The effect of extraction of the intrafascicular contents of peripheral nerve trunks on perineurial structure

Summary The intrafascicular contents have been extracted from the tibial nerve of the rabbit through perineurial incisions. Within 6–8 days following this procedure, the perineurial cells separate from one another, become dissociated from their basement membranes and assume a fibroblast-like appearance. The intrafascicular space becomes populated with endoneurial fibroblasts. With the ingrowth of regenerating axons, bundles of axons and associated Schwann cells become surrounded by cells of fibroblastic appearance which undergo perineurial transformation resulting in the development of multiple small fascicles. The cells of the surrounding perineurium appear to reassume a lamellar organization and to reestablish contacts with each other with the formation of junctional complexes. It is therefore suggested that neural structures may be responsible for the development and maintenance of the structural organization of the perineurium.     

A study of the perineurial diffusion barrier of a peripheral ganglion

Summary The perineurial diffusion barrier to horseradish peroxidase (HRP) and ferritin was investigated in superior cervical ganglia of rats and mice. The ganglion was surrounded by a delicate epineurium and 2–5 perineurial lamellae joined by zonulae occludentes and desmosomes.Following local application of tracers the animals were killed after 5, 30, and 60 min and the distribution of HRP and ferritin was studied by light and electron microscopy. The inner layers of the ganglionic perineurium prevented diffusion of both HRP and ferritin into the endoneurium. Owing to the fewness of the perineurial lamellae investing the ganglion. HRP had often extended to the innermost lamella 60 min after application.HRP and ferritin were present in vesicles of ganglionic perineurial cells. There was no passage of tracers via intercellular junctions.     

Involvement of the perineurium in experimental allergic neuritis: Electron microscopic observations

Summary Electron microscopic observations on the perineurium in EAN are described. Extravasated serum protein was observed in the endoneurial space and also between the cellular laminae of the perineurium. A mechanism of macropinocytotic transport of protein across the perineurium is proposed. The observations are related to the known properties of the perineurium as a diffusion barrier and are interpreted as a mechanism by the perineurium to restore the composition of the endoneurial fluid.     

Morphological study of peripheral nerve changes induced by chloroquine treatment

Summary Nerve biopsies were performed in four patients with suspected chloroquine induced neuromyopathy. Three of the patients were treated with high doses of chloroquine for connective tissue disease, while one patient was taking this drug as malaria prophylaxis. Morphological studies demonstrated the presence of segmental demyelination and remyelination in all cases. Cytoplasmic inclusions were observed in Schwann cells, in perineurial and endothelial cells, and in some interstitial cells. They were never observed within axons. Occasional curvilinear profiles were seen in perineurial and Schwann cells. Perineurial calcifications were observed in two cases. The results of this morphological study suggest that chloroquine neuropathy is essentially due primary involvement of Schwann cells.     

Ultrastructural changes in glial cells during regeneration of cockroach peripheral nerve

After peripheral nerve 5 in the cockroach Periplaneta americana was cut, changes occurring in the glial cells in the proximal stump were studied immediately after damage and during the process of nerve regeneration. During the first week haemocytes accumulated outside the nerve and morphologically similar granule-containing cells appeared inside the nerve. These cells were involved in phagocytic activity. Between the second and the fourth week, signs of regeneration were distinguishable; many small axonal sprouts were formed which were surrounded by glial processes, and the nerve stump increased in length. During this period the glial cells produced large amounts of extracellular material in which the bundles of axons and glia were embedded. The structural differences between glial and perineurial cells were lost during these stages of regeneration and there was no restriction to the penetration of the extracellular tracer lanthanum. After 8 weeks, reinnervation of the muscles had taken place, perineurial and glial cells were again distinguishable, and the perineurial cells were able to exclude lanthanum.     

Impaired development of the rat perineurium by undernutrition

Summary Enzyme activity of adenosinetriphosphatase, NADH₂-tetrazolium reductase and lactate dehydrogenase was studied in the rat perineurium 10, 20, 30, and 90 days post partum. The effect of undernutrition was shown by a lack of enzyme activity in rats 30 days post partum in contrast to control animals. 30 days also corresponds to the time when, in normal rats, the perineurial diffusion barrier to exogenous macromolecules becomes established. In undernourished rats this diffusion barrier does not appear. At 90 days post partum raised enzyme activities indicate a high metabolic turnover in the perineurium even in animals with undernutrition.     

Focal mucoid degeneration of peripheral nerve

Summary Focal mucoid degeneration was found in a N. suralis biopsy of a 8 year old child, diagnosed clinically and electrophysiologically as progressive muscular atrophy Charcot-Marie-Tooth.     

Barriers and transport properties of the perineurium

Summary The permeability properties of the perineurium in sciatic nerves of 12-week-old rats were studied. The penetration of¹²⁵I-labeled albumin and horseradish peroxidase into the perineurium was investigated electronmicroscopically 10, 30, and 120 min after the local extraneural application of the tracers. The autoradiographic study included age-matched protein-deprived rats. It was concluded that the perineurium acted as a diffusion barrier but also permitted a slow passage of the macromolecules into the endoneurium. The result indicates that this penetration to some extent is due to vesicular transport across the perineurial cells. The significance of these barrier and transport properties of the perineurium is discussed. No obvious differences in perineurial permeability between normal and protein-deprived rats were obtained.     

脊髓发育不良的外科病理解剖学研究

目的研究脊髓发育不良的临床病理解剖学。方法依据112例术前病史、体检、影像学、尿流和肛肠动力学、排尿性膀胱尿道造影(VCUG)、EMG检查评价并行脊髓手术治疗。术中观察脊髓形态学改变并留取组织学标本。结果按照椎管内病变及其脊髓病理解剖改变将其分为终丝拴系、脊髓粘连、脊髓脂肪瘤、囊性占位、脊髓纵裂、静态病变六型及若干亚型。结论脊髓发育不良主要为一进行性加重的动态病理过程,其脊髓神经损害的病理解剖学基础是椎管内病变及其脊髓、神经根的形态学改变,应尽早诊断和椎管内手术治疗以改善预后。     

Dynamic aspects of peripheral nerve changes in progressive neural muscular atrophy

Summary Serial nerve biopsies were performed at an early, and at an advanced stage of the disease in 2 patients with progressive neural muscular atrophy. The early biopsy showed a complete loss of the large diameter and thickly myelinated fibres, as well as an expansion of the endoneurial interstitium in both cases. Myelinated and unmyelinated fibres exhibited axonal degeneration in all biopsies occasionally. Onion bulb formation, a typical feature of peripheral neuropathy in neural muscular atrophy, was found to be prominent only in the latter biopsies. As regards the formal pathogenesis of hypertrophic neuropathy in neural muscular atrophy, axonal dystrophy and interstitial changes of the endoneurium were regarded as primary phenomena, demyelination and onion bulb formation as secondary. A possible causal relation between axonal dystrophy and interstitial changes, observed in these cases, is discussed in the light of the present literature.

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Zusammenfassung Bei 2 Patienten mit progressiver neuraler Muskelatrophie wurden Nervenbiopsien jeweils in einem frühen und in einem fortgeschrittenerem Stadium der Erkrankung entnommen und verglichen. In beiden Fällen zeigten bereits die frühen Biopsien ein völliges Fehlen der großkalibrigen, dickbemarkten Axone. Ebenfalls als frühe Veränderung wurde eine Erweiterung des endoneuralen Interstitiums festgestellt. Eine geringe Anzahl der vorhandenen bemarkten und unbemarkten Axone in allen Biopsien wies degenerative Veränderungen auf. Die für die progressive neurale Muskelatrophie typische Zwiebelschalenbildung der Schwannschen Zellen — möglicherweise eine Reaktion auf wiederholte De-und Remyelinisierungsvorgänge um dystrophische Axone — trat erst in den späteren Biopsien deutlicher hervor. Hinsichtlich der formalen Genese der hypertrophischen Neuropathie bei neuraler Muskelatrophie sind nach diesen Beobachtungen axonale Dystrophie und interstitielle Veränderungen des Endoneuriums als primäre Entmarkung und Zwiebelschalenbildung als sekundäre Phänomene zu betrachten. Die Möglichkeit einer kausalen Beziehung zwischen axonaler Dystrophie und interstitiellen Veränderungen wird an Hand der vorliegenden Befunde und Literatur diskutiert.

     

Barriers of peripheral nerve towards exogenous peroxidase in normal and protein deprived rats

Summary The protective barriers of the sciatic nerve in protein deprived and normal rats have been studied. Horseradish peroxidase (HRP) was applied extraneurally in rats aged between 4 and 26 weeks. The spread of the tracer was investigated 2 h, 24 h, and 3 days after application. Passage of tracer into the endoneurium was found in all rats but decreased with age. Within the endoneurium, HRP was phagocytized by normally occurring endoneurial histiocytes, which constitute part of the protective barrier system of peripheral nerves. The functional development of the nerve protective barriers was retarded in protein deprived rats. Observations made in this study support the concept of a transperineurial vesicular transport of macromolecules.     

Comparative ultrastructural observations on peripheral nerve abnormalities in the late infantile,juvenile and late onset forms of metachromatic leukodystrophy

Summary The ultrastructural findings in nerve biopsies from two cases of late onset metachromatic leukodystrophy were compared with those in cases of late infantile and juvenile onset. Hypertrophic changes and regenerating clusters were more evident in the late onset cases, in which macrophages were less frequent, presumably reflecting the chronicity of the disorder in this form. Inclusions within Schwann cells and endoneurial macrophages were similar in all four cases. Myelin figures, in which the periodicity of major dense lines was 8 nm, were present in Schwann cells associated with myelinated axons. The electron lucent zones between the major dense lines were bisected by lines of lesser electron density. These inclusions were probably related to myelin breakdown. All other inclusions displayed a periodicity of 5.8 nm and consisted of zebra bodies, vacuoles containing irregularly orientated lamellar material and stacks of flattened discs. These inclusions represented the metachromatic sulphatide deposits. Occasional inclusion bodies were observed within axons.     

Basic pathology of the peripheral nerve

Peripheral nerve pathology encompasses a complex array of disease processes that are poorly understood. This article provides a substrate for communication between pathologists and radiologists who are involved in the diagnosis and treatment of patients with peripheral neuropathy. The article is organized into sections on normal histology, routine morphologic techniques used in the study of peripheral nerve, and the basic disease patterns, followed by a brief discussion of selected neuropathies.     

Effects of the bile salt sodium deoxycholate, protamine, and inflammatory mediators on the potassium permeability of the frog nerve perineurium

An electrophysiological method was used to measure the potassium permeability (P_K) of the perineurium of the sciatic nerve of frogs Rana temporaria and R. pipiens. Isolated but intact nerves were mounted in a grease-gap chamber, and compound action potential and DC potential monitored. Change in the DC potential (ΔDC) in response to challenge with 100 mM [K⁺] Ringer was used to assess the K⁺ permeability of the perineurium, since change in DC potential under these conditions reflected changes in the axonal resting potential. The permeability of the perineurium was calculated from the published calibration curve relating ΔDC to bathing [K⁺] in desheathed nerves of Abbott et al. (1997). In the control condition, P_K was <1.1×10⁻⁶ cm·s⁻¹. The bile salt sodium deoxycholate (DOC, 1–4 mM) caused a dose-dependent increase in P_K, which reached a maximum of 1.7×10⁻⁵ cm·s⁻¹ after 2-min exposure to 4 mM DOC, but access of K⁺ to the endoneurial compartment was more restricted after DOC than after desheathing. Protamine phosphate (1 mM) and protamine sulphate (0.1–5 mg/ml equals 0.125–6.25 mM) had no effect on P_K. Neither histamine (0.4–40 mg/ml), bradykinin (0.1–5 mg/ml) nor serotonin (5-hydroxytryptamine, 0.1–5 mg/ml) affected P_K. The frog nerve perineurium appears to be relatively insensitive to chemical agents and inflammatory mediators, in contrast to the endothelial cells forming the endoneurial blood–nerve barrier and the blood–brain barrier.     

慢性硬膜下血肿外膜的超微结构观察

目的 通过对慢性硬膜下血肿(CSDH)外膜的超微结构观测,探讨CSDH发生和发展的病理学基础. 方法 收集天津医科大学总医院神经外科自2008年1月至2009年1月间行血肿清除术的8例CSDH患者的外膜标本,其中CT显示血肿密度为低密度2例,等密度2例,高密度2例,混杂密度2例.应用光镜和电镜观察血肿外膜上新生血管的形态和结构. 结果 光镜下可见血肿外膜大量新生的毛细血管扩张充血,并可见含铁血黄素沉积.电镜下可见血肿外膜组织含大量成纤维细胞和毛细血管;部分毛细血管内皮细胞结构异常,可见损伤内皮细胞,不连续,毛细血管周围常有红细胞渗出;部分毛细血管结构完整,扩张不明显,血管中有微血栓形成、组织中嗜酸性粒细胞增多,颗粒大,部分与成纤维细胞接触,有时可见中性粒细胞和巨噬细胞,成纤维细胞活化明显,呈增殖状态.毛细血管内皮细胞的结构异常和红细胞渗出在血肿密度为高密度者的标本中最为明显. 结论 CSDH外膜新生血管的形成及反复再出血是CSDH发生和发展过程中的关键因素.     

Peripheral nerve pathology in rats with streptozotocin-induced insulinoma

Peripheral nerve structure was systematically examined in rats with insulinoma induced by streptozotocin (STZ). Normal Wistar rats, aged 3 months (n = 10), were treated with intravenous injections of STZ (20 mg/ kg) and housed in plastic cages with free access to water and chow until 24 months of age. Three rats with insulinoma survived and were examined pathologically. Age-matched normal Wistar rats (n = 6) were used for comparison. The insulinoma-bearing rats showed a marked increase in body weight and decrease in blood glucose. In a teased nerve fiber study of the sciatic nerve, the percentage of abnormal fibers undergoing axonal degeneration and de- and remyelination in age-matched normal control rats was 3.9 ± 2.5% (means ± SD), whereas in the three insulinoma-bearing rats 49%, 50%, and 24%, respectively, of the fibers showed such changes. Regenerating fibers were also numerous in each insulinoma-bearing rat (36%, 42% and 27%, respectively). Morphometric analysis revealed smaller mean myelinated fiber and axonal areas in all the nerves examined (sciatic, tibial and sural) in insulinoma-bearing rats as compared to those in age-matched normal rats. Fiber area frequency histograms showed a decrease in large myelinated fibers and an increase in small regenerated fibers in insulinoma-bearing rats. Ultrastructurally, endoneurial microvessels exhibited a narrowed vascular lumen with swollen endothelial cells and vacuolar degeneration of pericytes, suggesting an involvement of vascular changes in the neuropathic development. The present study demonstrated marked structural changes in both motor and sensory peripheral nerves of rats bearing experimentally induced insulinoma. We consider that axonal degeneration, regeneration and demyelination constitute the main pathology in the peripheral nerves of insulinoma-bearing rats, although no particular difference in severity of the lesions between sensory and motor and between proximal and distal nerves was apparent. Received: 24 October 1995 / Revised, accepted: 27 December 1995     

An ultrastructural study of dynorphin-immunoreactive nerve fibers and terminals in the celiac-superior mesenteric ganglion of the guinea pig

Dynorphin-immunoreactive nerve fibers and terminals were identified in the celiac-superior mesenteric ganglion of the guinea pig at the ultrastructural level with the peroxidase-antiperoxidase technique. The immunostained material was localized in the large dense core vesicles of the terminals but was also present diffusely in the axoplasm. The terminals formed numerous axodendritic and a few axosomatic contacts, interpreted as synapses, with the principal ganglion cells. These findings suggest that dynorphin plays a role as a neurotransmitter or neuromodulator in the ganglion and, taken together with earlier findings, indicate an involvement of dynorphin neurons in the intestino-intestinal inhibitory reflex.     

Ultrastructure of peripheral nerve in Cockayne's syndrome

Summary The ultrastructure of sural nerve biopsies was studied in two sisters with Cockayne's syndrome. Both had severe physical and mental retardation and evidence of peripheral neuropathy. Striking alterations in the myelin sheath with relative preservation of the axis cylinder were noted in both. There were also electron dense bodies in the Schwann cells. These findings support the suggestion that Cockayne's syndrome may be a form of leukodystrophy.