An immunohistochemical study of MAP2 and clathrin in gerbil hippocampus after cerebral ischemia

Changes in MAP2 and clathrin immunoreactivity were studied in gerbil hippocampus after transient cerebral ischemia. MAP2 immuno-reactivity decreased significantly by 1 h in the subiculum-CA1 and CA2 areas which correspond to reactive change, while no decrease was observed in CA1 until day 4. Before the initiation of delayed neuronal death, MAP2 immunoreactivity was not changed in CA1. On the other hand clathrin immunoreactivity increased in the pyramidal cell layer of CA1 by 3 h after ischemia and remained high for 2 days. Clathrin immunoreactivity in the pyramidal cell layer of CA1 diminished after delayed neuronal death. The transient change of clathrin was noted especially in CA1 in the period prior to delayed neuronal death. These results imply an abnormal change in clathrin turnover after ischemia, which may participate in the pathogenesis of delayed neuronal death.     

Focal ischemia of the rat brain,with special reference to the influence of plasma glucose concentration

Summary Focal cerebral ischemia was induced by occlusion of the right middle cerebral artery in hypoglycemic, normoglycemic, as well as in acute and chronic diabetic rats. The brain damage was studied after 4 days. The volume of infarction was decreased in hypoglycemia (29±19 mm³ (mean±SD) versus 58±35 mm³,P<0.0046), unaltered in acute diabetes (61±45 mm³), and increased in chronic diabetes (91±22 mm³,P<0.0463). The cortex adjacent to the infarct showed selective neuronal injury affecting the cortical layers 2 and 3. The damage was enhanced by hypoglycemia and prevented in most of the diabetic animals. The findings indicate that different mechanisms cause infarction and selective neuronal injury outside infarcts, but that both are influenced by the plasma glucose concentration.     

蛋白激酶C激活调控FOS表达参与缺血诱导神经元凋亡的研究

目的：探讨蛋白激酶C（PKC）与神经元凋亡的可能机制，方法：采用大鼠全脑缺血模型，观察脑缺血／再灌流后PKC活性，FOS表达及神经元凋亡的变化。结果：脑缺血／再灌流可以导致PKC的移位激活伴FOS表达及神经元凋亡的增加；用蛋白激酶C抑制剂灯盏花可以阻止上述变化。结论：蛋白激酶C的激活可能通过促进FOS表达参与了脑缺血／再灌流诱导的神经元凋亡。     

沙土鼠短暂性脑缺血后海马损伤的形态学特征

本实验通过结扎沙土鼠双侧颈总动脉20分钟,再灌流7天内,动态观察背侧海马组织的形态学变化。光镜观察表明:海马各区对缺血的反应性不同,其中以 CA_1区锥体细胞对缺血最为敏感,并且 CA_1区神经元的损伤是迟发性的,再灌流4天后才出现大量神经元的坏死、消失,即“迟发性神经元死亡”(NDN)。电镜下发现:缺血再灌流早期(1～2天),CA_1区神经细胞质内有大量粗面内质网增多。本实验结果表明:短暂性脑缺血所致的海马损伤与脑组织其他区域神经元损伤不同。     

Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.     

Phosphorylation of neurofilament H subunit as related to arrangement of neurofilaments

To find out what causes differences in phosphorylation states in neurofilaments (NF), we selected two types of dendrite, one provided with very few NFs (Purkinje cell) and the other with relatively many (anterior horn cell). We examined these with four monoclonal antibodies selected by the Western blot analysis, two (NE14 and SMI31) recongnizing only phosphorylated, SMI32 recognizing only nonphosphorylated, and N52 recognizing phosphorylation-independent epitopes of NF-H. The immunoperoxidase labeling of dendrites, and also of perikarya, in both neurons was detectable with all four antibodies. After the tissue was treated with Triton X-100, the labeling was still detectable with SMI32 or N52, but undetectable with NE14 and SMI31. The brain homogenate Triton-extracted supernatant after centrifugation at 100,000g for 1 hr showed the staining of NE14, SMI31, and N52 but not that of SMI32. In Purkinje cell dendrite and perikaryon, NFs always appeared singly. In the immunogold labeling, they were labeled only with SMI32 or N52. Labeling by NE14 or SMI31 was distributed throughout the cytoplasm and hardly associated with NFs. In the anterior horn cell dendrite and perikaryon, NFs appeared both single and in bundles. They were predominantly labeled with SMI31 or N52 when they were single, and with NE14, SMI31, or N52 when they were bundled. Even in one NF, portions that appeared single were labeled mostly with SMI32 or N52, while the remainder, to which other NFs approached closely, were labeled mostly with NE14, SMI31, or N52. Thus, when NFs appear singly, NF-H in their projections or cross-bridges with other organelles is not phosphorylated, while when NFs are bundled, NF-H is phosphorylated in crossbridges between NF core filaments. These data may explain why the NF-H is heavily phosphorylated in axons, where NFs are abundant, and not in dendrites and perikarya, where NFs are sparse. Wiley-Liss, Inc.     

Reduction in acute rejections decreases chronic rejection graft failure in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Chronic rejection accounted for 32% of all graft losses in 7123 pediatric transplants. In a previous study acute, multiple acute and late acute rejections were risk factors for the development of chronic rejection. We postulated that the recent decrease in acute rejections would translate into a lower risk for chronic rejection among patients with recent transplants. We reviewed our data on patients transplanted from 1995 to 2000, and using multivariate analysis and a proportional hazards model developed risk factors for patients whose grafts had failed due to chronic rejection. A late initial rejection increased the risk of chronic rejection graft failure 3.6-fold (p < 0.001), while a second rejection resulted in further increase of 4.2-fold (p < 0.001). Recipients who received less than 5 mg/kg of cyclosporine at 30 days post-transplant had a relative risk (RR) of 1.9 (p = 0.02). Patients transplanted from 1995 to 2000 had a significantly lower risk (RR = 0.54, p < 0.001) of graft failure from chronic rejection than those who received their transplants earlier (1987-94). Since we were able to demonstrate that there is a decreased risk of chronic rejection graft failure in our study cohort, we would conclude that the goal of future transplants should be to minimize acute rejections.     

杜仲对糖尿病大鼠扑捉行为和阴茎组织神经传导通路的影响

目的:探讨杜仲改善勃起功能的药效和病理学机制。方法:雄性糖尿病(DM)大鼠30只随机分为3组:A组(10只,DM大鼠赋形剂灌胃组)、B组(10只,DM大鼠西地那非灌胃组)、C组(10只,DM大鼠杜仲灌胃组)及10只正常对照组大鼠(赋形剂灌胃,D组);灌胃4周后观察4组大鼠扑捉行为,透射电镜检查阴茎组织有髓神经纤维超微特征;用免疫组化二步法显示阴茎组织中神经元型一氧化氮合酶(nNOS)的表达。结果:与A组比较,C组大鼠扑捉次数显著增多(P<0.05),阴茎组织中nNOS表达显著增强(P<0.001)。透射电镜显示:A组大鼠阴茎组织有髓神经纤维排布失序,部分变性、板层分离形成透明空泡或网络状,C组大鼠有髓神经纤维排列规整,板层结构清晰。结论:杜仲可通过减轻有髓神经的损伤、增强阴茎组织中nNOS表达改善ED。     

Epileptic seizures,arthrogryposis, and migrational brain disorders: a syndrome?

Introduction – Arthrogryposis multiplex congenita (AMC) may be associated with multiple developmental defects. In some severely affected newborns with AMC, autopsy studies have suggested a common mechanism of malmigration at the spinal and cerebral levels. To our knowledge, a constellation of arthrogryposis, epileptic seizures, and brain migrational anomalies in adult patients has not previously been described in a clinical material. Material and methods – Six consecutive adult patients with arthrogryposis multiplex congenita and epileptic seizures form the basis of the present study. Five patients had joint contractures and reduced muscle volume restricted to the lower extremities, whereas one patient had predominantly upper extremity affection. They were studied with magnetic resonance imaging (MRI), EEG, EMG, a neuropsychological test battery, and chromosome analysis. Results – Four of them had clear evidence of migrational brain disorders, demonstrated by MRI, in three of them roughly corresponding to the focal epileptiform EEG activity. Five of the patients had partial seizures, whereas one only had generalized tonic-clonic seizures. The MRI findings included polymicrogyria, pachygyria, and fused schizencephaly. Four had neurogenic EMG changes, one had myopathic EMG features, and one had an unremarkable EMG pattern in affected muscles. All patients witL demonstrable migrational disorders showed abnormal neuropsychological features. Three patients were mentally retarded. A chromosome abnormality in the form of a ring chromosome 18 was present in one patient. Conclusion – We suggest that AMC, epileptic seizures, and migrational brain disorders may form the integral parts of a hitherto undescribed syndrome in adults. A wide-spread defect in neuronal migration along the entire neural axis may be the underlying mechanism of the cerebral and the peripheral symptoms.     

DNA限制性内切酶分析应用于伴放线放线杆菌的鉴定和分型

本文用限制性内切酶分析(REA)作伴放线放线杆菌(Aa)的鉴定和分型研究,提取Aa染色体DNA,井分别用BamHI、HindⅢ,Sal Ⅰ和Xho Ⅰ消化,作琼脂糖凝胶电泳。结果显示,Aa和嗜沫嗜血杆菌的DNA片段图谱明显不同;分属于两种不同血清型的两株Aa菌株,其DNA片段图谱也明显不同。这表明,REA可用于Aa菌的鉴定和分型,在所用的4种酶中,以Sal Ⅰ和Xho Ⅰ消化的DNA片段图谱差异最明显。