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OBJECTIVE To set up an intranasal ovalbumin-induced animal model of allergic rhinitis(AR) accompanied with olfactory dysfunction in mice. By observing the olfactory pathway in mice using manganese-enhanced magnetic resonance imaging (MEMRI) and the relatively morphologic structural and immunological changes in olfactory epithelium, the influence of AR on olfactory receptor neurons(ORNs) was studied.METHODS Forty SD mice were randomly divided into two groups, the research group(n=30) and the control group(n=10). The research group was intraperitoneally injected and intranasal application of ovalbumin to establish an AR mice model. The olfactory function of the mice was evaluated by buried food test(BFT). ELISA was performed to measure the level of IgE in serum. MEMRI images were acquired with a 7.0 T micro-MR scanner. HE staining and immunohistochemistry were used to observe the tissues morphology change of olfactory mucosa and OMP expression.RESULTS The olfactory function evaluation of the AR mice model indicated that the incidence of olfactory dysfunction in AR mice was 40.0%. The AR mice with olfactory dysfunction had no signal enhancement in MEMRI. The olfactory epithelium became thinner, layer numbers of ORNs were decreased with disorder arrangement and the OMP expression was decreased in AR mice with olfactory dysfunction compared with that in AR mice without olfactory dysfunction(P=0.018) and the control group(P=0.0141).CONCLUSION An animal model of AR accompanied with olfactory dysfunction in mice was successfully established. The influence of AR on ORNs and thus cause the change of the olfactory pathway is one of the major pathogenesis of olfactory dysfunction in AR.
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<p><b>OBJECTIVE</b>To study the olfactory function in rats by manganese-enhanced magnetic resonance imaging (MEMRI) and explore the regeneration of olfactory system from the imaging.</p><p><b>METHODS</b>Thirty-five adult male Sprague-Dawley (SD) rats were randomly divided into three groups. Twenty rats with bilateral nasal instillation of TritonX-100 were used as olfactory dysfunction model group (M group). The rats in this group received menthocamphorate stimulation. Ten rats with bilateral nasal instillation of sterile saline were used as olfactory normal group (N group), and were randomly divided into two groups:one group received menthocamphorate stimulation (N1 group), another group received odorless air (N2 group). The remaining five rats were used as the blank control (control group). All images were acquired with a 7.0 T micro-MR scanner. Signal-to-noise ratios (SNR) in the olfactory bulb (OB) were measured by Image J.</p><p><b>RESULTS</b>MEMRI could clearly show the normal olfactory pathway in rats. MEMRI displayed a reversible change during the stages of olfactory recovery after injury. For the olfactory dysfunction model group (M group), the total volume of rat olfactory bulb at the initial, the 10th day, the 20th day, the 30th day and the 60th day were (49.44 ± 0.81), (32.85 ± 0.79), (27.78 ± 1.07), (35.89 ± 1.04), (43.63 ± 1.13) mm(3) respectively. At the 20th day after olfactory injury, the SNR in the OB was the lowest for 9.78 ± 0.07, when at the 60th day, the SNR recovered to 30.68 ± 1.01, which increased to near normal (N1group, 33.08 ± 0.15; N2 group, 31.31 ± 1.12), the SNR had no significant difference among the three groups (F = 3.04, P > 0.05).</p><p><b>CONCLUSION</b>The MEMRI is an objective method to detect the olfactory function, and the olfactory system has the regenerative property after injury.</p>
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Animals , Male , Rats , Magnetic Resonance Imaging , Methods , Manganese , Olfactory Bulb , Olfactory Pathways , Rats, Sprague-Dawley , SmellABSTRACT
Objective To label neural stem cells (NSCs) with superparamagnetic iron oxides (SPIO) and to explore the tropism of NSCs after transplantation into the hippocampus of APP/PS1 AD mice by MRI.Methods NSCs from C57BL/6 mouse were cultured and identified.Feridex and Poly-L-Lysine were added into the medium to be co-cultured to make magnetic labeled NSCs and transmission electron microscopy was used to identify the iron particles in NSCs.Transgenic (tg) and wild-type (wt) mice at 12 months of age were divided into three groups: SPIOs labeled NSCs group (A and C),unlabeled NSCs group(B).Feridex-labeled NSCs were migrated into the hippocampus of APP/PS1 AD mice to monitor in vivo by MRI.After 1,2,4 and 6 weeks,the mice were sacrificed and their brain tissues were sectioned to investigate the migration of SPIO labeled NSCs and compared with MRI.Results NSCs of C57BL/6 mice were cultured successfully.Transmission electron microscope showed visible iron granules in cytoplasm.MRI detection of labeled cells: T2WI and T2* WI showed remarkable low signal intensity at the hippocampus injection points 1 week after transplantation,particularly on T2* WI.Area of low signal intensity enlarged increasingly along the injection points after 2 weeks.At 4 weeks,area of low signal intensity spread throughout the hippocampus,but intensity shadowed Six weeks later,low signal intensity almost disappeared.There was no obvious low signal change in unlabeled cell transplantation group.For wt mice,size and location of low signal did not appear obvious change at all designated time points.Prussian blue positive cells were observed in the hippocampus,indicating that NSCs labeled with SPIO could survive,migrate and differentiate in the brain of the APP/PS1 AD mice.Changes of pathology were well correlated with the area where a signal intensity loss was observed in MRI 1,2,4 and 6 weeks after transplantation Conclusions Diffuse migration of transplanted NSCs labeled with SPIO is observed in the hippocampus in APP/PS1 tg mice,and MRI technique is an ideal method for tracking labeled stem cells after grafting in vivo.
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Objective To explore the effect of neural stem cell(NSCs) transplantation on proton magnetic resonance spectroscopy (1H-MRS) and the behavior in APP/PS1 double transgenic AD mice.Methods NSCs from C57BL/6 mice were cultured and amplified.APP/PS1 double transgenic AD mice (n=30) aged 12 months were used as the study group,and mild-type mice (n=15) were used as the control group(group C).Animals in the study group were randomly divided into two subgroups:one receiving NSCs (group A) and the other receiving PBS transplantation (group B) in bilateral hippocampal CA1 of the AD model mice.Animals in the group C were not treated.1 H-MRS and Morris water maze (MWM) were performed before transplantation and 4 weeks after transplantation,and compared with the histopathological results.Results 1H-MRS showed that there was no significant change in NAA/Cr(1.01±0.08 and 1.03±0.05) and mI/Cr (0.69±0.05 and 0.71±0.06) ratios between group A and group B before transplantation (P＞ 0.05),but the changes were significant compared with the group C (NAA/ Cr:1.21±0.05; mI/Cr:0.58±0.06) (P＜0.05).Four weeks after transplantation,NAA/ Cr ratio(1.18± 0.09) was increased and mI/Cr ratio (0.53±0.04) was decreased in group A.The difference was significant compared with the group B at the same time points (P＜0.05).MWM showed the escape latency in group A was significantly shorter than that in group B after transplantation (P＜0.05).In addition,group A also showed an exclusive preference for the target quadrant,and spent more time ((35.21±5.44) s) in the 3rd quadrant compared with group B (P＜0.05).For number of platform crossings,similar results were also shown (5.75± 3.23).Nissl's staining showed that the number of neurons in the hippocampal area increased more significantly in group A than those in group B(P＜0.05).Conclusion NSCs transplantation can improve spatial learning and memory via neurons regeneration in APP/PS1 double transgenic AD mice,and 1H-MRS is able to display intracranial metabolite changes after NSCs transplantation.
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Objective To explore the value of 1H-MRS on the evaluation of Alzheimer's disease (AD) with neural stem cells (NSCs) transplantation in an APP-PS1 double transgenic (tg) AD mouse model.Methods NSCs from C57BL/6 mice were cultured and amplified.APP-PS1 tg mice (n =30) aged 12 months were used as the study group,and mild-type mice (n =15) were used as the control group.Animals in the study group were randomized into two subgroups,the AD mice in one subgroup received NSCs transplantation (NSCs group) and in another subgroup received phosphate buffer saline (PBS,PBS group)in bilateral hippocampal CA1.Animals in the control group were not treated.Using a 7.0 T high-fieldstrength MR imager,1H-MRS was performed before and 6 weeks after transplantation to measure the area under the peak of n-acetyl aspartate (NAA),glutamate (Glu),myo-inositol ( mI),choline (Cho) and creatine (Cr) in the hippocampal area,NAA/Cr,Glu/Cr,mI/Cr and Cho/Cr ratio were calculated and compared with histopathological results (including Nissl's staining and electron microscope examination).Comparisons among NSCs,PBS and control groups were conducted by one-way ANOVA.Results NSCs from C57BL/6 mice were cultured successfully. Before transplantation,the mean NAA/Cr,Glu/Cr and mI/Cr in NSCs,PBS and control groups were 0.89 ± 0.05,0.88 ± 0.04 and 1.15 ± 0.05,0.40 ± 0.03,0.39 ± 0.03 and 0.45 ± 0.05,0.67 ± 0.05,0.67 ± 0.05 and 0.52 ± 0.04,respectively,and differences were statistically significant (F =148.918,7.529,59.468,P ＜ 0.01 ). There were no significant differences in NAA/Cr,mI/Cr and Glu/Cr ratios between NSCs and PBS groups before transplantation (t =0.147,0.096,0.207,P ＞ 0.05 ),but the differences were significant compared with the control group (t =0.255,0.467,0.171 and t =0.269,0.527,0.151,P ＜0.05).Six weeks after transplantation,the mean NAA/Cr,Glu/Cr and mI/Cr in three groups were 1.13 ±0.07,0.86 ±0.05 and 1.14 ±0.05,0.45 ± 0.04,0.38 ± 0.02 and 0.44 ± 0.03,0.58 ± 0.04,0.67 ± 0.04 and 0.53 ± 0.04,respectively,and differences were statistically significant ( F =112.092,23.076,44.367,P ＜ 0.01 ).NAA/Cr and Glu/Cr ratios were increased and mI/Cr was decreased in NSCs group,and the difference was significant compared with PBS group at the same time point ( t =0.271,0.071,0.089,P ＜ 0.05 ).There were no significant differences in NAA/Cr and Glu/Cr ( t =0.013,0.012,P ＞ 0.05 ),but there was a significant difference in mI/Cr between NSCs and control groups ( t =0.046,P ＜ 0.05).There were no significant differences in Cho before and after transplantation among the three groups (P ＞ 0.05 ). Nissl's staining showed that the number of neurons in the hippocampal area increased more significantly in tg mice receiving NSCs than that without receiving NSCs.Electron microscopy showed that most hippocampal NSCs in NSCs group were morphologically normal with abundant organelles,while hippocampal NSCs in PBS group were swollen with sparse synapses.Conclusion 1H-MRS is able to display intracranial metabolite changes before and after NSCs in APP-PS1 double transgenic AD mice and has an applicable value in evaluating the therapeutic effect of NSCs on AD.
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Objective To study the role of manganese-enhanced MRI(MEMRI) in the depiction of cortical architecture of rat brain after systemic administration of Mn~(2+) through caudal vein and compare the effects of normal or opened blood-brain barrier on the manganese-enhanced MRI. Methods Fifteen SD rats were randomly divided into three groups according to ranked list of random. Blood-brain barrier was opened in short time by the injection of 30% mannitol via the right internal carotid artery, in group A, then 100 mmol/L MnCl_2 physiologic saline solution was delivered through vena caudalis, and MRI was performed 12 hours later. In group B, 100 mmol/L MnCl_2 physiologic saline solutions was administrated through vena caudalis, following normal saline injection into the right internal carotid artery, and MRI was performed 12 hours later. The group C served as normal control group. All images were acquired with a 7.0 T microMR scanner. Signal-to-noise ratios (SNR) in regions of interest were measured by Paravision 4.0 and the differences of three groups were compared by using one-way ANOVA. The differences of SNR on both sides of hemispheres were compared by using paired t test. Results MEMRI could show the gray matter and white matter of rat brain and the anatomy borders between somatosensory cortex and motor cortex clearly. Periventricular structures such as hippocampus, dentate gyms, habenula united, and olfactory bulb could also be showed clearly. Symmetrical enhancement on both sides of the cortex and banded structures was shown clearly in group B. The SNR increased and the differences were significant in right cerebral cortex, both sides of cerebellar cortex, hippocampus and pituitary, among three groups (right cerebral cortex 35.2±7.0,30.1±2.4,26.6±2.8,F =4.36,P=0.038;left cerebellar cortex 27.1±5.2,29.4±3.8,19.4±4.5, F=6.66, P=0.011;right cerebellar cortex 27.8±3.8,28.5±4.2,20.4±4.8, F=5.84, P=0.017; left hippocampus 34.5±4.9,38.1±5.3,24.5±3.6, F=11.38, P=0.002; right hippocampus 35.3±5.5, 37.6±4.7,25.6±3.0,F=9.93,P=0.003;pituitary 39.5±3.8,52.6±9.1,26.2±4.2,F=22.80, P=0.001) after systemic administration of Mn~(2+). Asymmetric enhancement on two sides of cortex was shown in group A. The mannitol-infused side was enhanced obviously but displayed blurring banded structures. However,the SNR differences of both sides of hemispheres in group A and B were not significant (P >0.05). Conclusions After systemic administration of MnCl_2 through vena caudalis, MEMRI could map the laminar architectures and the anatomy border of functional zone of somatosensory cortex specifically. High concentration of mannitol could open blood brain barrier(BBB) effectively and have distinct impacts on the architectures displayed in MEMRI. Opening or maintaining BBB in MEMRI had respective characteristics, and it should be selected according to practical needs.
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Objective To explore changes of metabolites in APP/ PS1 double transgenie mice of Alzbeimer disease (AD) by 1H-MR spectroscopy (1H-MRS) and the application value of in early diagnosis of AD.Methods 1H-MRS was performed in 35 APP/PS1 transgenie mice of AD ( study group) and 20 wild type mice ( control group) at age of 3, 6 and 9 months using a 7.0 T MR system.Sub-peak areas of N-acetyl aspartate (NAA), myo-inositol (mI) and creatine (Cr) in the cerebral cortex and hippocampus were measured, and the NAA/Cr and mI/Cr ratios were calculated.The changes in pathology between the two groups were compared.Using the lower limit of 95% confidence interval (CI) of the ml/Cr ratio and the upper limit of 95% CI of the NAA/Cr ratio of AD mice as the threshold, their influences on sensitivity,specificity and accuracy of various age groups of AD animals were compared.Comparison of the 1H-MRS indexes between study mice and wild type mice at each time point were conducted by a two-sample t test.Results The mean mI/Cr ratios of AD mice were 0.68± 0.03, 0.72± 0.04, and 0.77 ± 0.04 respectively at 3, 6 and 9 months of age; while they were 0.63 ± 0.04, 0.64 ± 0.03, and 0.64 ± 0.04 respoetively in control group, the difference was significant ( t = 2.814, 5.146, 14.437, P < 0.01 ).Compared with the control group, the mI/Cr ratio of the 3-month-old AD mice of the study group was significantly increased,and histological examination showed proliferation and activation of neuroglial cells in the cerebral cortex and hippoeampus.The mean NAA/Cr ratio were 1.17 ±0.08, 1.04 ±0.05, and 0.90 ±0.05 respectively at 3,6 and 9 months of age in study group, while they were 1.18 ±0.07, 1.16 ±0.07, and 1.18 ±0.08respectively in control group.There were no significant difference ( t = 0.752, P > 0.05 ) between the study group and control group at 3 months of age, and the NAA/Cr ratio decreased significantly only at 6 and 9 months of age ( t = - 8.514, - 5.646, P < 0.01 ).The immunohistochemical exam demonstrated the appearance of Aβ plaque.According to threshold of mI/Cr, the sensitivity of AD mice of 3, 6 and 9 months of age was 80% (28/35), 84% ( 26/31 ) and 85% ( 23/27 ), and the specificity was 85% ( 17/20 ),94% (17/18) and 100% ( 16/16), and the accuracy was 82% (45/55), 88% (43/49) and 91% (39/43),respectively.For NAA/Cr, the sensitivity of AD mice of 6 and 9 months of age was 84% (26/31) and 89% (24/27), and the specificity was 89% (16/18) and 100% (16/16), and the accuracy was 86% (42/49) and 93% (40/43), respectively.Conclusions NAA and mI are the most sensitive and specific markers for early assessment of AD, and change of mI is earlier than that of NAA.Quantitative analysis of mI may provide important clues for early diagnosis of AD.
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Objective To study the developmental process of the region of basal nuclei of postmortem fetuses by 3.0 T and 7.0 T MRI.Methods One hundred and thirty-one postmortem fetuses of 14 to 40 weeks of gestational age(GA)were scanned by 3.0 T MR,of which 11 fetuses of 14-27 weeks of GA were chosen and scanned by 7.0 T MR. The time when the structures in the region of basal nuclei could be detected and the changes of MR signal intensity were analyzed for MRI of different Tesla.Results On 3.0 T MRI.the dorsal thalamus could be delineated as early as 14 weeks of GA. The germinal matrix, caudate nucleus,and putamen could be visualized as early as 15 weeks of GA. The globus pallidus could be described as early as 18 weeks of GA.and the internal capsule and external capsule could be shown as early as 20 weeks of GA. The signal of the caudate nucleus during 15-30 weeks of GA was relatively hypointense on T1WI and hyperintense on T2WI.but during 31-40 weeks of GA, it was relatively hyperintense on T1WI and hypointense on T2WI. The putamen had a relatively high signal intensity on T1WI and low signal intemity on T1WI during 15-17 weeks of GA, and it appeared patchy during 18-25 weeks of GA,then it had a relatively low signal intensity on T1WI and high signal intensity on T2WI during 26-30 weeks of GA, and during 31-40 weeks of GA,its signal intensity was relatively high on T1WI and low on T2WI.The globus pallidus had a relatively high signal intensity on T1WI and low signal intensity on T2WI during 20-40 weeks of GA Compared to the 3.0 T MRI,the T2 images of 7.0 T MRl were more clear,and most structures in the region of basal nuclei could be clearly displayed as early as 16 weeks of GA.such as the germinal matrix,caudate nucleus,dorsal thalamus,putamen,globus pallidus,internal capsule,and external capsule.The claustrum could be delineated as early as 18 weeks of GA on 7.0 T MRI. Conclusions 3.0 T MRI could show the developmental process of the region of basal nuclei well,but the T2 images of 7.0 TMRl were comparatively better.
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Objective To study the capability of high field MRI in demonstrating the post-mortem fetal brains at different gestational age(GA).Methods One hundred and eight post-mortem fetal brains of 14-40 weeks GA were evaluated by 3.0 T MRI. Eleven brains of 14 to 27 weeks GA with good 3.0 T MRI images were chosen and scanned by 7.0 T MRI. The developing sulci, layered structures of fetal cerebral cortex and basal nuclei were evaluated on MRI of different Tesla(3.0 T and 7.0 T)and their results analyzed. Results On T_1 WI of 3.0 T MRI, the layered structures of fetal cerebral cortex were present at 14 weeks GA, the sulci were more accurately identified after 16 weeks GA. The basal nuclei were clearly distinguishable after 20 weeks GA. and these structures were better visualized as the GA increased. On T_2WI of 7.0 T MRI, the sulei, layered structures of fetal cerebral cortex and basal nuclei were shown more clearly at the same GA when compared to 3.0 T, especially the sulci at the early developmental stages. Conclusions T_1 WI of 3.0 T MRI could show the developing structures of post-mortem fetal brain well, but the T_2 WI of 7.0 T MRI were comparatively better.