in immature mice, and to evaluate the reproducibility of this model compared with a conventional hypoxia-ischemia (HI) model.

A highly reproducible model of cerebral ischemia/reperfusion with extended survival in CB-17 mice.

To simulate the clinical and pathologic situation in patients with stroke, as well as to evaluate future potential therapeutic approaches, it is essential to have a highly reproducible model that displays long-term survival. Though a range of rodent models has been employed in the literature, there are questions regarding reproducibility, especially in terms of ischemic zone (i.e.

Leptomeningeal-derived doublecortin-expressing cells in poststroke brain.

Increasing evidence indicates that neural stem/progenitor cells (NSPCs) reside in many regions of the central nervous system (CNS), including the subventricular zone (SVZ) of the lateral ventricle, subgranular zone of the hippocampal dentate gyrus, cortex, striatum, and spinal cord. Using a murine model of cortical infarction, we recently demonstrated that the leptomeninges (pia mater), which cover the entire cortex, also exhibit NSPC activity in response to ischemia. Pial-ischemia-induced NSPCs expressed NSPC markers such as nestin, formed neurosphere-like cell clusters with self-renewal activity, and differentiated into neurons, astrocytes, and oligodendrocytes, although they were not identical to previously reported NSPCs, such as SVZ astrocytes, ependymal cells, oligodendrocyte precursor cells, and reactive astrocytes.

Human umbilical cord provides a significant source of unexpanded mesenchymal stromal cells.

Background Aims: Human mesenchymal stromal cells (MSC) have considerable potential for cell-based therapies, including applications for regenerative medicine and immune suppression in graft-versus-host disease (GvHD). However, harvesting cells from the human body can cause iatrogenic disorders and in vitro expansion of MSC carries a risk of tumorigenesis and/or expansion of unexpected cell populations.

Methods: Given these problems, we have focused on umbilical cord, a tissue obtained with few ethical problems that contains significant numbers of MSC.

[Cell based therapy for patients after cerebral embolism].

Neuronal stem cells are mobilized after cerebral infarction. We had shown that appropriate support of these stem cells, achieved by therapeutic angiogenesis, enhances neurological recovery in experimental stroke model. Based on these observations, we started cell based therapy using autologous bone marrow mononuclear cells for patients after cerebral embolism as phase 1/2a clinical trial.

Cell-based therapy to promote angiogenesis in the brain following ischemic damage.

Cell-based therapies are a novel approach for regeneration of microvasculature. We have shown that administration of CD34-positive cells, the rich cell fraction of endothelial progenitor cells, after stroke induces angiogenesis that results in enhanced endogenous neurogenesis and functional recovery in a murine model. Moreover, injury-induced neurogenesis occurs in the human brain following a stroke during the acute to sub-acute period.

Cerebral blood flow during reperfusion predicts later brain damage in a mouse and a rat model of neonatal hypoxic-ischemic encephalopathy.

Children with severe neonatal hypoxic-ischemic encephalopathy (HIE) die or develop life-long neurological impairments such as cerebral palsy and mental retardation. Decreased regional cerebral blood flow (CBF) is believed to be the predominant factor that determines the level of tissue injury in the immature brain. However, the spatio-temporal profiles of CBF after neonatal HIE are not well understood.

Cilostazol reduces the risk of hemorrhagic infarction after administration of tissue-type plasminogen activator in a murine stroke model.

Background And Purpose: Prior use of antiplatelet agents improves stroke outcome in patients undergoing thrombolytic therapy as shown by reduced arterial reocclusion, although the risk of cerebral hemorrhage can be increased.

Methods: The effect of cilostazol, an antiplatelet drug that improves endothelial function through upregulation of intracellular cAMP, on cerebral hemorrhage after thrombolytic therapy was investigated using a highly reproducible transient ischemia model.

Results: Treatment with cilostazol for 7 days before ischemia significantly suppressed the risk and severity of cerebral hemorrhage after injection of tissue-type plasminogen activator, although treatment with aspirin had no such protective effect compared with nontreated mice.

Progesterone and allopregnanolone exacerbate hypoxic-ischemic brain injury in immature rats.

Progesterone and its metabolite, allopregnanolone, are neurosteroids that are present at high concentrations in fetal brains that decrease right after birth. Allopregnanolone is a potent positive modulator of γ-aminobutyric acid A (GABA(A)) receptor function. We examined the effect of exogenous administration of these steroids on hypoxic-ischemic encephalopathy in immature rats.

A Reproducible and Simple Model of Permanent Cerebral Ischemia in CB-17 and SCID Mice.

In order to evaluate novel stroke therapies, it is essential to utilize a highly reproducible model of focal cerebral ischemia. Though a range of rodent stroke models has been employed in the literature, there are persistent issues regarding reproducibility of the ischemic zone, as there is considerable inter-animal and inter-laboratory variation. We have developed a highly reproducible model of stroke that involves direct electrocoagulation of the MCA in SCID (CB-17/lcr-scid/scidJcl) and CB-17 (CB-17/lcr-+/+Jcl) mice.

Reduced ischemic brain injury by partial rejuvenation of bone marrow cells in aged rats.

Circulating bone marrow-derived immature cells, including endothelial progenitor cells, have been implicated in homeostasis of the microvasculature. Decreased levels of circulating endothelial progenitor cells, associated with aging and/or cardiovascular risk factors, correlate with poor clinical outcomes in a range of cardiovascular diseases. Herein, we transplanted bone marrow cells from young stroke-prone spontaneously hypertensive rats (SHR-SP) into aged SHR-SP, the latter not exposed to radiation or chemotherapy.

Telmisartan suppresses cerebral injury in a murine model of transient focal ischemia.

The beneficial effects of angiotensin II type 1 (AT1) receptor blockers (ARB) in cerebrovascular disease have been shown in clinical trials. However, the effects of ARBs vary based on their unique pharmacologic properties. In this study, we focused on telmisartan, a fat-soluble ARB with selective peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist activity, and investigated its effects on ischemic injury in cerebral vasculature using murine models of both transient and permanent focal ischemia.

Injury-induced neural stem/progenitor cells in post-stroke human cerebral cortex.

Increasing evidence points to accelerated neurogenesis after stroke, and support of such endogenous neurogenesis has been shown to improve stroke outcome in experimental animal models. The present study analyses post-stroke cerebral cortex after cardiogenic embolism in autoptic human brain. Induction of nestin- and musashi-1-positive cells, potential neural stem/progenitor cells, was observed at the site of ischemic lesions from day 1 after stroke.

Circulating CD34-positive cells have prognostic value for neurologic function in patients with past cerebral infarction.

Increasing evidence points to a role for circulating endothelial progenitors, including populations of CD34-positive (CD34(+)) cells present in peripheral blood, in vascular homeostasis and neovascularization. In this report, circulating CD34(+) cells in individuals with a history of cerebral infarction were correlated with changes in neurologic function over a period of 1 year. Patients with decreased levels of CD34(+) cells displayed significant worsening in neurologic function, evaluated by the Barthel Index and Clinical Dementia Rating.

Increase in circulating CD34-positive cells in patients with angiographic evidence of moyamoya-like vessels.

Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34-positive (CD34(+)) cells, in maintenance of cerebral blood flow. In this study, we investigated the link between the level of circulating CD34(+) cells and neovascularization at ischemic brain. Compared with control subjects, a remarkable increase of circulating CD34(+) cells was observed in patients with angiographic moyamoya vessels, although no significant change was observed in patients with major cerebral artery occlusion (or severe stenosis) but without moyamoya vessels.

Hyper-IgM syndrome with putative dominant negative mutation in activation-induced cytidine deaminase.

Background: Hyper-IgM immunodeficiency is an immunologic disorder characterized by normal or increased serum IgM levels and reduced serum IgG and IgA levels caused by the disruption of Ig class switching in B cells. The gene encoding activation-induced cytidine deaminase (AID) is responsible for the autosomal recessive form of hyper-IgM syndrome.

Objective: To investigate the relationship between the AID gene mutation and the clinical phenotype, we analyzed the AID gene in a female Japanese patient with the autosomal recessive form of hyper-IgM syndrome.