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1.
MRI at 7 Tesla has been used to investigate the accumulation of manganese in the occipital cortex of common marmoset monkeys (Callithrix jacchus) after administering four fractionated injections of 30 mg/kg MnCl2 · 4H2O in the tail vein. We found a statistically significant decrease in T1 in the primary (V1) and secondary (V2) areas of the visual cortex caused by an accumulation of manganese. The larger T1 shortening in V1 (ΔT1 = 640 ms) relative to V2 (ΔT1 = 490 ms) allowed us to robustly detect the V1/V2 border in vivo using heavily T1‐weighted MRI. Furthermore, the dorso‐medial (DM) and middle‐temporal (MT) areas of the visual pathway could be identified by their T1‐weighted enhancement. We showed by comparison to histological sections stained for cytochrome oxidase (CO) activity that the extent of V1 is accurately identified throughout the visual cortex by manganese‐enhanced MRI (MEMRI). This provides a means of visualizing functional cortical regions in vivo and could be used in longitudinal studies of phenomena such as cortical plasticity, and for non‐destructive localization of cortical regions to guide in the implementation of functional techniques. Published in 2009 by John Wiley & Sons, Ltd.  相似文献   

2.
Aim and methods: We investigated the immunohistochemical alterations of S100β‐, S100‐, glial fibrillary acidic protein (GFAP)‐ and isolectin B4‐positive cells in the hippocampus after 5 min of transient cerebral ischaemia in gerbils. We also examined the effect of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase inhibitor pitavastatin against neuronal damage in the hippocampal CA1 sector after ischaemia. Results: Severe neuronal damage was observed in the hippocampal CA1 pyramidal neurons from 5 days after ischaemia. GFAP‐positive cells increased gradually in the hippocampus from 5 days after ischaemia. Five and 14 days after ischaemia, significant increases in the number of GFAP‐positive cells and isolectin B4‐positive cells were observed in the hippocampal CA1 and CA3 sector. Mild increases in the number of S100 and S100β‐positive cells were observed in the hippocampal CA1 sector from 1 h to 2 days after ischaemia. Thereafter, S100β‐positive cells increased in the hippocampal CA1 sector after ischaemia, whereas S100‐positive cells decreased in this region. In our double‐labelled immunostainings, S100 and S100β immunoreactivity was found in GFAP‐positive astrocytes, but not in isolectin B4‐positive microglia. Pharmacological study showed that HMG‐CoA reductase inhibitor, pitavastatin, can protect against the hippocampal CA1 neuronal damage after ischaemia. This drug also prevented increases in the number of GFAP‐positive astrocytes, isolectin B4‐positive microglia, S100‐positive astrocytes and S100β‐positive astrocytes after ischaemia. Conclusion: The present study demonstrates that pitavastatin can decrease the neuronal damage of hippocampal CA1 sector after ischaemia. This beneficial effect may be, at least in part, mediated by inhibiting the expression of astrocytic activation in the hippocampus at the acute phase after ischaemia. Thus the modulation of astrocytic activation may offer a novel therapeutic strategy of ischaemic brain damage.  相似文献   

3.
Manganese‐enhanced MRI (MEMRI) is an increasingly used imaging method in animal research, which enables improved T1‐weighted tissue contrast. Furthermore accumulation of manganese in activated neurons allows visualization of neuronal activity. However, at higher concentrations manganese (Mn2+) exhibits toxic side effects that interfere with the animals' behaviour and well‐being. Therefore, when optimizing MEMRI protocols, a compromise has to be found between minimizing side effects and intensifying image contrast. Recently, a low concentrated fractionated Mn2+ application scheme has been proposed as a promising alternative. In this study, we investigated effects of different fractionated Mn2+ dosing schemes on vegetative, behavioural and endocrine markers, and MEMRI signal contrast in C57BL/6N mice. Measurements of the animals' well‐being included telemetric monitoring of body temperature and locomotion, control of weight and observation of behavioural parameters during the time course of the injection protocols. Corticosterone levels after Mn2+ application served as endocrine marker of the stress response. We compared three MnCl2 · 4H2O application protocols: 3 times 60 mg/kg with an inter‐injection interval of 48 h, six times 30 mg/kg with an inter‐injection interval of 48 h, and 8 times 30 mg/kg with an inter‐injection interval of 24 h (referred to as 3 × 60/48, 6 × 30/48 and 8 × 30/24, respectively). Both the 6 × 30/48 and the 8 × 30/24 protocols showed attenuated effects on animals' well‐being as compared to the 3 × 60/48 scheme. Best MEMRI signal contrast was observed for the 8 × 30/24 protocol. Together, these results argue for a fractionated application scheme such as 30 mg/kg every 24 h for 8 days to provide sufficient MEMRI signal contrast while minimizing toxic side effects and distress. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   

4.
Manganese‐enhanced MRI studies have proven to be useful in monitoring physiological activities associated with calcium ions (Ca2+) due to the paramagnetic property of the manganese ion (Mn2+), which makes it an excellent probe of Ca2+. In this study, we developed a method in which a Mn2+‐enhanced T1‐map MRI could enable the monitoring of Ca2+ influx during the early stages of intestinal ischemia–reperfusion (I/R) injury. The Mn2+ infusion protocol was optimized by obtaining dose‐dependent and time‐course wash‐out curves using a Mn2+‐enhanced T1‐map MRI of rabbit abdomens following an intravenous infusion of 50 mmol/l MnCl2 (5–10 nmol/g body weight (BW)). In the rabbit model of intestinal I/R injury, T1 values were derived from the T1 maps in the intestinal wall region and revealed a relationship between the dose of the infused MnCl2 and the intestinal wall relaxation time. Significant Mn2+ clearance was also observed over time in control animals after the infusion of Mn2+ at a dose of 10 nmol/g BW. This technique was also shown to be sensitive enough to monitor variations in calcium ion homeostasis in vivo after small intestinal I/R injury. The T1 values of the intestinal I/R group were significantly lower (P < 0.05) than that of the control group at 5, 10, and 15 min after Mn2+ infusion. Our data suggest that MnCl2 has the potential to be an MRI contrast agent that can be effectively used to monitor changes in intracellular Ca2+ homeostasis during the early stages of intestinal I/R injury. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

5.
This study aimed to explore the optimal dose and manner of administration for visualization of the auditory pathway on manganese‐enhanced MRI (ME MRI). Twenty‐four healthy male Sprague–Dawley rats were randomly divided into three experimental groups (n = 8 for Groups A, B and C). The rats in Groups A, B and C were subjected to MnCl2 injection through the tympanum, inner ear endolymph and perilymph, respectively (0.2 M for four rats and 0.4 M for the others in each group) and observed at 1, 2, 3, 4, 7 and 10 days after the operation with 3.0 T MRI. The signal intensity (SI) and dynamic changes of the auditory pathways at various times, and at two doses through three injection routes, were compared by statistical analysis. Administration of MnCl2 through the perilymph best showed the complete auditory pathway (P < 0.01), whereas administration though the tympanum only demonstrated part of the pathway. The SI was highest at 24 h after administration of the tracer and began to decline at 48 h. The SI of the auditory cortex was higher after the injection of 0.4 M MnCl2 than that of 0.2 M MnCl2. ME MRI best demonstrated the whole auditory pathway at 24 h after the injection of 0.4 M MnCl2 through the perilymph in the rat, which provided an optimal method for the study of ME MRI of the auditory pathway in the animal model.  相似文献   

6.
Manganese-enhanced magnetic resonance imaging is a technique that employs the divalent ion of the paramagnetic metal manganese (Mn2+) as an effective contrast agent to visualize, in vivo, the mammalian brain. As total achievable contrast is directly proportional to the net amount of Mn2+ accumulated in the brain, there is a great interest in optimizing administration protocols to increase the effective delivery of Mn2+ to the brain while avoiding the toxic effects of Mn2+ overexposure. In this study, we investigated outcomes following continuous slow systemic infusion of manganese chloride (MnCl2) into the mouse via mini-osmotic pump administration. The effects of increasing fractionated rates of Mn2+ infusion on signal enhancement in regions of the brain were analyzed in a three-treatment study. We acquired whole-brain 3-D T1-weighted images and performed region of interest quantitative analysis to compare mean normalized signal in Mn2+ treatments spanning 3, 7, or 14 days of infusion (rates of 1, 0.5, and 0.25 μL/h, respectively). Evidence of Mn2+ transport at the conclusion of each infusion treatment was observed throughout the brains of normally behaving mice. Regions of particular Mn2+ accumulation include the olfactory bulbs, cortex, infralimbic cortex, habenula, thalamus, hippocampal formation, amygdala, hypothalamus, inferior colliculus, and cerebellum. Signals measured at the completion of each infusion treatment indicate comparable means for all examined fractionated rates of Mn2+ infusion. In this current study, we achieved a significantly higher dose of Mn2+ (180 mg/kg) than that employed in previous studies without any observable toxic effects on animal physiology or behavior.  相似文献   

7.
The aim of this study was to provide data on the dose dependence of manganese‐enhanced MRI (MEMRI) in the visual pathway of experimental rats and to study the toxicity of MnCl2 to the retina. Sprague–Dawley rats were intravitreally injected with 2 μL of 0, 10, 25, 50, 75, 100, 150 and 300 mm MnCl2, respectively. The contrast‐to‐noise ratio (CNR) of MEMRI for optic nerve enhancement was measured at different concentrations of MnCl2. Simultaneously, the toxicity of manganese was evaluated by counting retinal ganglion cells and by retinal histological examination using light microscopy and transmission electron microscopy. The CNR increased with increasing concentration of MnCl2 up to 75 mm . Retinal ganglion cell densities were reduced significantly when the concentration of MnCl2 in the intravitreal injection was equal to or greater than 75 mm . Increasing numbers of ribosomes in retinal ganglion cells were first detected at 25 mm of MnCl2. The retinal toxicity of MnCl2 at higher concentration also included mitochondrial pathology and cell disruption of retinal ganglion cells, as well as abnormalities of photoreceptor and retinal pigment epithelium cells. It can be concluded that intravitreal injection of MnCl2 induces retinal cell damage that appears to start from 25 mm . The concentration of MnCl2 should not exceed 25 mm through intravitreal injection for visual pathway MEMRI in the rat. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

8.
Exaggerated cardiovascular reactivity to acute psychological stress is associated with an increased risk of developing cardiovascular disease. The amygdala and hippocampus have been implicated in centrally mediating stressor‐evoked cardiovascular reactivity. However, little is known about the associations of amygdala and hippocampus morphology with stressor‐evoked cardiovascular reactivity. Forty (Mage = 19.05, SD = 0.22 years) healthy young women completed two separate testing sessions. Session 1 assessed multiple parameters of cardiovascular physiology at rest and during a validated psychological stress task (Paced Auditory Serial Addition Test), using electrocardiography, Doppler echocardiography, and blood pressure monitoring. In Session 2, 1 year later, structural MRI was conducted. Brain structural volumes were computed using automated segmentation methods. Regression analyses, following Benjamini‐Hochberg correction, showed that greater heart rate and cardiac output reactivity were associated with reduced amygdala and hippocampus gray matter volume. Systolic blood pressure reactivity was associated with reduced hippocampus volume. In contrast, no associations between diastolic blood pressure, mean arterial blood pressure, stroke volume, or total peripheral resistance reactivity with amygdala or hippocampus volumes were apparent. Comparison analyses examining insula volume found no significant associations. Some indicators of greater stressor‐evoked cardiovascular reactivity associate with reduced amygdala and hippocampus gray matter volume, but the mechanisms of this association warrant further study.  相似文献   

9.
Contrast‐enhanced T1‐ and T2‐weighted MRI at 9.4 T and in‐plane resolutions of 25 and 30 µm has been demonstrated to differentiate between neural tissues in mouse brain in vivo, including granule cell layers, principal cell layers, general neuropil, specialized neuropil and white matter. In T1‐weighted MRI of the olfactory bulb, hippocampus and cerebellum, contrast obtained by the intracranial administration of gadopentetate dimeglumine (Gd‐DTPA) reflects the extra‐ and intracellular spaces of gray matter in agreement with histological data. General neuropil areas are highlighted, whereas other tissues present with lower signal intensities. The induced contrast is similar to that in plain T2‐weighted MRI, but offers a 16–30‐fold higher contrast‐to‐noise ratio. Systemic administration of manganese chloride increases the signal‐to‐noise ratio in T1‐weighted MRI to a significantly greater extent in principal cell layers and specialized neuropil than in granule cell layers, whereas gadolinium‐enhanced MRI indicates no larger intracellular spaces in these tissues. Granule cell layers are enhanced no more than general neuropil by manganese, whereas gadolinium‐enhanced MRI indicates significantly larger intracellular spaces in the cell layers. These discrepancies suggest that the signal increase after manganese administration reflects cellular activity which is disproportionate to the intracellular space. As a result, principal cell layers and specialized neuropil become highlighted, whereas granule cell layers, general neuropil and white matter present with lower signal intensities. Copyright © 2013 John Wiley & Sons, Ltd.  相似文献   

10.
The sodium–calcium exchanger (NCX) is one of the transporters contributing to the control of intracellular calcium (Ca2+) concentration by normally mediating net Ca2+ efflux. However, the reverse mode of the NCX can cause intracellular Ca2+ concentration overload, which exacerbates the myocardial tissue injury resulting from ischemia. Although the NCX inhibitor SEA0400 has been shown to therapeutically reduce myocardial injury, no in vivo technique exists to monitor intracellular Ca2+ fluctuations produced by this drug. Cardiac manganese‐enhanced MRI (MEMRI) may indirectly assess Ca2+ efflux by estimating changes in manganese (Mn2+) content in vivo, since Mn2+ has been suggested as a surrogate marker for Ca2+. This study used the MEMRI technique to examine the temporal features of cardiac Mn2+ efflux by implementing a T1‐mapping method and inhibiting the NCX with SEA0400. The change in 1H2O longitudinal relaxation rate, ΔR1, in the left ventricular free wall, was calculated at different time points following infusion of 190 nmol/g manganese chloride (MnCl2) in healthy adult male mice. The results showed 50% MEMRI signal attenuation at 3.4 ± 0.6 h post‐MnCl2 infusion without drug intervention. Furthermore, treatment with 50 ± 0.2 mg/kg of SEA0400 significantly reduced the rate of decrease in ΔR1. At 4.9–5.9 h post‐MnCl2 infusion, the average ΔR1 values for the two groups treated with SEA0400 were 2.46 ± 0.29 and 1.72 ± 0.24 s?1 for 50 and 20 mg/kg doses, respectively, as compared to the value of 1.27 ± 0.28 s?1 for the control group. When this in vivo data were compared to ex vivo absolute manganese content data, the MEMRI T1‐mapping technique was shown to effectively quantify Mn2+ efflux rates in the myocardium. Therefore, combining an NCX inhibitor with MEMRI may be a useful technique for assessing Mn2+ transport mechanisms and rates in vivo, which may reflect changes in Ca2+ transport. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

11.
Manganese‐enhanced MRI (MEMRI) with topical loading of MnCl2 provides optic nerve enhancement comparable to that seen by intravitreal injection. However, the impact of this novel and non‐invasive Mn2+ loading method on visual function requires further assessments. The objective of this study is to determine the optimal topical Mn2+ loading dosage for MEMRI and to assess visual function after MnCl2 loading. Intravitreal administration was performed to compare the two approaches of MnCl2 loading. Twenty‐four hours after topical loading of 0, 0.5, 0.75, and 1 M MnCl2, T1‐weighted, T2‐weighted, diffusion tensor imaging and visual acuity (VA) assessments were performed to determine the best topical loading dosage for MEMRI measurements and to assess the integrity of retinas and optic nerves. Mice were perfusion fixed immediately after in vivo experiments for hematoxylin and eosin and immunohistochemistry staining. Topical loading of 1 M MnCl2 damaged the retinal photoreceptor layer with no detectable damage to retina ganglion cell layers or prechiasmatic optic nerves. For the topical loading, 0.75 M MnCl2 was required to see sufficient enhancement of the optic nerve. At this concentration the visual function was significantly affected, followed by a slow recovery. Intravitreal injection (0.25 μL of 0.2 M MnCl2) slightly affected VA, with full recovery a day later. To conclude, intravitreal MnCl2injection provides more reproducible results with less adverse side‐effects than topical loading. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

12.
Kainic acid‐induced (KA) hippocampal damage leads to neuronal death and further synaptic plasticity. Formation of aberrant as well as of functional connections after such procedure has been documented. However, the impact of such structural plasticity on cell activation along time after damage and in face of a behavioral demand has not been explored. We evaluated if the mRNA and protein levels of plasticity‐related protein synaptophysin (Syp and SYP, respectively) and activity‐regulated cytoskeleton‐associated protein mRNA and protein levels (Arc and Arc, respectively) in the dentate gyrus were differentially modulated in time in response to a spatial‐exploratory task after KA‐induced hippocampal damage. In addition, we analyzed Arc+/NeuN+ immunopositive cells in the different experimental conditions. We infused KA intrahippocampally to young‐adult rats and 10 or 30 days post‐lesion (dpl) animals performed a hippocampus‐activating spatial‐exploratory task. Our results show that Syp mRNA levels significantly increase at 10dpl and return to control levels after 30dpl, whereas SYP protein levels are diminished at 10dpl, but significantly increase at 30dpl, as compared to 10dpl. Arc mRNA and protein levels are both increased at 30dpl as compared to sham. Also the number of NeuN+/Arc+ cells significantly increases at 30dpl in the group with a spatial‐exploratory demand. These results provide information on the long‐term modifications associated to structural plasticity and neuronal activation in the dentate gyrus after excitotoxic damage and in face of a spatial‐exploratory behavior. Anat Rec, 300:425–432, 2017. © 2016 Wiley Periodicals, Inc.  相似文献   

13.
DNA mutations play a crucial role in the origins of cancer, and the clonal expansion of mutant cells is one of the fundamental steps in multistage carcinogenesis. In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N ‐ ethyl‐N‐nitrosourea (ENU) with the persistence of ENU‐induced mutant clones in transgenic gpt delta B6C3F1 mice. The induced gpt mutations afforded no selective advantage in the mouse cells and could be distinguished by a mutational spectrum that is characteristic of ENU treatment. The gpt mutations were passengers of the mutant cell of origin and its daughter cells and thus could be used as neutral markers of clones that arose and persisted in the tissues. Female B6C3F1 mice exposed for 1 month to 200 ppm ENU in the drinking water developed early thymic lymphomas and late liver and lung tumors. To assay gpt mutations, we sampled the thymus, liver, lung, and small intestine of female gpt delta mice at 3 days, 4 weeks, and 8 weeks after the end of ENU exposure. Our results reveal that, in all four tissues, the ENU‐induced gpt mutations persisted for weeks after the end of mutagen exposure. Clonal expansion of mutant cells was observed in the thymus and small intestine, with the thymus showing larger clone sizes. These results indicate that the clearance of mutant cells and the potential for clonal expansion during normal tissue growth depends on tissue type and that these factors may affect the sensitivity of different tissues to carcinogenesis. Environ. Mol. Mutagen. 58:592–606, 2017. © 2017 Wiley Periodicals, Inc.  相似文献   

14.
In this work, we report a monodisperse bifunctional nanoparticle system, MIO@SiO2‐RITC, as an MRI contrast agent [core, manganese iron oxide (MIO); shell, amorphous silica conjugated with rhodamine B isothiocyanate (RITC)]. It was prepared by thermal decomposition and modified microemulsion methods. The nanoparticles with varying iron to manganese ratios displayed different saturated magnetizations and relaxivities. In vivo MRI of rats injected intravenously with MIO@SiO2‐RITC nanoparticles exhibited enhancement of the T1 contrast in brain tissue, in particular a time‐delayed enhancement in the hippocampus, pituitary gland, striatum and cerebellum. This is attributable to the gradual degradation of MIO@SiO2‐RITC nanoparticles in the liver, resulting in the slow release of manganese(II) [Mn(II)] into the blood pool and, subsequently, accumulation in the brain tissue. Thus, T1‐weighted contrast enhancement was clearly detected in the anatomic structure of the brain as time progressed. In addition, T2*‐weighted images of the liver showed a gradual darkening effect. Here, we demonstrate the concept of the slow release of Mn(II) for neuroimaging. This new nanoparticle‐based manganese contrast agent allows one simple intravenous injection (rather than multiple infusions) of Mn(II) precursor, and results in delineation of the detailed anatomic neuroarchitecture in MRI; hence, this provides the advantage of the long‐term study of neural function. Copyright © 2013 John Wiley & Sons, Ltd.  相似文献   

15.
This investigation was designed to determine whether l-DOPA treatment improves the motor alterations observed after divalent and trivalent manganese (Mn) mixture inhalation on mice to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl2) and manganese acetate (Mn(OAc)3), 1 h twice a week for 5 months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. Overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn exposure period, 10 mice were orally treated with 7.5 mg/kg l-DOPA. After 5 months of Mn-mixture inhalation striatal dopamine content decreased 71%, mice developed evident deficits in motor performance manifested as akinesia, postural instability and action tremor; these alterations were reverted with l-DOPA treatment. Our results suggest that the motor alterations induced by the inhalation of the combination of MnCl2/Mn(OAc)3 are related to nigrostriatal dopaminergic function providing new light on the understanding of manganese neurotoxicity as a suitable Parkinson disease experimental model.  相似文献   

16.
Cerebrovascular abnormality is frequently accompanied by cognitive dysfunctions, such as dementia. Antibodies against the α1‐adrenoceptor (α1‐AR) can be found in patients with Alzheimer's disease with cerebrovascular disease, and have been shown to affect the larger vessels of the brain in rodents. However, the impact of α1‐AR antibodies on the cerebral vasculature remains unclear. In the present study, we established a neuroimaging method to measure the relative cerebral blood volume (rCBV) in small rodents with the ultimate goal to detect changes in blood vessel density and/or vessel size induced by α1‐AR antibodies. For this purpose, mapping of R2* and R2 was performed using MRI at 9.4 T, before and after the injection of intravascular iron oxide particles (ferumoxytol). The change in the transverse relaxation rates (ΔR2*, ΔR2) showed a significant rCBV decrease in the cerebrum, cortex and hippocampus of rats (except hippocampal ΔR2), which was more pronounced for ΔR2* than for ΔR2. Immunohistological analyses confirmed that the α1‐AR antibody induced blood vessel deficiencies. Our findings support the hypothesis that α1‐AR antibodies lead to cerebral vessel damage throughout the brain, which can be monitored by MRI‐derived rCBV, a non‐invasive neuroimaging method. This demonstrates the value of rCBV estimation by ferumoxytol‐enhanced MRI at 9.4 T, and further underlines the significance of this antibody in brain diseases involving vasculature impairments, such as dementia. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

17.
Long-term adrenalectomy induces a dramatic loss of cells in the dentate gyrus and CA1-CA4 fields of the hippocampus resulting in an impairment of cognitive functions such as spatial learning, memory and exploratory behaviour. Muscarinic M1 and M4 receptor levels in the hippocampus and entorhinal cortex of adult male Wistar rats were examined 3, 14, 30, 90, and 150 days after adrenalectomy. Receptor levels in the entorhinal cortex and the hippocampus were determined by quantitative autoradiography using 125I-M1-toxin-1 and 125I-M4-toxin-1, M1 and M4 subtype selective antagonists, respectively. Moreover, the level of hippocampal M1 and M4 muscarinic receptors were evaluated 1 month after adrenalectomy by immunoblot analysis. Adrenalectomy induced apoptotic processes were examined by analysing apoptotic markers using Western blot analysis. No significant changes were observed in the level of muscarinic M1 receptors in the entorhinal cortex, the dentate gyrus and in the different CA fields of the hippocampus of adrenalectomized (ADX) rats. However, M4 receptors showed a significant decrease in the entorhinal cortex (at 3 days), dentate gyrus and CA4 (at 14 days), CA3 (at 30 days), and CA2 and CA1 (at 90 days) after adrenalectomy. Moreover, a decrease in the level of M4 receptors was detected in ADX rats 1 month after adrenalectomy as compared with sham groups using M4 specific antibody. Apoptotic markers such as PARP and p53 were significantly increased whereas Bcl-2 marker was decreased in ADX rat brain homogenates compared to controls. Our results show that M1 and M4 receptors are differentially affected by adrenalectomy and indicate that these subtypes have different functions in the hippocampus. Our data on time and region-dependent decreases in hippocampal M4 receptors indicate that the M4 receptor subtype is influenced by adrenal hormones and suggest that the M4 receptor might be linked to memory function in the hippocampus.  相似文献   

18.
The present study examined the effect of glucocorticoid manipulations on local cerebral blood flow in the hippocampus. We measured local cerebral blood flow in the hippocampus at 1-h intervals over a 1-day period in freely moving rats, by means of the H2 clearance method, before and after sham adrenalectomy, adrenalectomy or adrenalectomy with corticosterone replacement. We also measured local cerebral blood flow in the prefrontal cortex before and after adrenalectomy. Four weeks after the adrenalectomy, hippocampal blood flow at each time of day was an average of 47% greater than before the operation, showing diurnal variation as before. After the sham adrenalectomy or adrenalectomy with corticosterone replacement, hippocampal blood flow did not change significantly with respect to either its level or its diurnal variation. Local cerebral blood flow in the prefrontal cortex increased by only 19% after adrenalectomy. The present study demonstrates that adrenalectomy causes a remarkable increase in hippocampal blood flow, probably due to a lack of corticosterone.  相似文献   

19.
Conflicting evidence exists regarding whether focal cerebral infarction contributes to cerebral amyloid‐β (Aβ) deposition, as observed in Alzheimer's disease. In this study, we aimed to evaluate the presence of Aβ deposits in the ipsilateral thalamus and hippocampus 12 months post‐stroke in non‐human primates, whose brains are structurally and functionally similar to that of humans. Four young male cynomolgus monkeys were subjected to unilateral permanent middle cerebral artery occlusion (MCAO), and another four sham‐operated monkeys served as controls. All monkeys underwent magnetic resonance imaging examination on post‐operative day 7 to assess the location and size of the infarction. The numbers of neurons, astrocytes, microglia and the Aβ load in the non‐affected thalamus and hippocampus ipsilaterally remote from infarct foci were examined immunohistochemically at sacrifice 12 months after operation. Thioflavin S and Congo Red stainings were used to identify amyloid deposits. Multiple Aβ antibodies recognizing both the N‐terminal and C‐terminal epitopes of Aβ peptides were used to avoid antibody cross‐reactivity. Aβ levels in cerebrospinal fluid (CSF) and plasma were examined using enzyme‐linked immunosorbent assay. The initial infarct was restricted to the left temporal, parietal, insular cortex and the subcortical white matter, while the thalamus and hippocampus remained intact. Of note, there were fewer neurons and more glia in the ipsilateral thalamus and hippocampus in the MCAO group at 12 months post‐stroke compared to the control group (all P < 0.05). However, there was no sign of extracellular Aβ plaques in the thalamus or hippocampus. No statistically significant difference was found in CSF or plasma levels of Aβ40, Aβ42 or the Aβ40/Aβ42 ratio between the two groups (P > 0.05). These results suggest that significant secondary neuronal loss and reactive gliosis occur in the non‐affected thalamus and hippocampus without Aβ deposits in the late period after MCAO in non‐human primates.  相似文献   

20.
Enteric contrast agents are important in gastrointestinal MRI. However, no currently available agent is well established as the standard of care. In this study, in vitro relaxivities of manganese threonine chelate (Mn‐Thr), a common nutritional food supplement, were measured at 1.5 T and 3 T with further investigation of its efficacy and safety in vivo as an enteric contrast agent. According to the calculated relaxivities, T1W and T2W TSE sequences of Mn‐Thr solutions at different concentrations were acquired, and the optimal concentration for dark lumen imaging on both T1W and T2W images was determined in vitro. To validate the optimal concentration in vivo, eight Sprague‐Dawley rats were randomly divided into two groups. Each group received rectal injection of either 2.00 g/L (about 3.80 mM) Mn‐Thr or saline as an enteric contrast agent and underwent MRI. After a time interval of one week, the same procedures were repeated with the alternative contrast agent. Animals were sacrificed after the second MRI. Tissue manganese quantification and histopathological examination were obtained. Qualitative MR image quality assessments were performed and compared between Mn‐Thr and saline. Measured T1 and T2 relaxivities of Mn‐Thr were significantly higher than those of MnCl2 in vitro (p < 0.05). At the concentration of 2.00 g/L (about 3.80 mM), Mn‐Thr produced a dark lumen on T1W and T2W images both in vitro and in vivo. Compared with saline, Mn‐Thr showed significantly more homogenous luminal signal and increased bowel wall conspicuity in image quality assessments. Tissue manganese concentrations were not significantly different between two groups. Histopathological examinations were normal in both groups. Our data suggest that Mn‐Thr possesses favorable paramagnetic properties and can create a homogenous dark lumen on T1W and T2W images without obvious side effects in healthy rats. As a commercially available nutritional food supplement, Mn‐Thr appears to be a promising enteric contrast agent for MRI.  相似文献   

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