Correlación entre escalas visuales de atrofia entorrinal y temporomesial con volumetría hipocampal / Correlation between visual scales of entorhinal and temporomesial atrophy with hippocampal volumetry

Resumen Objetivo: En pacientes con enfermedad de Alzheimer (EA) se han descrito cambios neuropatológicos tempranos en la corteza entorrinal, que anteceden el compromiso temporomesial. La evaluación de la atrofia hipocampal mediante escalas visuales y volumetría son herramientas útiles en la valoración de pacientes con deterioro cognitivo. Nuestro objetivo es establecer la correlación entre la evaluación visual de la atrofia de la corteza entorrinal (ACE), la atrofia temporomesial (ATM) y el volumen hipocampal. Material y métodos: Estudio retrospectivo de corte transversal. Se incluyeron pacientes con queja cognitiva y resonancia magnética (RM) cerebral. Se utilizaron escalas visuales de ACE y ATM. Se midió el volumen hipocampal mediante el software volBrain 1.0. Resultados: Se incluyeron 48 pacientes, 31 eran mujeres (64,6%). Mediana de edad: 76,5 (RIQ: 69-83). La correlación entre las escalas visuales ACE y la ATM del lado derecho fue de 0,67 p < 0,0001) y del lado izquierdo de 0,69 (p < 0,0001). Encontramos correlación negativa moderada entre la ACE y el volumen hipocampal, del lado derecho fue de –0,59 (p < 0,0001) y del lado izquierdo de –0,42 (p = 0,003). Conclusión: La escala de ACE muestra moderada correlación con la escala de ATM y con el volumen hipocampal. Su uso podría aportar información valiosa para valoración de trastornos cognitivos.

Abstract Objective: In patients with Alzheimer’s disease (AD), early neuropathological changes in the entorhinal cortex have been described, which precede temporomesial involvement. The evaluation of hippocampal atrophy using visual scales and volumetry are useful tools in the assessment of patients with cognitive impairment. Our objective is to establish the correlation between the visual evaluations of entorhinal cortex atrophy (ECA), temporomesial atrophy (TMA), and hippocampal volume. Material and methods: Retrospective cross-sectional study. Patients with cognitive complaint and brain magnetic resonance imaging (MRI) were included. ACE and TMA visual scales were used. Hippocampal volume was measured using the volBrain 1.0 software. Results: Forty-eight patients were included, 31 were women (64.6%). Median age was 76.5 (IQR: 69-83). The correlation between ECA and TMA on the right side was 0.67 (p < 0.0001) and on the left side was 0.69 (p < 0.0001). We found a negative moderate correlation between ECA and hippocampal volume, on the right side it was –0.59 (p < 0.0001) and on the left side it was –0.42 (p = 0.003). Conclusion: The ECA scale shows high correlation with the TMA scale and moderate correlation with hippocampal volume. Its use could provide valuable information for the assessment of cognitive disorders.

Association between the entorhinal cortex and cognitive function in traumatic brain injury based on structural magnetic resonance imaging / 西安交通大学学报(医学版)

【Objective】 To explore the relationship between changes in the entorhinal cortex （EC） of traumatic brain injury （TBI） and cognitive function based on structural magnetic resonance imaging. 【Methods】 MRI was performed in 26 patients with clinically confirmed TBI after admission， and the Mini-mental State Examination （MMSE） was followed up 6 months later. The TBI patients were classified as mild TBI and moderate to severe TBI according to the post-traumatic Glasgow coma scale （GCS）. We compared the differences in age， gender， education level， hypertension， diabetes， TBI operation history， and follow-up MMSE between the two groups. Then the morphology， surface area， volume and thickness of the patient’s EC were evaluated using the visual score and Freesurfer software， and finally the correlation between EC parameters and MMSE was analyzed. 【Results】 The study included 12 cases of mild TBI and 14 cases of moderate to severe TBI. There were no statistical differences in age， gender， years of education， hypertension， diabetes or TBI operation history. However， the two groups differed significantly in follow-up MMSE. Visual evaluation showed statistical difference in the left EC scores. Structural MRI showed that the volume and thickness of left EC were statistically different between the two groups. The correlation analysis showed that there was a positive correlation between the thickness of left EC and MMSE （r=0.430， P<0.05）. 【Conclusion】 Entorhinal cortex atrophy after TBI is related to the severity of trauma， and it can reflect the long-term cognitive level of patients， which can be used as a noninvasive and reliable imaging marker for evaluating cognitive impairment after TBI.

Atrophy of entorhinal cortex in evaluation of cognitive performance in patients with diabetes mellitus / 中国医学影像技术

Objective To evaluate the potential cerebral cortical volume alterations in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI) compared with T2DM patients and healthy controls,and to observe the correlations with the scores of neuropsychological scales.Methods Cortical volume based on high-resolution MR T1WI data from 30 healthy controls (HC),30 T2DM patients and 30 T2DM with MCI patients were evaluated with FreeSurfer software and compared with variance analysis.The correlations between cerebral cortical volume which had statistical difference and the scores of neuropsychological scales were analyzed.Results There were significant differences in auditory verbal learning test (AVLT) scores,complex figure test-delayed recall (20 min) scores,digit symbol-coding subtest scores,MoCA scores and higher trail-making test-A scores,as well as trail-making test-B scores between T2DM and T2DM with MCI patients (all P＜0.05).Compared with T2DM patients,cortical volume of left entorhinal cortex,left lateral orbitofrontal gyrus,left posterior cingulate gyrus and the right lateral orbitofrontal gyrus,right pars orbitalis,right insula reduced in T2DM with MCI patients (all P＜0.05).In T2DM with MCI patients,AVLT scores were positively correlated with volume of the left entorhinal cortex (r=0.452,P=0.018).Conclusion Several cortical volume reductions are exhibited in T2DM patients with MCI.The volume of the left entorhinal cortex may be a potential biomarker to diagnose and evaluate MCI in T2DM.

Role of mammalian target of rapamycin in synaptic plasticity of entorhinal area-hippocampal formation in rats with inflammatory pain / 中华麻醉学杂志

Objective To evaluate the role of mammalian target of rapamycin (mTOR) in the synaptic plasticity of entorhinal area-hippocampal formation in rats with inflammatory pain.Methods Twenty-four healthy adult male Sprague-Dawley rats,weighing 180-240 g,were divided into 4 groups (n =6 each) by using a random number table method:control group (group C),inflammatory pain group (group IP),dimethyl sulfoxide (DMSO) group and mTOR inhibitor rapamycin group (group R).Inflammatory pain model was established by subcutaneous injection of 50 μl bee venom into the plantar surface of the left hindpaw.The equal volume of normal saline was subcutaneously injected into the plantar surface of the left hindpaw in group C.In group DMSO,2％ DMSO was administered by intragastric gavage for 3 days,1 ml per day,and the inflammatory pain model was established at 1 h after administration on 3rd day.In group R,rapamycin was administered by intragastric gavage for 3 days,1 ml per day,and the inflammatory pain model was established at 1 h after administration on 3rd day.Mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 2 h after establishing the model.The rats were sacrificed after measurement of the pain threshold,and hippocampi were removed to prepare hippocampal slices.Hippocampal CA1 region and dentate gyrus (DG region) were located with an inverted microscope.Planar microelectrode array technique was used to record the number of channels and the standardized amplitude of evoked effective field excitatory postsynaptic potentials (fEPSPs) (fEPSPs amplitude＞20％ of the baseline value) at different stimulus intensities.Results Compared with group C,MWT was significantly decreased,TWL was shortened,the number of effective fEPSP channels at different stimulus intensities was increased,and the amplitude of standardized fEPSPs in hippocampal DG and CA1 regions was increased in group IP (P＜0.05 or 0.01),and no significant change was found in the parameters mentioned above in group R (P＞0.05).Compared with group IP,MWT was significantly increased,TWL was prolonged,the number of effective fEPSP channels at different stimulus intensities was decreased,and the amplitude of standardized fEPSPs in hippocampal DG and CA1 regions was decreased in group R (P＜0.05 or 0.01),and no significant change was found in the parameters mentioned above in group DMSO (P＞0.05).Conclusion mTOR is involved in the changes in the synaptic plasticity of entorhinal areahippocampal formation in rats with inflammatory pain.

Neuropathological findings in entorhinal cortex of subjects aged 50 years or older and their correlation with dementia in a sample from Southern Brazil / Achados neuropatológicos no córtex entorrinal de encéfalos de indivíduos acima de 50 anos e sua correlação com demência numa amostra do Sul do Brasil

ABSTRACT. Introduction: The aims of this study were to survey neurodegenerative changes detected by abnormal protein deposits in the Entorhinal Cortex (EC) of subjects aged 50 years or older and to correlate these findings with suspected dementia, as detected by the IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) . Methods: Fourteen brains were submitted to the immunohistochemistry technique for different proteins (beta-amyloid, tau, -synuclein and phospho-TDP-43) and data obtained compared with IQCODE scores. Results: Fifty-seven percent of the individuals exhibited IQCODE results compatible with dementia, being classified into the demented group (DG): 87.5% of patients had neuropathological findings corresponding to Alzheimer's-like brain pathology (ALBP). Of the patients in the non-demented group (NDG), 16.7% met neuropathological criteria for ALBP. All individuals in the DG showed deposits of more than one kind of protein in the EC. The most common association was hyperphosphorylated tau and beta-amyloid protein (87.5%). Discussion: Most individuals with dementia had neuropathological findings of ALBP, as did one individual with no signs of dementia, characterizing a preclinical stage. The results of this study suggest that deposits of a single type of anomalous protein are normal findings in an aging brain, while more than one kind of protein or the combined presence of anomalous protein deposits indicate the presence of dementia.

RESUMO. Introdução: Este trabalho visa avaliar alterações neurodegenerativas detectadas por depósitos proteicos anormais em Córtex Entorrinal (CE) de indivíduos acima de 50 anos e correlacionar os achados com suspeição de demência detectada por meio do IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly). Métodos: Catorze encéfalos foram submetidos à técnica imuno-histoquímica para diferentes proteínas (beta-amiloide, tau, alfa-sinucleína e fosfo-TDP-43) e esses dados foram comparados com os valores obtidos pelo IQCODE. Resultados: 57% dos indivíduos mostraram resultados de IQCODE compatíveis com demência, sendo classificados no grupo com demência (GD): 87,5% desses pacientes tinham achados neuropatológicos correspondentes a patologia cerebral Alzheimer-símile (ALBP). Entre os pacientes do grupo sem demência (GSD), 16,7% apresentaram critérios neuropatológicos para ALBP. Todos os indivíduos do GD tinham depósitos de mais de um tipo de proteína no CE. A associação proteica mais comum foi tau hiperfosforilada e proteína beta-amiloide (87,5%). Discussão: A maioria dos indivíduos com demência apresentaram achados neuropatológicos de ALBP e um indivíduo, que não tinha evidências de demência, apresentou achados compatíveis com ALBP, caracterizando um estágio pré-clínico. Este trabalho sugere que depósitos de um único tipo de proteína anômala são achados normais do cérebro em envelhecimento, enquanto mais de um tipo de proteínas ou a presença combinada de depósitos proteicos anômalos indica manifestações de demência.

Mechanism of low-dose ketamine-induced reduction of cognitive dysfunction following sevoflurane anesthesia in aged rats: plasticity of dendritic spines in entorhinal cortical neurons / 中华麻醉学杂志

Objective To investigate the relationship between the plasticity of dendritic spines in entorhinal cortical neurons and mechanism of low-dose ketamine-induced reduction of cognitive dysfunction following sevoflurane anesthesia in aged rats.Methods Thirty-six pathogen-free healthy male SpragueDawley rats,aged 18 months,weighing 500-600 g,were divided into 3 groups (n=12 each) using a random number table:control group (group C),sevoflurane anesthesia group (group Sev) and ketamine group (group K).Group C received no treatment.Group Sev inhaled the mixture of air (flow rate 1 L/min) and 3.6％ sevoflurane for 3 h.In group K,ketamine 10 mg/kg was injected intraperitoneally,and 5 min later the mixture of air (flow rate 1 L/min) and 3.6％ sevoflurane was inhaled for 3 h.Open field test and Morris water maze test were performed 3 days after anesthesia.After the behavioral tests,the animals were sacrificed,and their brains were removed and cut into sections for determination of the density of neurons,density of dendritic spines,and expression of postsynaptic density protein-95 (PSD-95) and synaptophysin (SY38) in superficial laminaes (Ⅱ-Ⅲ) of entorhinal cortex using Nissl's staining,Golgi staining and immunohistochemistry,respectively.Results Compared with group C,the time of staying at the central region was significantly shortened,the escape latency was prolonged,the density of dendritic spines was decreased,and the expression of PSD-95 and SY38 was down-regulated in group Sev (P＜0.05).Compared with group Sev,the time of staying at the central region was significantly prolonged,the escape latency was shortened,the density of dendritic spines was increased,and the expression of PSD-95 and SY38 was upregulated in group K (P＜0.05).There were no significant differences in the density of neurons in entorhinal cortex between the three groups (P＞0.05).Conclusion The mechanism by which low-dose ketamine attenuates cognitive dysfunction induced by sevoflurane anesthesia may be related to the enhanced plasticity of dendritic spines in entorhinal cortical neurons of aged rats.

Effects of lentiviral delivery in different brain regions on transfection of rat dentate gyrus neurons / 中华行为医学与脑科学杂志

Objective To explore the effect of lentiviral delivery green fluorescent protein in different brain regions on the transfection of dentate gyrus neurons.Methods Lenti-pSyn-EGFP was stereotaxic injected into dentate gyrus (DG),Cornu Ammonis 1 (CAl) of hippocampus and medial entorhinal cortex (EC) of rats.All animals were perfused with 4％ paraformaldehyde.Their brains were cut into 30 μm sections which were performed with Nissl fluorescent staining.Results The resuts showed that the GFP positive cells in DG area of DG,CA1,EC,DG-EC groups were (18.0± 1.0),(17.0±0.6),(17.3±0.6),(18.3±0.6) respectively,and there was no statistical difference among each group(P＞0.05).Conclusion Lentivirus delivery in EC and CA1 both can transfect DG neurons.This is a useful method to transfect dentate gyrus neurons instead of injecting lentivirus into DG directly and avoid the lesion of DG.

The clinical value of olfactory functional magnetic resonance imaging in early diagnosis of Alzheimer's disease / 中国基层医药

Objective To investigate the clinical value of olfactory functional magnetic resonance imaging in early diagnosis of Alzheimer's disease (AD).Methods 43 patients with mild cognitive impairment were selected,in the same period,49 cases of patients with AD were selected as the AD patients group,and 53 normal populations were selected as the control group.The neuropsychological of all cases were assessed by using MMSE scale,MoCA scale and CDR Scale.Siemens 3.0T MRI machines were used according to event -related design approach for olfactory cor-tex conducted fMRI scans.The matlab7.0 and SPM8 data preprocessing tools were used to image analysis.The prima-ry olfactory cortex volumes and activation voxels numbers of the three groups were compared.The correlations of acti-vation voxels numbers and primary olfactory cortex volumes and neuropsychological scores were analyzed.Results The primary olfactory cortex volumes of the control group,patients with mild cognitive impairment and AD patients were (3 846 ±517)mm3 ,(2 863 ±367)mm3 and (2 214 ±283)mm3 ,respectively,pairwise comparison,the control group >mild cognitive impairment >AD patients,the differences were statistically significant (compared with the con-trol group,t =16.835 and 34.716,compared with mild cognitive impairment group,t =19.753,P mild cognitive impairment >AD patients,the differences were statistically significant (compared with the control group,t =47.916 and 72.954,compared with mild cognitive impairment group,t =37.382,P <0.05).Partial correlation analysis showed that the activation voxels num-bers of the three groups were positively correlated with primary olfactory cortex volume,MMSE score and MOCA score (r =0.397,0.462 and 0.494,all P <0.05).Conclusion Olfactory fMRI in patients with AD might reflect the changes in the entorhinal cortex caused by pathological changes.It could provide clues and information for the early diagnosis of AD.

Changes in regional cerebral blood flow in patients with amnestic mild cognitive impairment and Alzheimer's disease / 中华老年医学杂志

Objective To investigate the changes in regional cerebral blood flow and its relationship with atrophy of the entorhinal cortex in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD).Methods Twenty eight patients including ten cases with aMCI,nine case with mild AD and nine cases with moderate to severe AD were enrolled.The cognitive function was evaluated by revised version of Hasegawa's Dementia Scale (HDS-R) and Alzheimer's Disease Assessment Scale-cognitive part (ADAS-cog).Regional cerebral blood flow was evaluated by 99mTc-ECD SPECT and easy Z score imaging system (eZIS).Z scores of voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) were used to assess the degree of atrophy of the entorhinal cortex.Results The Z-score in eZIS was lower in mild to severe AD group than in aMCI group [(1.57±0.46),(1.50±0.54) vs.(1.00±0.50),F=4.58,P=0.022],which showed that the regional cerebral blood flow of cingulate was lower in AD group than in aMCI group.The Z-score in eZIS in bilateral frontal lobes and left hippocampus were higher in moderate to severe AD group than those in aMCI group than in aMCI and mild AD group respectively [(1.43± 0.79) vs.(0.67±0.50),(0.88±0.64); (1.43±0.79) vs.(0.67±0.50),(0.75±0.46); (1.86± 0.50) vs.(1.33±0.50),(1.75±0.46),F=2.90,3.81 and 3.06,respectively,P=0.077,0.039 and 0.068],which showed that the regional cerebral blood flow of bilateral frontal lobes and left hippocampus were lower in moderate to severe AD group than in aMCI group.The score of HDS-R had a negative correlation (r =-0.568,-0.481,P=0.004,0.017) and the score of ADAS-cog had a positive correlation (r=0.462,0.459; P =0.030,0.032) with regional cerebral blood flow in hippocampus.Conclusions The regional cerebral blood flow of cingulate gyrus is decreased in early stage of AD,and involves in frontal lobe and hippocampus along with the deterioration of diseases.The changes of cognitive function are correlated with cerebral blood flow in hippocampus.The Z-score in eZIS can effectively evaluate the changes of regional cerebral blood flow in aMCI and AD patients.

MRI volumetric analysis of olfaction-related cortex in olfactory dysfunction patients after upper respiratory tract infections / 中华放射学杂志

Objective To measure the volume of olfaction-related cortex in olfactory dysfunction patients after upper respiratory tract infections via MRI,and to analyze the differences in the volume of olfaction-related cortex.Methods Fifteen olfactory dysfunction patients after upper respiratory tract infections (patient group) and fifteen age-and gender-matched normal volunteers (control group) were enrolled in this study to undergo 1.5 Tesla MR scanning.The volumes of olfaction-related cortex,including entorhinal cortex (EC),perirhinal cortex (PRC) and insular cortex (IC),were drawn and computed with Dr.View software.Olfactory function test was performed with the Sniffin' Sticks method which consisted of three tests:odor threshold (THR),odor discrimination (DIS),odor identification (ID),and their sum score (TDI).Statistical differences in the volumetric measures of bilateral EC,PRC,and IC between patient and control group were analyzed by analysis of covariance (ANCOVA) with age and intracranial volume (ICV) as covariates.Statistical differences in the olfactory function between patient and control group were analyzed by ANCOVA with age as a covariate.Results (1) The EC volume of patient group in the left and right side were (1.5 ± 0.3),(1.6 ± 0.1) cm3,while the control group were (1.7 ± 0.2),(1.8 ± 0.3) cm3 ; The PRC volume of patient group in the left and right side were (1.9 ± 0.4),(1.9 ± 0.3) cm3,and the control group were (2.5 ± 0.8),(2.3 ± 0.7) cm3 ; The IC volume of patient group in the left and right side were (5.2 ± 0.4),(5.8 ± 0.5) cm3,and the control group were (5.8 ± 0.8),(6.7 ± 0.2) cm3.EC,PRC and IC volumes of patient group and control group were measured and the results showed that the olfaction-related cortex volume was decreased in patient group showing significant statistical difference (F =4.913,4.793,7.832,5.574,9.842,7.221,P ＜ 0.05).(2) Olfactory function test of patient group and control group was performed and the results showed that the scores of patient group were lower than that of control group,and the differences were significant (F =54.508,118.774,93.039,53.692,74.139,53.626,91.842,91.696,P ＜ 0.01).Conclusions It is feasible to measure the volumes of olfaction-related cortex with MRI,and the volumes of EC,PRC and IC decreased in olfactory dysfunction patients after upper respiratory tract infections compared with normal people.

Correlation of the volume of the hippocampus and entorhinal cortex of mild cognitive impairment and Alzheimer's disease / 中国综合临床

Objective To investigate the imaging features of hippocampus and entorhinal cortex in the normal,mild cognitive impairment(MCI) and Alzheimer's disease (AD),and explore the value of diagnosing MCI and AD by using the method of MRI measuring the volume of hippocampus and entorhinal cortex.Method One hundred and twenty-two people including 42 cases of MCI,38 cases of AD,and 42 cases of noroal cognition(NC) were selected as our subjects from health examination persons both in hospital and outpatient service.All were performed general examination and neuropsychological scale evaluation.The volume of hippocampus and entorhinal cortex were measured by using MRI.The correlation between the volumetric changes of hippocampus and entorhinal cortex with scores of mini-mental state examination (MMSE) and Montreal Cognitive Assessment(MoCA) was analyzed.Results The volume of hippocampus and entorhinal cortex in the MCI group,AD group and NC group were (6.29 ± 1.13)cm3 and (2.71 ± 0.51) cm3,(6.27 ± 1.11) cm3 and (2.09 ±0.68) cm3,(7.01 ±0.92) cm3 and (3.12 ±0.34) cm3 respectively.The volume of MCI group was obviously smaller than that of NC group (P ＜ 0.05).The volume of AD group was smaller than that of NC group(P ＜0.01).The volume of AD group was obviously smaller than that of MCI group(P ＜0.01).There was positive correlation between hippocampus volume,the volume of entorhinal cortex and MMSE scores (r =0.770,0.811 ; P ＜ 0.01).Meanwhile,hippocampal volume,volume of entorhinal cortex were positive correlated with MoCA (r =0.810,0.842; P ＜ 0.01).Conclusion The atrophy of entorhinal cortex and hippocampus is closely related to cognitive disorder.The MRI measuring of the volume of entorhinal cortex and hippocampus has a potential value in diagnosing and distinguishing of MCI and NC.

The diagnostic value of medial temporal volume change in Alzheimer's disease / 中华行为医学与脑科学杂志

ObjectiveTo study the metastructure volumes of medial temporal lobe in diagnosis the patients with Alzheimer's disease (AD) using 3 dimensional MRI.Methods23 AD patients according to DSM-Ⅳ criteria and 23 normal controls (NC) were examined with 3D-MRI.Hippocampus formation,amygdala,entorhinal cortex ( EC ),perirhinal cortex ( PC),and comu temporale were measured with 3D-MRI.ResultsSensitivity and specificity of diagnosis AD were 73.9％,97％ ( Hippocampus formation) ;39.1％,95.7％ (amygdala) ;73.9％,95.7％ (EC) ;95.7％,87.0％ (PC) and 34.8％,39.1％ ( cornu temporale).Overall discriminate function =cornu temporal × 3.887 + PC × 5.960 - EC × 0.074 + amygdale × 3.489 + hippocampus formation × 6.656- 22.449.Over-all-accuracy was 91.3％.ConclusionThe total volume of PC can better diagnosis the mild to moderate AD than other structure of medial temporal lobe.The changes of the medial temporal lobe volume could be used in diagnosis the patients with Alzheimer's disease.

Distribution and expression of Semaphorins-3A protein in brain of developing rats / 中华行为医学与脑科学杂志

Objective To study the distribution and expression of Semaphorins-3A protein in brain of postnatal rats.Methods Semaphorins-3A positive cells were observed by immunohistochemistry in the cerebral cortex,hippocampus,dentate gyms and entorhinal cortex in postnatal 0d,7d,14d,21 d and 28d of Sprague Dawley rats.Results Semaphorins-3A positive cells widely distributed in the granule cell layer ( Ⅱ ),external pyramidal cell layer ( Ⅲ ),internal granular cell layer ( Ⅳ ),pyramidal cell layer ( Ⅴ ) and layer of polymorphous cells ( Ⅵ ),in addition to the molecular layer ( Ⅰ ) of the parietal,occipital,frontal,temporal,insular,cingulate cortex,piriform cortex and entorhinal cortex with postnatal 0d,7d,14d,21d and 28d rats.The amount of semaphorins-3A positive cells(IOD) in the entorhinal cortex was 84916.23 ± 3266.34 in P0d,77711.41 ± 2634.26 in P7d,74124.25 ± 3989.09 in P14d,65887.63 ± 3406.57 in P21d and 57705.96 ± 3136.35 in P28d,meanwhile the region of semaphorins-3A positive cells narrowed in the part level with Ⅱ -Ⅵ levels of cortex.Similarly semaphorins-3A positive cells distributed mainly in granule cell layer of dentate gyrus,CA1,CA3 region and only a few of semaphorins-3A positive cells scattered in the multi-line layer in hippocampus.The expression level of semaphorins-3Awas significant difference among postnatal 0d,7d,14d,21d and 28d rats (P＜0.01).Conclusion Semaphorins-3A positive cells widely distribute in the various cortex and hippocampus in developing rat brain,and the region of semaphorins-3A is reduced with age growth of rats.

The anatomical and functional changes in the primary olfactory cortex of Alzheimer disease and mild cognitive impairment patients / 中华放射学杂志

Objective To determine the volume reduction of the primary olfactory cortex (POC) in patients with Alzheimer disease (AD) and investigate the potential relationship of functional olfactory activation and anatomical atrophy changes. Methods Twelve patients with AD, eight patients with mild cognitive impairment (MCI) and twenty normal controls (NC) underwent standardized UPSIT (University of Pennsylvania smell identification test) behavior smell test and neuropsychological tests. Then all of the subjects underwent the high resolution MRI and an olfactory fMRI scan on a 3T system. Volumetric measurement of the POC was conducted and the areas were also saved as a ROI which would be used during the processing of fMRI data to get the activation voxels in local region. The Kruskal-Wallis rank test was used to examine the significance of POC volume and activation in three groups, If P-value was less than 0.05,Bonferroni method was used for multiple comparisons. The correlation between the anatomical volume and functional activation was analyzed with partial correlation adjusted for age. Results The POC volume of NC, MCI and AD groups were 3024--4734, 1409--4553 and 1561--3759 mm~3, and the medians were 3749, 2752 and 2156 mm~3. The activation voxels of each group were 0--2360, 0--2160 and 0--100 mm~3, while the medians were 430, 40 and 0 mm~3. There were significant differences of both POC volume atrophy and activation between the three groups, with a trend of reduction from NC to MCI to AD group (H is 14.942 and 16.587, both P<0.05). The volume of olfactory activation at POC was highly correlated with the volume of POC (r=0.364, P=0.023). Conclusions In this study, we explored the morphological and functional changes in the POC. It is revealed that POC suffers prominent local atrophy and dysfunction as well as hippocampus in AD. These results can provide neuropathological and neurofunctional bases for olfactory deficit in Alzheimer Disease.

Changes of the Cholinergic Innervation to the Hippocampus after Entorhinal Cortex Lesion in Rat / 대한해부학회지

The hippocampus is known as involved in learning and memory functions and the entorhinal cortex plays a crucial role as a gateway connecting the several areas and hippocampal formation. Entorhinal cortex lesions have been employed in numerous studies as the Alzheimer's disease model. The purpose of this study were to identify the CNS hip-pocampal and cholinergic pathway and to investigate the morphological changes of the hippocampal cholinergic inner-vations by using the Pseudorabies virus injection into the hippocampus after entorhinal cortex lesions. The pseudorabies virus and double labelled neurons (ChAT and PRV) were distributed at several different nuclei including agranular insular cortex, bed nucleus of stria terminalis, central amygdala, globus pallidus, lateral segment, lateral hypothalamic area, laterodorsal tegmental nucleus, medial septal nucleus, mesencephalic reticular nucleus, periaqueductal gray matter and substantia innominata The morphological changes were observed in the hippocampal cholinergic innervation after entorhinal cortex lesions. These data suggested that the hippocampal cholinergic innervation showed morphological changes throughout the whole brain areas after entorhinal cortex lesion.

Immunocytochemical Study on the Changes of Cell-Death Controlling Factors in the Hippocampal Formation and Entorhinal Cortex of Aged Rats / 신경정신의학

OBJECTIVES: Hippocampal formation and entorhinal cortex play a part in learning and memory. This study sought to investigate the change of cell-death controlling factors in the hippocampal formation and entorhinal cortex of aged rats. METHODS: Ten aged rats and ten controls were studied. We performed immunocytochemical method using antibodies against NOS, VIP, c-fos , bcl-2, bax and p53 and in situ hybridization. RESULTS: 1) The number of nNOS-immunoreactive(IR) neurons in the entorhinal cortex was significantly decreased in the aged rats(>30%). Morphologically, the number of dendritic branches seemed to be decreased and the length of dendrites showed a tendency to by shortened in the aged group. A major loss of nNOS mRNA positive neurons was observed in the hippocampal formation of the aged rats(>30%). 2) VIP-IR neurons were predominantly bipolar cell. VIP-IR cells were mildly decreased in the hippocampus and subiculum(30%). 4) Bcl-2 mRNA positive neurons were moderately decreased in the hippocampus, subiculum and entorhinal cortex(15-30%), and severely decreased in dentate gyrus of the aged rats(>30%). 5) Bax-IR neurons were similarly distributed between the control and the aged rats, but bax-IR neurons of the aged group, as compared to the control group, were weakly immunostained. 6) P53-IR neurons were only observed in hippocampal CA1 region of the aged rats. CONCLUSION: These results indicate the involvement of neuronal system containing NOS, VIP, c-fos, bcl-2 and p53 in the brain aging process, and provide the morphological evidence for the changes in immunoreactivity of cell-death controlling factors in the hippocampal formation and entorhinal cortex of aged rats.

Effect of Panax ginseng on latency of passive avoidance response and neuronal damage of hippocampus

The effects of crude saponin (SAP) and alkaloid (ALK) fractions of Panax ginseng C.A. Meyer on the detrimental effects of electroconvulsive shock (ECS) and scopolamine on passive avoidance response (PAR) were studied in male Sprague-Dawley rats, referring their effects on the neuronal injury and plasticity of hippocampus in response to electrolytic lesion of left entorhinal cortex (ECL). The detrimental ECS effect on PAR was attenuated by pre- and post-treatments with SAP and ALK, respectively, or by pretreatment with aminoguanidine (AG), an inhibitor of diamine oxidase and NO synthase. And the detrimental scopolamine effect on PAR was also inhibited by pretreatment with ALK or AG, and by posttreatment with SAP or ALK, respectively. On the 7th day after ECL, the brain sections stained by cresyl violet and by acetylcholinesterase (AChE) histochemistry, respectively, showed the chromatolysis and numeral decrease of neurons and the reduction of AChE reactivity in the hippocampus CA1 area and to a lesser extent, in the dentate gyrus. The neuronal cell death of the CA1 area was significantly reduced by SAP, ALK, or AG, and the reduction of AChE reactivity was significantly attenuated by SAP or ALK and to a lesser extent by AG. These results suggests that the protective effect of ginseng SAP and ALK fractions on ECS- or scopolamine-induced impairment of PAR may be ascribed in part to preservation of hippocampal neurons, particularly cholinergic neurons.

Effects of Iodine Deficiency and Hypothyroidism during Pregnancy on the Protein Expressions of cAMP Response Element-Binding Protein in the Entorhinal Cortex of Pups / 环境与健康杂志

Objective To observe the effect of iodine deficiency and hypothyroidism on the protein expressions of CREB in the entorhinal cortex of pups.Methods Twenty-eight female Wistar clean rats after pregnancy were randomly divided into control group,hypothyroid 1,2 group and iodine deficient group(7 in each group).From GD6 till PN28,iodine-deficient group was administered with iodine-deficient diet [iodine content:(14.11 ?1.96) ng/g] and tap water;hypothyroid 1 and 2 group were administered with 5 mg/L and 15 mg/L PTU in the drinking water and fed with normal diet [iodine content:(470.50?46.52) ng/g].Control group received tap water and normal diet during the experiment.Five pups from each group were sacrificed and intracardiac perfused at PN7,PN14,PN21,PN28 and PN42.Brains were removed,fixed and sectioned coronally.All sections were observed and were analyzed for the protein expression of CREB by immunohistochemistry in the entorhinal cortex.Results At PN7,there was no significant difference in the expression of Ng in all four groups.At PN14 and PN21,the expression of CREB in the entorhinal cortex in hypothyroid 1,2 group and iodine deficient group were significantly lower than those of controls(P