实验性鼠脑缺血时脑细胞线粒体酶活性的变化──人工虫草菌丝的抗线粒体损害作用

本文对鼠脑缺血后脑细胞线粒体柠檬酸合成酶（ＣＳ），琥珀酸脱氢酶（ＳＤＨ）活性进行测定，并用人工虫草菌丝对各缺血时间组进行治疗，结合电镜对各实验组线粒体形态进行观察，发现鼠脑缺血早期即有线粒体形态学改变及ＣＳ、ＳＤＨ活性降低。应用人工虫草菌丝后，线粒体ＣＳ、ＳＤＨ活性有所增高。而线粒体形态学恢复的变化不大。揭示线粒体酶活性变化先于形态学改变。     

Anatomy and pathology of extrapyramidal diseases

An overview of the anatomy of the basal ganglion system has been presented in conjunction with a brief outline of the diseases associated with it. The etiology of these degenerative diseases has been discussed, and the major morphologic changes at the macroscopic level are given. The probable pathologic and morphologic substrates of movement disorders have been suggested.     

Pediatric metrizamide CT cisternography: cerebrospinal fluid circulation and hydrocephalus

The technique of intrathecal enhancement using metrizamide (Amipaque) combined with CT imaging enables both the morphologic and dynamic (serial) evaluation of the intracranial cerebrospinal fluid pathways. Three distinct metrizamide CT cisternographic patterns (delayed, intermediate, and normal) emerge in pediatric patients with hydrocephalus. The findings correlate well with radionuclide cisternographic patterns; however, CT also provides excellent morphologic definition.     

A quantitative magnetic resonance imaging analysis of the cerebellar deficit hypothesis of dyslexia

Recent evidence suggests that the primary source of dysfunction in dyslexia is the cerebellum. To examine the cerebellar deficit hypothesis of dyslexia, 20 children with dyslexia and 20 children without dyslexia were assessed using neuropsychological testing and quantitative magnetic resonance imaging. Results demonstrated that the volumes of both hemispheres and the vermis were not statistically significantly different between groups. However, children without dyslexia demonstrated greater rightward cerebellar hemisphere asymmetry. The relationship between cerebellar morphologic structure and phonological processing was assessed. For children without dyslexia, bilateral hemisphere volume moderately correlated with phonological awareness and phonological short-term memory. Hemisphere asymmetry moderately correlated with rapid naming errors, and the anterior vermis volume moderately correlated with phonological awareness. For children with dyslexia, the only statistically significant correlation was between rapid naming errors and the left hemisphere volume. Evidence suggests that atypical cerebellar morphologic structure may have a role in dyslexia for a subgroup of individuals. Although children with and without attention-deficit/hyperactivity disorder did not differ in cerebellar morphologic structure, the anterior vermis volume moderately correlated with inattention, hyperactivity, and impulsivity, while the right hemisphere volume moderately correlated with inattention and hyperactivity. Our findings provide mixed support for the cerebellar deficit hypothesis of dyslexia. Although cerebellar morphologic structure is atypical in some individuals with dyslexia, it is inconsistently related to cognitive or motor dysfunction. In our sample, cerebellar morphologic structure may be related to about one-third of cases of dyslexia. Hence, dyslexia may be best accounted for by a combination of cortical and cerebellar contributions.     

Synaptic and morphologic properties in vitro of premotor rat nucleus tractus solitarius neurons labeled transneuronally from the stomach

Neurons in the rat nucleus tractus solitarius (NTS) possess morphologic characteristics that have been correlated with the type of synaptic information they receive. These features have been described for viscerosensory neurons but not for premotor NTS neurons. The morphologic and synaptic features of neurons in the rat caudal NTS were assessed using whole-cell patch-clamp recordings and biocytin labeling in brainstem slices. Gastric-related premotor NTS neurons were identified for recording after inoculation of the stomach wall with a transneuronal retrograde viral label that reports enhanced green fluorescent protein. Three morphologic groups of NTS neurons were identified based on quantitative aspects of soma area and proximal dendritic arborization, measures that were consistent across slice recordings. The most common type of cell (group I) had relatively small somata and one to three sparsely branching dendrites, whereas the other groups had larger somata and more than three dendrites, which branched predominantly close to (group II) or distant from (group III) the soma. Voltage-clamp recordings revealed spontaneous excitatory and inhibitory postsynaptic currents in all neurons, regardless of morphology. Gastric-related premotor NTS neurons composed two of the three morphologic types (i.e., groups I and II). Compared with unlabeled neurons, these cells were less likely to receive constant-latency synaptic input from the tractus solitarius. These results refute the hypothesis that general patterns of synaptic input to NTS neurons depend on morphology. Gastric premotor neurons comprise a subset of NTS morphologic types, the organization of the viscerosensory input to which has yet to be defined.     

Correlation of morphologic brain lesions with physiologic alterations and blood-brain barrier impairment in 3-intropropionic acid toxicity in rats

Summary 3-Nitropropionic acid (NPA), a toxin which irreversibly inhibits the Krebs cycle enzyme succinate dehydrogenase, causes severe neurologic disease and a specific pattern of morphologic brain damage when given subcutaneously to rats. To determine whether hypotension or hypoxemia were necessary for development of morphologic brain lesions in NPA neurotoxicity, systemic blood pressure and arterial blood gases were measured in NPA-intoxicated rats. The extent and distribution of albumin extravasation was examined by immunohistochemistry, and was compared to the extent and severity of morphological injury in the caudate-putamen. Neither hypotension nor hypoxemia were necessary for the development of morphologic injury in the brains of NPA-intoxicated rats. In fact, intoxicated rats had significantly higher systolic blood pressure and arterial blood oxygen than did controls. Arterial bicarbonate and pH were significantly lower in intoxicated rats than controls, however, suggesting that acidosis may be involved in the pathogenesis of NPA toxicity. When morphologic injury was severe, albumin extravasation was extensive occupying approximately 30%–80% of the lesion area in the caudate-putamen of NPA-intoxicated rats. When morphologic injury was mild, albumin extravasation was absent, or limited to small cuffs around individual capillaries (<1% of the lesion area). There was no leakage of albumin in the cerebral cortex, which was resistant to morphologic injury. It was concluded that leakage of protein-rich fluid into cerebral parenchyma from blood-brain barrier impairment is not responsible for the initiation of morphologic injury in NPA toxicity, but may contribute to the severity of injury later in the evolution of brain lesions.Supported by US Public Health Service grant numbers 5 T15 CA09408 and 5T32 ES07152 awarded by the National Cancer Institute and the National Institute of Environmental Health Sciences, and by the CSU Agricultural Experiment Station/USDA Animal Health and Disease Research Program     

Flunarizine limits hypoxia-ischemia induced morphologic injury in immature rat brain

We examined the impact of pre-treatment with the calcium antagonist flunarizine on the development of hypoxic-ischemic brain injury in the immature rat. Unilateral carotid artery ligation and subsequent exposure to 2 hours of 8% oxygen in 7-day-old rats was used as a model for perinatal hypoxic-ischemic encephalopathy. This procedure leads to atrophy in the cerebral hemisphere ipsilateral to carotid occlusion, with prominent foci of neuronal infarction in the caudate-putamen (striatum). The morphologic injury develops after 1 1/2 hours of hypoxia; and there is an equivalent time threshold for duration of hypoxic exposure needed to acutely stimulate dopamine release in the ipsilateral striatum. Parenteral administration of 30 mg/kg of flunarizine before hypoxic exposure limited both the release of dopamine acutely and the extent of morphologic damage observed two weeks after the insult. Oral administration of 30 mg/kg of flunarizine in a different vehicle prevented morphologic damage but had no effect on stimulated dopamine release. The drug vehicle for the parenteral preparation also prevented tissue injury, but to a lesser degree than flunarizine. However the parenteral vehicle was equipotent with parenteral flunarizine in limiting acute stimulation of dopamine release. The results demonstrate that flunarizine has potent neuroprotective properties against morphologic brain injury from hypoxia-ischemia, acting by a mechanism which is independent of effects on dopamine release.     

Methods for measuring brain morphologic features on magnetic resonance images. Validation and normal aging

In this article, methods for measuring brain morphologic features on magnetic resonance images are described and normative data are provided for six morphologic variables. An estimated function relating age (ranging from 8 to 79 years) to average values is given for each measure. A linear decrease over the age range is observed in the volume of the cerebrum. Linear increases are observed in measures of ventricular and sulcal fluid. A curvilinear decrease in cortical volume is found and is demonstrable even in young adults. Highly nonlinear increases in the volume of signal hyperintensities are observed in cortical and subcortical regions. The methods described may be used to provide an age-adjusted index of morphologic abnormality for each subject on any of the measures. They are currently in use in ongoing neurobehavioral studies of patients with nonfocal brain abnormalities and primary disorders of affect and cognition.     

PPACK attenuates plasmin-induced changes in endothelial integrity

In order to determine whether plasmin affects endothelial cell integrity directly, confluent bovine aortic endothelial cells were treated with plasminogen and a plasminogen activator. The permeability of the monolayer to [¹²⁵I]-albumin was shown to be increased significantly (P < 0.01) with a concomitant decrease in viability. Plasmin activity correlated significantly with endothelial cell permeability (p < 0.004; R = 0.82). Coincubation with D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone, a tripeptide inhibitor of plasmin, reduced the increase in endothelial permeability induced by plasmin by 59% (p = 0.033). Monolayers studied in parallel were stained with rhodamine-phalloidin to visualize F-actin. There were significant morphologic changes in the endothelial monolayers exposed to plasmin compared to control monolayers, and these changes could be attenuated by coincubation with D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone. These studies show that: 1) plasmin induces significant increases in endothelial cell permeability with accompanying morphologic changes; and 2) these deleterious functional and morphologic effects can be attenuated by coincubation with the plasmin inhibitor, D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone.     

脑出血大鼠肠黏膜组织形态学变化与血浆儿茶酚胺水平的关系

目的探讨脑出血大鼠肠黏膜组织形态学变化与血浆儿茶酚胺(肾上腺素、去甲肾上腺素)水平之间的关系。方法制作脑出血大鼠模型,检测正常组、假手术组及脑出血后24h、48h、72h(每组8只)肠黏膜组织形态学参数及血浆肾上腺素、去甲肾上腺素水平。进行空肠黏膜组织形态学参数值与血浆肾上腺素、去甲肾上腺素水平之间的相关分析。结果小肠绒毛高度与血浆肾上腺素(r=-0.566,P<0.01)、血浆去甲肾上腺素(r=-0.545,P<0.01);绒毛面积与血浆肾上腺素(r=-0.755,P<0.01)、血浆去甲肾上腺素(r=-0.702,P<0.01);黏膜厚度与血浆肾上腺素(r=-0.478,P<0.01)、血浆去甲肾上腺素(r=-0.405,P<0.01);肠壁厚度与与血浆肾上腺素(r=-0.536,P<0.01)、血浆去甲肾上腺素肠(r=-0.489,P<0.01)均成显著的负相关。结论脑出血时肠黏膜组织形态学变化与血浆儿茶酚胺水平呈负相关。     

The cochlea in fetuses with neural tube defects

In this study different malformations of the cochlea could be demonstrated. Nevertheless, we could not delineate a distinct malformation of the inner ear, that can be linked to a neural tube defect.Neural tube defects are a frequent and heterogeneous group of malformations, ranging from the survivable spina bifida to fatal anencephaly. In multiple animal models an involvement of the vestibulocochlear system has been demonstrated. In this article human fetal temporal bones of neural tube defects were analysed in a multimodular work-up.The morphologic study was performed with light microscopy, transmission electron microscopy and synchrotron radiation-based microcomputed tomography. Immunohistochemistry for different neuronal markers such as peripherin, beta-III-tubulin and vimentin helped to evaluate ontogenetic tissue development.Eight fetal temporal bones with neural tube defects and five control temporal bones were included into the morphologic study. The morphologic results of the neural tube defect temporal bones showed six regularly developed cochleas and two with only a single cochlear turn. Three of the neural tube defect temporal bones were further examined with immunohistochemical analysis. No differences in the staining pattern for peripherin, beta-III-tubulin and vimentin were detected.     

Neuroanatomical clues to altered neuronal activity in epilepsy: from ultrastructure to signaling pathways of dentate granule cells

The dynamic aspects of epilepsy, in which seizures occur sporadically and are interspersed with periods of relatively normal brain function, present special challenges for neuroanatomical studies. Although numerous morphologic changes can be identified during the chronic period, the relationship of many of these changes to seizure generation and propagation remains unclear. Mossy fiber sprouting is an example of a frequently observed morphologic change for which a functional role in epilepsy continues to be debated. This review focuses on neuroanatomically identified changes that would support high levels of activity in reorganized mossy fibers and potentially associated granule cell activation. Early ultrastructural studies of reorganized mossy fiber terminals in human temporal lobe epilepsy tissue have identified morphologic substrates for highly efficacious excitatory connections among granule cells. If similar connections in animal models contribute to seizure activity, activation of granule cells would be expected. Increased labeling with two activity-related markers, Fos and phosphorylated extracellular signal-regulated kinase, has suggested increased activity of dentate granule cells at the time of spontaneous seizures in a mouse model of epilepsy. However, neuroanatomical support for a direct link between activation of reorganized mossy fiber terminals and increased granule cell activity remains elusive. As novel activity-related markers are developed, it may yet be possible to demonstrate such functional links and allow mapping of seizure activity throughout the brain. Relating patterns of neuronal activity during seizures to the underlying morphologic changes could provide important new insights into the basic mechanisms of epilepsy and seizure generation.     

Chronic cerebellar stimulation in the monkey. Electron microscopic and biochemical observations.

The effects of chronic electrical stimulation to the surface of cerebellum in the Macaca mulatta monkey were studied with morphologic and biochemical techniques. There was considerable damage and loss of Purkinje cells in all specimens examined, including an area without electrodes, but the greatest changes appeared in tissue beneath the cathode and anode. Despite the damage, normal appearing synapses persisted in the molecular layer of all specimens. Fibrous glial processes were more numerous beneath the cathode. There were abnormalities in gamma-amino butyric acid (GABA) and polyamine concentrations in virtually all specimens, consistent with the morphologic evidence of widespread tissue damage.     

Neck and low back pain: neuroimaging

Spine imaging accounts for a major share of expenses related to neck and back pain. Improving image quality translates into better morphologic evaluation of the spine. Unfortunately, the morphologic abnormalities on spine imaging are common and nonspecific, obscuring the relevance to patient symptomatology. Furthermore, distinction between degenerative and age-related changes is not clear. The key is clinical correlation of imaging findings. This article presents a concise and illustrated discussion of spinal neuroimaging related to neck and back pain, with emphasis on degenerative disease.     

Regional variation of brain gangliosides in feline GM1 gangliosidosis

The morphopathologic abnormalities characterizing the gangliosidoses, e.g., meganeurites and aberrant secondary neurites with associated dendritic spines and synapses, show pronounced regional variation. Because gangliosides are thought to be the causative agents, we undertook to detect possible variation in concentration or composition that would correlate with those morphologic findings. A gradient in total ganglioside and GM1 concentration was found corresponding to cerebral cortex greater than caudate = thalamus greater than cerebellum, similar to the morphologic gradient. In addition, the fatty acid compositions were variable, the proportion of docosanoate (22:0) following the same gradient. The possibility that these variations in ganglioside content and composition might influence the growth of aberrant neurites and related structures is discussed.     

Multiple neuromuscular abnormalities in a paranoid schizophrenic

A broad range of skeletal muscle fiber abnormalities has been reported previously in muscle biopsy specimens from psychotic patients. In our experience, individual patients manifest only a few types of lesions; but we now have studied a paranoid schizophrenic patient whose skeletal muscle fibers show virtually the entire range of morphologic abnormalities. In addition to the morphologic abnormalities of skeletal muscle fibers, we also noted increases branching of subterminal motor nerves with enlarged endplates and chronic elevations of serum creatine phosphokinase activity. Despite this, the patient had minimal clinical evidence of neuromuscular dysfunction. The variety of types of neuromuscular dysfunctions found in this patient suggests their etiology may be related.     

Morphologic and chemical biopsy findings in mucolipidosis IV

Based on typical clinical and morphologic features, biopsy findings in an 18-year-old girl afflicted with mucolipidosis IV are reported. She had had corneal clouding since early childhood, psychomotor retardation resulting in severe mental impairment, and pigmentary retinopathy. Biopsies of skeletal muscle, rectum, skin, and lymphocytes revealed by light microscopy increased activity of acid phosphatase and by electron microscopy, membranous and vacuolar lysosomal residual bodies in numerous cells, including striated muscle fibers and lymphocytes. An unidentified lipid was encountered by means of thin-layer chromatography in the muscle biopsy. Thus, skeletal muscle, rectum, skin, and lymphocytes are equally suitable for in vivo morphologic diagnosis of mucolipidosis IV.     

An anatomic study of the Martin-Gruber anastomosis: electrodiagnostic implications

This study aimed to clarify the morphologic variations of the Martin-Gruber anastomosis (MGA) by tracing the anastomotic fascicles. We used 102 upper limbs, and MGA was found in 39.2%. Among 12 instances of MGA between the branches innervating the flexor digitorum profundus muscle, eight anastomotic branches solely innervated the muscle without crossover from median to ulnar nerve. The results of the present study showed three morphologic features of MGA that could not be detected by an electrodiagnostic method.     

Beneficial effect of nimodipine on metabolic and functional disturbances in rabbit hippocampus following complete cerebral ischemia

We investigated the effects of intravenous application of nimodipine on the neurophysiologic, biochemical, and morphologic consequences of 15 minutes of global cerebral ischemia in seven rabbits. In vivo dialysis of the hippocampus was used to determine changes in extracellular concentrations of extracellular calcium and amino acids and blood-brain barrier permeability. Ischemia without treatment produced a rapid disappearance of electroencephalographic activity, a decrease in the concentration of extracellular calcium, the release of neuroactive amino acids, and leakage of methionine to the tissue fluid, plus a significant increase of the blood-brain barrier permeability to fluorescein. Except for permeability and electroencephalographic activity, these parameters normalized during 45 minutes of recirculation; permeability and activity failed to normalize completely during 3 hours of recirculation. After 3 hours of recirculation, morphologic changes in the CA1 hippocampal area were observed. Treatment with nimodipine significantly enhanced electroencephalographic activity recovery and normalization during recirculation, reduced the decrease in extracellular calcium concentration, and prevented the increased permeability of the blood-brain barrier. Nimodipine protected the CA1 area from early morphologic changes and reduced leakage of methionine from brain cells. The beneficial cytoprotective effect of nimodipine, probably related to normalization of calcium homeostasis and blood-brain barrier permeability after ischemia, may reflect both vascular and cellular sites of action.