主动脉瓣退行性变发病机制的研究进展

主动脉瓣退行性变导致的主动脉瓣狭窄已成为西方国家主动脉瓣置换的最常见原因,该病早期的表现为主动脉瓣硬化。即使在血流动力学没有显著阻塞的情况下,主动脉瓣退行性变造成的心血管原因死亡的风险也增加到50%。我国渐入老龄社会,可以预见将会有更多的人患主动脉瓣退行性变。主动脉瓣退行性变的发病是一个主动的过程,在其发病中有多机制的参与:血流动力学的影响、炎症、脂质沉积、细胞外的基质重构、骨化和遗传学均参与了这一过程,对此做一综述。     

Entorhinal cortex lesion or intrahippocampal colchicine injection increases peripheral type benzodiazepine binding sites in rat hippocampus

The peripheral type benzodiazepine binding site (PTBBS) has been proposed to be a good marker for reactive glial cells following brain insults. In the present study, homogenate binding of 3H-Ro5-4864 and quantitative autoradiography of 3H-PK-11195 binding (two ligands for the PTBBS) were used to assess the distribution, time-course and extent of reactive gliosis in the hippocampus following deafferentation by unilateral entorhinal cortex lesion or neuronal death produced by intrahippocampal colchicine injection. Intrahippocampal colchicine injections produced a 3-fold increase in 3H-Ro5-4864 binding in the dentate gyrus within 2 days. This effect was doubled in animals pretreated with the lysosomal inhibitor chloroquine. Quantitative autoradiography of 3H-PK-11195 binding 1 or 2 weeks after colchicine injection indicated that the increase in binding was restricted to the dorsal hippocampus both rostrally and caudally and was present in the dentate gyrus and CA1. Following a unilateral electrolytic lesion of the entorhinal cortex, the binding of 3H-Ro5-4864 to homogenates of the dentate gyrus was doubled 18 h after the lesion, reached a maximum at 4 days post-lesion, and returned to control values by 2 months after the lesion. A transient increase in binding was also observed 2 and 4 days post-lesion in the dentate gyrus contralateral to the lesion side. Autoradiography of 3H-PK-11195 binding indicated that the increase in PTBBS following entorhinal cortex lesion was restricted to the molecular layer of the dentate gyrus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prolonged alcohol intake leads to irreversible loss of vasopressin and oxytocin neurons in the paraventricular nucleus of the hypothalamus

Previous data revealed that numerous neurons in the supraoptic nucleus degenerate after prolonged ethanol exposure, and that the surviving neurons increase their activity in order to prevent dramatic changes in water metabolism. Conversely, excess alcohol does not induce cell death in the suprachiasmatic nucleus, but leads to depression of neuropeptide synthesis that is further aggravated by withdrawal. The aim of the present study is to characterize the effects of prolonged ethanol exposure on the magnocellular neurons of the paraventricular nucleus (PVN) in order to establish whether or not magnocellular neurons display a common pattern of reaction to excess alcohol, irrespective of the hypothalamic cell group they belong. Using conventional histological techniques, immunohistochemistry and in situ hybridization, the structural organization and the synthesis and expression of vasopressin (VP) and oxytocin (OXT) in the magnocellular component of the PVN were studied under normal conditions and following chronic ethanol treatment (6 or 10 months) and withdrawal (4 months after 6 months of alcohol intake). After ethanol treatment, there was a marked decrease in the number of VP- and OXT-immunoreactive magnocellular neurons that was attributable to cell death. The surviving neurons were hypertrophied and the VP and OXT mRNA levels in the PVN unchanged. Withdrawal did not alter the number of VP- and OXT-producing neurons or the gene expression of these peptides. These results substantiate the view that after prolonged ethanol exposure numerous neurons of the hypothalamic magnocellular system degenerate, but the mRNA levels of VP and OXT are not decreased due to compensatory changes undergone by the surviving neurons.     

Brain-derived neurotrophic factor (BDNF) prevents lesion-induced axonal die-back in young rat optic nerve

Lesions of the optic nerve in young animals lead to rapid retrograde degeneration of the axon stumps and to death of retinal ganglion cells. We injected different neurotrophic factors into the eye at the time of an intracranial freeze-crush lesion of the optic nerve in 8 day old rats. Optic nerve axons were visualized by anterograde tracing with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and by electron microscopy. The lesion induced a rapid die-back of the axons, which could be prevented by BDNF and to a lesser extent by neurotrophin-3 (NT-3) or ciliary neurotrophic factor (CNTF). No effect was seen in animals injected with nerve growth factor (NGF) or a mixture of acidic and basic fibroblast growth factor (FGF). In contrast to this effect on the axons, none of these factors was able to counteract the rapidly progressing degeneration of the retinal ganglion cells. These results suggest a selective influence of BDNF on the mechanisms responsible for the maintenance of optic nerve axons.     

颅脑撞击伤并发眼部损伤的实验研究

目的：研究颅脑撞击伤时眼组织的损伤，为早期救治的时机提供实验依据．方法：采用ＢＩＭ－Ⅱ型生物撞击机，建立以额顶为着力部位的家兔重度颅脑撞击伤后眼部损伤的实验动物模型．致伤家兔１７只，分４个时相活杀后，对视神经、视网膜及色素膜作了组织病理学观察．结果：１７只兔伤后经解剖证实均为重度颅脑伤，以蛛网膜下腔出血和脑挫裂伤为主．１７只兔均出现眼部损伤．大体观察：球后段视神经鞘膜下积血，眼底镜下部分兔眼表现为视网膜水肿、出血．光镜观察：伤后６小时内表现为球后视神经蛛网膜下腔出血，脉络膜血管普遍扩张，视神经纤维层水肿，６小时后均出现后极部视网膜脱离，视网膜下蛋白样渗出，视细胞外节变性和消失．结论：颅脑撞击伤后眼组织损害是间接损伤，早期表现为局部循环障碍，晚期出现组织细胞变性坏死．     

Anatomic evidence for a neurotoxic effect of (±)-fenfluramine upon serotonergic projections in the rat

Immunocytochemistry was used to determine whether (±)-fenfluramine causes structural damage to serotonergic (5-HT) neurons. Sections from rat forebrain were examined 4 h, 36 h and 2 weeks after various dose regimens of fenfluramine. At all time points there was a reduction of fine 5-HT axon terminals in the forebrain, while beaded axons were spared. The presence of markedly swollen, fragmented 5-HT axons 36 h after injection is indicative of axonal degeneration, and provides morphologic evidence for a neurotoxic effect of (±)-fenfluramine upon 5-HT axon terminals.     

Encephalopathie bei Thiaminmangel des Nerzes

Summary Tissue lesions of thiamine deficiency in mink (Mustela vison) are predominantly located in the brain. Macroscopic lesions are bilateral symmetrical hemorrhages in the brain stem. Microscopically, signs of disturbance of vascular permeability and proliferation of endothelial cells may be found. Other lesions include a spongy appearance of the neuropil, homogenisation of axons, focal demyelination and occasionally malacias. Ischemic degeneration of neurons may be present in nuclei of the brain stem. The histologic lesions in some areas are similar to those of the pseudoencephalitic syndrome which is characteristic for Wernicke's encephalopathy in man.

     

The effect of varying periods of administration and the cessation of administration of sodium diethyldithiocarbamate upon the central nervous system of domestic fowl

Summary Nerve fibre degeneration occurred in the white matter of the spinal cord of cocks following the daily oral administration of sodium diethyldithiocarbamate (NaDDC) for 4 weeks or more. Lesions were also found in birds that had received the compound for 3 weeks and were killed 3 weeks after cessation of administration. Following the cessation of administration of NaDDC to ataxic birds their coordination improved. After a time the number of degenerating fibres in the spinal cord decreased and fibrous gliosis occurred in the ventral but not in the lateral columns.     

Familial ataxia of the rabbit Sawin-Anders type

Summary This hereditary animal ataxia is selective in its sites of involvement within the nervous system, which include principally the central cerebellar, vestibular and cochlear nuclei. Ultrastructural detail has been described for central cerebellar and vestibular nuclei. Herein the cochlear complex of 18 rabbits with this ataxic condition (ax/ax from the strain AX of the Jackson Laboratory) have been examined. The gene is a lethal one, but the animals were used before they became moribund and between 7 and 57 days after the onset of symptoms.By light microscopy nine cell types (Osen, 1969a, b; 1970) have been identified in the cochlear nuclei of the cat. That distribution can also be identified in electron micrographs of rabbit cochlear nuclei, providing there is a singular opportunity to compare cellular vulnerabilities within the ataxic condition, and establish the principal features of associated neuropil alterations. The cochlear nuclei, cerebellar cortex and central nuclei, and the vestibular nuclei, arise from the ependyma of the rhombic lip of the fourth ventricle, making them close allies in their genetic origins.Pathological alterations were evident in scattered neurons from all nuclear sources by 7–15 days following symptom onset. At 15 days the number of altered neurons evident in electronmicrographs had increased markedly, cells becoming involved at a more rapid pace than those already affected could be removed. Much glycogen is evident from 7 days onwards in both neuropil and neurons. It occurs in considerable amounts in astrocytic processes and less abundantly in endbulbs and somata. By 20 to 25 days spongioform changes in neuropil are prominent, and thereafter the extracellular spaces coalesce to produce a lacunar appearance showing little glycogen. It would appear, therefore, that all neuron types, the endbulbs, and the astrocytic processes are markedly involved simultaneously in the spongioform transformation which features this type of ataxia. Involvement of cochlear nuclei only differs in pathological detail from that found at the other involved sites, and the differences seen relate principally to the architectonics of the nuclei, including size and density of the packing of contained elements.Aided by USPHS Program Project Grant NS-04513, NIH Research Grants RR-00251, from the Division of Research Resources, HO-01496, from the National Institute of Child Health and Human Development, and allocations from General Research Support Grant RR-05545 from the Division of Research Resources to the Jackson Laboratory.     

眼底血管造影联合频域光相干断层扫描同步检查法对渗出性老年性黄斑变性脉络膜新生血管的诊断价值

Objective To evaluate the diagnostic value of Heidelberg retinal angiography(HRA) combined with optical coherence tomography (OCT) to detect neovascularization (CNV) in exudative age-related macular degeneration (AMD) patients. Methods This is a cross-sectional study of a series of clinical cases. AMD diagnosis was established by international standard vision chart, Slit lamp microscope, direct or indirect ophthalmoscope examination. A total of 50 eyes (42 cases) of exudative AMD received HRA and frequency domain OCT scan. All 50 eyes received fundus fluorescein angiography (FFA) and frequency-domain OCT simultaneously, and among them 15 eyes also received indocyanine green angiography (ICGA) at the same time. FFA and ICGA were carried out by conventional methods, CNV was localized by real-time Localization technology of frequency domain OCT. In the radial and grid-like section from the areas with strong fluorescence, image acquisition settings are 7 μm fault for each frame, 30° intervals for radialsection, 10 vertical and 10 horizontal scan lines for grid-like section. CNV can be divided into 4 types (typical CNV, partial typical CNV, occult CNV, CNV scarring) according to their boundaries demonstrated in FFA. Based on the features of the OCT images, there were 3 types of integrated image (sub-RPE type, sub-retinal type and mixed type). Results CNV was detected in all 50 eyes. There were 4 eyes (8%) of typical CNV, 11 eyes (22%) of partial typical CNV, 32 eyes (64 %, including 27 eyes of RPE detachment and 5 eyes of passive late leakage) of occult CNV and 3 eyes (6%) of CNV scarring. There were 4 eyes (8%) of sub-RPE type (CNV under the RPE light band) , 16 eyes (32%) of sub-retinal type(interrupted light band of RPE and choroid capillary layer) and 30 eyes (60%) of mixed type of integrated image. Conclusion The image integration technology of the HRA and frequency domain OCT system provide a valuable tool to classify and measure CNV, which will benefit the clinical treatment of AMD patients.