Alterations to cognitive abilities and functional networks in rats post broad-band intense noise exposure.

This study aimed to investigate the alterations of cognition and functional connectivity post noise, and find the progress and neural substrates of noise induced hearing loss (NIHL)-associated cognitive impairment. We exposed rats to 122 dB broad-band noise for 2 h to induce hearing loss and the auditory function was assessed by measuring auditory brainstem response thresholds. Morris water maze test and resting state MRI were computed at 0 day, 1, 3, 6 months post noise to reveal cognitive ability and neural substrate. The interregional connections in the auditory network and default mode network, as well as the connections using the auditory cortex and cingulate cortex as seeds were also examined addtionally. The deficit in spatial learning/memory was only observed at 6 months after noise exposure. The internal connections in the auditory network and default mode network were enhanced at 0 day and decreased at 6 months post noise. The connectivity using the auditory cortex and cingulate cortex as seeds generally followed the rule of "enhancement-normal-decrease-widely decrease". A new model accounting for arousal, dementia, motor control of NIHL in is proposed. Our study highlights the fundamental flexibility of neural systems, and may also point toward novel therapeutic strategies for treating sensory disorders.

Visualizing myocardial inflammation in a rat model of type 4 cardiorenal syndrome by dual-modality molecular imaging.

Type 4 cardiorenal syndrome (CRS) is a life-threatening world health problem in which chronic kidney disease leads to progressive cardiovascular disease. In type 4 CRS, cardiac inflammation is an excellent target for both detection and therapy; however, this progression was underestimated by previous studies due to the lack of effective detection methods. To noninvasively visualize cardiac inflammation and monitor therapeutic efficacy of anti-inflammatory treatment in type 4 CRS, we here synthesized a dual-modality magneto-fluorescent nanoparticle (MNP) by combining ultrasmall superparamagnetic iron oxide nanoparticle and Rhodamine B for both magnetic resonance imaging (MRI) and optical imaging. This dual-functional MNP exhibited excellent performance such as high r2 relaxivity coefficient (283.4 mM(-1) s(-1)), high magnetism (96.7 emu/g iron) and a near neutral surface charge to minimize the reticuloendothelial system uptake. In vivo cardiac MRI showed significant negative contrast in the type 4 CRS rats, and the signal intensity on optical imaging was significantly higher in the type 4 CRS group compared with sham-operated and drug-treated groups. The specific targeting profile of MNPs to monocyte-macrophages was proven by histopathological analysis. Taken together, we demonstrate that this dual-modality strategy is feasible for noninvasively assessing myocardial inflammation and monitoring therapeutic efficacy in type 4 CRS.

Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network.

Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus-hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed.

[Mapping fetal brain development in the second trimester with 7.0T magnetic resonance imaging].

OBJECTIVE: To obtain the three dimensional visualization model with normal measurements of fetal brain in the second trimester and analyze the developmental changes with gestational age (GA), sexual dimorphisms and cerebral asymmetries. METHODS: The brains of 69 fetal specimens of 12 - 22 weeks GA were scanned by 7.0T magnetic resonance imaging (MRI). The developing structures were analyzed and a three dimensional visualization model was rebuilt with Amira 4.1 software. RESULTS: Most sulci, except for postcentral and intraparietal sulcus, were present until 22 weeks GA. And none developed secondary branches. Laminar organization, described as early as 12 weeks GA, was delineated as layers with different signal intensities and became typical after 16 weeks GA. Basal nuclei was distinctly visible. Brains had different growth rates linearly increasing with GA. But neither sexual dimorphisms nor cerebral asymmetries was detected. CONCLUSIONS: The initial developmental stage of fetal brain occurs at 12 - 22 weeks GA. The developing structures may be distinctly visualized on 7.0T post-mortem MRI. And the three dimensional visualization model aids greatly in the precise cognition of immature brain.

Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice.

Proton magnetic resonance spectroscopy ((1)H-MRS) and the Morris water maze (MWM) have played an important role in Alzheimer's disease (AD) research. The aim of this study was to determine whether (1)H-MRS and the MWM can detect for early AD in APP/PS1 transgenic (tg) mice. (1)H-MRS was performed in 20 tg mice and 15 wild-type mice at 3, 5 and 8 months of age. The concentration of N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), choline (Cho) and creatine (Cr) in the hippocampus were measured, and the NAA/Cr, Glu/Cr, mI/Cr and Cho/Cr ratios were quantified. Additionally, the spatial learning and memory of the mice were evaluated by MWM. The (1)H-MRS revealed that mI levels in tg mice were significantly higher at 3 months of age compared to wt mice, while the NAA and Glu levels in 5- and 8-month-old tg mice were significantly decreased (p<0.05). Additionally, significant cognitive changes only occurred at 8 months of age in APP/PS1 tg mice. These results indicated that metabolic changes preceded overt cognitive dysfunctions in early-stage AD, suggesting that (1)H-MRS is a more sensitive biomarker for assessing early AD.

(1)H-MRS evaluation of therapeutic effect of neural stem cell transplantation on Alzheimer's disease in AßPP/PS1 double transgenic mice.

The aim of this work was to explore the applicable value of (1)H-MRS evaluation on the treatment of Alzheimer's disease (AD) with neural stem cell (NSC) transplantation by quantitative analysis of metabolite changes in the hippocampal area in AßPP/PS1 transgenic (tg) mice. The tg mice (n = 30) aged 12 months were randomized into two subgroups: One receiving NSCs and the other receiving PBS transplantation in the bilateral hippocampal CA1 region. The wild-type mice (n = 15) were used as the control group. (1)H-MRS was performed before transplantation and 6 weeks after transplantation to measure the change of N-acetylaspartate (NAA), myo-inositol (mI), glutamate (Glu), choline (Cho), and creatine (Cr) in the hippocampus. Results showed NAA and Glu levels were increased and mI level was decreased in NSC group compared with the PBS group at six weeks after transplantation (p < 0.05). There was no significant difference in NAA and Glu (p > 0.05), and there was significant difference in mI (p < 0.05) between NSC and control groups. However, there was no significant difference in Cho before and after transplantation among the three groups (p > 0.05). Histology showed the number of neurons in the hippocampal CA1 region increased significantly in the NSC group than those in the PBS group (p < 0.05), and the number of astrocytes significantly decreased in the NSC group compared with the PBS group. Ultrastructure showed that the neurons in the NSC group were morphologically normal. In conclusion, (1)H-MRS can display intracranial metabolite changes before and after NSC transplantation in tg mice and has a applicable value in evaluating the therapeutic effect of NSCs on AD.

[Modeling of acute thromboembolic stroke in mice].

OBJECTIVE: To evaluate the controllability and reproducibility of a acute thromboembolic cerebral ischemia model for studying molecular imaging and thrombolysis in mice by 7.0 Tesla magnetic resonance imaging (MRI). METHODS: Twenty-four male C57BL/6J mice were randomly divided into embolic group (n = 14) and sham-operated group (n = 10). To prepare rich fibrin and optimal length of clots and measure diameters of clots under microscope, the clots were injected into internal carotid artery via a microcatheter inserted from external carotid artery to bifurcation of common carotid artery in embolic group. In sham-operated group, phosphate-buffered saline containing bovine serum albumin was injected similarly. At 1, 3 or 24 h after injection of clots or phosphate-buffered saline containing bovine serum albumin, mice underwent 7.0 Tesla magnetic resonance imaging including sequences of magnetic resonance angiography (MRA), diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) by arterial spin labeling technology (ASL) and T(2) weighted imaging (T(2)WI) so as to evaluate the occlusive rate of middle cerebral artery (MCA) and the change of relative cerebral blood flow (rCBF) and lesion volumes. Triphenyl tetrazolium chloride (TTC) stain was performed at 24 h. RESULTS: The diameters of clots were 162 ± 14 µm. In embolic group at 1, 3 or 24 h after injection of clots, the occlusive rate of MCA was 78.6%, 71.4% and 57.1% respectively. And the values of rCBF decrease in mice showing occlusion of MCA in MRA images. The percents of rCBF value in embolic group were 26% ± 10% at 1 h and 26% ± 15% at 3 h respectively. They were significantly lower than the percents of rCBF value in sham-operated group at the same time points. The percents of infarct volumes at 24 h were 30% ± 4% from T(2)WI images and 30% ± 16% from TTC images. In sham-operated groups, both MRI and TTC images were negative. CONCLUSION: A murine model of acute thromboembolic cerebral ischemia has been successfully established. The improved method is both stable and feasible. It may be readily evaluated from multi-parameter imaging by 7.0 Tesla magnetic resonance imaging.

[Manganese enhanced magnetic resonance imaging for tracing corticospinal tracts in rat brain using 7.0 T MRI].

OBJECTIVE: To investigate the methods of manganese enhanced magnetic resonance imaging in 7.0 T magnetic field for tracing corticospinal tract in rat brain in vivo. METHODS: 0.4 microl volume of 1 mol/L aqueous solution of MnCl(2) was injected into the primary motor cortex of 9 SD rats under stereotaxis. MRI studies were performed for tracing corticospinal tract and other coherent nerve tracts before injection and 24 hours, 48 hours, 72 hours, 7 days after injection respectively using 7.0T Micro-MRI. RESULTS: Corticospinal tract was visualized perfectly from primary motor cortex, thalamus, cerebral peduncle to pons at different time points after Mn(2+) administration, and the best contrast was achieved after 24-48 h. At the same time, a small quantity of Mn(2+) reached the opposite somatosensory cortex through the corpus callosum. CONCLUSION: Manganese enhanced MRI visualizes perfectly the transport of Mn(2+) through axoplasmic flow in corticospinal tracts. This method may be used to investigate the change of corticospinal tract and the functional connectivity between two sides of hemisphere in rat brain.

Role of myo-inositol by magnetic resonance spectroscopy in early diagnosis of Alzheimer's disease in APP/PS1 transgenic mice.

BACKGROUND/AIMS: To explore the potential value of myo-inositol (mIns), which is regarded as a biomarker for early diagnosis of Alzheimer's disease, in APP/PS1 transgenic (tg) mice detected by (1)H-MRS. METHODS: (1)H-MRS was performed in 30 APP/PS1 tg mice and 20 wild-type (wt) littermates at 3, 5 and 8 months of age. Areas under the peak of N-acetylaspartate (NAA), mIns and creatine (Cr) in the frontal cortex and hippocampus were measured, and the NAA/Cr and mIns/Cr ratios were analyzed quantitatively. RESULTS: Compared with the wt mice, the mIns/Cr ratio of the 3-month-old tg mice was significantly higher (p < 0.05), and pathology showed activation and proliferation of astrocytes in the frontal cortex and hippocampus. The concentration of NAA was significantly lower at 8 and 8 months of age (p < 0.05). According to the threshold of mIns/Cr that was adopted to separate the tg from the wt mice, the rate of correct predictions was 82, 94 and 95%, respectively, for 3, 5 and 8 months. CONCLUSION: Of the early AD metabolites as detected by (1)H-MRS, mIns is the most valuable marker for assessment of AD. Quantitative analysis of mIns may provide important clues for early diagnosis of AD.