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31.
Kennedy PG 《Journal of neuroimmunology》1999,100(1-2):36-41
Drug treatment of late-stage human African Trypanosomiasis (HAT) in which the central nervous system (CNS) is involved may be complicated by a severe post-treatment reactive encephalopathy (PTRE) which can be fatal in up to 10% of cases. In order to understand the immunopathogenesis of this complication, an experimental mouse model has been developed that mirrors many of the pathological features of the PTRE in humans, and which allows various anti-inflammatory therapeutic regimes to be evaluated. Following the development of the PTRE in this model a number of cytokines are increased within the CNS including tumour necrosis factor (TNF) alpha, interleukins 1, 4 and 6, and macrophage inflammatory protein (MIP)-1. These cytokines appear at the same time as astrocyte activation which is an early event occurring before the development of the marked meningoencephalitic inflammatory response. The immunosuppressant drug azathioprine prevents but does not reduce the severity of an established PTRE and has a minimal effect on astrocyte activation. The ornithine decarboxylase inhibitor eflornithine prevents the induction, and ameliorates the severity, of the PTRE, and also reduces the degree of astrocyte activation. The Substance P antagonist RP-67,580 ameliorates the severity of an established PTRE, and also reduces astrocyte activation, indicating an important role of SP in the generation of the inflammatory response. Continued use of this mouse model should lead to further enhancement of our understanding of the pathogenesis of the PTRE and to improved drug regimes to prevent and/or treat it. 相似文献
32.
Plasticity of the corticospinal tract following midthoracic spinal injury in the postnatal rat 总被引:3,自引:0,他引:3
Rats received a midthoracic spinal cord "overhemisection" including right hemicord and left dorsal funiculus at birth (neonatal operates, N = 15) or 21 days of age (weanling operates, N = 14). In a second experiment neonatal (N = 6), 6-day (N = 3), and 12-day (N = 7) rats sustained a right sensorimotor cortex (SmI) ablation to destroy the left corticospinal tract (CST) at the same time as the spinal injury (double lesion operates). Later (3-12 months) injections of 3H-proline and autoradiography were used to label the left or right CST. The results of the first experiment showed that most right CST axons failed to grow around the spinal lesion in neonatal operates (N = 9). There was an increase in the density of label, mainly to CST projection areas, in a 1-mm zone rostral to the lesion. However, left CST axons bypassed the lesion by growing through the intact tissue in neonatal operates (N = 6). These displaced axons were consistently located within the dorsal portion of the lateral funiculus (dLF) and remained within that location caudal to the lesion, an area normally containing only a few CST axons. In spite of this abnormal position, these axons terminated bilaterally throughout the remainder of the cord in normal CST sites. In weanling operates, CST axons severed by the lesion did not regenerate around the lesion site. An increased density of label over the few spared axons within the left dLF and in CST projection zones immediately caudal to the lesion site suggested axonal sprouting by these axons. The results of the second experiment showed that the lack of growth of right CST axons around this injury in neonatal operates was, at least partially, due to an interaction with left CST axons. In neonatal double lesion operates, right CST axons grew around the spinal injury for a varying distance within the left dLF and distributed bilaterally to normal CST sites. The number of right CST axons bypassing the lesion was related to the configuration of the lesion site. A smaller number of right CST axons bypassed the lesion in 6-day double lesion operates and most terminated within 2-3 mm of the lesion site. Right CST axons failed to grow around this injury in 12-day double lesion operates.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
33.
Torbjörn U. C. Järbe 《Psychopharmacology》1976,49(1):33-40
Experiment 1. Gerbils were trained in a T-shaped maze to discriminate the effects produced by pentobarbital (P-barb. 15 mg/kg, i.p.) and the effects of saline. The response, a left or right turn in the maze, was thus contingent upon the prevailing training condition (P-barb. or saline). The criterion of performing 8 correct first trial choices in 10 consecutive sessions was reached within 20 training sessions. Tests with descending doses of P-barb. yielded an ED50 of 9 mg/kg. Tests with phenobarbital (40 mg/kg) or diazepam (2 and 4 mg/kg) solely maintained the drug response. P-barb. discrimination was reversed by megimide (ED50: 8.5–9.6 mg/kg) and metrazol (ED50: 24.9–27.9 mg/kg). Thus megimide was approximately 3 times more effective than metrazol. Metrazol (40 and 80 mg/kg) also counteracted the phenobarbital and diazepam response. Picrotoxin (2.5 and 5 mg/kg) was less effective whereas caffeine (100 mg/kg) and piracetam (100–1000 mg/kg) did not upset P-barb. discrimination.
Experiment 2. Naive gerbils had to discriminate mixtures of P-barb. (15 mg/kg) plus either 40 or 80 mg/kg of metrazol from saline already at the start of the discriminative training. The drug combinations produced discriminable effects since most gerbils reached the acquisition criterion (8/10), although more slowly than gerbils trained with P-barb. solely. Gerbils trained without a drug stimulus (saline vs. saline) never attained the criterion during 60 consecutive sessions. In conclusion, reversal of established discrimination (Expt. 1) does not necessarily mean that the same drug combination lacks discriminable effects as demonstrated in Experiment 2. 相似文献
34.
Matthew L. Hanley Gertrude B. Elion O. Michael Colvin Paul L. Modrich Stephen Keir David J. Adams Darell D. Bigner Henry S. Friedman 《Cancer chemotherapy and pharmacology》1998,42(6):479-482
Purpose: The activity of vinorellbine, a new semisynthetic vinca alkaloid, was evaluated against a battery of human tumor xenografts
derived from adult and pediatric CNS malignancies. Methods: Tumors included adult high-grade gliomas (D-54 MG, D-245 MG), childhood high-grade gliomas (D-212 MG, D-456 MG), medulloblastomas
(D-341 MED, D-487 MED), ependymomas (D-612 EP, D-528 EP), and a mismatch repair-deficient procarbazine-resistant glioma [D-245
MG (PR)]. Tumors were grown subcutaneously in athymic nude mice and vinorelbine was administered at a dose of 11 mg/kg on
days 1, 5, and 9. Additionally, vinorelbine was also administered in combination with BCNU against D-54 MG. Results: Vinorelbine produced statistically significant growth delays in D-456 MG, D-245 MG, and D-245 MG (PR). No statistically
significant growth delays were observed in D-54 MG, D-487 MED, D-212 MG, D-528 EP, D-341 MED or D-612 EP. The antitumor effects
of the vinorelbine/BCNU combination were additive. Growth delays observed in the procarbazine-resistant line [D-245 MG (PR)]
were greater than twofold the delays seen in the parent line (D-245 MG). Vincristine was equally potent against D-245 MG and
D-245 MG (PR). Taxol demonstrated little activity against D-245 MG but produced 32- and 18-day growth delays in D245 MG (PR).
Conclusions: These studies indicate that vinorelbine possesses antitumor activity against several glioma tumor xenografts with marked
activity in a mismatch repair deficient-tumor.
Received: 10 February 1998 / Accepted: 1 April 1998 相似文献
35.
王建军 《中国神经肿瘤杂志》2005,3(2):88-91
背景与目的:中枢神经系统疾病冰冻切片诊断的误诊率较其他脏器相对较高,文献报导误诊率在1.6-13.2%,误诊率较高的肿瘤包括脑膜间叶性肿瘤,血管母细胞瘤,淋巴瘤及少枝胶质细胞瘤。本文总结和探讨神经系统病变术中诊断存在的问题,以提高神经系统病变术中诊断的质量。方法:我们回顾性地研究了4年中所进行的135例神经外科术中送检冰冻标本的诊断,并对照相应石蜡标本的诊断结果进行了分析比较。结果:发现冰冻切片诊断错误9例,误诊率为6.67%。误诊病例包括:星形细胞瘤1/73例(误诊率1.4%),室管膜瘤3/4例(误诊率75%),小脑髓母细胞瘤1,5例(误诊率20%),嗅神经母细胞瘤1,2例(误诊率50%),中枢神经细胞瘤1,2例(误诊率50%),脉络丛肿瘤1,2例(误诊率50%),非肿瘤性病变1,9例(误诊率11.1%)。结论:发生在脑室外的室管膜瘤易发生误诊;小脑髓母细胞瘤、嗅神经母细胞瘤等出现滤泡样结构或表现出结节样的结构时可能与转移性低分化癌混淆;脑组织中血管畸形伴血肿形成,由于常并发出现显著的胶质细胞反应而导致肿瘤的诊断。 相似文献
36.
目的研究中枢神经系统(central nervous system,CNS)损伤时,不同品系大鼠的表现,探索自身免疫神经保护的遗传特性。方法Sprague-Dawley(SD)大鼠、Wister大鼠各30只。髓鞘碱性蛋白(myelin basic protein,MBP)免疫后分别制备实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)和脊髓损伤动物模型,并进行EAE评分,损伤模型的行为学和组织学分析。结果Wister大鼠较SD大鼠EAE发病早、症状重、时间长;脊髓损伤后神经功能恢复结果亦差。结论对EAE敏感的Wister大鼠,体内缺乏自身免疫保护机制。不同品系大鼠在CNS损伤时,其遗传基因决定了最终的康复效果。 相似文献
37.
38.
Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential 总被引:1,自引:0,他引:1
Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities. 相似文献
39.
An-Shoei Yang Tung-Chuan Chiang Fu-Fa Hsu Mei-Hsiu Liao Lie-Hang Shen 《Drug and chemical toxicology》2013,36(4):529-533
S-3-iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide (IBZM) is one of the several benzamide derivatives showing a high affinity for the central nervous system (CNS) D2 dopamine receptor. Carrier-free [123I]IBZM is potentially useful as a nuclear medicine imaging agent for investigating the CNS D2 dopamine receptor in humans. This study describes the acute toxicity of IBZM and S-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide (BZM) in the rats. Treated rats were administered with IBZM at dose levels of 1 and 5 μg/kg and BZM at dose levels of 250 and 1250 μg/kg with dose volumes of 1 and 5 mL/kg. The control rats were administered 5 mL/kg of vehicle control. The rats were observed for 14 days. Observations included general demeanor, clinical signs, mortality, body weights/total body weight gains, and gross necropsy findings. None of the animals died during the 14-day study period. In female rats, the body weight gained at the first week of BZM treatment at a dose level of 1250 μg/kg and the total body weight gains of both IBZM treated groups were significantly higher than the control group (p < 0.05). 相似文献
40.
The 5th edition of the WHO Classification of Tumours of the Central Nervous System introduces new entities, and provides updated guidance regarding the diagnostic criteria for tumors of the central nervous system (CNS). CNS embryonal tumors and CNS non‐meningothelial mesenchymal tumors can be challenging for practicing pathologists, as the histologic features are not always specific to a particular entity, and integration of microscopic and molecular findings is necessary. This review on CNS embryonal and non‐meningothelial mesenchymal tumors is meant to provide an update with a focus on WHO changes and additions and on recent discoveries with diagnostic, prognostic, and therapeutic implications. 相似文献