大鼠脑梗死后神经前体细胞移行及电针作用的研究

目的研究成年大鼠脑梗死后电针作用对内源性神经前体细胞移行的影响。方法采用易卒中型肾性高血压大鼠(RHRSP),电凝法凝闭大脑中动脉(MCAO)。用Garcia评分、HE染色、免疫荧光等方法观察电针对脑梗死后1周、2周、3周、4周大鼠脑内梗死灶体积,行为学评分及5-溴脱氧尿核苷(Bromodeoxyuridine,Brdu)、Doublecortin(DCX)阳性细胞数的干预作用,并与脑梗死组和对照组比较。结果电针治疗后前3周梗死体积较脑梗死组缩小(P<0.05);电针后2d与3d大鼠行为学评分较梗死组高(P<0.05);MCAO后梗死灶边缘有Brdu阳性细胞和DCX阳性细胞分布。电针组Brdu阳性细胞较脑梗死组明显增加(P<0.05),电针组DCX阳性细胞数在1周末明显高于脑梗死组(P<0.05)。结论电针促进神经功能恢复,减小脑梗死体积,并使缺血灶周移行的神经前体细胞增多,可能与其改变脑内微环境密切相关。     

Organization and cellular arrangement of two neurogenic regions in the adult ferret (Mustela putorius furo) brain

In the adult mammalian brain, two neurogenic regions have been characterized, the subventricular zone (SVZ) of the lateral ventricle (LV) and the subgranular zone (SGZ) of the dentate gyrus (DG). Despite remarkable knowledge of rodents, the detailed arrangement of neurogenic regions in most mammals is poorly understood. In this study, we used immunohistochemistry and cell type‐specific antibodies to investigate the organization of two germinal regions in the adult ferret, which belongs to the order Carnivora and is widely used as a model animal with a gyrencephalic brain. From the SVZ to the olfactory bulb, doublecortin‐positive cells tended to organize in chain‐like clusters, which are surrounded by a meshwork of astrocytes. This structure is homologous to the rostral migratory stream (RMS) described in other species. Different from rodents, the horizontal limb of the RMS emerges directly from the LV, and the anterior region of the LV extends rostrally and reached the olfactory bulb. In the DG, glial fibrillary acidic protein‐positive cells with long radial processes as well as doublecortin‐positive cells are oriented in the SGZ. In both regions, doublecortin‐positive cells showed characteristic morphology and were positive for polysialylated‐neural cell adhesion molecule, beta‐III tubulin, and lamin B1 (intense staining). Proliferating cells were detected in both regions using antibodies against proliferating cell nuclear antigen and phospho‐histone H3. These observations demonstrate that the two neurogenic regions in ferrets have a similar cellular composition as those of other mammalian species despite anatomical differences in the brain. J. Comp. Neurol. 522:1818–1838, 2014. © 2013 Wiley Periodicals, Inc.     

Cells expressing markers of immature neurons in the amygdala of adult humans

The polysialylated form of the neuronal cell adhesion molecule (PSA‐NCAM) is expressed by immature neurons in the amygdala of adult mammals, including non‐human primates. In a recent report we have also described the presence of PSA‐NCAM‐expressing cells in the amygdala of adult humans. Although many of these cells have been classified as mature interneurons, some of them lacked mature neuronal markers, suggesting the presence of immature neurons. We have studied, using immunohistochemistry, the existence and distribution of these immature neurons using post mortem material. We have also analysed the presence of proliferating cells and the association between immature neurons and specialised astrocytes. These parameters have also been studied for comparative purposes in the amygdalae of cats and squirrel monkeys. Our results demonstrate that cells coexpressing doublecortin and PSA‐NCAM, but lacking neuronal nuclear antigen expression, were present in the amygdala of adult humans. These cells were organised in elongated clusters, which were located between the white matter of the dorsal hippocampus and the basolateral amygdaloid nucleus. These clusters were not associated with astroglial specialised structures. No cells expressing the proliferative marker Ki67 were observed in the amygdaloid parenchyma, although some of them were found in the vicinity of the lateral ventricle. Immature neurons were also present in the amygdala of squirrel monkeys and cats. These cells also appeared clustered in monkeys, although not as organised as in humans. In cats these cells are scarce, appear isolated and most of the PSA‐NCAM‐expressing structures corresponded to processes apparently originating from the paleocortical layer II.     

Where and what is the paralaminar nucleus? A review on a unique and frequently overlooked area of the primate amygdala

The primate amygdala is composed of multiple subnuclei that play distinct roles in amygdala function. While some nuclei have been areas of focused investigation, others remain virtually unknown. One of the more obscure regions of the amygdala is the paralaminar nucleus (PL). The PL in humans and non-human primates is relatively expanded compared to lower species. Long considered to be part of the basal nucleus, the PL has several interesting features that make it unique. These features include a dense concentration of small cells, high concentrations of receptors for corticotropin releasing hormone and benzodiazepines, and dense innervation of serotonergic fibers. More recently, high concentrations of immature-appearing cells have been noted in the primate PL, suggesting special mechanisms of neural plasticity. Following a brief overview of amygdala structure and function, this review will provide an introduction to the history, embryology, anatomical connectivity, immunohistochemical and cytoarchitectural properties of the PL. Our conclusion is that the PL is a unique subregion of the amygdala that may yield important clues about the normal growth and function of the amygdala, particularly in higher species.     

Involvement of Brain‐Derived Neurotrophic Factor and Neurogenesis in Oestradiol Neuroprotection of the Hippocampus of Hypertensive Rats

The hippocampus of spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)‐salt hypertensive rats shows decreased cell proliferation and astrogliosis as well as a reduced number of hilar cells. These defects are corrected after administration of 17β‐oestradiol (E₂) for 2 weeks. The present work investigated whether E₂ treatment of SHR and of hypertensive DOCA‐salt male rats modulated the expression of brain‐derived neurotrophic factor (BDNF), a neurotrophin involved in hippocampal neurogenesis. The neurogenic response to E₂ was simultaneously determined by counting the number of doublecortin‐immunopositive immature neurones in the subgranular zone of the dentate gyrus. Both hypertensive models showed decreased expression of BDNF mRNA in the granular zone of the dentate gyrus, without changes in CA1 or CA3 pyramidal cell layers, decreased BDNF protein levels in whole hippocampal tissue, low density of doublecortin (DCX)‐positive immature neurones in the subgranule zone and decreased length of DCX+ neurites in the dentate gyrus. After s.c. implantation of a single E₂ pellet for 2 weeks, BDNF mRNA in the dentate gyrus, BDNF protein in whole hippocampus, DCX immunopositive cells and the length of DCX+ neurites were significantly raised in both SHR and DOCA‐salt‐treated rats. These results indicate that: (i) low BDNF expression and deficient neurogenesis distinguished the hippocampus of SHR and DOCA‐salt hypertensive rats and (ii) E₂ was able to normalise these biologically important functions in the hippocampus of hypertensive animals.     

Adult dorsal root ganglia sensory neurons express the early neuronal fate marker doublecortin

It has been widely accepted that doublecortin (DCX) may represent a neuronal fate marker transiently expressed by immature neurons during development of the central and peripheral nervous tissue and in neurogenic areas of the adult brain. Previous work described the presence of DCX in the developing dorsal root ganglia (DRG), structures of the peripheral nervous system originating from the neural crest, but no information is available on its expression in adulthood. To this purpose, we have performed an immunohistochemical and biochemical analysis for DCX expression in DRG from adult male mice and rats. To our surprise, we demonstrated that the majority of DRG neurons do express DCX, both in somata and in fibers. DCX(+) cells have been characterized morphologically and phenotypically with well-established markers of DRG neuronal subpopulations. A large number of DCX(+) cells belong to the small and medium-sized nociceptive neurons. Additionally, DCX immunoreactivity is present in the spinal cord dorsal horns, the projection area of DRG neurons. The novel and unexpected localization for DCX protein opens up new, interesting vistas on the functional role of this protein in mature neurons and in particular in sensory neurons.     

Effects of Nelumbo nucifera rhizome extract on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia animal model

A large aquatic herb, Nelumbo nucifera Gaertn, has psychopharmacological effects similar to minor tranquillizers and antistress agents. This study examined the effects of Nelumbo nucifera rhizome extracts (NRE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of a rat model of scopolamine-induced amnesia. Immunohistochemical markers included Ki67, an endogenous marker for active cell cycle, and doublecortin (DCX), a marker for immature neurons and migratory neuroblasts. Scopolamine was administered for 28 days via an ALzet minipump (44 mg/mL delivered at 2.5 μL/h). NRE was administered by gavage, 1 g/kg per day for 28 days. The administration of scopolamine significantly reduced the number of Ki67- and DCX-immunoreactive cells in the DG, whereas scopolamine did not induce any significant changes in mature neurons in the DG. The administration of NRE significantly ameliorated the scopolamine-induced reduction of Ki67- and DCX-immunoreactive cells in the DG. In addition, the administration of NRE significantly restored the scopolamine-induced reduction of brain-derived neurotrophic factor in DG homogenates. These results suggest that NRE can ameliorate the scopolamine-induced reductions of cell proliferation, neuroblast differentiation and BDNF levels.     

Brief treatment with the glucocorticoid receptor antagonist mifepristone normalises the corticosterone-induced reduction of adult hippocampal neurogenesis

The glucocorticoid receptor antagonist mifepristone has been shown to rapidly and effectively ameliorate symptoms of psychotic major depression. To better understand its mechanism, we investigated mifepristone's cellular effects, and found that it rapidly reversed a chronic corticosterone-induced reduction of adult neurogenesis in rats. Unlike other antidepressants, mifepristone is particularly potent in a high corticosterone environment. These data indicate that similarly to its clinical efficacy, mifepristone's effects on adult neurogenesis are rapid and positive, and may therefore be important for its mechanism of action.