Ultrastucture of the central nervous system after prolonged hypoxia

Summary Chronic hypoxia was induced in rats by subjecting them to a low oxygen atmosphere (10% O₂ and 90% N₂) up to 24 days. Electron microscopy revealed striking alterations in nerve cells of the central nervous system. During the first 4 days, moderate swelling was noted in the Golgi complex in the mitochondria of some neurons. From the 6th to 24th days, alterations of these organelles became more pronounced: Many neurons and their processes exhibited varying degrees of cytoplasmic swelling, and inclusion bodies resembling myelin-figures were found in the perikaryon. Bizarre forms of tubular profiles occurred within the axoplasm of many nerve fibers. The presynaptic terminals became greatly enlarged, containing either unusual multilamellar bodies or clumped vesicles. These results indicated that prolonged hypoxia causes profound changes in the central nervous tissue that do not occur in the acute state.This study was supported by the Dorothy R. Victor Memorial Fund, the Lusyd Wright Hitchcock Memorial Research Fund and the Buswell Foundation.     

Early central nervous system lesions in experimental hypercholesterolemia in normal and subdiabetic rabbits

Summary Biochemical and morphologic studies were carried out on the early effect of hypercholesterolemia on the central nervous system in both metabolically normal and subdiabetic rabbits. Major biochemical difference was the elevation of non-esterified cholesterol in the subdiabetic animals. Histologically, Alzheimer type II astrocytosis was noted in the basal ganglia of the subdiabetic rabbits during the 4th week. The astrocytosis extended into the entire protion of the cerebrum and cerebellum during 2 to 4 months. In the metabolically normal rabbits on the cholesterol diet, on the other hand, similar astrocytic changes were noted after 2 months. Despite the fact that cholesterol crystals had frequently been noted in the capillary walls of the viscera after the 2nd week, similar changes were not observed in the blood vessels of the brains of both the subdiabetic and the metabolically normal rabbits during the 4 months of cholesterol feeding. These observations suggest that cholesterol deposits in the vascular walls are determined by the different rates of lipid metabolism in each individual organ.Supported by grants from the National Institutes of Health (A-2203) and the National Tay-Sachs and Allied Diseases Association, Inc.     

Superficial siderosis of the central nervous system

Summary The clinical and necropsy findings are described in nine cases of superficial siderosis of the central nervous system. Four of these had undergone cerebral hemispherectomy in childhood. All four showed multiple haemorrhagic spots in the cavity membrane and the walls of the remaining lateral ventricle. Of the other cases, to had repeated ruptures of cerebral aneurysms; one showed a destructive lesion of the cerebellar vermis; one, a hydrocephalic child, showed evidence of repeated haemorrhage in the area of a malformed aqueduct; and the last, a baby, had bilateral subdural haematomata.From the histological similarities of these cases and previously reported ones, and from the reported findings in experimental animals, it is argued that the common cause of superficial siderosis is recurrent intraventricular or subarachnoid haemorrhage.

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Zusammenfassung Klinischer Verlauf und Autopsiebefunde von 9 Fällen mit Randzonensiderose des ZNS werden beschrieben. Bei 4 Fällen war eine Hemisphärektomie in der Kindheit erfolgt. Sie boten multiple Blutungsreste in der Membran der Resthöhle sowie in den Wänden der verbliebenen Seitenventrikel. Von den übrigen Beobachtungen boten 2 wiederholte Aneurysmarupturen von Hirngefäßen; 1mal bestand eine destruktive Läsion im Kleinhirnwurm. 1 hydrocephales Kind bot Hinweise auf wiederholte Blutungen im Bereich einer Fehlbildung des Aquädukts. Der letzte Fall, 1 Kleinkind, bot beidseitiges subdurales Hämatom.Auf Grund der histologischen Ähnlichkeiten dieser Fälle und früherer Beobachtungen sowie tierexperimenteller Befunde werden als gemeinsame Ursachen der Randzonensiderose wiederholte Blutungen in den inneren oder äußeren Hohlräume des ZNS angenommen.

     

A periaxonal net in the zebrafish central nervous system

We produced a monoclonal antibody, named A20, which specifically recognizes a 35 kDa protein and stains myelinated axons in zebrafish brain. The A20 antigen is located at the outside of the myelin layer of large axons, and comprises a fine meshwork composed of thin unit fibers about 1-2 microm in length and about 100-200 nm in thickness. The unit fibers form pentagonal and hexagonal structures, which further polymerize into an envelope structure on the axons. The A20 monoclonal antibody did not stain neuronal cell bodies nor synapses. Instead, the distribution of the A20 antigen was along axons, practically coincident with the distribution of myelin basic protein. The monoclonal antibody stained only axons in the central nervous system (CNS), and not the extracellular matrix surrounding Schwann cells. These results suggest that this antigenic meshwork (which we call the periaxonal net) is synthesized by oligodendrocytes. During the development of the zebrafish brain, the periaxonal net appeared after the formation of myelin on the axons. The periaxonal net developed first at the brain stem, then gradually appeared at the caudal end of the spinal cord. The thickness of the periaxonal net around the Mauthner axon changed during development. Although the thickness of the Mauthner axon continues to grow throughout life, the thickness of periaxonal net stopped growing at 6 months after fertilization.     

Evaluation of central nervous system involvement in uncomplicated optic neuritis after prolonged follow-up

Magnetic resonance imaging (MRI), multimodal evoked responses (ER) and HLA antigens were examined in 10 patients with idiopathic acute optic neuritis (ON) without any clinical symptoms or signs of multiple sclerosis (MS) during 9-14 years. In MRI, abnormalities compatible with MS were seen in 4 patients. In spite of clinically unilateral ON, a bilateral abnormality in visual evoked responses (VER) was seen in 3 of 9 cases. Brain stem auditory evoked responses (BAER) were normal in all cases, short latency somatosensory evoked response (SER) in all but one. The cerebrospinal fluid at time of ON showed signs of demyelination in one case only. The frequency of HLA antigens DR2 (78%) and B18 (40%) was significantly increased in comparison to healthy controls. MRI seems to be the most sensitive method in the detection of cerebral lesions of MS, especially in mild or asymptomatic forms of the disease. The present techniques are, however, mostly unable to demonstrate optic nerve lesions which more reliably can be evaluated by VERs. The question whether idiopathic ON represents a form of MS solely, cannot be resolved.     

Parkinsonian syndrome and central nervous system lymphoma involving the substantia nigra

Summary The clinical history and postmortem neuropathologic findings of a case of cerebral lymphoma revealed by a typical parkinsonian syndrome are reported. The clinical symptoms initially improved with dopa therapy. The tumor was classified as a diffuse, non-cleaved, large-cell lymphoma of B-cell origin producing monoclonal lambda light chains. The substantia nigra was infiltrated by the tumor and showed neuronal loss and extraneuronal pigment. The most striking histological feature was the presence of neuronophagic-like nodules composed of lymphomatous cells both in the locus niger and in the left thalamus. No tumoral mass effect and no histological stigmata of other etiologies of parkinsonian syndromes were observed. A hypothesis is that the neuronophagic-like nodules may reflect a neuronotoxic activity of the lymphoma and may be considered at the origin of parkinsonism.     

Ultrastructure of the microvasculature in experimental cerebral infarction

Summary Structural evaluation of cerebral infarction in twelve squirrel monkeys was conducted for the purpose of elucidating some aspects of the pathogenesis of regional cerebral ischemia.The changes observed first were interpreted as indicative of alterations in the permeability of the vascular walls. It is suggested that during the early stages of infarction, emigration of fluid, particles and cells may occur in a transendothelial fashion. Arguments to prove the preservation of the microcirculation within the infarcted area are presented.Hypoxemia, as judged by the relative structural integrity of mitochondria, does not seem to be the most important pathogenetic factor in the development of cerebral ischemic necrosis.This work was conducted during the author's tenure at the Cerebrovascular Research Center of the University of Tennessee Medical Units; it was partially supported by USPHS Grants HE 11794 and NS 06826.     

Intracytoplasmic hyaline inclusion bodies in the nerve cells of the hypoglossal nucleus in human autopsy material

Summary Intracytoplasmic hyaline inclusion bodies were found in the nerve cells of the hypoglossal nucleus in 150 cases out of 518 consecutive autopsy cases. These inclusion bodies are histomorphologically, histochemically and topographically distinct from any others previously described. Their incidence was found to increase with age. A high incidence among young patients with chronic alcoholism was also observed.

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Zusammenfassung Intracytoplasmische hyaline Einschlußkörperchen wurden in Nervenzellen des Nucleus hypoglossus in 150 von 518 laufenden Sektionsfällen gefunden. Diese Einschlußkörperchen lassen sich histomorphologisch, histochemisch und topographisch von allen früher beschriebenen unterscheiden. Sie traten vermehrt mit steigendem Alter auf und werden auch vermehrt bei jungen Patienten mit chronischem Alkoholismus beobachtet.

     

Phenothiazines reduce ischemic damage to the central nervous system

We found substantial alterations in reactions catalyzed by calcium/phospholipid-dependent and calcium/calmodulin-dependent protein kinases during CNS ischemia which suggested that phenothiazines, drugs capable of inhibiting these reactions, might reduce neurologic damage. To test this hypothesis, we used chlorpromazine and trifluoperazine. Both drugs reduced neurologic function deficits relative to controls in a rabbit multiple cerebral embolism model and a rabbit spinal cord ischemia model. Chlorpromazine was effective despite reduction of blood pressure, and trifluoperazine did not alter blood pressure. These findings suggest that phenothiazines may be useful for preserving neurologic function when administered shortly after the onset of CNS ischemia.     

促红细胞生成素在中枢神经系统缺氧／缺血时的保护作用

促红细胞生成素（Erythropoietin,Epo)因在红细胞生成时发挥重要作用被认识，但是Epo也产生和分布于中枢神经系统（central nervous system,CNS)。缺氧时，Epo通过对神经干细胞的调节，对抗细胞凋亡，发挥神经营养作用，因而对CNS具有保护功能，目前，对Epo的介导的细胞内信息传递已有认识，很可能为CNS缺氧／缺血性疾病的治疗开辟新途径。     

促红细胞生成素在中枢神经系统缺氧/缺血时的保护作用

促红细胞生成素(Erythropoietin,Epo)因在红细胞生成时发挥重要作用而被认识,但是Epo也产生和分布于中枢神经系统(central nervous system,CNS).缺氧时,Epo通过对神经干细胞的调节,对抗细胞凋亡,发挥神经营养作用,因而对CNS具有保护功能.目前,对Epo所介导的细胞内信息传递已有所认识,很可能为CNS缺氧/缺血性疾病的治疗开辟新途径.     

Lesions of the rostral ventrolateral medulla reduce the cerebrovascular response to hypoxia

Sympathoexcitatory neurons of the rostral ventrolateral medulla are tonically active and required for maintenance of resting levels of arterial pressure. They are also selectively excited by hypoxia and responsible for the associated sympathoexcitation. Since electrical or chemical stimulation of RVL will increase regional cerebral blood flow (rCBF) independently of changes in regional cerebral glucose utilization (rCGU) we investigated whether the RVL was also required to maintain resting levels of rCBF and also participated in the cerebrovascular vasodilation elicited by hypoxia. Rats were anesthetized (chloralose; 40 mg/kg, s.c.), paralyzed (tubocurarine) and ventilated (100% O₂). rCBF was measured in 10 dissected brain regions using [¹⁴C]iodoantipyrine; rCGU was measured by 2-deoxy-d-[¹⁴C]glucose. in controls (n = 6) rCBF ranged56 ± 5 in corpus callosum to101 ± 6ml/min× 100g in inferior colliculus. Hypoxic-hypoxia (PaO₂ - 36 ± 1mmHg, n = 6) increased rCBF in all structures maximally, at 204% of control, in occipital cortex. Hypercapnia (PaCO₂ = 63.5 ± 0.9, n =5) also increased rCBFP < 0.01) maximally to 199% of control in superior colliculus, Spinal cord transection with maintenance of arterial pressure did not affect resting rCBF and increased the vasodilation to hypoxia (PaO₂ = 39 ± 1mmHg, n = 5) from 2- to 3-fold in all structuresP < 0.01). Bilateral lesions within the RVL had no effect on resting rCBF or rCGU. However, they significantly reduced, in all areas by 50–69% (P < 0.01, n = 5), the cerebrovascular dilation elicited by hypoxia but not hypercapnia, Bilateral lesions in the spinal trigeminal nucleus (PaO₂ = 35 ± 1; n = 6), or transection of the IXth and Xth cranical nerves did not affect the rCBF response to hypoxia(PaO₂ = 41 ± 2; n = 6) (P > 0.05) indicating that the effect of RVL Lesions was not attributable to interference with arterial baro- or chemoreceptor reflexes. We conclude that neurons within RVL are not responsible for maintaining tonic levels of rCBF. However they contribute to the cerebrovascular vasodilation elicited by hypoxia but not hypercapnia. The cerebrovascular response to hypoxia appears reflexive and, in part, due to stimulation of oxygen-sensing neurons in RVL. In contrast, the vasodilation elicited by hypercapnia reflects local chemical signals in the cerebral microcirculation     

肝移植患者术后住院期间的中枢神经系统并发症

目的探讨肝移植术后住院期间中枢神经系统并发症的发病情况、临床和神经影像学特征及可能的危险因素及预后。方法对中山大学附属第一医院1996年1月至2005年6月间共337例患者的358次肝移植手术进行回顾性研究。结果术后住院期间患者出现中枢神经系统并发症共58例，发生率16．2％，病死率41．4％。最常见的表现为肝移植脑病（10．3％），次之为癫痫（4．5％）和脑血管疾病（2．8％）。与无中枢神经系统并发症的肝移植患者相比，术后发生中枢神经系统并发症者的年龄、是否再次肝移植及病死率差异有统计学意义（P〈0．05）。结论肝移植术后住院期间中枢神经系统并发症的发生率及病死率较高，直接影响患者的生活质量及预后。年龄偏大、再次肝移植可能是其危险因素。     

Effects of hypoxia and hypercapnic hypoxia on the ultrastructure of central nervous synapses

Pronounced ultrastructural changes in the presynaptic terminals of central nervous tissues of rats were observed after various durations of sustained hypoxia or hypercapnic hypoxia. Two distinct types of morphological alterations were found. In the first type, the presynaptic terminal was greatly enlarged, measuring 3–10 μm in the greatest diameter. These terminals contained unusual multilamellar bodies in the form of compact lamellar whorls or loosely arranged concentric lamellae. The second type of terminal changes consisted of aggregated or clumped vesicles, often surrounded by attenuated glial processes. The first type of altered terminals occurred predominantly in the deep cerebellar nuclei, while the second type was present in all regions of the central nervous system examined.