CEREBRAL AMYLOIDOSIS IN SCRAPIE IN THE MOUSE: EFFECT OF AGENT STRAIN AND MOUSE GENOTYPE

Cerebral amyloid deposits, predominantly in the form of discrete plaques are common in mice infected with certain scrapie isolates. In this paper the incidences of cerebral amyloidois occurring with different combinations of agent strain and mouse genotype are investigated. Seven different agents from four primary sources were studied in three mouse genotypes (C57BL, VM and their F₁ cross). It is shown that the degree of amyloidosis is a passageable characteristic of the agent depending also on host genotype. However, the amyloid incidence is not influenced by the agent and mouse genotype independently but depends on a specific interaction between the two. For two scrapie agents, 22A and ME7 there is a correlation between incubation period and the incidence of cerebral amyloid in the three mouse genotypes. The degree of cerebral amyloid for ME7 remains unaffected by passage through the two genotypes of mouse, C57BL and VM, and through another species, a Cheviot sheep.     

PARTIAL DEMYELINATION OF CAT SPINAL CORD AFTER X-IRRADIATION AND SURGICAL INTERFERENCE

Following 4000 rad of X-irradiation and transplantation of sciatic nerve over the dorsal columns, extensive partial demyelination occurred in some animals. This dose of radiation inhibits remyelination so this phenomenon could be studied knowing that remylination was absent. Partial demyelination was characterized by translocation of myclin to form large myelin ovoids which remained associated with the remaining thinned myelin sheath: nodal widening, involvement of one paranode only, transition from thin to thick myelin along an internode, enlargement and disorientated oligodendrocyte tongues were also features of this change. It is concluded that partial demyelination results when oligodendrocytes have to function in a sub-optimal environment.     

THE ORGANIZATION OF ASTROCYTES IN ORGANOTYPIC MOUSE SPINAL CORD CULTURE: AN ELECTRON MICROSCOPE STUDY

The organization of astrocytes in myelinated culture of mouse spinal cord tissue was analysed ultrastructurally and compared with the pattern in vivo. Astrocyte cell bodies and their processes, connected by punctate adhesions and gap junctions, formed a continuous layer around the entire explant. Throughout the parenchyma, thin astrocytic processes penetrated the neuropil, separated neurons, and invested some synaptic complexes. Others formed flattened sheets and contacted directly with the basal surface of ependymal cells. In the absence of mesenchymal elements, astrocytes in vitro occasionally possessed fragments of basal lamina on the surface of the explant and around minute intercellular spaces. Except for an incomplete basal lamina, these findings indicate that astrocytes in vitro are organized in a manner essentially identical to the situation in vivo.     

ALTERED BRAIN WAVE ACTIVITY IN PERSONS WITH CHRONIC SPINAL CORD INJURY

This study investigated brain wave activity associated with spinal cord injury (SCI). Electroencephalograms (EEG) were compared between 10 individuals with SCI and 10 age and sex matched able-bodied controls using a 64-channel EEG montage. SCI participants had chronic (>12 months) paraplegic clinically complete injuries. The 64 channels of EEG data were spread diffusely over the cortex and were compared for delta (2–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–30 Hz) wave components of the EEG frequency spectra. No significant magnitude or directional changes were found in the delta (2–4 Hz) or theta (4–8 Hz) wave frequency bands between these two groups. However, significant and consistent decreased alpha wave (8–13 Hz) and increased beta wave activity (13–30 Hz) were found in the SCI participants across the cortex compared to the able-bodied control group. These findings suggest that the SCI group have increased neural processing compared to the able-bodied individuals, which may be related to ongoing reorganization of brain structures following SCI.     

nov基因在不同种属动物脊髓中的表达

用地高辛标记的cRNA探针原位杂交方法研究了鲢、青蛙、蛇、鸡、牛、犬和猫脊髓中肾母细胞瘤过度表达基因（nov）mRNA阳性神经元的种系发育。结果显示，低等脊椎动物鲢、青蛙和蛇脊髓中仅有少量novmRNA阳性神经元，分布于灰质腹角。鸡脊髓中阳性神经元除主要分布于脊髓腹角外，中央灰质也有少量分布。哺乳动物牛、大和猫脊髓灰质中novmRNA阳性神经元分布广泛，背腹角、中央灰质及中央核区都检测到很强的杂交信号。以上结果表明，nov基因在从低等脊椎动物到高等脊椎动物的进化过程中非常保守，这种保守性提示nov基因在脊髓神经元发育、分化及正常生理功能中可能具有重要作用。     

EFFECT OF ROUTE OF INFECTION ON THE FREQUENCY AND DISTRIBUTION OF CEREBRAL AMYLOID PLAQUES IN SCRAPIE MICE

Cerebral amyloid plaques are a conspicuous pathological feature in mice infected with certain strains of scrapie. The origin of the amyloid protein in these plaques, whether it is locally or systemically synthesized, and the mechanisms leading to its deposition are not known. The frequency of plaques and their distribution in the brain are greatly influenced by the route of injection of the scrapie inoculum. Intracerebral injection consistently results in greater numbers of plaques than are obtained if the same inoculum is introduced peripherally. Following intracerebral injection, plaques are commonly seen in areas close to the lateral ventricles, for example the corpus callosum and hippocampus, whereas they are absent from these areas with peripheral routes. Furthermore, when left- and right- sided intracerebral injections are compared, plaques are more frequent on the side of injection. These results suggest that the distribution of amyloid plaques is influenced either by the localization of some component of the inoculum or by traumatic damage at injection. The most plausible explanation is that amyloid deposition is associated with local concentrations of scrapie infectivity and that the amyloid protein originates in the brain.     

THE PATHOGENESIS AND PATHWAY INTO THE CENTRAL NERVOUS SYSTEM AFTER INTRAOCULAR INFECTION OF HERPES SIMPLEX VIRUS TYPE I IN RABBITS

Herpes simplex virus (HSV) type I was injected into the right eye of 18-day-old New Zealand albino rabbits and the animals were killed on the fourth and eighth days after inoculation. Longitudinal section of the optic nerves and chiasma showed that both myelinated axons and neuroglial cells crossed at the chiasma. Semi-serial (1 μm) and ultrathin sections showed the presence of HSV in both astrocytes and oligodendrocytes, although no particles were seen in the myelinated axons; the infected cells were confined to the medial side of the right optic nerve. HSV travels centropetally along the optic pathway and slowly spreads laterally by cell-to-cell infection. The virus does not appear to kill the astrocytes and oligodendrocytes, and also does not directly damage the myelin sheath.     

胎脑提取液与桥接物联合应用对脊髓损伤修复的影响

研究胎脑提取液对脊髓损伤修复的影响。用ＳＤ大鼠４０ 只,过半切除长约０５ ｃｍ 的左下胸段（Ｔ８,Ｔ９）脊髓,肌基膜管（ＭＢＬ）桥接脊髓缺损。局部用药组将ＭＢＬ浸泡于胎脑提取液（ＥＦＢ）中,全身用药组腹腔注射ＥＦＢ,生理盐水（ＮＳ）作对照。实验组动物行为学测试指标和斜板试验ＩＰ分数均明显优于对照组;实验组术后６ 周可测到ＳＥＰ波形,而对照组未测到;实验组ＭＢＬ与脊髓融合,ＭＢＬ内有髓神经纤维髓鞘较厚,轴突直径较粗,腰部脊神经节细胞结构完整,均优于对照组;图像分析显示实验组ＭＢＬ内有髓神经纤维数、轴突直径和脊神经节细胞数均优于对照组。局部和全身应用ＥＦＢ对脊髓损伤修复均有明显促进作用     

ULTRASTRUCTURE OF AXOTOMIZED ALPHA AND GAMMA MOTONEURONS IN THE CAT THORACIC SPINAL CORD

Using horseradish peroxidase as a retrograde marker, the ultrastructural response of alpha and gamma motoneuronal cell bodies in the cat thoracic spinal cord has been compared 1-8 days following intercostal nerve transection and ligation. By light microscopy, reduction of Nissl body size, together with nuclear and nucleolar alterations were seen in alpha motoneurons 4-8 days following axotomy, but not at any stage in axotomized gamma motoneurons. In the electron microscope, disorganization of Nissl body ultrastructure was seen in both alpha and gamma motoneurons 2 days following axotomy. Only in alpha motoneurons, however, did these disorganized Nissl bodies subsequently fragment into smaller pieces. Both alpha and gamma motoneurons lost synapses following axotomy, but the proportional loss from gamma motoneurons was two-fold greater than that from alpha motoneurons. Loss of synaptic terminals with flattened synaptic vesicles was two-fold higher than that of synaptic terminals with round synaptic vesicles from axotomized gamma motoneurons, whereas axotomized alpha motoneurons lost both types of synaptic terminal equally.     

MULTIPLE SCLEROSIS: RELATION TO SCRAPIE AND SLOW INFECTION; AGEING AND MEASLES

Multiple Sclerosis (MS) is shown to have no relation to scrapie and the evidence for a "slow infective" aetiology is very meagre. It is not related to an ageing process during which scrapie-like antigens make their appearance as they do in young animal with the disease. The emergence of scrapie-like antigens in ageing tissues is discussed. The increased sensitization of MS lymphocytes to scrapie, as opposed to normal brain (or spleen), is not characteristic of the disease, but occurs in other conditions with astroglial overgrowth. On the other hand, special lymphocyte sensitivity to inhibition by linoleic acid is limited to MS (and not shared by scrapie). The familial background of MS is briefly discussed, and an important line of study which might bring together classical genetic markers, HLA studies, and linoleic acid lymphocyte study is indicated. The role commonly ascribed to measles is critically reviewed. Measles may be of special importance in one (childhood-acquired) group of MS subjects, but there is no evidence of a special role in most cases. Raised antibodies to viruses other than measles have, however, been described. It is concluded that an immunological mechanism is still the most likely "final common path" by which MS lesions develop.     

P物质及福尔马林增强前生长抑素原mRNA在大鼠脊髓的表达

应用原位杂交法和放射免疫测定法，观察P物质（SP）及福尔马林对脊髓前生长抑素原（PPS）mRNA表达和SP样免疫活性物（Ir－SP）含量的影响。结累表明足底注射福尔马林150μl，脊髓PPS－mRNA1h开始升高，2h明显增多，4h达高峰。同时Ir－SP的含量1h增多，2h稍有下降。大鼠鞘内注射SP1h，脊髓PPS－mRNA变化不明显，2h明显增多，4h达高峰。说明SP及伤害性刺激可促使SOM转录、合成。     

NEURAL TISSUE GRAFTS AND REPAIR OF THE INJURED SPINAL CORD

Neural tissue grafting presently stands as one of the more intriguing experimental strategies being applied to the problem of spinal cord regeneration. The following annotation presents an overview of recent investigations which have shown: that peripheral nerve grafts can stimulate axonal outgrowth in many descending and ascending fibre populations of the injured spinal cord and that central nervous system (CNS) implants, derived from segmental and supraspinal levels of the embryonic neuraxis, may likewise have the potential for promoting repair of damaged intraspinal neural circuitries in adult and neonatal recipients.     

A MODEL OF CHRONIC SPINAL CORD COMPRESSION IN THE CAT

Fish C.J. & Blakemore W.F. (1983) Neuropathology and Applied Neurobiology 9 , 109–120
A model of chronic spinal cord compression in the cat
An experimental method of producing chronic compression of the cat spinal cord is described. A ligature placed around the lumbar spinal cord of 3-month-old kittens restricts the growth of the spinal cord to produce compression with a slow onset and an insidious progression. The methods of following the clinical progress of affected animals and of sampling the spinal cord after perfusion fixation are presented. The sampling method used allowed analysis of the three dimensional distribution of the pathological changes caused by the compression. These changes were not symmetrically distributed: the spinal cord caudal to the ligature became swollen and extensive partial demyelination occurred under the ligature and caudal to it, in the swollen region of the cord, whereas cranial to the ligature there was only minimal damage. It is concluded that the method produces a useful model of chronic compression of the spinal cord, which will be of value in studying partial demyelination.     

培养纯化的人胎儿许旺细胞在脱髓鞘大鼠脊髓内的成活和迁移

许旺细胞是周围神经系统的髓鞘形成细胞，它能修复遗传性或物理，化学因素导致的中枢脱髓鞘损伤，本实验用荧光素Ｈｏｅｃｈｓｔ３３３４２标记体培养的人胎儿许旺细胞并将其移植于１％溶血卵磷酯造成的脱髓鞘大鼠脊髓内，直接观察许旺细胞的成活和迁移，实验结果显示人胎儿许旺细胞特异性地朝脱髓鞘损伤方向迁移，迁移的速度约２ｍｍ／ｄ，迁移途径主要软脊膜，室管膜以及血管周间隙，亦有部分细胞在白质内迁移，移植１个月后，细胞