Amiodarone-induced experimental acute neuropathy in rats.

Amiodarone was injected endoneurially at increasing doses into the exposed tibial nerve of rats to study its electrophysiologic and pathologic effects on peripheral nerve fibers. Forty-five male Wistar rats were used, and each of the following concentrations was injected into 15 nerves: 25 micrograms/mL, 50 micrograms/mL, and 100 micrograms/mL. Microinjection of a 25 micrograms/mL concentration of amiodarone resulted in a subacute, incomplete conduction block evident at day 3 postinjection. This conduction block remained stable until day 10 and recovery was complete at day 35. Microinjection of a 50 micrograms/mL concentration of amiodarone produced a faster evolving conduction block, and significant axon degeneration (approximately 40% of fibers). Injection of a 100 micrograms/mL concentration resulted in severe acute motor axon degeneration followed by complete but delayed regeneration. Results of morphological studies closely correlated with electrophysiological findings. Amiodarone thus seems to have a direct toxic effect on axons at high concentrations in the peripheral nerve, and we suggest that different pathological changes described in human amiodarone neuropathy could be related to different concentrations of the drug in the nerve, perhaps due to variability of blood-nerve barrier efficacy.     

Deficient activation of microglia during optic nerve degeneration

Transection of an optic nerve (ON) is followed by slow removal of myelin. We studied microglia for the expression of molecules that characterize activated myelin phagocytosing macrophages: MAC-1, FcγII/III receptor (FcR), MAC-2, and F4/80. In-vitro, microglia expressed all molecules and phagocytosed myelin. In-vivo, intact ON displayed high levels of MAC-1, little FcR and F4/80, and no MAC-2. The expression of these molecules was upregulated differentially in in-vivo degenerating ON: MAC-1 uniformly, FcR and F4/80 variably, and MAC-2 sporadically. The distribution of MAC-2 expression correlated best with a pattern of sporadic structural degeneration. Thus in-vivo, ON injury is followed by deficient microglia activation, which we suggest contributes significantly to the slow clearance of myelin.     

Diagnostic imaging of spinal cord lesions

Magnetic resonance imaging (MRI) has greatly facilitated morphologic evaluation of spinal cord lesions. Eleven cases representative of inflammatory, demyelinating, neoplastic and vascular diseases, are presented which illustrate and summarize important abnormal features in spinal cord imaging, particularly MR findings. Recently, specialised techniques such as MR angiography, fat-inhibiting methods, dynamic MRI and functional imaging have been developed. These methods have facilitated not only lesion diagnosis but also qualitative assessment, and are being used to analyze pathophysiology. Comprehensive diagnoses based on such modalities may be important in determining indications for surgery or defining the extent of surgery or the intensity of other treatments.     

Conduction studies in peripheral cat nerve using implanted electrodes: III. The effects of prolonged constriction on the distal nerve segment

Electrophysiological properties were monitored in detail in chronically constricted peripheral nerves by implanted, multicontact nerve cuff electrodes and correlated with morphometric histology in selected cases. The physiological and histological responses in nerve to a range of constricting cuffs of standard sizes were readily graded. The initial response to any significant constriction was a transient, focal conduction slowing or block at the constriction, followed by more protracted distal effects; the latter ranged from loss of excitability consistent with "dying-back" degeneration to reductions in conduction velocity consistent with histologically observed atrophy. Smaller myelinated fibers tended to have similar but less pronounced changes than larger diameter fibers. Recordings from ventral and dorsal roots showed that distal degeneration was more pronounced in motor than in sensory fibers of similar caliber. Electronmicroscopical measurements showed that basal laminas were relatively preserved around even the most atrophic and demyelinated axons. Perimeter measurements of the basal lamina could be used to estimate the diameter of the original nerve fiber.     

MR properties of excised neural tissue following experimentally induced demyelination

Changes in the magnetic resonance (MR) parameters of demyelinated neural tissue were measured in vitro using an experimental animal model. A tellurium (Te) diet was applied to weanling rats to induce the demyelination process in the sciatic nerve. The quantitative MR parameters, such as T(1), T(2) relaxation time constants and magnetization transfer (MT) were measured each day after applying the Te diet (up to 7 days) and were found to be substantially different from those of normal nerves. An increase in the average T(1) and T(2) was observed along with a decrease in the MT ratio (MTR) and the quantitative MT parameter M(0B), which describes the semisolid pool of protons. Most of the MR parameters correlated very well with the myelin fraction of neural tissue evaluated by quantitative histopathology. The T(2) relaxation spectrum provided the most efficient quantitative assessment of changes in neural tissue microstructure and its analysis resulted in a powerful tool to distinguish the processes of demyelination and inflammation. In comparison, the MT measurements were less successful.     

钾离子对体外培养中枢神经髓鞘形成的影响──一种新的体外培养中枢神经脱髓鞘模型的建立

本文应用组织培养和电镜等方法研究了ＫＣＩ对体外培养中枢神经系统髓鞘形成的影响。结果表明：体外培养Ｂ６Ｃ３小鼠小脑组织髓鞘形成的关键期是１０～１４ｄ，在１０～１２ｄ时体外培养的小脑组织对ＫＣＩ最为敏感；当培养液内ＫＣＩ浓度达到３０ｍｍｏｌ／Ｌ时，即可完全抑制髓鞘形成。本文对钾离子引起体外培养中枢神经组织脱髓鞘的机制进行了讨论。     

Sensory nerve pathology in amyotrophic lateral sclerosis

Summary A detailed morphometric study was performed on sural nerve biopsies to determine the consistency of sensory nerve pathology in amyotrophic lateral slcerosis (ALS) and to seek a correlation between the severity of peripheral nerve pathology and disease duration. Nerve biopsies from patients with ALS consistently showed evidence of early axonal atrophy, increased remylination and a shift in the diameter distributions curve towards smaller fiber diameters. Importantly, the severity of sensory nerve pathlogy in ALS patients correlated with disease duration. The peripheral nerve sodium pump concentration of patients was not reduced. It is concluded that an ingravescent dorsal root ganglion neuronopathy is seen in the incipient stages of ALS, preferentially affecting the largest neurons and resulting in turn in progressive axonal atrophy, secondary demyelination-remyelination and finally in nerve fiber degeneration. Etiologically, a parallel involvement of motor and sensory neurons suggests a more widespread metabolic disturbance in ALS than simply sick motor neurons.Supported by a grant from the New Zealand Neurological Foundation     

脉络宁注射液治疗半面痉挛的实验研究

目的:探讨脉络宁对半面痉挛脱髓鞘面神经的保护作用,为半面痉挛的治疗提供依据。方法:将24只新西兰大白兔随机分为对照组、脉络宁组和生理盐水组,在手术显微镜下分离出其茎乳孔处的面神经主干和颞浅动脉,使二者密切接触,以制备半面痉挛动物模型;术后第5周起对脉络宁组和生理盐水组分别自耳缘静脉推注脉络宁注射液和生理盐水持续2周;第7周取3组动物血清测定丙二醛(MDA)和超氧化物歧化酶(SOD),并处死取材行面神经光、电镜观察。结果:脉络宁组血清MDA明显低于生理盐水组(P<0.05),SOD明显高于生理盐水组(P<0.01),而与对照组比较变化不明显(P>0.05)。生理盐水组面神经纤维溃变明显,髓鞘松解分离,轴突肿胀有空泡或全部消失;脉络宁组面神经病变较轻。结论:脉络宁注射液对半面痉挛脱髓鞘面神经有明显的保护作用,对半面痉挛的治疗具有极其重要的应用价值。     

Blood-brain barrier disruption and complement activation in the brain following rapid correction of chronic hyponatremia

In previous studies we developed a rat model in which demyelination is reproducibly produced following rapid correction of chronic hyponatremia and demonstrated that the development of demyelination in this model is strongly associated with NMR indices of blood-brain barrier (BBB) disruption. Because complement is toxic to oligodendrocytes, we evaluated the hypothesis that BBB disruption precipitated by correction of hypoosmolality is followed by an influx of complement into the brain, which then contributes to the demyelination that occurs under these conditions. We studied four groups of rats with immunocytochemical analysis using primary antibodies to IgG and the C3d split-fragment of activated complement: (1) normal rats; (2) rats in which hyponatremia was maintained for 7 days; (3) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 20 h prior to perfusion; and (4) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 5 days prior to perfusion. In normonatremic and uncorrected hyponatremic rats only background staining was observed in areas lacking a BBB and in blood vessel walls, whereas marked increases in IgG and C3d staining were seen in the brains of rats both 20 h and 5 days after rapid correction of hyponatremia. The staining intensity was significantly correlated with the degree of neurological impairment. These results provide evidence for functional BBB disruption following rapid correction of hyponatremia and support the hypothesis that complement activation may be involved in the pathogenesis of osmotic demyelination.