Tetramethylpyrazine reverses intracerebroventricular streptozotocin-induced memory deficits by inhibiting GSK-3ß.

Brain dysfunction, especially cognitive impairment, is one of the main complications in Alzheimer's disease (AD), which threatens the health of 46.8 million people worldwide. At present, the pathogenesis of cognitive dysfunction is only partially understood, and effective therapies for memory loss in AD remain elusive. Tetramethylpyrazine (TMP) is one of the major bioactive compounds purified from Chuanxiong, a Chinese herb used for the treatment of neurovascular and cardiovascular diseases. The neuroprotective properties of TMP are evident in some neurodegenerative diseases, including Parkinson's disease. However, whether TMP plays a neuroprotective role in AD is still unknown. Here, we report that 2-week treatment with TMP rescued both short-term and long-term fear memory impairment induced by intracerebroventricular injection of streptozotocin in a well-known AD rat model. Administration of TMP also restored spatial learning and memory retention abilities in streptozotocin-injected rats. Furthermore, TMP inhibited the activity of GSK-3ß, an important kinase that mediates hippocampal synaptic and memory disorders in diabetes mellitus. Finally, we found that TMP treatment restored the function of cholinergic neurons. Our data suggest that dietary uptake of TMP can provide protection against memory loss in AD, and the inhibition of GSK-3ß may play an important role in this protective effect.

Minocycline ameliorates D-galactose-induced memory deficits and loss of Arc/Arg3.1 expression.

Dysfunction of learning and memory is widely found in many neurological diseases. Understanding how to preserve the normal function of learning and memory will be extremely beneficial for the treatment of these diseases. However, the possible protective effect of minocycline in memory impairment is unknown. We used the well-established D-galactose rat amnesia model and two behavioral tasks, the Morris water maze and the step-down task, for memory evaluation. Western blot and PCR were used to examine the protein and mRNA levels of Arc/Arg3.1. We report that minocycline supplementation ameliorates both the spatial and fear memory deficits caused by D-galactose. We also found that Arc/Arg3.1, c-fos, and brain-derived neurotrophic factor levels are decreased in the D-galactose animal model, and that minocycline reverses the protein and mRNA levels of Arc in the hippocampus, suggesting the potential role of Arc/Arg3.1 in minocycline's neuroprotective mechanism. Our study strongly suggests that minocycline can be used as a novel treatment for memory impairment in neurological diseases.

[Research for the antiapoptotic mechanisms of bone marrow mesenchymal stem cells in the treatment of brain ischemia stroke].

OBJECTIVE: To evaluate the anti-apoptosis role of bone marrow mesenchymal stem cells (BMMCs) transplantation to cell cerebral brain ischemia mice. METHODS: BMMCs were separated through Ficoll from bone marrow, after amplified in vitro, flow cytometry was used to identify the surface markers. Then cells were transplanted into Middle cerebral artery occlusion (MACO) mice, in situ cell death detection kit and Western blot were used to examine the cell apoptosis. Immunofluorescence and Western blot were used to detect the expression of eNOS, ICAM-1, CD31 which are related to the repair of vascular endothelial cells. RESULTS: After BMMCs transplantation, the number of apoptosis cells was decreased from (78.2±1.4) to (12.8±3.0), P<0.05. The expression of eNOS (80.0±6.2 vs 31.2±1.6, P<0.01) and CD31 (85±3 vs 45±5, P<0.01), were higher than MACO, while ICAM-1 was lower than MACO (34.1±2.2 vs 85.2±2.8, P<0.01). CONCLUSION: BMMCs reduce the cell apoptosis of ischemia mice through regulate the expression of vascular endothelial cells relate genes.

Lithiation Depth Regulation of Silicon Anodes toward Excellent Stability.

Silicon (Si) is an appealing choice of anode for next-generation lithium ion batteries with high energy density, but its dramatic volume expansion makes it a tremendous challenge to achieve acceptable stability. Herein, we demonstrate that no capacity decay is observed during the testing period when the lithiation depth of Si nanoparticles is regulated at 2000 mAh g-1 or below, the fracture of Si anode films is well mitigated under suitable regulation of lithiation depth, and the cycled Si remains particulate without turning flocculent as under full lithiation. In addition, the solid electrolyte interphase (SEI) with a LiF-dominated outer region produced under lithiation regulation could better passivate the Si anodes and prevent further electrolyte decomposition than the mosaic-type SEI formed under full lithiation. Regulating lithiation depth proved to be a feasible solution to the pressing volume issues, and optimization of capacity utilization should be considered as much as materials-level optimization.

Underlying Mechanisms of Memory Deficits Induced by Etomidate Anesthesia in Aged Rat Model: Critical Role of Immediate Early Genes.

BACKGROUND: Etomidate (R-1-[1-ethylphenyl] imidazole-5-ethyl ester) is a widely used anesthetic drug that had been reported to contribute to cognitive deficits after general surgery. However, its underlying mechanisms have not been fully elucidated. In this study, we aimed to explore the neurobiological mechanisms of cognitive impairments that caused by etomidate. METHODS: A total of 30 Sprague-Dawley rats were used and divided into two groups randomly to receive a single injection of etomidate or vehicle. Then, the rats' spatial memory ability and neuronal survival were evaluated using the Morris water maze test and Nissl staining, respectively. Furthermore, we analyzed levels of oxidative stress, as well as cyclic adenosine 3',5'-monophosphate response element-binding (CREB) protein phosphorylation and immediate early gene (IEG, including Arc, c-fos, and Egr1) expression levels using Western blot analysis. RESULTS: Compared with vehicle-treated rats, the etomidate-treated rats displayed impaired spatial learning (day 4: 27.26 ± 5.33 s vs. 35.52 ± 3.88 s, t = 2.988, P = 0.0068; day 5: 15.84 ± 4.02 s vs. 30.67 ± 4.23 s, t = 3.013, P = 0.0057; day 6: 9.47 ± 2.35 s vs. 25.66 ± 4.16 s, t = 3.567, P = 0.0036) and memory ability (crossing times: 4.40 ± 1.18 vs. 2.06 ± 0.80, t = 2.896, P = 0.0072; duration: 34.00 ± 4.24 s vs. 18.07 ± 4.79 s, t = 3.023, P = 0.0053; total swimming distance: 40.73 ± 3.45 cm vs. 27.40 ± 6.56 cm, t = 2.798, P = 0.0086) but no neuronal death. Furthermore, etomidate did not cause oxidative stress or deficits in CREB phosphorylation. The levels of multiple IEGs (Arc: vehicle treated rats 100%, etomidate treated rats 86%, t = 2.876, P = 0.0086; c-fos: Vehicle treated rats 100%, etomidate treated rats 72%, t = 2.996, P = 0.0076; Egr1: Vehicle treated rats 100%, etomidate treated rats 58%, t = 3.011, P = 0.0057) were significantly reduced in hippocampi of etomidate-treated rats. CONCLUSION: Our data suggested that etomidate might induce memory impairment in rats via inhibition of IEG expression.

The effects of Gouqi extracts on Morris maze learning in the APP/PS1 double transgenic mouse model of Alzheimer's disease.

The present study examined the effects of Gouqi (Lycium barbarum) on the learning and memory abilities of an APP/PS1 double transgenic mouse model of Alzheimer's disease. We employed a Morris water maze to examine the spatial memory in this mice line with or without Gouqi extracts treatment. We identified that 2 weeks of oral administration of Gouqi extracts at 10 mg/kg improved the performance of the APP/PS1 mice in the learning and the memory retrieval phases of the Morris maze. In correlation with this, the levels of Aß(1-42) in hippocampal tissue were reduced by the Gouqi treatment. We conclude that pharmacological treatment with Gouqi extracts is beneficial at the later stages of Alzheimer's disease.

Application of pulse acoustic microscopy technique for 3D imaging bulk microstructure of carbon fiber-reinforced composites.

Impulse acoustic microscopy technique is applied for 3D imaging of bulk microstructure of composite materials. Short pulses of focused high-frequency ultrasound have been employed for layer-by-layer imaging of internal microstructure of carbon fiber-reinforced composite (CFRC) laminates. The method provides spatial resolution of 60 microm and in-depth resolution of 80 microm, approximately. Echo signals reflected from structural units--plies, fiber bundles; and microflaws form acoustic images of microstructure at different depth inside samples. The images make it possible to see ply arrays, packing of bundles in plies; binding material distribution over the specimen body. They reveal failure of interply adhesion, buckling of single plies and fiber bundles, internal defoliations and disbonds, voids in the specimen body. The series of successive images offer outstanding possibilities to reconstruct the bulk structure, to estimate local variations of properties, topological and geometrical characteristics of structural components. The imaging technique has been applied to study different types of fiber packing--unidirectional, cross-ply and woven laminates. Mechanisms of ultrasonic contrast for diverse elements in acoustic images of CFRC laminate bulk microstructure and structural defects are discussed.

Local administration of vasoactive intestinal peptide after nerve transection accelerates early myelination and growth of regenerating axons.

Our goal was to determine whether local injections of vasoactive intestinal peptide (VIP) promote early stages of regeneration after nerve transection. Sciatic nerves were transected bilaterally in 2 groups of 10 adult mice. In the first group, 15 microg (20 microL) of VIP were injected twice daily into the gap between transected ends of the right sciatic nerve for 7 days (4 mice) or 14 days (6 mice). The same number of mice in the second group received placebo injections (20 microL of 0.9% sterile saline) in the same site, twice daily, for the same periods. After 7 days, axon sizes, relationships with Schwann cells and degree of myelination were compared in electron micrographs of transversely sectioned distal ends of proximal stumps. Fourteen days after transection, light and electron microscopy were used to compare and measure axons and myelin sheaths in the transection gap, 2-mm distal to the ends of proximal stumps. Distal ends of VIP-treated proximal stumps contained larger axons 7 days after transection. More axons were in 1:1 relationships with Schwann cells and some of them were surrounded by thin myelin sheaths. In placebo-treated proximal stumps, axons were smaller, few were in 1:1 relationships with Schwann cells and no myelin sheaths were observed. In VIP-treated transection gaps, measurements 14 days after transection showed that larger axons were more numerous and their myelin sheaths were thicker. Our results suggest that in this nerve transection model, local administration of VIP promotes and accelerates early myelination and growth of regenerating axons.