Subacute Neurological Deterioration with Selective Axonal Injury in Patients with Acute Ischemic Stroke following Reperfusion of Middle Cerebral Artery Occlusion

To date, the long-term effects of reperfusion on the salvaged brain tissues have not been addressed in the literature. We report 4 cases presenting subacute neurological deteriorations with selective axonal injury following reperfusion therapies for acute ischemic stroke. Our case series based on 4 patients showed common features distinct from those of early reperfusion injury in that (1) the neurological symptoms developed after 1-2 months of reperfusion therapies, (2) these symptoms were accompanied by the subcortical white matter changes on brain MRI, and (3) these findings were mostly reversible with time. This suggests that axons in the reperfused brain may be vulnerable to further neurological injury

A Study of Micronucleus Induction with Methyl Formate and 2-Methylbutane in Bone Marrow Cells of Male ICR Mice

Objectives: We investigated the genotoxicity of two chemicals, methyl formate and 2-methylbutane, using male ICR mice bone marrow cells for the screening of micronucleus induction. Although these two chemicals have already been tested numerous times, a micronucleus test has not been conducted and the amounts used have recently been increased.Methods: 7 week male ICR mice were tested at dosages of 250, 500, and 1,000mg/kg for methyl formate and 500, 1,000, and 2,000mg/kg for 2-methlybutane, respectively. After 24 hours of oral administration with the two chemicals, the mice were sacrificed and their bone marrow cells were prepared for smearing slides.Results: As a result of counting the micronucleated polychromatic erythrocyte (MNPCE) of 2,000 polychromatic erythrocytes (PCE), all treated groups expressed no statistically significant increase of MNPCE compared to the negative control group. There were no clinical signs related with the oral exposure of these two chemicals.Conclusion: It was concluded that the two chemicals did not induce micronucleus in the bone marrow cells of ICR mice, and there was no direct proportion with dosage. These results indicate that the two chemicals have no mutagenic potential under each study condition

Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.</p> <p>Results</p> <p>From hESCs, we derived NESs, the <it>in-vitro </it>version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of <it>in-vivo</it>-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their <it>in-vivo </it>counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons.</p> <p>Conclusion</p> <p>Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an <it>in-vitro </it>model for <it>in-vivo </it>neurogenesis.</p

Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an alzheimer's disease model mouse

<p>Abstract</p> <p>Background</p> <p>Alzheimer's Disease (AD) is the most common of the conformational neurodegenerative disorders characterized by the conversion of a normal biological protein into a β-sheet-rich pathological isoform. In AD the normal soluble Aβ (sAβ) forms oligomers and fibrils which assemble into neuritic plaques. The most toxic form of Aβ is thought to be oligomeric. A recent study reveals the cellular prion protein, PrP^C, to be a receptor for Aβ oligomers. Aβ oligomers suppress LTP signal in murine hippocampal slices but activity remains when pretreated with the PrP monoclonal anti-PrP antibody, 6D11. We hypothesized that targeting of PrP^Cto prevent Aβ oligomer-related cognitive deficits is a potentially novel therapeutic approach. APP/PS1 transgenic mice aged 8 months were intraperitoneally (i.p.) injected with 1 mg 6D11 for 5 days/week for 2 weeks. Two wild-type control groups were given either the same 6D11 injections or vehicle solution. Additional groups of APP/PS1 transgenic mice were given either i.p. injections of vehicle solution or the same dose of mouse IgG over the same period. The mice were then subjected to cognitive behavioral testing using a radial arm maze, over a period of 10 days. At the conclusion of behavioral testing, animals were sacrificed and brain tissue was analyzed biochemically or immunohistochemically for the levels of amyloid plaques, PrP^C, synaptophysin, Aβ40/42 and Aβ oligomers.</p> <p>Results</p> <p>Behavioral testing showed a marked decrease in errors in 6D11 treated APP/PS1 Tg mice compared with the non-6D11 treated Tg groups (p < 0.0001). 6D11 treated APP/PS1 Tg mice behaved the same as wild-type controls indicating a recovery in cognitive learning, even after this short term 6D11 treatment. Brain tissue analysis from both treated and vehicle treated APP/PS1 groups indicate no significant differences in amyloid plaque burden, Aβ40/42, PrP^Cor Aβ oligomer levels. 6D11 treated APP/PS1 Tg mice had significantly greater synaptophysin immunoreactivity in the dentate gyrus molecular layer of the hippocampus compared to vehicle treated APP/PS1 Tg mice (p < 0.05).</p> <p>Conclusions</p> <p>Even short term treatment with monoclonal antibodies such as 6D11 or other compounds which block the binding of Aβ oligomers to PrP^Ccan be used to treat cognitive deficits in aged AD transgenic mice.</p

Therapeutic Effects of Holmium-166 Chitosan Complex in Rat Brain Tumor Model

This study examined the effectiveness of Holmium-166 (Ho-166) chitosan complex therapy for a malignant glioma. Cultured C6 glioma cells (100,000 in 5 µl) were injected into the caudate/putamen of 200 - 250 gram Wistar rats. Five days later, a Ho-166 chitosan complex was injected into the same site of the glioma injection. Four injection doses were administered: the control group received PBS 10 µl, group 1 received an injection of 100 µCi (10 µl), group 2 received an injection of 50 µCi (5 µl), and group 3 received an injection of 10 µCi (1 µl). The average tumor volume for each group was 1.385 mm3 for the control group, 0.036 mm3 for group 1, 0.104 mm3 for group 2, and 0.111 mm3 for group 3. Compared with the control group, the size of the tumors in groups 1, 2 and 3 was reduced by an average of 97.4%, 92.5% and 91.9%, respectively. The Kaplan-Meier survival curve of group 2 was the longest, followed by groups 3, group 1 and the control. The mean survival was 22.8, 59, 60, and 44.6 days for the control group and groups 3, 2 and 1, respectively. H-E staining revealed that group 2 yielded the best results in the destruction of the malignant glioma. TUNEL staining and immunohistochemical studies indicated apoptotic features. The Ho-166 chitosan complex proved to be effective in destroying the malignant glioma

Properties of Central Caustics in Planetary Microlensing

To maximize the number of planet detections, current microlensing follow-up observations are focusing on high-magnification events which have a higher chance of being perturbed by central caustics. In this paper, we investigate the properties of central caustics and the perturbations induced by them. We derive analytic expressions of the location, size, and shape of the central caustic as a function of the star-planet separation, $s$, and the planet/star mass ratio, $q$, under the planetary perturbative approximation and compare the results with those based on numerical computations. While it has been known that the size of the planetary caustic is \propto \sqrt{q}, we find from this work that the dependence of the size of the central caustic on $q$ is linear, i.e., \propto q, implying that the central caustic shrinks much more rapidly with the decrease of $q$ compared to the planetary caustic. The central-caustic size depends also on the star-planet separation. If the size of the caustic is defined as the separation between the two cusps on the star-planet axis (horizontal width), we find that the dependence of the central-caustic size on the separation is \propto (s+1/s). While the size of the central caustic depends both on $s$ and q, its shape defined as the vertical/horizontal width ratio, R_c, is solely dependent on the planetary separation and we derive an analytic relation between R_c and s. Due to the smaller size of the central caustic combined with much more rapid decrease of its size with the decrease of q, the effect of finite source size on the perturbation induced by the central caustic is much more severe than the effect on the perturbation induced by the planetary caustic. Abridged.Comment: 5 pages, 4 figures, ApJ accepte