White and gray matter integrity evaluated by MRI-DTI can serve as noninvasive and reliable indicators of structural and functional alterations in chronic neurotrauma.

We aimed to evaluate whether white and gray matter microstructure changes observed with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI) can be used to reflect the progression of chronic brain trauma. The MRI-DTI parameters, neuropathologic changes, and behavioral performance of adult male Wistar rats that underwent moderate (2.1 atm on day "0") or repeated mild (1.5 atm on days "0" and "2") traumatic brain injury (TBI or rmTBI) or sham operation were evaluated at 7 days, 14 days, and 1-9 months after surgery. Neurobehavioral tests showed that TBI causes long-term motor, cognitive and neurological deficits, whereas rmTBI results in more significant deficits in these paradigms. Both histology and MRI show that rmTBI causes more significant changes in brain lesion volumes than TBI. In vivo DTI further reveals that TBI and rmTBI cause persistent microstructural changes in white matter tracts (such as the body of the corpus callosum, splenium of corpus callus, internal capsule and/or angular bundle) of both two hemispheres. Luxol fast blue measurements reveal similar myelin loss (as well as reduction in white matter thickness) in ipsilateral and contralateral hemispheres as observed by DTI analysis in injured rats. These data indicate that the disintegration of microstructural changes in white and gray matter parameters analyzed by MRI-DTI can serve as noninvasive and reliable markers of structural and functional level alterations in chronic TBI.

Post-ischemic protection of hepatocyte growth factor requires the type II transmembrane serine protease matriptase-A reciprocal regulation of the two for neuroprotection in stroke brain.

In a rat middle cerebral artery occlusion (MACo) model of ischemic stroke, intracerebroventricular administration of human recombinant hepatocyte growth factor (HGF) mitigated motor impairment and cortical infarction. Recombinant HGF reduced MCAo-induced TNFα and IL1ß expression, and alleviated perilesional reactivation of microglia and astrocyte. All of the aforementioned beneficial effects of HGF were antagonized by an inhibitor to the type II transmembrane serine protease matriptase (MTP). MCAo upregulated MTP mRNA and protein in the lesioned cortex. MTP protein, not the mRNA, was increased further by recombinant HGF but reduced when MTP inhibitor (MTPi) was added to the treatment. Changes of the endogenous active HGF by MCAo, HGF or MTPi paralleled with the changes of MTP protein under the same conditions whilst neither HGF mRNA nor the total endogenous HGF protein were altered. These data showed that the therapeutic effects of HGF in stroke brain is attributed to its proteolytic activation and that MTP is a main protease of the event. MCAo enhanced MTP mRNA and thus protein expression; the initial use of the recombinant active HGF stabilized MCAo-induced MTP protein and subsequent activation of endogenous latent HGF which in turn stabilized further MTP protein. A reciprocal regulation between MTP and HGF appears to be present where MTP promotes HGF activation and the active HGF prevents MTP protein turnover. This study, for the first time, shows that MTP can participate in neural protection in stroke brain through activation of HGF. The cycles of HGF-MTP regulation achieved preservation of the neurological activity.

Low-Temperature Cu/SiO2 Hybrid Bonding with Low Contact Resistance Using (111)-Oriented Cu Surfaces.

We adopted (111)-oriented Cu with high surface diffusivity to achieve low-temperature and low-pressure Cu/SiO2 hybrid bonding. Electroplating was employed to fabricate arrays of Cu vias with 78% (111) surface grains. The bonding temperature can be lowered to 200 °C, and the pressure is as low as 1.06 MPa. The bonding process can be accomplished by a 12-inch wafer-to-wafer scheme. The measured specific contact resistance is 1.2 × 10-9 Ω·cm2, which is the lowest value reported in related literature for Cu-Cu joints bonded below 300 °C. The joints possess excellent thermal stability up to 375 °C. The bonding mechanism is also presented to provide more understanding on hybrid bonding.

Spatiotemporal characterisation of ischaemic lesions in transient stroke animal models using diffusion free water elimination and mapping MRI with echo time dependence.

BACKGROUND AND PURPOSE: The excess fluid as a result of vasogenic oedema and the subsequent tissue cavitation obscure the microstructural characterisation of ischaemic tissue by conventional diffusion and relaxometry MRI. They lead to a pseudo-normalisation of the water diffusivity and transverse relaxation time maps in the subacute and chronic phases of stroke. Within the context of diffusion MRI, the free water elimination and mapping method (FWE) with echo time dependence has been proposed as a promising approach to measure the amount of free fluid in brain tissue robustly and to eliminate its biasing effect on other biomarkers. In this longitudinal study of transient middle cerebral artery occlusion (MCAo) in the rat brain, we investigated the use of FWE MRI with echo time dependence for the characterisation of the tissue microstructure and explored the potential of the free water fraction as a novel biomarker of ischaemic tissue condition. METHODS: Adult rats received a transient MCAo. Diffusion- and transverse relaxation-weighted MRI experiments were performed longitudinally, pre-occlusion and on days 1, 3, 4, 5, 6, 7 and 10 after MCAo on four rats. Histology was performed for non-stroke and 1, 3 and 10 days after MCAo on three different rats at each time point. RESULTS: The free water fraction was homogeneously increased in the ischaemic cortex one day after stroke. Between three and ten days after stroke, the core of the ischaemic tissue showed a progressive normalisation in the amount of free water, whereas the inner and outer border zones of the ischaemic cortex depicted a large, monotonous increase with time. The specific lesions in brain sections were verified by H&E and immunostaining. The tissue-specific diffusion and relaxometry MRI metrics in the ischaemic cortex were significantly different compared to their conventional counterpart. CONCLUSIONS: Our results demonstrate that the free water fraction in FWE MRI with echo time dependence is a valuable biomarker, sensitive to the progressive degeneration in ischaemic tissue. We showed that part of the heterogeneity previously observed in conventional parameter maps can be accounted for by a heterogeneous distribution of free water in the tissue. Our results suggest that the temporal evolution of the free fluid fraction map at the core and inner border zone can be associated with the pathological changes linked to the evolution of vasogenic oedema. Namely, the homogeneous increase in free water one day after stroke and its tendency to normalise in the core of the ischaemic cortex starting three days after stroke, followed by a progressive increase in free water at the inner border zone from three to ten days after stroke. Finally, the monotonous increase in free fluid in the outer border zone of the cortex reflects the formation of fluid-filled cysts.

Post-treatment with Posiphen Reduces Endoplasmic Reticulum Stress and Neurodegeneration in Stroke Brain.

Acetylcholinesterase (AChE) inhibitors have protective and anti-inflammatory actions against brain injury, mediated by nicotinic α7 cholinergic receptor activation. The use of AChE inhibitors in patients is limited by systemic cholinergic side effects. Posiphen, a stereoisomer of the AChE inhibitor Phenserine, lacks AChE inhibitor activity. The purpose of this study is to determine the protective effect of Posiphen in cellular and animal models of stroke. Both Posiphen and Phenserine reduced glutamate-mediated neuronal loss in co-cultures of primary cortical cells and microglia. Phenserine-, but not Posiphen-, mediated neuroprotection was diminished by the nicotinic α7 receptor antagonist methyllycaconitine. Posiphen antagonized NMDA-mediated Ca++ influx, thapsigargin-mediated neuronal loss and ER stress in cultured cells. Early post-treatment with Posiphen reduced ER stress signals, IBA1 immunoreactivity, TUNEL and infarction in the ischemic cortex, as well as neurological deficits in stroke rats. These findings indicate that Posiphen is neuroprotective against stroke through regulating Ca++i and ER stress.

Effects of signal averaging, gradient encoding scheme, and spatial resolution on diffusion kurtosis imaging: An empirical study using 7T MRI.

BACKGROUND: Although diffusion gradient directions and b-values have been optimized for diffusion kurtosis imaging (DKI), little is known about the effect of signal averaging on DKI reliability. PURPOSE: To evaluate how signal averaging influences the reliability of DKI indices using two gradient encoding schemes with three spatial resolutions. STUDY TYPE: Prospective. ANIMAL MODEL: Fifteen naïve Sprague-Dawley rats. FIELD STRENGTH/SEQUENCE: DKI was performed at 7T using two schemes (30 directions with three b-values [30d-3b] and six directions with 15 b-values [6d-15b]), three resolutions, and eight repetitions. ASSESSMENT: DKI reliability was assessed using voxelwise relative error (σ) and test-retest error of fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) within gray matter (GM) and white matter (WM). The number of excitations (NEX) was optimized by considering DKI reliability. The influence of the partial volume effect (PVE) was also assessed. STATISTICAL TEST: One-way analysis of variance. RESULTS: The 30d-3b scheme, compared with the 6d-15b scheme, exhibited apparently smaller σFA and σMK (eg, at NEX 1, in GM, for three resolutions, σFA : 19.9-38.2% vs. 34.2-61.4%, σMK : 6.9-11.4% vs. 14.1-15.4%) and similar σMD (all differences between two schemes <1.6%). The optimal NEX was determined as 2 for enabling a reliable measurement of DKI-derived indices. The PVE at the lowest resolution apparently increased σFA for both schemes (19.9% for 30d-3b and 34.2% for 6d-15b) and σMK for the 6d-15b scheme (14.7%) in GM, and exerted lower effects on MK values for the 30d-3b scheme (P > 0.05). DATA CONCLUSION: A higher number of diffusion directions would benefit FA and MK estimation. A higher spatial resolution helps to reduce PVE. By using the 30d-3b scheme, MK is considered a robust index to reflect microstructural changes in GM and WM. We propose a systematic approach to determine the optimal DKI protocols for appropriate preclinical settings. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1593-1603.

Wharton' jelly mesenchymal stromal cell therapy for ischemic brain injury.

Increasing evidence have supported that Wharton's jelly mesenchymal stem cell (WJ-MSCs) have immunomodulatory and protective effects against several diseases including kidney, liver pathologies, and heart injury. Few in vitro studies have reported that WJ-MSCs reduced inflammation in hippocampal slices after oxygen-glucose deprivation. We recently reported the neuroprotective effects of human WJ-MSCs (hWJ-MSCs) in rats exposed to a transient right middle cerebral artery occlusion. hWJ-MSCs transplantation significantly reduced brain infarction and microglia activation in the penumbra leading with a significant reduction of neurological deficits. Interestingly, the grafted hWJ-MSCs in the ischemic core were mostly incorporated into IBA1 (+) cells, suggesting that hWJ-MSCs were immunorejected by the host. The immune rejection of hWJ-MSCs was reduced in after cyclosporine A treatment. Moreover, the glia cell line-derived neurotrophic factor expression was significantly increased in the host brain after hWJ-MSCs transplantation. In conclusion, these results suggest that the protective effect of hWJ-MSCs may be due to the secretion of trophic factors rather than to the survival of grafted cells. This paper is a review article. Referred literature in this paper has been listed in the references section. The data sets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

Neuroprotective Action of Human Wharton's Jelly-Derived Mesenchymal Stromal Cell Transplants in a Rodent Model of Stroke.

Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs) have distinct immunomodulatory and protective effects against kidney, liver, or heart injury. Limited studies have shown that WJ-MSCs attenuates oxygen-glucose deprivation-mediated inflammation in hippocampal slices. The neuroprotective effect of intracerebral WJ-MSC transplantation against stroke has not been well characterized. The purpose of this study was to examine the neuroprotective effect of human WJ-MSC (hWJ-MSC) transplants in an animal model of stroke. Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic frame. hWJ-MSCs, pre-labeled with chloromethyl benzamide 1,1'-dioctadecyl-3,3,3'3'- tetramethylindocarbocyanine perchlorate (CM-Dil), were transplanted to the right cerebral cortex at 10 min before a transient (60 min) right middle cerebral artery occlusion (MCAo). Transplantation of hWJ-MSCs significantly reduced neurological deficits at 3 and 5 days after MCAo. hWJ-MSC transplants also significantly reduced brain infarction and microglia activation in the penumbra. Grafted cells carrying CM-Dil fluorescence were identified at the grafted site in the ischemic core; these cells were mostly incorporated into ionized calcium-binding adaptor molecule (+) cells, suggesting these xenograft cells were immuno-rejected by the host. In another set of animals, hWJ-MSCs were transplanted in cyclosporine (CsA)-treated rats. hWJ-MSC transplants significantly reduced brain infarction, improved neurological function, and reduced neuroinflammation. Less phagocytosis of CM-dil-labeled grafted cells was found in the host brain after CsA treatment. Transplantation of hWJ-MSC significantly increased glia cell line-derived neurotrophic factor expression in the host brain. Taken together, our data support that intracerebral transplantation of hWJ-MSCs reduced neurodegeneration and inflammation in the stroke brain. The protective effect did not depend on the survival of grafted cells but may be indirectly mediated through the production of protective trophic factors from the transplants.

Diffusion MRI quantifies early axonal loss in the presence of nerve swelling.

BACKGROUND: Magnetic resonance imaging markers have been widely used to detect and quantify white matter pathologies in multiple sclerosis. We have recently developed a diffusion basis spectrum imaging (DBSI) to distinguish and quantify co-existing axonal injury, demyelination, and inflammation in multiple sclerosis patients and animal models. It could serve as a longitudinal marker for axonal loss, a primary cause of permanent neurological impairments and disease progression. METHODS: Eight 10-week-old female C57BL/6 mice underwent optic nerve DBSI, followed by a week-long recuperation prior to active immunization for experimental autoimmune encephalomyelitis (EAE). Visual acuity of all mice was assessed daily. Longitudinal DBSI was performed in mouse optic nerves at baseline (naïve, before immunization), before, during, and after the onset of optic neuritis. Tissues were perfusion fixed after final in vivo scans. The correlation between DBSI detected pathologies and corresponding immunohistochemistry markers was quantitatively assessed. RESULTS: In this cohort of EAE mice, monocular vision impairment occurred in all animals. In vivo DBSI detected, differentiated, and quantified optic nerve inflammation, demyelination, and axonal injury/loss, correlating nerve pathologies with visual acuity at different time points of acute optic neuritis. DBSI quantified, in the presence of optic nerve swelling, ~15% axonal loss at the onset of optic neuritis in EAE mice. CONCLUSIONS: Our findings support the notion that axonal loss could occur early in EAE mice. DBSI detected pathologies in the posterior visual pathway unreachable by optical coherence tomography and without confounding inflammation induced optic nerve swelling. DBSI could thus decipher the interrelationship among various pathological components and the role each plays in disease progression. Quantification of the rate of axonal loss could potentially serve as the biomarker to predict treatment outcome and to determine when progressive disease starts.

Transplantation of human placenta-derived multipotent stem cells reduces ischemic brain injury in adult rats.

After the onset of stroke, a series of progressive and degenerative reactions, including inflammation, is activated, which leads to cell death. We recently reported that human placenta-derived multipotent stem cells (hPDMCs) process potent anti-inflammatory effects. In this study, we examined the protective effect of hPDMC transplants in a rodent model of stroke. Adult male Sprague-Dawley rats were anesthetized. hPDMCs labeled with a vital dye of fluorescing microparticles, DiI, or vehicle were transplanted into three cortical areas adjacent to the right middle cerebral artery (MCA). Five minutes after grafting, the right MCA was transiently occluded for 60 min. Stroke animals receiving hPDMCs showed a significant behavioral improvement and reduction in lesion volume examined by T2-weighted images 4 days poststroke. Brain tissues were collected 1 day later. Human-specific marker HuNu immunoreactivity and DiI fluorescence were found at the hPDMC graft sites, suggesting the survival of hPDMCs in host brain. Grafting of hPDMCs suppressed IBA1 immunoreactivity and deramification of IBA1(+) cells in the perilesioned area, suggesting activation of microglia was attenuated by the transplants. Taken together, our data indicate that hPDMC transplantation reduced cortical lesions and behavioral deficits in adult stroke rats, and these cells could serve as a unique anti-inflammatory reservoir for the treatment of ischemic brain injury.

Enhanced Retinal Ganglion Cell Survival in Glaucoma by Hypoxic Postconditioning After Disease Onset.

The neuroprotective efficacy of adaptive epigenetics, wherein beneficial gene expression changes are induced by nonharmful "conditioning" stimuli, is now well established in several acute, preclinical central nervous system injury models. Recently, in a mouse model of glaucoma, we demonstrated retinal ganglion cell (RGC) protection by repetitively "preconditioning" with hypoxia prior to disease onset, indicating an epigenetic approach may also yield benefits in chronic neurodegenerative disease. Herein, we determined whether presenting the repetitive hypoxic stimulus after disease initiation [repetitive hypoxic "postconditioning" (RH-Post)] could afford similar functional and morphologic protection against glaucomatous RGC injury. Chronic elevations in intraocular pressure (IOP) were induced unilaterally in adult male C57BL/6 mice by episcleral vein ligation. Mice were randomized to an RH-Post [1 h of systemic hypoxia (11% oxygen) every other day, starting 4 days after IOP elevation] or an untreated control group. After 3 weeks of experimental glaucoma, the 21-27% reduction and 5-25% prolongation in flash visual-evoked potential amplitudes and latencies, respectively, and the 30% impairment in visual acuity were robustly improved in RH-Post-treated mice, as was the 17% loss in RGC soma number and 20% reduction in axon integrity. These protective effects were observed without RH-Post affecting IOP. The present findings demonstrate that functional and morphologic protection of RGCs can be realized by stimulating epigenetic responses during the early stages of disease, and thus constitute a new conceptual approach to glaucoma therapeutics.

Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema.

The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA) and increased radial diffusivity, while less significantly increased axial diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and axial diffusivity with limited impact on radial diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, axial or radial diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice.

Axonal transport rate decreased at the onset of optic neuritis in EAE mice.

Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an inflammatory demyelinating neurodegenerative disease. Impaired axonal transport has been considered as an early event of neurodegenerative diseases. However, few studies have assessed the integrity of axonal transport in MS or its animal models. We hypothesize that axonal transport impairment occurs at the onset of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice. In this study, we employed manganese-enhanced MRI (MEMRI) to assess axonal transport in optic nerves in EAE mice at the onset of optic neuritis. Axonal transport was assessed as (a) optic nerve Mn(2+) accumulation rate (in % signal change/h) by measuring the rate of increased total optic nerve signal enhancement, and (b) Mn(2+) transport rate (in mm/h) by measuring the rate of change in optic nerve length enhanced by Mn(2+). Compared to sham-treated healthy mice, Mn(2+) accumulation rate was significantly decreased by 19% and 38% for EAE mice with moderate and severe optic neuritis, respectively. The axonal transport rate of Mn(2+) was significantly decreased by 43% and 65% for EAE mice with moderate and severe optic neuritis, respectively. The degree of axonal transport deficit correlated with the extent of impaired visual function and diminished microtubule-associated tubulins, as well as the severity of inflammation, demyelination, and axonal injury at the onset of optic neuritis.

Diffusion fMRI detects white-matter dysfunction in mice with acute optic neuritis.

Optic neuritis is a frequent and early symptom of multiple sclerosis (MS). Conventional magnetic resonance (MR) techniques provide means to assess multiple MS-related pathologies, including axonal injury, demyelination, and inflammation. A method to directly and non-invasively probe white-matter function could further elucidate the interplay of underlying pathologies and functional impairments. Previously, we demonstrated a significant 27% activation-associated decrease in the apparent diffusion coefficient of water perpendicular to the axonal fibers (ADC⊥) in normal C57BL/6 mouse optic nerve with visual stimulation using diffusion fMRI. Here we apply this approach to explore the relationship between visual acuity, optic nerve pathology, and diffusion fMRI in the experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis. Visual stimulation produced a significant 25% (vs. baseline) ADC⊥ decrease in sham EAE optic nerves, while only a 7% (vs. baseline) ADC⊥ decrease was seen in EAE mice with acute optic neuritis. The reduced activation-associated ADC⊥ response correlated with post-MRI immunohistochemistry determined pathologies (including inflammation, demyelination, and axonal injury). The negative correlation between activation-associated ADC⊥ response and visual acuity was also found when pooling EAE-affected and sham groups under our experimental criteria. Results suggest that reduction in diffusion fMRI directly reflects impaired axonal-activation in EAE mice with optic neuritis. Diffusion fMRI holds promise for directly gauging in vivo white-matter dysfunction or therapeutic responses in MS patients.

Manganese-enhanced MRI (MEMRI) via topical loading of Mn(2+) significantly impairs mouse visual acuity: a comparison with intravitreal injection.

Manganese-enhanced MRI (MEMRI) with topical loading of MnCl2 provides optic nerve enhancement comparable to that seen by intravitreal injection. However, the impact of this novel and non-invasive Mn(2+) loading method on visual function requires further assessments. The objective of this study is to determine the optimal topical Mn(2+) loading dosage for MEMRI and to assess visual function after MnCl2 loading. Intravitreal administration was performed to compare the two approaches of MnCl2 loading. Twenty-four hours after topical loading of 0, 0.5, 0.75, and 1 M MnCl2 , T1 -weighted, T2-weighted, diffusion tensor imaging and visual acuity (VA) assessments were performed to determine the best topical loading dosage for MEMRI measurements and to assess the integrity of retinas and optic nerves. Mice were perfusion fixed immediately after in vivo experiments for hematoxylin and eosin and immunohistochemistry staining. Topical loading of 1 M MnCl2 damaged the retinal photoreceptor layer with no detectable damage to retina ganglion cell layers or prechiasmatic optic nerves. For the topical loading, 0.75 M MnCl2 was required to see sufficient enhancement of the optic nerve. At this concentration the visual function was significantly affected, followed by a slow recovery. Intravitreal injection (0.25 µL of 0.2 M MnCl2 ) slightly affected VA, with full recovery a day later. To conclude, intravitreal MnCl2 injection provides more reproducible results with less adverse side-effects than topical loading.

Cell swelling contributes to thickening of low-dose N-methyl-D-aspartate-induced retinal edema.

PURPOSE: The contribution of cell swelling versus vascular leakage in retinal edema remains largely undefined. The objective of this study was to use in vivo magnetic resonance imaging (MRI) to assess retinal cell swelling in the edematous mouse retina. METHODS: Inner retinal edema was induced by intravitreal injection of 2.5 nmol N-methyl-D-aspartate (NMDA). To assess retinal cell swelling, diffusion MRI was performed at baseline, 3-hours, 1 day, 3 days, and 7 days (n ≥ 5 at each time point) after NMDA injection. To detect retinal vascular leakage, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced MRI was performed at baseline, 3 hours and 1 day (n = 5 for each group) after NMDA injection. Upon the completion of MRI, mouse eyes were enucleated, cryosectioned, and stained for assessing retinal layer thickness and cell death. RESULTS: Inner retinal cell swelling was hyperintense on diffusion-weighted images at 3 hours and 1 day after NMDA injection. The thickened inner retina was also seen in anatomic MRI and histology. Quantitatively, inner retinal apparent diffusion coefficient (ADC) decreased approximately 20% at 3 hours and 1 day after NMDA injection (P < 0.05 compared with baseline), suggesting cell swelling. Systematic injection of paramagnetic Gd-DTPA did not alter vitreous longitudinal relaxation time (T1) at baseline or at 3 hours after NMDA injection. In contrast, vitreous T1 in mice decreased 16 ± 6% (P < 0.05), reflecting retinal vascular leakage at 1 day after NMDA injection. CONCLUSIONS: Noninvasive diffusion MRI was performed to detect retinal cell swelling in vivo. Our results demonstrated that retinal cell swelling could directly lead to retinal thickening independent of vascular leakage.

High catalytic activity for CO oxidation of gold nanoparticles confined in acidic support Al-SBA-15 at low temperatures.

While there is a large number of recent studies of Au nanocatalysts supported on metal oxides, low-temperature CO oxidation under an acidic environment has not yet been accomplished. Over a novel acidic Al-SBA-15 support, uniformly distributed gold nanoparticles with sizes approximately 2.7 nm were obtained by a successive procedure of aminosilane grafting, gold adsorption-reduction, and then high-temperature hydrogen treatment. The catalyst system, Au@Al-SBA-15, exhibits extraordinarily high activity for CO oxidation at 80 degrees C. By varying the Si/Al ratio of the support, the dependence of the catalytic activity on the support Si/Al ratio was found in the CO oxidation reaction.