Objective : Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods : Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results : Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU- and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. Conclusion : Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.
Hwang, Joonseok;Lee, A Leum;Chang, Kee Hyun;Hong, Hyun Sook
Investigative Magnetic Resonance Imaging
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v.19
no.3
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pp.186-190
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2015
Acute disseminated encephalomyelitis (ADEM) is a demyelinating and inflammatory condition of the central nervous system, occurring predominantly in white matter. ADEM involving the rhombencephalon without affecting the white matter is very rare. Here, we present an unusual case of ADEM involving only the rhombencephalon in a 4-year-old Asian girl. The patient complained of pain in the right lower extremities, general weakness, ataxia, and dysarthria. The initial brain CT showed subtle ill-defined low-density lesions in the pons and medulla. On brain MRI, T2 high signal intensity (T2-HSI) lesions with mild swelling were present in the pons, both middle cerebellar peduncles, and the anterior medulla. The initial diagnosis was viral encephalitis involving the rhombencephalon. Curiously, a cerebrospinal fluid (CSF) study revealed no cellularity, and negative viral marker findings. Three weeks later, follow up brain MRI showed that the extent of the T2-HSI lesions in the brain stem had decreased. After reinvestigation, it was found that she had a prior history of upper respiratory infection. In this case, we report the very rare case of a patient showing isolated involvement of the rhombencephalon in ADEM, mimicking viral rhombencephalitis on CT and MR imaging. ADEM can involve unusual sites such as the rhombencephalon in isolation, without involvement of the white matter or deep gray matter and, therefore, should be considered even when it appears in unusual anatomical areas. Thorough history taking is important for making a correct diagnosis.
Cavernous hemangioma can occur in the entire brain but rarely in cerebellum, especially in the pediatric age group. Headache, seizure, gait disturbance, recurrent bleeding may be seen. This tumor is a relatively benign condition but if the lesion located in the posterior fossa or the brain stem bleeds, irreversible brain damage may occur because of its restrictive space. Moreover, it must be differentiated from malignant tumors. We report 12.6 year-old boy who represented posterior neck myalgia as the presenting symptom. The pain continued for about a month despite analgesic medications. Brain MRI showed intracranial hemorrhage in the left cerebellum (4.5 cm) representing repeated hemorrhages at different times and originated from the cavernous hemangioma accompanied by mild hydrocephalus. The lesion was surgically removed successfully and the cavernous hemangioma was confirmed by pathologic findings. After the follow-up period of 14 months, he is in good condition without any complications.
In 1997 when cloned sheep Dolly and soon after Polly were born, it had become head-line news because in the former the nucleus that gave rise to the lamb came from cells of six-year-old adult sheep and in the latter case a foreign gene was inserted into the donor nucleus to make the cloned sheep produce human protein, factor IX, in e milk. In the last few years, once the realm of science fiction, cloned mammals especially in livestock have become almost commonplace. What the press accounts often fail to convey, however, is that behind every success lie hundreds of failures. Many of the nuclear-transferred egg cells fail to undergo normal cell divisions. Even when an embryo does successfully implant in the womb, pregnancy often ends in miscarriage. A significant fraction of the animals that are born die shortly after birth and some of those that survived have serious developmental abnormalities. Efficiency remains at less than one % out of some hundred attempts to clone an animal. These facts show that something is fundamentally wrong and enormous hurdles must be overcome before cloning becomes practical. Cloning researchers now tent to put aside their effort to create live animals in order to probe the fundamental questions on cell biology including stem cells, the questions of whether the hereditary material in the nucleus of each cell remains intact throughout development, and how transferred nucleus is reprogrammed exactly like the zygotic nucleus. Stem cells are defined as those cells which can divide to produce a daughter cell like themselves (self-renewal) as well as a daughter cell that will give rise to specific differentiated cells (cell-differentiation). Multicellular organisms are formed from a single totipotent stem cell commonly called fertilized egg or zygote. As this cell and its progeny undergo cell divisions the potency of the stem cells in each tissue and organ become gradually restricted in the order of totipotent, pluripotent, and multipotent. The differentiation potential of multipotent stem cells in each tissue has been thought to be limited to cell lineages present in the organ from which they were derived. Recent studies, however, revealed that multipotent stem cells derived from adult tissues have much wider differentiation potential than was previously thought. These cells can differentiate into developmentally unrelated cell types, such as nerve stem cell into blood cells or muscle stem cell into brain cells. Neural stem cells isolated from the adult forebrain were recently shown to be capable of repopulating the hematopoietic system and produce blood cells in irradiated condition. In plants although the term$\boxDr$ stem cell$\boxUl$is not used, some cells in the second layer of tunica at the apical meristem of shoot, some nucellar cells surrounding the embryo sac, and initial cells of adventive buds are considered to be equivalent to the totipotent stem cells of mammals. The telomere ends of linear eukaryotic chromosomes cannot be replicated because the RNA primer at the end of a completed lagging strand cannot be replaced with DNA, causing 5' end gap. A chromosome would be shortened by the length of RNA primer with every cycle of DNA replication and cell division. Essential genes located near the ends of chromosomes would inevitably be deleted by end-shortening, thereby killing the descendants of the original cells. Telomeric DNA has an unusual sequence consisting of up to 1,000 or more tandem repeat of a simple sequence. For example, chromosome of mammal including human has the repeating telomeric sequence of TTAGGG and that of higher plant is TTTAGGG. This non-genic tandem repeat prevents the death of cell despite the continued shortening of chromosome length. In contrast with the somatic cells germ line cells have the mechanism to fill-up the 5' end gap of telomere, thus maintaining the original length of chromosome. Cem line cells exhibit active enzyme telomerase which functions to maintain the stable length of telomere. Some of the cloned animals are reported prematurely getting old. It has to be ascertained whether the multipotent stem cells in the tissues of adult mammals have the original telomeres or shortened telomeres.
The purpose of this study is to evaluate the contribution of $^{18}$ F-FDG brain PET in the differentiating Idiopathic parkinson's diesease (IPD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). We studied 24 patients with parkinsonism : 8 patients (mean age 67.9$\pm$10.7 y: M/F : 3/5) with IPD, 9 patients (57.9$\pm$9.2 y : M/F : 4/5) with MSA and 7 patients (67.6$\pm$4.8 y : M/F 3/4) with PSP. All patients with parkinsonism and 22 age-matched normal controls underwent $^{18}$ F FDG PET in 3D mode after the injection of 370 MBq $^{118}$ F FDG. The patients with IPD, MSh and PSP were compared with a normal control group by a two-sided t-test of SPM99 (uncorrected P<0.001, extent threshold>100 voxel). All three parkinsonism groups, showed significant hypometabolism in the cerebral neocortex compared to the normal control group. However, the three groups displayed different metabolism in the subcortical structure, brain stem, and cerebellum. In IPD, there was no significant hypometabolism in the putamen, brain stem and cerebellum. However, MSA patients showed significant hypometabolism in the striatum, pons, and cerebellum compared to the normal controls and IPD patients. In addition, PSP showed significant hypometabolism in the caudate nuclei, the thalamus, midbrain, and the cingulate gyrus compared to the normal controls, the IPD, and MSA groups (IPD vs Normal sensitivity/specificity : 75%/l00%, MSA vs Normal sensitivity/specificity :100%/87%, PSP vs Normal sensitivity/specificity : 86%/94%). Our results show that the regional metabolism of IPD, MSA, and PSP is different mainly in the striatum, thalamus, brain stem and cerebellum. An assessment of the $^{18}$ F-FDG PET scan images using SPM may be a useful adjunct to a clinical examination in making a differential diagnosis of Parkinsonism.
Human embryonic stem cells have been highlighted as a valuable cellular source in the regenerative medicine field, due to their pluripotency. However, there is the challenge of the establishment of specific functional cell type forms of undifferentiated human embryonic stem cells (hESC). To establish and purify functional cell types from hESCs, we differentiated undifferentiated hESCs into vascular lineage cells and sorted the specific cell population from the whole cell population, depending on their cell volume, and compared them with the non-sorted cell population. We observed that about 10% of the PECAM positive population existed in the VEGF induced differentiating human embryoid body (hEB), and differentiated hEBs were made into single cells for cell transplantation. After making single cells, we performed cell sorting using a fluorescence-activated cell sorter (FACs), according to their cell volume on the basis of FSC region gating, and compared their therapeutic capacity with the non-sorted cell population through cell transplantation into hindlimb ischemic disease model mice. 4 Weeks after cell transplantation, the recovery rate of blood perfusion reached 54% and 17% in the FSC regions of sorted cells- and non-sorted cells, respectively. This result suggests that derivation of a functional cell population from hESCs can be performed through cell sorting on the basis of cell volume after preliminary differentiation induction. This approach may then greatly contribute to overcoming the limitations of marker sorting.
Purpose : The purpose of this study is to establish the method generating human brain anatomical connectivity from Korean children and evaluating the network topological properties using small-world network analysis. Materials and Methods : Using diffusion tensor images (DTI) and parcellation maps of structural MRIs acquired from twelve healthy Korean children, we generated a brain structural connectivity matrix for individual. We applied one sample t-test to the connectivity maps to derive a representative anatomical connectivity for the group. By spatially normalizing the white matter bundles of participants into a template standard space, we obtained the anatomical brain network model. Network properties including clustering coefficient, characteristic path length, and global/local efficiency were also calculated. Results : We found that the structural connectivity of Korean children group preserves the small-world properties. The anatomical connectivity map obtained in this study showed that children group had higher intra-hemispheric connectivity than inter-hemispheric connectivity. We also observed that the neural connectivity of the group is high between brain stem and motorsensory areas. Conclusion : We suggested a method to examine the anatomical brain network of Korean children group. The proposed method can be used to evaluate the efficiency of anatomical brain networks in people with disease.
Baek, Hee Jo;Han, Dong Kyun;Kim, Young Ok;Choi, Ic Sun;Hwang, Tai Ju;Kook, Hoon
Clinical and Experimental Pediatrics
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v.52
no.6
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pp.713-716
/
2009
Facial palsy as the presenting symptom of leukemia is very rare, especially in acute myeloid leukemia. A review of the medical literature identified reports on 8 children with AML who had facial paralysis as the presenting sign. Whole brain irradiation (WBI) has been applied in most cases. We present the cases of 3 such children. Achieving a remission without WBI, the patients underwent stem cell transplantations (SCTs). Two patients remain event-free 52 months and 62 months after allotransplants. Facial palsy was the harbinger of leukemic relapse in one case after autotransplant. This patient is disease-free 59 months after unrelated SCT rescue. Facial palsy persisted in 2 cases. Allogeneic SCT without WBI may be an effective therapy in patients presenting with facial palsy. A brief review of the literature is presented here.
It is commonly acknowledged that bone morphogenic protein (BMP-2) functions as a potential osteogenic inducer in bone formation. Recently, several papers reported that bone marrow-derived stem cell (BMSC) from human is not responsive to BMP-2 in comparison to high capacity of BMP-2 in the osteoinduction of stromal cell derived from bone marrow of rodent animals such as rat or mouse. In this study, we characterized BMSC derived from 11 years old donor for the responsiveness to rhBMP-2, dexamethasone (Dex) and 1,25-dihydroxyvitamin D (vitamin D), in order to analyze their function in the early osteogenesis. The effect of over mentioned agents was evaluated by means of assessing alkaline phosphatase (ALP) activity/staining, RT-PCR analysis and von Kossa staining. In addition, we analyzed the meaning of expressed several osteoblastic markers such as alkaline phosphatase, collagen typeI, osteopontin, bone sialoprotein and osteocalcin with relation to either differentiation or mineralization. Only in the presence of Dex, human BMSC could commit osteoblastic differentiation and matrix mineralization, and either BMP-2 or vitamin D treatment was not able to induce. But BMP-2 or Vitamin D showed potential synergy effect with Dex. ALP and bone sialoprotein were clearly expressed in response of Dex treatment compared to weak expression of osteopontin in early osteogenesis. Therefore, we expect that this study will contribute partly to elucidiating early osteogenesis mechanism in human, but variations among bone marrow donors must be considered through further study.
Toxic lesions of styrene in the Japanese Medaka (Oryzias latipes) were compared with those of styrene oxide, the active metabolite of styrene, using embryo-larval assays. The developmental stages of Japanese Medaka (Oryzias latipes) treated with both chemicals were not altered and progressed normally. However, styrene oxide was more toxic than styrene in terms of causing death and lesions . High concentrations of styrene (higher than 4.9 ppm) and styrene oxide (higher than 2.4 ppm), resulting in more than 50% mortality, caused similar lesions of cardiovascular system, craniofacial bone formation and spinal deformities, although a number of lesions were not observed by both chemicals . In the group treated with styrene, eyeball sizes and intereye distances were reduced, while, in the group treated with styrene oxide , the eyes and eye cups were not developed and two eyes were sometimes fused. In addition, styrene oxide caused the lesion which involved the posterior brain and brain stem were herniated through the spinal cord . The noticeable difference of toxic symptoms between these two chemicals was the time of onset. Toxicities of cardiovascular system and craniofacial bone formation appeared on day 3 of development in styrene oxide treated group, but, styrene treated group staned to show hemorrhages on day 3 and the craniofacial malformation were appeared on day 5, These differences between two chemicals may be due to the metabolism of styrene to styrene oxide, the reactive intermediate.
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