Disruption of thalamic connectivity in Alzheimer's disease: a diffusion tensor imaging study.

The aim of this study was to evaluate the structural integrity of the thalamic connectivity of specific fiber tracts in different stages of Alzheimer's disease (AD) using diffusion tensor imaging (DTI). Thirty-five patients with AD and 22 normal control (NC) subjects were recruited. Based on Mini Mental State Examination score, the AD patients were divided into three subgroups for comparison with the NC group: mild (mi-AD, n = 14), moderate (mo-AD, n = 12), and severe (se-AD, n = 9) AD. The fornix (FX), anterior thalamic radiation (ATR), and posterior thalamic radiation (PTR) were selected to represent the thalamic connectivity with other brain regions. The fornix was divided into the column and body of the fornix (FX-1) and the bilateral fornix (crus)/stria terminalis (FX-2/ST) based on the atlas. Through the atlas-based analysis and fiber tracking method, we measured fractional anisotropy (FA), mean diffusivity (MD), and tract volume to reflect the microstructural and macrostructural changes of these fibers during AD progression. There were significant differences in the FA and MD of all fibers, except the right PTR, between the AD and NC subjects. Further subgroup analyses revealed that the mi-AD subgroup had decreased FA only in the FX-1 and increased MD in the FX-1 and bilateral ATR, the mo-AD subgroup showed declined FA and increased MD in the FX-1, bilateral FX-2/ST and ATR; the se-AD subgroup exhibited lower FA and higher MD values in all fibers except the right PTR. We also found reduced tract volume values in the FX and left ATR in the AD patients. Further subgroup analyses revealed that these differences only existed in the se-AD patients. Our DTI analyses indicate that the integrity of thalamic connectivity is progressively disrupted following cognitive decline in AD and that DTI parameters in the column and body of the fornix show promise as potential markers for the early diagnosis of AD and for monitoring disease progression.

Changes in the numbers of ribbon synapses and expression of RIBEYE in salicylate-induced tinnitus.

BACKGROUND: This study was performed to explore the mechanism underlying tinnitus by investigating the changes in the synaptic ribbons and RIBEYE expression in cochlear inner hair cells in salicylate-induced tinnitus. METHODS: C57BL/6J mice were injected with salicylate (350 mg/kg) for 10 days and grouped. Behavioral procedures were performed to assess whether the animals experienced tinnitus. The specific presynaptic RIBEYE protein and non-specific postsynaptic glutamate receptor 2&3 protein in basilar membrane samples were examined by immunofluorescent labeling. RT-PCR and Western blot assays were used to examine RIBEYE expression. Serial sections were used to build three-dimensional models using 3ds MAX software to evaluate the changes in the synaptic ribbons. RESULTS: The administration of salicylate increased false positives in the behavioral procedure from 3 d to 10 d. The membrane profiles of inner hair cells in all mice were intact. The number of synaptic ribbons in the salicylate group increased on the 7(th) d and decreased on the 9(th) and 10(th) d. mRNA and protein expression of RIBEYE were initially up-regulated and later down-regulated by injecting salicylate for 10 consecutive days. CONCLUSION: This change in the ribbon synapses of cochlear inner hair cells in salicylate-induced mice might serve as a compensatory mechanism in the early stages of ototoxicity and contribute to tinnitus later. The alteration of RIBEYE expression could be responsible for the changes in the morphology of ribbon synapses and for salicylate-induced tinnitus.

In situ growth of monodispersed Fe3O4 nanoparticles on graphene for the removal of heavy metals and aromatic compounds.

We report on the efficient removal of heavy metal ions and aromatic compounds from simulated wastewater with a nanocomposite. The nanocomposite was obtained via thermal decomposition of the precursor Fe(acac)3 onto the surface of graphene, modified by diethylenetriamine pentaacetic anhydride through dopamine. It was found that the maximum adsorption capacity of the nanocomposite toward Cu(2+) and naphthalene was 207.9 and 72.2 mg g(-1) respectively, displaying a high efficiency for the removal of heavy metal ions as well as aromatic compounds at pH 7.0 and 293 K. The Langmuir for naphthalene and the Freundlich for the Cu(2+) adsorption isotherms were applicable for describing the removal processes. Furthermore, the nanocomposite was carefully examined by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Raman spectra, and UV-vis spectroscopy. This work provides a very efficient, fast and convenient approach to exploring a promising nanocomposite for water treatment.

Association between serum cystatin C level and post-stroke cognitive impairment in patients with acute mild ischemic stroke.

BACKGROUND: Mild ischemic stroke (MIS) has been proved to be closely related to post-stroke cognitive impairment (PSCI). However, there are relatively few studies on the risk factors of MIS. We aimed to evaluate the relationship between serum cystatin C (CysC) level and cognitive function in patients with acute MIS. METHODS: Four hundred consecutive patients with acute MIS were screened and 281 patients were eligible for this study. The serum CysC levels were detected within 24 h after admission. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) at 3 months after acute MIS. Logistic regression was used to identify the predictors of PSCI, and the receiver operating characteristic (ROC) curve was applied to explore the optimal cut-off value. RESULTS: One hundred sixty-four (58.4%) patients were diagnosed with PSCI at 3 months follow-up. The serum CysC levels in patients with PSCI were significantly higher than patients without PSCI (p < .001). The binary logistic regression analysis showed that higher serum CysC level was an independent predictor for PSCI at 3 months (odds ratio [OR], 5.745; 95% confidence interval, [CI], 1.089-30.311; p = 0.039). The ROC curve showed that area under the curve (AUC) was 0.723, and at a 0.945 mg/l CysC cut-off point, the sensitivity and specificity for PSCI at 3 months were 79.9% and 58.1%, respectively. CONCLUSION: Our findings suggested that the serum CysC levels were increased after acute MIS, and higher serum CysC levels at baseline might be an independent risk factor for PSCI in patients with acute MIS, but further research are warranted.

Mild encephalitis/encephalopathy with a reversible splenial lesion secondary to encephalitis complicated by hyponatremia: A case report and literature review.

RATIONALE: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is an infection-associated encephalitis/encephalopathy syndrome that is predominately caused by a virus. MERS has no direct association with central nervous system (CNS) infections or inflammation. Non-CNS infections may cause reversible lesion in the splenium of corpus callosum. Recently, there have been reports of many patients with hyponatremia related MERS. Interleukin-6 (IL-6) was also found elevated in serum and in cerebrospinal fluid (CSF) in patients with MERS. The role of IL-6 in the non-osmotic release of vasopressin is crucial. Persistent hyponatremia may be linked to this effect. The following is a case report of MERS secondary to encephalitis, complicated by hyponatremia. We will summarize the latest research and progress regarding MERS. PATIENT CONCERNS: A 31-year-old man was admitted to our department with a 5-day history of fever and headache. His initial diagnosis was encephalitis and hyponatremia; during this period the patient also developed MERS secondary to the encephalitis. DIAGNOSES: Encephalitis was diagnosed by reviewing the history of fever, headache, neck rigidity and Kerning sign (+) on clinical examination. Lab tests revealed: serum VCA IgG (+), EBNA-1 IgG (-), EBV IgM (-), and inflammation in the analysis of CSF. Cranial MRI+C showed that the blood vessels on the surface of the brain were obviously increasing and thickening and diffuse slow waves were detected on the electroencephalogram (EEG). The patient's hyponatremia aggravated on the third day of hospitalization. On the fourth day of hospitalization, the patient was somnolent, apathetic, and slow. Magnetic resonance imaging (MRI) of the brain, with a T2-weighted fluid attenuated inversion recovery image, showed high-signal intensity in the splenium of the corpus callosum (SCC) on the fifth day of hospitalization. Diffusion-weighted imaging (DWI) showed splenial hyperintensity as a "boomerang sign" and reduced diffusion on apparent diffusion coefficient (ADC) maps. Cranial MRI findings returned to normal after 1 month. The diagnosis of MERS was confirmed. INTERVENTIONS: We administered an intravenous drip infusion of acyclovir and prescribed oral sodium supplementation. OUTCOMES: The patient's neurological symptoms gradually improved. The MRI lesion in the SCC disappeared on the 30th day. LESSONS: In patients with encephalitis accompanied by hyponatremia, elevated IL-6 or urinary ß2-microglobulin (ß2MG), and exacerbations such as sudden somnolence, delirium, confusion, and seizures, the possibility of secondary MERS should be investigated, in addition to the progression of encephalitis.

DT(270-326) , a Truncated Diphtheria Toxin, Increases Blood-Tumor Barrier Permeability by Upregulating the Expression of Caveolin-1.

AIM: The nontoxic mutant of diphtheria toxin (DT) has been demonstrated to act as a receptor-specific carrier protein to delivery drug into brain. Recent research showed that the truncated "receptorless" DT was still capable of being internalized into cells. This study investigated the effects and potential mechanisms of DT(270-326) , a truncated "receptorless" DT, on the permeability of the blood-tumor barrier (BTB). METHODS: BTB and GECs were subjected to DT(270-326) treatment. HRP flux assays, immunofluorescent, co-immunoprecipitation, Western blot, CCK-8, and Flow cytometry analysis were used to evaluate the effects of DT(270-326) administration. RESULTS: Our results revealed that 5 µM of DT(270-326) significantly increased the permeability of BTBin vitro, which reached its peak at 6 h. The permeability was reduced by pretreatment with filipinIII. DT(270-326) co-localized and interacted with caveolin-1 via its caveolin-binding motif. The mRNA and protein expression levels of caveolin-1 were identical with the changes of BTB permeability. The upregulated expression of caveolin-1 was associated with Src kinase-dependent tyrosine phosphorylation of caveolin-1, which subsequently induced phosphorylation and inactivation of the transcription factor Egr-1. The combination of DT(270-326) with doxorubicin significantly enhanced the loss of cell viability and apoptosis of U87 glioma cells in contrast to doxorubicin alone. CONCLUSIONS: DT(270-326) might provide a novel strategy to increase the delivery of macromolecular therapeutic agents across the BTB.

Effect of salicylate on the large GABAergic neurons in the inferior colliculus of rats.

Salicylate, the anti-inflammatory component of aspirin, induces transient tinnitus and hearing loss in clinical and animal experiments. However, the affected sites and mechanisms of generation remain unclear. Recently, down-regulation of inhibitory transmission mediated by γ-aminobutyric acid type A receptors was suggested to be crucial in generating tinnitus. However, the cell-specific pathways involved in this process were far from being understood. Here, we describe changes of inhibitory neurotransmitter, receptor, and glutamatergic axosomatic terminals in certain large GABAergic neurons (LGNs) in the inferior colliculus of rats treated with high doses of salicylate. Based on these results, we suggest that salicylate may affect inhibitory projection pathways from the inferior colliculus to the auditory cortex and lead to neural hyperactivity, perhaps by affecting the function of the LGNs.

Effects of synaptic plasticity regulated by 17beta-estradiol on learning and memory in rats with Alzheimer's disease.

OBJECTIVE: To investigate whether estrogen modulates learning and memory and long-term potentiation (LTP) in the hippocampus of rats with Alzheimer's disease (AD). METHODS: The rats were divided into ovariectomy (OVX) and estrogen replacement therapy (ERT) groups. Rats in the ERT group received OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1 microL (10 microg/microL) amyloid-beta peptide 1-40(Abeta1-40) into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological method, respectively. RESULTS: The escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group (P< 0.05). Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency stimulation (HFS), compared with that in OVX group (P< 0.01). CONCLUSION: ERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in AD rats.