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Sleep exerts important functions in the regulation of cognition and emotion. Recent studies have found that sleep disorder is one of the important risk factors for Alzheimer's disease (AD), but the effects of chronic sleep deprivation on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1/tau triple transgenic AD model (3xTg-AD) mice and wild type (WT) mice (n = 8 for each group) were subjected to chronic sleep deprivation by using the modified multiple platform method, with 20 h of sleep deprivation each day for 21 days. Then, open field test, elevated plus maze test, sugar water preference test, object recognition test, Y maze test and conditioned fear memory test were performed to evaluate anxiety- and depression-like behaviors, and multiple cognitive functions. In addition, the immunohistochemistry technique was used to observe pathological characteristics in the hippocampus of mice. The results showed that: (1) Chronic sleep deprivation did not affect anxiety- (P = 0.539) and depression-like behaviors (P = 0.874) in 3xTg-AD mice; (2) Chronic sleep deprivation exacerbated the impairments of object recognition memory (P < 0.001), working memory (P = 0.002) and the conditioned fear memory (P = 0.039) in 3xTg-AD mice; (3) Chronic sleep deprivation increased amyloid β (Aβ) deposition (P < 0.001) and microglial activation (P < 0.001) in the hippocampus of 3xTg-AD mice, without inducing abnormal tau phosphorylation and neurofibrillary tangles. These results indicate that chronic sleep deprivation exacerbates the impairments of recognition memory, working memory and conditioned fear memory in 3xTg-AD mice by aggravating Aβ deposition and the excessive activation of microglia in the hippocampus.
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Animais , Masculino , Camundongos , Doença de Alzheimer , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide/genética , Cognição , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-1 , Privação do Sono , Proteínas tauRESUMO
Laparotomy should be routinely performed in the cases of abdominal gunshot wounds. However, recent studies found that 20%-30% abdominal gunshot wounds were non therapeutic or negective, and some complications secondary to laparotomy, such as local infection, often developed. Selective non-operative management (SNOM) can reduce the incidence of operative complications, length of hospitalization, and medical cost, thus has been recommended for the patients with abdominal blunt and stabbing wounds. However, it remains obscure whether SNOM is suitable for patients with abdominal gunshot wounds and which patients should be suitable for SNOM. This paper aims to review the important findings from questionnaire survey, clinical practice studies, and large-scale systematic reviews, and then propose how to identify the candidates for SNOM, hoping to be helpful for improving our management strategy of abdominal gunshot wounds.
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Objective ToexplorethevalueofMRIiterativedecompositionofwaterandfatwithechoasymmetryandleastsquares estimationquantificationsequence(IDEALIQ)techniquetoevaluatemyelosuppressionduringradiotherapyandchemotherapyincervicalcancer. Methods 25femalesubjectswereenrolledinthisstudy,whowereclinicallydiagnosedascervicalcancerandacceptedtheradiotherapyand chemotherapy.AllthesubjectswereperformedwithsagittalMRIIDEALIQscansineachweek’streatmentandattheendofwhole fiveweeks’therapy,soeachpatienthad6timesMRIscans.ROIweremanuallyplacedonL4,L5andS1vertebralbodyandsubcutaneousfatto measurethefatfraction.ThefatfractioncolorimageswerereconstructedonaAW (AdvantageWorkstation)4.6workstation.Results Asthe radiationandchemotherapyprocess,thevaluesoffatfractionincreasedprogressivelyonL4,L5andS1vertebralbody(P<0.001), whilethefatfractionvaluesinsubcutaneousfatappearedstableallthetime(P=0.987).Conclusion MRIIDEALIQtechniquecan evaluatethereal-timefatfraction,andradiotherapyandchemotherapyplansmaybeoptimizedaccordingtothefatfractionresult.
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Purpose To investigate the value of application of D2-40/CD34-CK cocktail antibodies by double immunohistochemical staining for assessment of lymphovascular invasion (LVI) and to determine its prognostic significance in colorectal cancer with insufficient lymph node harvest. Methods Specimens from 133 cases of colorectal cancer with less than 12 lymph nodes were selected. HE staining and double immunohistochemical staining of the cocktail antibodies were performed to compare the difference of the two methods in screening for LVI. The The relationship between LVI confirmed by cocktail antibody immunohistochemical staining and clinicopathological characteristics and overall survival (OS) of patients was analyzed. Results (1) The detection rates of cocktail antibody double immunohistochemical staining and HE staining for LVI were 42.9％ (57/133) and 21.8％ (29/133) with statistically significant difference (P < 0.001). (2) The presence of LVI confirmed by double staining was significantly associated with Dukes staging, depth of invasion, clinical stages, lymph node metastasis and tumor budding (P < 0.05). (3) The presence of LVI, the location and extent of LVI, and the number of tumor cells in thrombus ≥5.5 for cases with LVI ≤2 clusters, were significantly associated with OS (P < 0.05). Conclusion D2-40/CD34-CK cocktail antibodies double staining is superior to routine HE staining in assessing LVI. LVI is intimately associated with tumor stage, lymph nodes metastasis and tumor budding, and it is an independent prognostic factor for CRC patients. It should be a supplementary examination for these patients with insufficient lymph node harvest.
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Objective To explore the value of intra-voxel incoherent motion diffusion weighted imaging(IVIM-DWI)in brain perfusion of early hypertensive patients. Methods Totally 36 hypertensive patients and 14 volunteers were recruited and scanned using routine MRI sequences including axial T2WI, T1WI, T2FLAIR, TOF-MRA and IVIM-DWI sequence. Perfusion-related diffusion coefficient (D*) values and perfusion fraction (f) values in various regions were measured separately.The independent sample t test was used to analyze the data.Results Compared with the volunteers,both D*values and f values in lenticular nucleus,thalamus,superior frontal gyrus,occipital lobe,genu of corpus callosum(CC)and posterior horns of periventricular WM, were found to be lower (P<0.05) in hypertensive patients. For other regions, there were no significant difference(P>0.05).Conclusion IVIM-DWI has the ability to detect subtle brain perfusion abnormalities at early stages of hypertension.It has an important value to the prevention and treatment of hypertensive encephalopathy.
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Objective To solve the problem of the low signal to noise ratio (SNR)and limited imaging quality using single pulse exciting method in magnetoacoustic imaging, as well as the limited imaging speed using wave averaging processing method to magnetoacoustic signal. Methods M-sequence coded exciting method was proposed to enhance SNR imaging efficiency. The SNR improvement and sidelobe level were investigated using M-sequence code by simulation and experiments.Results The SNR of magnetoacoustic signal were 19.4,29.6,and 40.4 dB respectively under 7,31 and 127 bit M-sequence coded excitation. Three bits of M-sequence coded excitation magnetoacoustic signals had the integrated sidelobe level being 14.1,10.0 and 7.6 dB,and the peak sidelobe level being 26.3,24.3 and 21.3 dB.In case the SNR was increased by 40 dB,127 bit of M-sequence coded excitation shortened the sampling and procession time from 53.1 s to 0.520 s when compared with singl-pulse excitation combined with waveform average.Conclusion The coded excitation is significant for magnetoacoustic signal SNR and imaging quality improvement.
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The anhydrite and gypsum are the main sulfate minerals during evaporation of seawater or lake.They record the information about relative hydrogeology and the composition of mother liquor.Boron is diffluent element, and often occurs in all kinds of evaporites.Presently, the boron isotope has been applied widely in mineral deposits forming, geochemistry and palaeoenvironment.However, there is little research about characteristic of boron isotope in anhydrite and gypsum minerals, because of the low content of boron and micro-solubility in water and hydrochloric acid.This study developed a method of extracting and purifying boron in anhydrite and gypsum by phase transformation and ion-exchange.Firstly, the samples were mixed with ammonium hydrogen carbonate to transform the calcium sulfate to calcium carbonate.And diluted hydrochloric acid (1 mol/L) was added to resolve calcium carbonate.The percent conversion was about 85%in the first stage, and up to complete resolution by repeating this process.Secondly, boron specific ion-exchange resin ( Amberlite IRA 743 ) was used to gather the boron ions fully and further refined the samples with more than 1 μg of boron by anionic and cationic resin mixed by Ion Exchange Ⅱ and Dowex 50 W × 8.Finally, according to the modified method by He, the values of boron isotope were determined by TIMS.The boron content is analytically pure gypsum was 3.501 ± 0.128 μg/g ( n=12 , RSD=3.6%) and the average recovery was 100.47%.Besides, the δ11B value of analytically pure gypsum added with NIST SRM 951 was 17.98‰±0.21‰ (n=3, RSD=1.2%).This method has good repeatability and can meet the requirements of boron isotopic measurement of anhydrite and gypsum.
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The specific loss of cholinergic neurons and the progressive deficits of cognitive function are the most primary characteristics of Alzheimer's disease (AD). Although the neurotoxicity of amyloid β protein (Aβ) in AD has been investigated extensively, it is still unclear whether the Aβ aggregated in the medial septum (MS), a major cholinergic nucleus projecting to the hippocampus, could affect hippocampal synaptic plasticity and further impair the memory behaviors. The present study investigated the effects of Aβ injection into the MS on hippocampal long-term potentiation (LTP) and cognitive behaviors of rats by using Morris water maze (MWM), Y maze and in vivo hippocampal LTP recording. The effects of kainic acid (KA), an agent with specific neurotoxicity to GABAergic neurons, were also observed. The results showed that: (1) Intra-MS injection of Aβ, not KA, impaired spatial learning and memory of rats in classical and reversal MWM tests; (2) Both Aβ and KA impaired novelty-seeking behavior of rats in Y maze; (3) Intra-MS injection of Aβ, not KA, suppressed in vivo hippocampal LTP in the CA1 region of rats; (4) Both Aβ and KA did not affect the motor ability in behavioral tests and the hippocampal paired-pulse facilitation (PPF) in electrophysiological recording. These results indicate that intra-MS injection of Aβ could impair spatial memory, cognitive flexibility and exploratory motivation, as well as hippocampal LTP in rats, suggesting that the cholinergic neurons in the MS and the septo-hippocampal projection could be important targets of neurotoxic Aβ, and the specific damage of cholinergic neurons in the MS is likely responsible for the impairments of hippocampal synaptic plasticity and cognitive function in AD.
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APP/PS1/tau triple transgenic (3xTg) mouse is a classical animal model of Alzheimer's disease (AD), which has abnormalities in recognition and electrophysiological properties at early 6-month-old age. However, few studies were performed by using simultaneously recording cognitive behavior and brain electrical activity in the conscious 3xTg mice. By using a new wireless recording system, we recorded hippocampal Theta oscillations in 3xTg mice during the process of fear conditioning test. The results showed that: (1) in training session, no significant difference in the fear behavior and hippocampal Theta activity was found between 3xTg mice and WT mice; (2) in test session, 3xTg mice showed a significant decrease in freezing ratio compared with WT mice when they were exposed to conditioning stimulus (CS); (3) the 3xTg mice showed lower peak power in Theta oscillation in both Pre-CS and CS duration compared with WT mice; (4) CS effectively induced an increase in the peak frequency of Theta oscillation in WT mice, but not in 3xTg mice. These results indicated that the impairment of cognition behavior in 3xTg mice was accompanied with the decreased peak power and peak frequency of Theta oscillation in the hippocampus, suggesting that a decline in Theta oscillation might be involved in the impairments of the fear conditioning, and the enhanced hippocampal Theta oscillation may be beneficial for improving AD cognitive function.
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OBJECTIVE@#To observe the gait changes of Alzheimer's disease PS1M146V/APPswe/tauP301L triple-transgenic (3xTg-AD) mice and to investigate the improvement effect of single chain variable domain antibody fragment 17 (scFv17) on the gait.@*METHODS@#In the present study, a selection of 6-month-old 3xTg-AD mice (=18) and C57BL/6 wild-type mice (=24) was performed. First, we observed their gait changes and found that the gait of 12-month-old 3xTg-AD mice was severely damaged. Then, the two groups of mice were randomly divided into four groups:WT+PBS(=12), WT+scFv17(=12), 3xTg-AD+PBS(=9) and 3xTg-AD+scFv17(=9). The gait behavior test and pathological test were performed after 12 weeks'continuous administration of scFv17 (1.5 mg/kg) or an equal volume of PBS (0.01 mol/L) by nasal gavage twice a week.@*RESULTS@#Compared with the same month old wild type mice, the rear track width of 12 month old 3xTg-AD mice was increased(<0.01), swing time percent was decreased (<0.01), stance time percent was increased(<0.01), so the ability of movement coordination and balance was seriously damaged. ScFv17 could improve the coordination and balance ability of 12 month old 3xTg-AD mice(<0.01). The morphological structure of 3xTg-AD mice cerebellar Purkinje cells was improved. The treatment of scFv17 increased the Nissl body number of the cerebellar Purkinje cells of 3xTg-AD mice (<0.01). scFv17 reduced the amyloid β protein (Aβ) plaques in the cerebellar cortex of 3xTg-AD mice (<0.01), and scFv17 reduced the intracellular neurofibrillary tangles (NFT) of the cerebellar Purkinje cells of the 3xTg-AD mice (<0.01).@*CONCLUSIONS@#The coordination and balance ability of 3xTg-AD mice was significantly impaired. ScFv17 can improve gait behaviour in the 3xTg-AD significantly.The mechanism may be related to the improvement of the structure and protein function of cerebellar Purkinje cells, and the eliminating of the Aβ plaques and the neurofibrillary tangles.
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Animais , Camundongos , Doença de Alzheimer , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide , Modelos Animais de Doenças , Marcha , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas tauRESUMO
Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation in the brain, as well as impaired cognitive behaviors. A sex difference in the prevalence of AD has been noted, while sex differences in the cerebral pathology and relevant molecular mechanisms are not well clarified. In the present study, we systematically investigated the sex differences in pathological characteristics and cognitive behavior in 12-month-old male and female APP/PS1/tau triple-transgenic AD mice (3×Tg-AD mice) and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofibrillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expression levels of hippocampal protein kinase A-cAMP response element-binding protein (PKA-CREB) and p38-mitogen-activated protein kinases (MAPK) also showed sex difference in the AD mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in the p-p38 in female, but not male, 3×Tg-AD mice. We suggest that an estrogen deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3×Tg-AD mice might be involved in the serious pathological and cognitive damage in these mice. Therefore, sex differences should be taken into account in investigating AD biomarkers and related target molecules, and estrogen supplementation or PKA-CREB-MAPK stabilization could be beneficial in relieving the pathological damage in AD and improving the cognitive behavior of reproductively-senescent females.
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Animais , Feminino , Humanos , Masculino , Doença de Alzheimer , Metabolismo , Patologia , Psicologia , Precursor de Proteína beta-Amiloide , Genética , Metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Metabolismo , Proteínas Quinases Dependentes de AMP Cíclico , Metabolismo , Modelos Animais de Doenças , Hipocampo , Metabolismo , Patologia , Inflamação , Metabolismo , Patologia , Psicologia , Aprendizagem em Labirinto , Fisiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Emaranhados Neurofibrilares , Metabolismo , Patologia , Placa Amiloide , Metabolismo , Patologia , Psicologia , Presenilina-1 , Genética , Metabolismo , Caracteres Sexuais , Memória Espacial , Fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno , Metabolismo , Proteínas tau , Genética , MetabolismoRESUMO
Alzheimer's disease (AD) is a progressively neurodegenerative disorder, which seriously affects human health but is still irreversible up to now. Recent studies indicate that type 2 diabetes mellitus (T2DM) is an important risk factor for AD, and the drugs used for treatment of T2DM have shown some neuroprotective effects in the treatment of AD. Glucagon-like peptide-1 (GLP-1)/ glucose-dependent insulinotropic polypeptide (GIP)/glucagon (Gcg) receptor Triagonist is a new monomeric polypeptide equally activating the GLP-1/GIP/Gcg receptors, which is built on the basis of GLP-1/Gcg receptor coagonist core sequence, and incorporated with partial amino acids of GIP. Recently, the Triagonist has been reported to be effective in alleviating diabetic complications in rodent models of obesity. The present study observed for the first time the cognitive improvement effects of the Triagonist in the triple-transgenic AD mice (3xTg-AD) by using multiple behavioral techniques, and explored its probable molecular mechanisms using ELISA and Western blot. The results showed that the chronic treatment with the Triagonist (i.p.) significantly reversed the impairments in working memory of 3xTg-AD mice, with an obvious increase in the percentage of correct spontaneous alternation in the Y maze; the Triagonist treatment also improved long-term spatial memory and re-learning ability of 3xTg-AD mice in classical Morris water maze and reverse water maze tests, with decreased escape latency in under water platform tests and increased swimming time in probe tests. ELISA and Western blot experiments showed that the Triagonist up-regulated the levels of cAMP, PKA and p-CREB in the hippocampus of 3xTg-AD mice. These results indicate that GLP-1/GIP/Gcg receptor Triagonist can improve the cognitive behaviors in 3xTg-AD mice, and the up-regulation of hippocampal cAMP/PKA/CREB signal pathway may mediate the neuroprotection of the Triagonist, suggesting that the GLP-1/GIP/Gcg receptor Triagonist may be a novel therapeutic strategy for the treatment of AD.
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The deposition of amyloid-β protein (Aβ) in the brain is the most important pathological feature of Alzheimer's disease (AD). The mechanism of Aβ neurotoxicity may be closely related to the disturbance of intracellular Cahomeostasis. Non-invasive micro-test technique (NMT) is a novel technique developed in recent years, which can be used to directly record transmembrane ion influx and efflux in a non-contact way by detecting the diffusion potentials outside of the membrane. The present study examined the effects of Aβpretreatment on glutamate (Glu)-induced Cainflux and low [Ca] solution-induced Caefflux in the hippocampal slices of C57BL/6 mice using NMT. The results showed that: (1) acute administration of Glu (2.5, 5, 10 mmol/L) evoked a persistent transmembrane Cainflux in hippocampal CA1 neurons, with a rapid onset and subsequent decay; (2) pretreatment with Aβ dose-dependently increased the average rate of Cainflux induced by Glu during the initial 5 min, which was blocked by NMDA receptor antagonist D-APV; (3) perfusion with low [Ca] artificial cerebrospinal fluid (aCSF) induced a continuous Caefflux, which was mostly blocked by KB-R7943, a specific antagonist of Na/Caexchanger; (4) Aβpretreatment partially inhibited the low [Ca] aCSF-induced Caefflux. These results indicate that Aβ not only facilitates Cainflux but also inhibits Caefflux, which jointly contribute to the Aβ-induced intracellular Caoverload; the potentiation of Aβ on Glu excitotoxicity is mainly mediated by NMDA receptors, while the target for Aβ to affect Caefflux was mainly Na/Caexchanger. NMT showed multiple advantages in detecting transmembrane Caflux in brain slices, such as non-invasiveness to target cells, fast, convenient and real-time acquisition of Caflux. Therefore, this study provided new experimental evidence for Aβ-induced Caoverload, as well as a novel application for NMT in measuring transmembrane Caflux of neurons in the brain.
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Objective To probe the value of 3.0T MRI in the preoperative assessment of rectal carcinoma.Methods The study recruited 41 patients who were confirmed by biopsy of rectal carcinoma and underwent conventional MRI, high-resolution MRI and diffusion weighted imaging(DWI), the distance from the inferior part of tumor to transitional skin and the percentage of circumferential invasion were measured, the tumor's T staging, N staging,and the status of circumferential resection margin(CRM) and extramural vascular invasion(EMVI) were assessed.MRI findings were compared with endoscope and postoperative pathological results.Results MRI could accurately show the distance from the inferior part of tumor to transitional skin(P>0.05);The mean percentage of circumferential invasion for the tumor with T1-T2 and T3 were 61%,83% respectively (P>0.05);The total accuracy of T,N staging diagnose were 80.5%,75.6% respectively, which had a better consistent with pathological T,N staging(Kappa=0.564,0.634);The total accuracy of CRM and EMVI diagnose were 90.2%,73.2% respectively,which had a better or moderate consistent with pathological diagnose(Kappa=0.765,0.461).Conclusion 3.0T MRI has the unique application in the preoperative assessment of rectal carcinoma, which can provide more comprehensive information for clinic.
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Objective To study the diffusion tensor imaging (DTI)features in acute cervical spinal cord injury (CSCI)and evaluate its clinical value.Methods Eight patients with acute CSCI (within 72 hours after onset)were performed conventional MRI and fast DTI scans (112 seconds)and diffusion tensor tractography (DTT)at 3.0T Siemens Trio Tim system.Meanwhile,the fractional anisotropy (FA) values and apparent diffusion coefficient (ADC)values were calculated separately in the site of lesions,the upper and lower sections to the lesions.Then the data were analyzed by paired-samples t test analysis with SPSS 13.0 software.Results Cervical spinal cord injury occurred likely in the sites of C5-C6 (account for 4/8)and C4-C5 (account for 3/8).All MRI and DTI images were satisfied for clinical diagnosis.The FA value and ADC value of injury lesions were markedly lower than that of the normal cord.Accordingly,the injury lesions on FA map and ADC map presented low signals.There were no significant differences of FA values and ADC values between the upper and lower sections to the lesions.DTT could help in displaying the disruption of spinal fiber tract in lancination case and distortion fibers in closed cervical spinal cord injury.Conclusion Fast DTI sequence at 3.0 Tesla may obtain the qualified spinal cord images.By calculation of FA values and ADC values in CSCI patients,DTI may play an important role in detecting the changes of anisotropy and water diffusion caused by myelin sheath injury and cytotoxic edema and vasogenic edema respectively.
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OBJECTIVE@#To explore the application value of postmortem multi-slice spiral computed tomography (MSCT) by observing and analyzing the injury features in the traffic accident victims.@*METHODS@#Ten traffic accident victims were scanned with whole body MSCT. The systemic autopsy was subsequently performed to compare with the results of MSCT. The advantages and disadvantages of autopsy and MSCT for obtaining the information of traffic accident injuries were then analyzed.@*RESULTS@#MSCT could reveal 3D shape of fractures clearly and detect air accumulation in different positions of the body, which showed the obvious advantages compared with autopsy. However, the resolution of MSCT was limited compared to the detection of organ and soft tissue injuries.@*CONCLUSION@#A combination of MSCT and autopsy is the best way for determining the manner and the cause of death in traffic fatality victims.
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Humanos , Acidentes de Trânsito , Autopsia , Fraturas Ósseas , Lesões dos Tecidos Moles , Tomografia Computadorizada EspiralRESUMO
The accumulation and neurotoxicity of amyloid β protein (Aβ) in the brain is one of major pathological hallmarks of Alzheimer's disease (AD). The effective drugs against Aβ have been still deficient up to now. According to a most recent study, (D-Ser2) Oxm, a new antidiabetic drug, not only improves the disorders in plasma glucose and insulin in type 2 diabetes mellitus (T2DM) rats, but also exerts positive effects on hippocampal neurogenesis and synaptogenesis. However, it is still unclear whether (D-Ser2)Oxm can directly protect cultured neurons against Aβ1-42-induced cytotoxicity. In the present study, we investigated the neuroprotective effects of (D-Ser2)Oxm on the cultured primary hippocampal neurons by testing the cell viability, neuronal apoptosis, mitochondrial membrane potential and intracellular calcium concentration. The results showed that treatment with (D-Ser2)Oxm effectively reversed Aβ1-42-induced decline in cell viability (P < 0.001), and this protective effect could be inhibited by the pretreatment with exendin(9-39), a GLP-1 receptor blocker. (D-Ser2)Oxm treatment also decreased Aβ1-42-induced neuronal early apoptosis and down-regulated apoptotic protein caspase3. Meantime, (D-Ser2)Oxm treatment inhibited Aβ1-42-induced [Ca(2+)]i elevation, mitochondrial membrane potential depolarization, and glycogen synthase kinase-3β (GSK3β) activation. These results suggest that (D-Ser2)Oxm can protect hippocampal neurons against Aβ1-42-induced cytotoxicity and this effect may be related to activation of GLP-1 receptors, regulation of intracellular calcium homeostasis and stabilization of mitochondrial membrane potential.
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Animais , Ratos , Peptídeos beta-Amiloides , Cálcio , Sobrevivência Celular , Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipocampo , Hipoglicemiantes , Insulina , Potencial da Membrana Mitocondrial , Neurogênese , Neurônios , Fármacos NeuroprotetoresRESUMO
<p><b>OBJECTIVE</b>The present study investigated the effects of rapamycin on Aβ1-42-induced deficits in working memory and synaptic plasticity.</p><p><b>METHODS</b>After bilateral hippocampal injection of Aβ1-42 and rapamycinin rats, spontaneous alternation in Y-maze and in vivo hippocampal long-term potentiation (LTP) of rats were recorded. All data were analized by two-way repeated measures analysis of variance (ANOVA).</p><p><b>RESULTS</b>(Hippocampal injection of Aβ1-42 alone impaired working memory of rats; (2) Rapamycin did not affect working memory of rats, but alleviated Aβ1-42-induced working memory deficits, compared with Aβ1-42 alone group; (Aβ1-42 remarkably suppressed in vivo hippocampal LTP of fEPSPs in the CA1 region; (4) Pretreatment with rapamycin prevented Aβ1-42-induced suppression of LTP.</p><p><b>CONCLUSION</b>These data indicates that rapamycin could protect against Aβ1-42-induced impairments in working memory and synaptic plasticity in rats.</p>
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Animais , Ratos , Peptídeos beta-Amiloides , Hipocampo , Potenciação de Longa Duração , Aprendizagem em Labirinto , Memória de Curto Prazo , Plasticidade Neuronal , Fragmentos de Peptídeos , Sirolimo , FarmacologiaRESUMO
Aim To investigate the curative effect of rAAV-PR39-ADM,which co-expressed the gene of an-tibacterial peptide (PR39 ) and adrenomedullin (ADM),in a rat cerebral ischemia/reperfusion (I/R) injury.Methods In vitro,Matrigel angiogenesis as-say was made with human umbilical vein endothelial cells.In vivo,the cerebral I/R model was established by the occlusion of the cerebral artery for 2h and then reperfused for 24 h.SD rats were randomly divided in-to sham group,I/R+normal saline group,I/R+null virus (AAV ) group, and IR +rAAV-PR39-ADM group.rAAV-PR39-ADM,saline and null virus were administered through the femoral vein after 24 h of the reperfusion in I/R group.MRI,neurological deficit score,TTC and HE staining were measured respective-ly 1 ,2,3 and 4 weeks after the injection in order to e-valuate the therapeutic efficacy.Results In vitro, rAAV-PR39-ADM group had significant angiogenic effect compared with sham group and null virus group. In vivo,successful I/R model was verified by the ima-ges of MRI.Compared with sham group,the nerve function defect score and the cerebral infarction size in each time nodes were significantly raised in I/R groups (P<0.01).There was no significant difference in in-farct size and nerve function defect score between I/R+normal saline group and I/R +null virus (AAV ) group,and obviously,the IR +rAAV-PR39-ADM group lowered these indexes compared with the other two groups.HE staining showed that the number of neurons,new capillaries vessels of I/R +PR39-ADM group were significantly more than those in group I/R and group I/R +null virus.Conclusion The treat-ment of rAAV-PR39-ADM promotes vascular forma-tion,neuron protection and reduces the infarct size in the model of cerebral ischemia/reperfusion.
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Objective To investigate the early diagnosis value of MR by detecting spinal inflammatory lesions in ankylosing spon-dylitis (AS).Methods Forty patients were involved in this study,including 20 cases with short inflammatory back pain (IBP)histo-ry (duration ≤18 months)and 20 cases with long IBP history (duration ≥24 months).MR images were analyzed retrospectively. Results Patients with a short history of IBP had 7 lesions in vertebral bodies (anterior/posterior spondylitis and spondylodiscitis) and 33 lesions in posterior spinal structures (arthritis of costovertebral joints,costotransversal joints,zygapophyseal joints and en-thesitis of spinal ligaments).Patients with a long history of IBP had 27 lesions in vertebral bodies and 24 lesions in posterior spinal structures.Patients with a short history of IBP had significantly more lesions in posterior spinal structures than in vertebral bodies with 82.5% (33/40)vs 1 7.5% (7/40),respectively (P <0.01).In contrast,patients with a long history of IBP had significantly more inflammation in vertebral bodies with 79.4% (27/34)vs 20.6% (7/34),respectively (P <0.01).Conclusion Inflammatory spinal lesions in patients with a short history of IBP are seen more often in the posterior structures.Early detection of inflammatory spinal lesions by MRI is useful for early diagnosis of AS.