胶质细胞源性神经营养因子干预视网膜色素变性给药方式的研究进展

视网膜色素变性（retinitis pigmentosa，RP）的治疗目前仍处于探索阶段。胶质细胞源性神经营养因子（glial cell line-derived neurotrophic factor，GDNF）是目前研究中重要的神经营养因子，但其传统给药方式生物利用度相对较低。近年来GDNF安全有效的给药方式成为研究热点，包括经病毒载体或非病毒载体的基因工程法释药技术、经聚合物释放系统释药技术、经细胞移植释药技术、小分子触发器诱导产生GDNF等。本文就GDNF干预RP的给药方式进行综述。     

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Scar formation after injury of the brain or spinal cord is a common event. While glial scar formation by astrocytes has been extensively studied, much less is known about the fibrotic scar, in particular after stroke. Platelet-derived growth factor receptor ß-expressing (PDGFRß⁺) pericytes have been suggested as a source of the fibrotic scar depositing fibrous extracellular matrix (ECM) proteins after detaching from the vessel wall. However, to what extent these parenchymal PDGFRß⁺ cells contribute to the fibrotic scar and whether targeting these cells affects fibrotic scar formation in stroke is still unclear. Here, we utilize male transgenic mice that after a permanent middle cerebral artery occlusion stroke model have a shift from a parenchymal to a perivascular location of PDGFRß⁺ cells due to the loss of regulator of G-protein signaling 5 in pericytes. We find that only a small fraction of parenchymal PDGFRß⁺ cells co-label with type I collagen and fibronectin. Consequently, a reduction in parenchymal PDGFRß⁺ cells by ca. 50% did not affect the overall type I collagen or fibronectin deposition after stroke. The redistribution of PDGFRß⁺ cells to a perivascular location, however, resulted in a reduced thickening of the vascular basement membrane and changed the temporal dynamics of glial scar maturation after stroke. We demonstrate that parenchymal PDGFRß⁺ cells are not the main contributor to the fibrotic ECM, and therefore targeting these cells might not impact on fibrotic scar formation after stroke.     

Lateral ventricular liponeurocytoma: Review of literature and case illustration

BackgroundLiponeurocytoma is an uncommon tumor of the central nervous system. It is very rare for this tumor to originate within the lateral ventricle. In the context of the rarity of this tumor entity, this review article aims to summarize the clinical, radiological, and pathological features of lateral ventricular liponeurocytoma to facilitate its diagnosis and management.MethodsHere, we conduct a systematic literature review using the Pubmed, Scopus, and Cochrane Library database for all cases of lateral ventricular liponeurocytoma. A case illustration complements this review.ResultsThe described cases from 1997 onward include 14 cases that have been published in full papers in the English literature. Six additional cases are reported in short English abstracts in full non-English papers, and one case was described in a central neurocytoma report. There is a definite male predominance of 70% (14 male) and a mean age of 37 years (range 24–62). Heterogenous enhancement and signals in magnetic resonant images (MRI) are the radiological characteristics. In all reported cases, the presence of lipocytes and fat vacuoles is considered the paramount histopathological feature. Total surgical resection was achieved in 80% (12 out of 15) of the cases. Only two cases (including ours) received radiation therapy. Recurrence was seen in two patients during follow-up that was treated by radiation therapy in one and surgery in the other. The proliferation index is mostly below 5% in all cases, with the Ki-67 range between < 1% to 10%.ConclusionsLateral ventricular liponeurocytoma has been treated effectively by surgical resection in a limited number of cases. The decision for radiation therapy is based on a high proliferation index and tumor recurrence.     

Clinicopathological features of low-grade malignant endolymphatic sac tumors

Background

Low-grade malignant endolymphatic sac tumor (ELST) is a rare neoplasm, occurring in the inner ear and invading the temporal bone. This study aims to investigate the clinicopathological features of low-grade malignant ELSTs.

Neurons and satellite glial cells in adult rat lumbar dorsal root ganglia express connexin 36

Previous studies have shown that following peripheral nerve injury there was a downregulation of the gap junction protein connexin 36 (Cx36) in the spinal cord; however, it is not known whether Cx36 protein is expressed in the dorsal root ganglia (DRGs), nor if its levels are altered following peripheral nerve injuries. Here we address these aspects in the adult rat lumbar DRG. Cx36 mRNA was detected using qRT-PCR, and Cx36 protein was identified in DRG sections using immunohistochemistry (IHC) and immunofluorescence (IF). Double staining revealed that Cx36 co-localizes with both anti-β-III tubulin, a neuronal marker, and anti-glutamine synthetase, a satellite glial cell (SGC) marker. In neurons, Cx36 staining was mostly uniform in somata and fibers of all sizes and its intensity increased at the cell membranes. This labeling pattern was in contrast with Cx36 IF dots mainly found at junctional membranes in islet beta cells used as a control tissue. Co-staining with anti-Cx43 and anti-Cx36 showed that whereas mostly uniform staining of Cx36 was found throughout neurons and SGCs, Cx43 IF puncta were localized to SGCs. Cx36 mRNA was expressed in normal lumbar DRG, and it was significantly down-regulated in L4 DRG of rats that underwent sciatic nerve injury resulting in persistent hypersensitivity. Collectively, these findings demonstrated that neurons and SGCs express Cx36 protein in normal DRG, and suggested that perturbation of Cx36 levels may contribute to chronic neuropathic pain resulting from a peripheral nerve injury.     

Past, present and future of A(2A) adenosine receptor antagonists in the therapy of Parkinson's disease

Several selective antagonists for adenosine A_2A receptors (A_2AR) are currently under evaluation in clinical trials (phases I to III) to treat Parkinson's disease, and they will probably soon reach the market. The usefulness of these antagonists has been deduced from studies demonstrating functional interactions between dopamine D₂ and adenosine A_2A receptors in the basal ganglia. At present it is believed that A_2AR antagonists can be used in combination with the dopamine precursor L-DOPA to minimize the motor symptoms of Parkinson's patients. However, a considerable body of data indicates that in addition to ameliorating motor symptoms, adenosine A_2AR antagonists may also prevent neurodegeneration. Despite these promising indications, one further issue must be considered in order to develop fully optimized antiparkinsonian drug therapy, namely the existence of (hetero)dimers/oligomers of G protein-coupled receptors, a topic that is currently the focus of intense debate within the scientific community. Dopamine D₂ receptors (D₂Rs) expressed in the striatum are known to form heteromers with A_2A adenosine receptors. Thus, the development of heteromer-specific A_2A receptor antagonists represents a promising strategy for the identification of more selective and safer drugs.     

联合检测血清S-100B蛋白、神经元特异性烯醇化酶、神经胶质纤维酸性蛋白对严重颅脑损伤诊断及预后的意义

目的探讨严重颅脑损伤后血清S-100B蛋白、神经元特异性烯醇化酶(NSE)、神经胶质纤维酸性蛋白(GFAP)水平变化及其临床意义。方法采用酶联免疫吸附法(ELISA)检测46例严重颅脑损伤患者伤后12、24h、3、7、14d血清S-100B蛋白、NSE、GFAP水平,其中12h～3d的平均值作为初期值结合格拉斯哥昏迷评分(GCS)分析;7～14d平均值作为后期值结合格拉斯哥预后评分(GOS)分析,并与峰值及平均值比较。结果 (1)严重颅脑损伤后血清S-100B蛋白、NSE、GFAP水平较对照组明显升高;(2)重型(GCS6～8分)与特重型颅脑损伤组(GCS 3～5分)相比,3种标记物均无显著性差异(P>0.05);(3)预后不良组(GOS 1～3分)标记物峰值、平均值及后期值均明显高于预后良好组(GOS 4～5分)(P<0.005),3个值均与预后呈负相关,后期值与预后的相关性最大。3种标记物中GFAP后期值差异尤为显著(P<0.001)。结论严重颅脑损伤后血清S-100B蛋白、NSE、GFAP水平升高,但不能作为评判重型颅脑损伤或特重型颅脑损伤的依据。3种标记物水平对评估重型颅脑损伤预后具有较高的特异性和敏感性,其中GFAP后期值是评估严重颅脑损伤预后的较好的指标。     

l‐DOPA‐induced dyskinesia in Parkinson's disease: Are neuroinflammation and astrocytes key elements?

Inflammation in Parkinson's disease (PD) is a new concept that has gained ground due to the potential of mitigating dopaminergic neuron death by decreasing inflammation. The solution to this question is likely to be complex. We propose here that the significance of inflammation in PD may go beyond the nigral cell death. The pathological process that underlies PD requires years to reach its full extent. A growing body of evidence has been accumulated on the presence of multiple inflammatory signs in the brain of PD patients even in very late stages of the disease. Because neuron‐microglia‐astrocyte interactions play a major role in the plasticity of neuronal response to l ‐DOPA in post‐synaptic neurons, we focused this review on our recent results of l ‐DOPA‐induced dyskinesia in rodents correlating it to significant findings regarding glial cells and neuroinflammation. We showed that in the rat model of PD/l ‐DOPA‐induced dyskinesia there was an increased expression of inflammatory markers, such as the enzymes COX2 in neurons and iNOS in glial cells, in the dopamine‐denervated striatum. The gliosis commonly seem in PD was associated with modifications in astrocytes and microglia that occur after chronic treatment with l ‐DOPA. Either as a cause, consequence, or promoter of progression of neuronal degeneration, inflammation plays a role in PD. The key aims of current PD research ought to be to elucidate (a) the time sequence in which the inflammatory factors act in PD patient brain and (b) the mechanisms by which neuroinflammatory response contributes to the collateral effects of l ‐DOPA treatment.