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aMCI and VCIND differ in cognitive function, memory strategy and sleep impairment; these characteristics are helpful to identify and distinguish patients with very early cognitive impairment. Our results also suggest that memory deficits are associated with sleep disturbance in aMCI and VCIND.

IntroductionThe spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury.MethodsRats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury.ResultsWe investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood–brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus.ConclusionsOur findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus.

Metal precursors employed in the bottom-up synthesis of metal nanoclusters (NCs) are of great importance in directing their composition and geometrical structure. In this work, a silver nanocluster co-protected by phosphine and thiolate, namely, [Ag39(PFBT)24(TPP)8]2– (Ag 39 , PFBT = pentafluorobenzenethiol, TPP = triphenylphosphine), was isolated and structurally characterized. It adopts a three-layered Ag13@Ag18@Ag8S24P8 core–shell structure. The Ag13@Ag18 kernel is unusual in multilayer noble metal NCs. By introducing a copper precursor in the synthesis, a bimetallic nanocluster [Ag37Cu2(PFBT)24(TPP)8]2– (Ag 37 Cu 2 ) with an identical structure to Ag 39 apart from two outer Ag atoms being substituted by Cu atoms was obtained. Astoundingly, the Cu precursor used in the synthesis was found to be critical in determining the final structure. The alteration of the Cu precursor led to the cocrystallization of the above alloy nanocluster with a Ag14 nanocluster, namely, [Ag37Cu2(PFBT)24(TPP)8]2–·[Ag14(PFBT)6(TPP)8] (Ag 37 Cu 2 ·Ag 14 ). The electronic structure analyzed by theoretical calculation reveals that Ag 39 is a 17-electron open-shell superatom. The optical absorption of Ag 39 , Ag 37 Cu 2 , and Ag 37 Cu 2 ·Ag 14 was compared and studied in detail. This work not only enriches the family of alloy metallic nanoclusters but also provides a metal NC-based cocrystal platform for in-depth study of its crystal growth and photophysical property.

Cerebral hypoperfusion is an important factor in the pathogenesis of cerebrovascular diseases and neurodegenerative disorders. We investigated the effects of memantine and rosuvastatin on both neovascularization and synaptic function in a rat model of chronic cerebral hypoperfusion, which was established by the bilateral common carotid occlusion (2VO) method. We tested learning and memory ability, synaptic function, circulating endothelial progenitor cell (EPC) number, expression of neurotrophic factors, and markers of neovasculogenesis and cell proliferation after memantine and/or rosuvastatin treatment. Rats treated with memantine and/or rosuvastatin showed significant improvement in Morris water maze task and long-term potentiation (LTP) in the hippocampus, compared with untreated 2VO model rats. Circulating EPCs, expression of brain-derived neurotrophic factor, and vascular endothelial growth factor, markers of microvessel density were increased by each of the three interventions. Rosuvastatin also increased cell proliferation in the hippocampus. Combined treatment with memantine and rosuvastatin showed greater effect on enhancement of LTP and expression of neurotrophic factors than either single medication treatment alone. Both memantine and rosuvastatin improved learning and memory, enhanced neovascularization and synaptic function, and upregulated neurotrophic factors in a rat model of chronic cerebral hypoperfusion.