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Sample records for cerebellar nerve cells

  1. Inverse Stochastic Resonance in Cerebellar Purkinje Cells.

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    Anatoly Buchin

    2016-08-01

    Full Text Available Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR. While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing.

  2. Cerebellar giant cell glioblastoma multiforme in an adult

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    Sudhansu Sekhar Mishra

    2014-01-01

    Full Text Available Cerebellar glioblastoma multiforme (GBM is a rare tumor that accounts for only 1% of all cases of GBM and its giant cell variant is even much rarely encountered in adults. A case of cerebellar giant cell GBM managed at our institution reporting its clinical presentation, radiological and histological findings, and treatment instituted is described. In conjunction, a literature review, including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options, and the behavior of such malignant tumor is presented. It is very important for the neurosurgeon to make the differential diagnosis between the cerebellar GBM, and other diseases such as metastasis, anaplastic astrocytomas, and cerebellar infarct because their treatment modalities, prognosis, and outcome are different.

  3. Spontaneous calcium waves in granule cells in cerebellar slice cultures

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    Apuschkin, Mia; Ougaard, Maria; Rekling, Jens C

    2013-01-01

    Multiple regions in the CNS display propagating correlated activity during embryonic and postnatal development. This activity can be recorded as waves of increased calcium concentrations in spiking neurons or glia cells, and have been suggested to be involved in patterning, axonal guidance and es......, that the propagating wave activity is carried through the tissue by axonal collaterals formed by neighboring granule cells, and further suggest that the correlated activity may be related to processes that ensure correct postnatal wiring of the cerebellar circuits....

  4. Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

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    Gilmer, Jesse I; Person, Abigail L

    2017-12-13

    Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs

  5. Cerebellar clear cell ependymoma in a 10 year old girl

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    Thinzar Aye Nyein; Moon, Ah Rim; Hwang, Sun Chul; Hong, Hyun Sook; Lee, A Leum; Chang, Kee Hyun; Kim, Hee Kyung; Chin, Su Sie [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Park, Ji Sang [Soonchunhyang University Gumi Hospital, Gumi (Korea, Republic of)

    2016-01-15

    Clear cell ependymoma (CCE) is a histological rare variant (1–5%) of ependymoma, which is distinguished from other histological subtypes by the presence of fusiform cells arrayed radially around small blood vessels. These alleged perivascular pseudorosettes are significant characteristic features of ependymomas. About 95% of infratentorial ependymomas are found in the fourth ventricle and the remainder occurs as cerebellopontine angle lesions. In previous reports, the cerebellum is found to be a rare location for ependymoma. In this study we report one case of CCE originating from the cerebellar hemisphere, showing unusual morphology on 3T MRI.

  6. Congenital Cerebellar Mixed Germ Cell Tumor Presenting with Hemorrhage in a Newborn

    International Nuclear Information System (INIS)

    Kim, Sung Mok; Kim, Ji Hye; Yoo, So Young; Park, Won Soon; Jang, Yun Sil; Shin, Hyung Jin; Suh, Yeon Lim

    2008-01-01

    We report here on a neonate with congenital cerebellar mixed germ cell tumor, and this initially presented as cerebellar hemorrhage. Postnatal cranial ultrasonography revealed an echogenic cerebellar mass that exhibited the signal characteristics of hemorrhage rather than tumor on MR images. The short-term follow-up images also suggested a resolving cerebellar hemorrhage. One month later, the neonate developed vomiting. A second set of MR images demonstrated an enlarged mass that exhibited changed signal intensity at the same site, which suggested a neoplasm. Histological examination after the surgical resection revealed a mixed germ cell tumor

  7. Cerebellar and basal ganglion involvement in Langerhans cell histiocytosis

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    Saatci, I.; Baskan, O.; Haliloglu, M.; Aydingoz, U. [Department of Radiology, Hacettepe University Hospital, Sihhiye 06100, Ankara (Turkey)

    1999-06-01

    Langerhans cell histiocytosis (LCH) is a disease of unknown cause characterised by proliferation of histiocytic granulomas in tissues; the primary cerebral manifestation is diabetes insipidus caused by hypothalamic infiltration. We present a patient in whom, except for the absence of high signal on T 1 weighting in the posterior pituitary, consistent with central diabetes insipidus, MRI showed no evidence of hypothalamic involvement by histiocytosis, despite the long duration of the disease. However, there was bilateral, symmetrical involvement of the cerebellum and globus pallidus in addition to a calvarial lesion. High signal in the cerebellar white matter on T 2-weighted images may represent demyelination, gliosis and cell loss, as previously reported on pathologic examination. (orig.) With 5 figs., 22 refs.

  8. Anterior Inferior Cerebellar Arteries Juxtaposed with the Internal Acoustic Meatus and Their Relationship to the Cranial Nerve VII/VIII Complex.

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    Alonso, Fernando; Kassem, Mohammad W; Iwanaga, Joe; Oskouian, Rod J; Loukas, Marios; Demerdash, Amin; Tubbs, R Shane

    2017-08-16

    Vascular loops in the cerebellopontine angle (CPA) and their relationship to cranial nerves have been used to explain neurological symptoms. The anterior inferior cerebellar artery (AICA) has variable branches producing vascular loops that can compress the facial cranial nerve (CN) VII and vestibulocochlear (CN VIII) nerves. AICA compression of the facial-vestibulocochlear nerve complex can lead to various clinical presentations, including hemifacial spasm (HFS), tinnitus, and hemiataxia. The formation of arterial loops inside or outside of the internal auditory meatus (IAM) can cause abutment or compression of CN VII and CN VIII. Twenty-five (50 sides) fresh adult cadavers underwent dissection of the cerebellopontine angle in the supine position. In regard to relationships between the AICA and the nerves of the facial/vestibulocochlear complex, 33 arteries (66%) traveled in a plane between the facial/nervus intermedius nerves and the cochlear and vestibular nerves. Five arteries (10%) traveled below the CN VII/VIII complex, six (12%) traveled posterior to the nerve complex, four (8%) formed a semi-circle around the upper half of the nerve complex, and two (4%) traveled between and partially separated the nervus intermedius and facial nerve proper. Our study found that the majority of AICA will travel in a plane between the facial/nervus intermedius nerves and the cochlear and vestibular nerves. Although the relationship between the AICA and porus acusticus and AICA and the nerves of the CN VII/VIII complex are variable, based on our findings, some themes exist. Surgeons should consider these with approaches to the cerebellopontine angle.

  9. Cerebellar and brainstem infarction as a complication of CT-guided transforaminal cervical nerve root block

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    Suresh, S. [The Royal National Orthopaedic Hospital NHS Trust, London (United Kingdom); Berman, J. [The Royal National Orthopaedic Hospital NHS Trust, Anaesthetic Department, London (United Kingdom); Connell, David A. [The Royal National Orthopaedic Hospital NHS Trust, Department of Radiology, London (United Kingdom)

    2007-05-15

    A 60-year-old man with a 4-year history of intractable neck pain and radicular pain in the C5 nerve root distribution presented to our department for a CT-guided transforaminal left C5 nerve root block. He had had a similar procedure on the right 2 months previously, and had significant improvement of his symptoms with considerable pain relief. On this occasion he was again accepted for the procedure after the risks and potential complications had been explained. Under CT guidance, a 25G spinal needle was introduced and after confirmation of the position of the needle, steroid was injected. Immediately the patient became unresponsive, and later developed a MR-proven infarct affecting the left vertebral artery (VA) territory. This is the first report of a major complication of a cervical root injection under CT guidance reported in the literature. We present this case report and the literature review of the potential complications of this procedure. (orig.)

  10. Cerebellar and brainstem infarction as a complication of CT-guided transforaminal cervical nerve root block

    International Nuclear Information System (INIS)

    Suresh, S.; Berman, J.; Connell, David A.

    2007-01-01

    A 60-year-old man with a 4-year history of intractable neck pain and radicular pain in the C5 nerve root distribution presented to our department for a CT-guided transforaminal left C5 nerve root block. He had had a similar procedure on the right 2 months previously, and had significant improvement of his symptoms with considerable pain relief. On this occasion he was again accepted for the procedure after the risks and potential complications had been explained. Under CT guidance, a 25G spinal needle was introduced and after confirmation of the position of the needle, steroid was injected. Immediately the patient became unresponsive, and later developed a MR-proven infarct affecting the left vertebral artery (VA) territory. This is the first report of a major complication of a cervical root injection under CT guidance reported in the literature. We present this case report and the literature review of the potential complications of this procedure. (orig.)

  11. Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

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    Su, Xin; Guan, Wuqiang; Yu, Yong-Chun; Fu, Yinghui

    2014-01-01

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1 + or nestin + stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU + cells in adult mouse cerebellum, and their quantity and density decreases significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU + cells, very few are mash1 + or nestin + stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1 + microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition

  12. Isolated abducens nerve palsy associated with subarachnoid hemorrhage: a localizing sign of ruptured posterior inferior cerebellar artery aneurysms.

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    Burkhardt, Jan-Karl; Winkler, Ethan A; Lasker, George F; Yue, John K; Lawton, Michael T

    2018-06-01

    OBJECTIVE Compressive cranial nerve syndromes can be useful bedside clues to the diagnosis of an enlarging intracranial aneurysm and can also guide subsequent evaluation, as with an acute oculomotor nerve (cranial nerve [CN] III) palsy that is presumed to be a posterior communicating artery aneurysm and a surgical emergency until proven otherwise. The CN VI has a short cisternal segment from the pontomedullary sulcus to Dorello's canal, remote from most PICA aneurysms but in the hemodynamic pathway of a rupturing PICA aneurysm that projects toward Dorello's canal. The authors describe a cranial nerve syndrome for posterior inferior cerebellar artery (PICA) aneurysms that associates subarachnoid hemorrhage (SAH) and an isolated abducens nerve (CN VI) palsy. METHODS Clinical and radiological data from 106 surgical patients with PICA aneurysms (66 ruptured and 40 unruptured) were retrospectively reviewed. Data from a group of 174 patients with other aneurysmal SAH (aSAH) were analyzed in a similar manner to control for nonspecific effects of SAH. Univariate statistical analysis compared incidence and risk factors associated with CN VI palsy in subarachnoid hemorrhage. RESULTS Overall, 13 (4.6%) of 280 patients had CN VI palsy at presentation, and all of them had ruptured aneurysms (representing 13 [5.4%] of the 240 cases of ruptured aneurysms). CN VI palsies were observed in 12 patients with ruptured PICA aneurysms (12/66 [18.1%]) and 1 patient with other aSAH (1/174 [0.1%], p < 0.0001). PICA aneurysm location in ruptured aneurysms was an independent predictor for CN VI palsy on multivariate analysis (p = 0.001). PICA aneurysm size was not significantly different in patients with or without CN VI palsy (average size 4.4 mm and 5.2 mm, respectively). Within the PICA aneurysm cohort, modified Fisher grade (p = 0.011) and presence of a thick cisternal SAH (modified Fisher Grades 3 and 4) (p = 0.003) were predictors of CN VI palsy. In all patients with ruptured PICA

  13. Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

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    Paolo eBotta

    2014-02-01

    Full Text Available Golgi cells (GoCs are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABAA receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na+/K+ pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABAA receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex.

  14. Genetic instability in nerve sheath cell tumors

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    Rogatto, Silvia Regina; Casartelli, Cacilda; Rainho, Claudia Aparecida

    1995-01-01

    After in vitro culture, we analyzed cytogenetically four acoustic nerve neurinomas, one intraspinal neurinoma and one neurofibroma obtainedfrom unrelated patients. Monosomy of chromosomes 22 and 16 was an abnormality common to all cases, followed in frequency by loss of chromosomes 18 (three cases...... by the presence of polyploid cells with inconsistent abnormalities, endoreduplications and telomeric associations resulting in dicentric chromosomes. It is probable that these cytogenetic abnormalities represent some kind of evolutionary advantage for the in vitro progression of nerve sheath tumors....

  15. Taste bud cells and nerves

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    武田,正子/内田,暢彦/鈴木,裕子; タケダ,マサコ/ウチダ,ノブヒコ/スズキ,ユウコ; TAKEDA,Masako/UCHIDA,Nobuhiko/SUZUKI,Yuko

    2002-01-01

    Sectioning of glossopharyngeal nerves which innervate the taste buds in the circumvallate papillae caused apoptosis of taste buds, the numbers decreasing and the taste buds disappearing after 11 days. This indicates that gustatory nerves may release a trophic substance that induces and maintains taste buds. Taste bud cells contain neurotrophins, NCAM, NSE, PGP9.5, and NeuroD which are specific markers of neurons. The BDNF and GDNF of neurotrophins, and Trk B and GFRαl of their receptors were ...

  16. Effects of ethanol and NAP on cerebellar expression of the neural cell adhesion molecule L1.

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    Devon M Fitzgerald

    Full Text Available The neural cell adhesion molecule L1 is critical for brain development and plays a role in learning and memory in the adult. Ethanol inhibits L1-mediated cell adhesion and neurite outgrowth in cerebellar granule neurons (CGNs, and these actions might underlie the cerebellar dysmorphology of fetal alcohol spectrum disorders. The peptide NAP potently blocks ethanol inhibition of L1 adhesion and prevents ethanol teratogenesis. We used quantitative RT-PCR and Western blotting of extracts of cerebellar slices, CGNs, and astrocytes from postnatal day 7 (PD7 rats to investigate whether ethanol and NAP act in part by regulating the expression of L1. Treatment of cerebellar slices with 20 mM ethanol, 10(-12 M NAP, or both for 4 hours, 24 hours, and 10 days did not significantly affect L1 mRNA and protein levels. Similar treatment for 4 or 24 hours did not regulate L1 expression in primary cultures of CGNs and astrocytes, the predominant cerebellar cell types. Because ethanol also damages the adult cerebellum, we studied the effects of chronic ethanol exposure in adult rats. One year of binge drinking did not alter L1 gene and protein expression in extracts from whole cerebellum. Thus, ethanol does not alter L1 expression in the developing or adult cerebellum; more likely, ethanol disrupts L1 function by modifying its conformation and signaling. Likewise, NAP antagonizes the actions of ethanol without altering L1 expression.

  17. N-methyl-D-aspartate promotes the survival of cerebellar granule cells in culture

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    Balázs, R; Jørgensen, Ole Steen; Hack, N

    1988-01-01

    Our previous studies on the survival-promoting influence of elevated concentrations of extracellular K+ ([K+]e) on cultured cerebellar granule cells led to the proposal that depolarization in vitro mimics the effect of the earliest afferent inputs received by the granule cells in vivo. This, in t...

  18. DNA damage and cell cycle events implicate cerebellar dentate nucleus neurons as targets of Alzheimer's disease

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    Yang Yan

    2010-12-01

    Full Text Available Abstract Background Although the cerebellum is considered to be predominantly involved in fine motor control, emerging evidence documents its participation in language, impulsive behavior and higher cognitive functions. While the specific connections of the cerebellar deep nuclei (CDN that are responsible for these functions are still being worked out, their deficiency has been termed "cerebellar cognitive affective syndrome" - a syndrome that bears a striking similarity to many of the symptoms of Alzheimer's disease (AD. Using ectopic cell cycle events and DNA damage markers as indexes of cellular distress, we have explored the neuropathological involvement of the CDN in human AD. Results We examined the human cerebellar dentate nucleus in 22 AD cases and 19 controls for the presence of neuronal cell cycle events and DNA damage using immunohistochemistry and fluorescence in situ hybridization. Both techniques revealed several instances of highly significant correlations. By contrast, neither amyloid plaque nor neurofibrillary tangle pathology was detected in this region, consistent with previous reports of human cerebellar pathology. Five cases of early stage AD were examined and while cell cycle and DNA damage markers were well advanced in the hippocampus of all five, few indicators of either cell cycle events (1 case or a DNA damage response (1 case were found in CDN. This implies that CDN neurons are most likely affected later in the course of AD. Clinical-pathological correlations revealed that cases with moderate to high levels of cell cycle activity in their CDN are highly likely to show deficits in unorthodox cerebellar functions including speech, language and motor planning. Conclusion Our results reveal that the CDN neurons are under cellular stress in AD and suggest that some of the non-motor symptoms found in patients with AD may be partly cerebellar in origin.

  19. Questioning the cerebellar doctrine

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    Galliano, Elisa; De Zeeuw, Chris I

    2014-01-01

    The basic principles of cerebellar function were originally described by Flourens, Cajal, and Marr/Albus/Ito, and they constitute the pillars of what can be considered to be the classic cerebellar doctrine. In their concepts, the main cerebellar function is to control motor behavior, Purkinje cells

  20. Distinct roles of neuroepithelial-like and radial glia-like progenitor cells in cerebellar regeneration.

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    Kaslin, Jan; Kroehne, Volker; Ganz, Julia; Hans, Stefan; Brand, Michael

    2017-04-15

    Zebrafish can regenerate after brain injury, and the regenerative process is driven by resident stem cells. Stem cells are heterogeneous in the vertebrate brain, but the significance of having heterogeneous stem cells in regeneration is not understood. Limited availability of specific stem cells might impair the regeneration of particular cell lineages. We studied regeneration of the adult zebrafish cerebellum, which contains two major stem and progenitor cell types: ventricular zone and neuroepithelial cells. Using conditional lineage tracing we demonstrate that cerebellar regeneration depends on the availability of specific stem cells. Radial glia-like cells are thought to be the predominant stem cell type in homeostasis and after injury. However, we find that radial glia-like cells play a minor role in adult cerebellar neurogenesis and in recovery after injury. Instead, we find that neuroepithelial cells are the predominant stem cell type supporting cerebellar regeneration after injury. Zebrafish are able to regenerate many, but not all, cell types in the cerebellum, which emphasizes the need to understand the contribution of different adult neural stem and progenitor cell subtypes in the vertebrate central nervous system. © 2017. Published by The Company of Biologists Ltd.

  1. N-methyl-D-aspartate promotes the survival of cerebellar granule cells: pharmacological characterization

    DEFF Research Database (Denmark)

    Balázs, R; Hack, N; Jørgensen, Ole Steen

    1989-01-01

    The survival of cerebellar granule cells in culture is promoted by chronic exposure to N-methyl-D-aspartate (NMDA). The effect is due to the stimulation of 'conventional' NMDA receptor-ionophore complex: it is concentration dependent, voltage dependent and blocked by the selective antagonists D-2...

  2. Weaver mutant mouse cerebellar granule cells respond normally to chronic depolarization

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    Bjerregaard, Annette; Mogensen, Helle Smidt; Hack, N

    1997-01-01

    We studied the effects of chronic K(+)-induced membrane depolarization and treatment with N-methyl-D-aspartate (NMDA) on cerebellar granule cells (CGCs) from weaver mutant mice and non-weaver litter-mates. The weaver mutation is a Gly-to-Ser substitution in a conserved region of the Girk2 G prote...

  3. Calcium Imaging Reveals Coordinated Simple Spike Pauses in Populations of Cerebellar Purkinje Cells

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    Jorge E. Ramirez

    2016-12-01

    Full Text Available The brain’s control of movement is thought to involve coordinated activity between cerebellar Purkinje cells. The results reported here demonstrate that somatic Ca2+ imaging is a faithful reporter of Na+-dependent “simple spike” pauses and enables us to optically record changes in firing rates in populations of Purkinje cells in brain slices and in vivo. This simultaneous calcium imaging of populations of Purkinje cells reveals a striking spatial organization of pauses in Purkinje cell activity between neighboring cells. The source of this organization is shown to be the presynaptic gamma-Aminobutyric acid producing (GABAergic network, and blocking ionotropic gamma-Aminobutyric acid receptor (GABAARs abolishes the synchrony. These data suggest that presynaptic interneurons synchronize (inactivity between neighboring Purkinje cells, and thereby maximize their effect on downstream targets in the deep cerebellar nuclei.

  4. Dynamic properties of sensory stimulation evoked responses in mouse cerebellar granule cell layer and molecular layer.

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    Bing, Yan-Hua; Zhang, Guang-Jian; Sun, Lei; Chu, Chun-Ping; Qiu, De-Lai

    2015-01-12

    Sensory information coming from climbing fiber and mossy fiber-granule cell pathways, generates motor-related outputs according to internal rules of integration and computation in the cerebellar cortex. However, the dynamic properties of sensory information processing in mouse cerebellar cortex are less understood. Here, we studied the dynamic properties of sensory stimulation-evoked responses in the cerebellar granule cell layer (GCL) and molecular layer (ML) by electrophysiological recordings method. Our data showed that air-puff stimulation (5-10 ms in duration) of the ipsilateral whisker pad evoked single-peak responses in the GCL and ML; whereas a duration of stimulation ≥30 ms in GCL and ≥60 ms in ML, evoked double-peak responses that corresponded with stimulation-on and -off responses via mossy fiber pathway. The highest frequency of stimulation train for evoking GCL responses was 33 Hz. In contrast, the highest frequency of stimulation train for evoking ML responses was 4 Hz. These results indicate that the cerebellar granule cells transfer the high-fidelity sensory information from mossy fibers, which is cut-off by molecular layer interneurons (MLIs). Our results suggest that the MLIs network acts as a low-pass filter during the processing of high-frequency sensory information. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Adult Stem Cell Based Enhancement of Nerve Conduit for Peripheral Nerve Repair

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    2016-10-01

    accompanied by injuries to peripheral nerves; if not repaired, the trauma can lead to significant dysfunction and disability . While nerves have the ability to...recovery, minimized disability , and increased quality of life for our wounded warriors. 2. KEYWORDS: Stem Cell, Nerve Conduit, Peripheral Nerve...would be a paradigm shift away from ordering X-rays at 10-12 weeks and only ordering a CT scan. It has the potential to change the standard of care

  6. Effect of gabazine on sensory stimulation train evoked response in mouse cerebellar Purkinje cells.

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    Bing, Yan-Hua; Jin, Wen-Zhe; Sun, Lei; Chu, Chun-Ping; Qiu, De-Lai

    2015-02-01

    Cerebellar Purkinje cells (PCs) respond to sensory stimulation via climbing fiber and mossy fiber-granule cell pathways, and generate motor-related outputs according to internal rules of integration and computation. However, the dynamic properties of sensory information processed by PC in mouse cerebellar cortex are currently unclear. In the present study, we examined the effects of the gamma-aminobutyric acid receptor A (GABA(A)) antagonist, gabazine, on the stimulation train on the simple spike firing of PCs by electrophysiological recordings method. Our data showed that the output of cerebellar PCs could be significantly affected by all pulses of the low-frequency (0.25 -2 Hz) sensory stimulation train, but only by the 1st and 2nd pulses of the high-frequency (≥ 4 Hz) sensory stimulation train. In the presence of gabazine (20 μM), each pulse of 1 Hz facial stimulation evoked simple spike firing in the PCs, but only the 1st and 2nd pulses of 4 Hz stimulation induced an increase in simple spike firing of the PCs. These results indicated that GABAA receptor-mediated inhibition did not significantly affect the frequency properties of sensory stimulation evoked responses in the mouse cerebellar PCs.

  7. A spiking network model of cerebellar Purkinje cells and molecular layer interneurons exhibiting irregular firing

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    William eLennon

    2014-12-01

    Full Text Available While the anatomy of the cerebellar microcircuit is well studied, how it implements cerebellar function is not understood. A number of models have been proposed to describe this mechanism but few emphasize the role of the vast network Purkinje cells (PKJs form with the molecular layer interneurons (MLIs – the stellate and basket cells. We propose a model of the MLI-PKJ network composed of simple spiking neurons incorporating the major anatomical and physiological features. In computer simulations, the model reproduces the irregular firing patterns observed in PKJs and MLIs in vitro and a shift toward faster, more regular firing patterns when inhibitory synaptic currents are blocked. In the model, the time between PKJ spikes is shown to be proportional to the amount of feedforward inhibition from an MLI on average. The two key elements of the model are: (1 spontaneously active PKJs and MLIs due to an endogenous depolarizing current, and (2 adherence to known anatomical connectivity along a parasagittal strip of cerebellar cortex. We propose this model to extend previous spiking network models of the cerebellum and for further computational investigation into the role of irregular firing and MLIs in cerebellar learning and function.

  8. The Knockout of Secretin in Cerebellar Purkinje Cells Impairs Mouse Motor Coordination and Motor Learning

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    Zhang, Li; Chung, Sookja Kim; Chow, Billy Kwok Chong

    2014-01-01

    Secretin (SCT) was first considered to be a gut hormone regulating gastrointestinal functions when discovered. Recently, however, central actions of SCT have drawn intense research interest and are supported by the broad distribution of SCT in specific neuronal populations and by in vivo physiological studies regarding its role in water homeostasis and food intake. The direct action of SCT on a central neuron was first discovered in cerebellar Purkinje cells in which SCT from cerebellar Purkinje cells was found to potentiate GABAergic inhibitory transmission from presynaptic basket cells. Because Purkinje neurons have a major role in motor coordination and learning functions, we hypothesize a behavioral modulatory function for SCT. In this study, we successfully generated a mouse model in which the SCT gene was deleted specifically in Purkinje cells. This mouse line was tested together with SCT knockout and SCT receptor knockout mice in a full battery of behavioral tasks. We found that the knockout of SCT in Purkinje neurons did not affect general motor ability or the anxiety level in open field tests. However, knockout mice did exhibit impairments in neuromuscular strength, motor coordination, and motor learning abilities, as shown by wire hanging, vertical climbing, and rotarod tests. In addition, SCT knockout in Purkinje cells possibly led to the delayed development of motor neurons, as supported by the later occurrence of key neural reflexes. In summary, our data suggest a role in motor coordination and motor learning for SCT expressed in cerebellar Purkinje cells. PMID:24356714

  9. Neural stem cells enhance nerve regeneration after sciatic nerve injury in rats.

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    Xu, Lin; Zhou, Shuai; Feng, Guo-Ying; Zhang, Lu-Ping; Zhao, Dong-Mei; Sun, Yi; Liu, Qian; Huang, Fei

    2012-10-01

    With the development of tissue engineering and the shortage of autologous nerve grafts in nerve reconstruction, cell transplantation in a conduit is an alternative strategy to improve nerve regeneration. The present study evaluated the effects and mechanism of brain-derived neural stem cells (NSCs) on sciatic nerve injury in rats. At the transection of the sciatic nerve, a 10-mm gap between the nerve stumps was bridged with a silicon conduit filled with 5 × 10(5) NSCs. In control experiments, the conduit was filled with nerve growth factor (NGF) or normal saline (NS). The functional and morphological properties of regenerated nerves were investigated, and expression of hepatocyte growth factor (HGF) and NGF was measured. One week later, there was no connection through the conduit. Four or eight weeks later, fibrous connections were evident between the proximal and distal segments. Motor function was revealed by measurement of the sciatic functional index (SFI) and sciatic nerve conduction velocity (NCV). Functional recovery in the NSC and NGF groups was significantly more advanced than that in the NS group. NSCs showed significant improvement in axon myelination of the regenerated nerves. Expression of NGF and HGF in the injured sciatic nerve was significantly lower in the NS group than in the NSCs and NGF groups. These results and other advantages of NSCs, such as ease of harvest and relative abundance, suggest that NSCs could be used clinically to enhance peripheral nerve repair.

  10. The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes.

    Science.gov (United States)

    Burroughs, Amelia; Wise, Andrew K; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y; Lang, Eric J; Apps, Richard; Cerminara, Nadia L

    2017-01-01

    Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes. Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets. The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear. We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number. This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition

  11. Evidence for evoked release of adenosine and glutamate from cultured cerebellar granule cells

    International Nuclear Information System (INIS)

    Schousboe, A.; Frandsen, A.; Drejer, J.

    1989-01-01

    Evoked release of [ 3 H]-D-aspartate which labels the neurotransmitter glutamate pool in cultured cerebellar granule cells was compared with evoked release of adenosine from similar cultures. It was found that both adenosine and [3H]-D-aspartate could be released from the neurons in a calcium dependent manner after depolarization of the cells with either 10-100 microM glutamate or 50 mM KCl. Cultures of cerebellar granule cells treated with 50 microM kainate to eliminate GABAergic neurons behaved in the same way. This together with the observation that cultured astrocytes did not exhibit a calcium dependent, potassium stimulated adenosine release strongly suggest that cerebellar granule cells release adenosine in a neurotransmitter-like fashion together with glutamate which is the classical neurotransmitter of these neurons. Studies of the metabolism of adenosine showed that in the granule cells adenosine is rapidly metabolized to ATP, ADP, and AMP, but in spite of this, adenosine was found to be released preferential to ATP

  12. Cell Signaling and Neurotoxicity: 3H-Arachidonic acid release (Phospholipase A2) in cerebellar granule neurons

    Science.gov (United States)

    Cell signaling is a complex process which controls basic cellular activities and coordinates actions to maintain normal cellular homeostasis. Alterations in signaling processes have been associated with neurological diseases such as Alzheimer's and cerebellar ataxia, as well as, ...

  13. Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Giorgio Grasselli

    2016-03-01

    Full Text Available The plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the cerebellar nuclei by generating a characteristic spike burst-pause sequence upon synaptic activation. Using patch-clamp recordings from mouse Purkinje cells, we find that depolarization-triggered intrinsic plasticity enhances spike firing and shortens the duration of spike pauses. Pause plasticity is absent from mice lacking SK2-type potassium channels (SK2−/− mice and in occlusion experiments using the SK channel blocker apamin, while apamin wash-in mimics pause reduction. Our findings demonstrate that spike pauses can be regulated through an activity-dependent, exclusively non-synaptic, SK2 channel-dependent mechanism and suggest that pause plasticity—by altering the Purkinje cell output—may be crucial to cerebellar information storage and learning.

  14. Superior and anterior inferior cerebellar arteries and their relationship with cerebello-pontine angle cranial nerves revisited in the light of cranial cephalometric indexes: a cadaveric study.

    Science.gov (United States)

    Habibi, Zohreh; Meybodi, Ali Tayebi; Maleki, Farid; Tabatabai, Seyed

    2011-01-01

    The aim was to clarify the anatomical features of the superior and anterior inferior cerebellar arteries in relation to the trigeminal nerve and acoustic-facial complex and to the bony structures of the skull in a sample of male Iranian cadavers. Bilateral dissections, calvariectomy, and brain evacuation were performed on 31 adult human fresh brains and skull bases to assess the neurovascular associations, and skull base morphometry. Equations were defined to estimate posterior fossa volume and the relationships between bony and neurovascular elements. Eight SCAs were duplicated from origin. There were 9 cases of SCA-trigeminal contacts, which were at the root entry zone in 7. Mean distance from the origin of AICA to the vertebrobasilar junction was 11.80 mm, while 79% of AICAs originated from the lower half of the BA. This was significantly associated with "posterior fossa funneling" and "basilar narrowing" indexes. In most cases AICA crossed the acoustic-facial complex and coursed between neural bundles (48.3%). The AICA reached or entered the internal acoustic canal in 22.6% of cases and was medial to porous in 77.4%. We documented anatomical variations of the superior and anterior inferior cerebellar arteries along with some cephalometric equations with relevant neurovascular anatomy in Iranian cadavers.

  15. The cerebellar Golgi cell and spatiotemporal organization of granular layer activity

    Directory of Open Access Journals (Sweden)

    Egidio eD‘Angelo

    2013-05-01

    Full Text Available The cerebellar granular layer has been suggested to perform a complex spatiotemporal reconfiguration of incoming mossy fiber signals. Central to this role is the inhibitory action exerted by Golgi cells over granule cells: Golgi cells inhibit granule cells through double feedforward and feedback inhibitory loops and generate a broad lateral inhibition that extends beyond the afferent synaptic field. This characteristic connectivity has recently been investigated in great detail and been correlated with specific functional properties of the neuron. These include theta-frequency pacemaking, network entrainment into coherent oscillations and phase resetting. Important advances have also been made in terms of determining the membrane and synaptic properties of the neuron, and clarifying the mechanisms of activation by input bursts. Moreover, voltage sensitive dye imaging and multi-electrode array recordings, combined with mathematical simulations based on realistic computational models, have improved our understanding of the impact of Golgi cell activity on granular layer circuit computations. These investigations have highlighted the critical role of Golgi cells in: generating dense clusters of granule cell activity organized in center-surround structures, implementing combinatorial operations on multiple mossy fiber inputs, regulating transmission gain and cut-off frequency, controlling spike timing and burst transmission, and determining the sign, intensity and extension of long-term synaptic plasticity at the mossy fiber-granule cell relay. This review considers recent advances in the field, highlighting the functional implications of Golgi cells for granular layer network computation and indicating new challenges for cerebellar research.

  16. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

    Energy Technology Data Exchange (ETDEWEB)

    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

    2015-08-07

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.

  17. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

    International Nuclear Information System (INIS)

    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki

    2015-01-01

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture

  18. Cerebellar T-cell lymphoma: an unusual primary intracranial neoplasm

    International Nuclear Information System (INIS)

    Knorr, J.R.; Ragland, R.L.; Stone, B.B.; Woda, B.A.; Gelber, N.D.

    1992-01-01

    Primary T-cell lymphoma within the central nervous system is extremely rare. Imaging characteristics appear indistinguishable from the more common B-cell lymphoma. A case of such a primary tumor is discussed and the MRI and CT findings presented. (orig.)

  19. Nerve Invasion by Epithelial Cells in Benign Breast Diseases

    Directory of Open Access Journals (Sweden)

    Yu-Jan Chan

    2009-03-01

    Full Text Available Nerve invasion by glandular epithelial cells in a lesion is usually regarded as invasive carcinoma. However, some benign conditions in the pancreas, prostate, breast and other organs may show involvement of nerve bundles by benign epithelial cells. We report an 18-year-old female with nerve invasion in benign breast disease. The lesion in her right breast revealed fibrocystic changes with ductal hyperplasia and stromal sclerosis. Perineural and intraneural involvement by bland-looking small ducts lined by 2 layers of cells including an outer layer of myoepithelial cells were found, suggestive of benign nerve invasion. There was no evidence of malignant cells in any of the sections. The patient remains well after 31 months of follow-up. About 44 cases of nerve invasion in benign breast diseases have been reported in the literature. It is necessary to carefully evaluate nerve involvement in breast lesions to avoid over-diagnosis and inappropriate operation.

  20. Serotonin Immunoreactive Cells and Nerve Fibers in the Mucosa of ...

    African Journals Online (AJOL)

    hydroxytryptamine) immunoreactivity in the pyloric mucosa of the rat stomach. The immunoreactive elements included the endocrine cells, mast cells and mucosal nerve fibers in the lamina propria. The immunopositive endocrine cells were oval in ...

  1. Common pediatric cerebellar tumors: correlation between cell densities and apparent diffusion coefficient metrics.

    Science.gov (United States)

    Koral, Korgün; Mathis, Derek; Gimi, Barjor; Gargan, Lynn; Weprin, Bradley; Bowers, Daniel C; Margraf, Linda

    2013-08-01

    To test whether there is correlation between cell densities and apparent diffusion coefficient (ADC) metrics of common pediatric cerebellar tumors. This study was reviewed for issues of patient safety and confidentiality and was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center and was compliant with HIPAA. The need for informed consent was waived. Ninety-five patients who had preoperative magnetic resonance imaging and surgical pathologic findings available between January 2003 and June 2011 were included. There were 37 pilocytic astrocytomas, 34 medulloblastomas (23 classic, eight desmoplastic-nodular, two large cell, one anaplastic), 17 ependymomas (13 World Health Organization [WHO] grade II, four WHO grade III), and seven atypical teratoid rhabdoid tumors. ADCs of solid tumor components and normal cerebellum were measured. Tumor-to-normal brain ADC ratios (hereafter, ADC ratio) were calculated. The medulloblastomas and ependymomas were subcategorized according to the latest WHO classification, and tumor cellularity was calculated. Correlation was sought between cell densities and mean tumor ADCs, minimum tumor ADCs, and ADC ratio. When all tumors were considered together, negative correlation was found between cellularity and mean tumor ADCs (ρ = -0.737, P correlation between cellularity and ADC ratio. Negative correlation was found between cellularity and minimum tumor ADC in atypical teratoid rhabdoid tumors (ρ = -0.786, P correlation was found between cellularity and mean tumor ADC and ADC ratio. There was no correlation between the ADC metrics and cellularity of the pilocytic astrocytomas, medulloblastomas, and ependymomas. Negative correlation was found between cellularity and ADC metrics of common pediatric cerebellar tumors. Although ADC metrics are useful in the preoperative diagnosis of common pediatric cerebellar tumors and this utility is generally attributed to differences in cellularity of tumors

  2. Questioning the cerebellar doctrine.

    Science.gov (United States)

    Galliano, Elisa; De Zeeuw, Chris I

    2014-01-01

    The basic principles of cerebellar function were originally described by Flourens, Cajal, and Marr/Albus/Ito, and they constitute the pillars of what can be considered to be the classic cerebellar doctrine. In their concepts, the main cerebellar function is to control motor behavior, Purkinje cells are the only cortical neuron receiving and integrating inputs from climbing fiber and mossy-parallel fiber pathways, and plastic modification at the parallel fiber synapses onto Purkinje cells constitutes the substrate of motor learning. Yet, because of recent technical advances and new angles of investigation, all pillars of the cerebellar doctrine now face regular re-examination. In this review, after summarizing the classic concepts and recent disputes, we attempt to synthesize an integrated view and propose a revisited version of the cerebellar doctrine. © 2014 Elsevier B.V. All rights reserved.

  3. Non-synaptic signaling from cerebellar climbing fibers modulates Golgi cell activity.

    Science.gov (United States)

    Nietz, Angela K; Vaden, Jada H; Coddington, Luke T; Overstreet-Wadiche, Linda; Wadiche, Jacques I

    2017-10-13

    Golgi cells are the principal inhibitory neurons at the input stage of the cerebellum, providing feedforward and feedback inhibition through mossy fiber and parallel fiber synapses. In vivo studies have shown that Golgi cell activity is regulated by climbing fiber stimulation, yet there is little functional or anatomical evidence for synapses between climbing fibers and Golgi cells. Here, we show that glutamate released from climbing fibers activates ionotropic and metabotropic receptors on Golgi cells through spillover-mediated transmission. The interplay of excitatory and inhibitory conductances provides flexible control over Golgi cell spiking, allowing either excitation or a biphasic sequence of excitation and inhibition following single climbing fiber stimulation. Together with prior studies of spillover transmission to molecular layer interneurons, these results reveal that climbing fibers exert control over inhibition at both the input and output layers of the cerebellar cortex.

  4. Neuroprotective Effect of Carnosine on Primary Culture of Rat Cerebellar Cells under Oxidative Stress.

    Science.gov (United States)

    Lopachev, A V; Lopacheva, O M; Abaimov, D A; Koroleva, O V; Vladychenskaya, E A; Erukhimovich, A A; Fedorova, T N

    2016-05-01

    Dipeptide carnosine (β-alanyl-L-histidine) is a natural antioxidant, but its protective effect under oxidative stress induced by neurotoxins is studied insufficiently. In this work, we show the neuroprotective effect of carnosine in primary cultures of rat cerebellar cells under oxidative stress induced by 1 mM 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH), which directly generates free radicals both in the medium and in the cells, and 20 nM rotenone, which increases the amount of intracellular reactive oxygen species (ROS). In both models, adding 2 mM carnosine to the incubation medium decreased cell death calculated using fluorescence microscopy and enhanced cell viability estimated by the MTT assay. The antioxidant effect of carnosine inside cultured cells was demonstrated using the fluorescence probe dichlorofluorescein. Carnosine reduced by half the increase in the number of ROS in neurons induced by 20 nM rotenone. Using iron-induced chemiluminescence, we showed that preincubation of primary neuronal cultures with 2 mM carnosine prevents the decrease in endogenous antioxidant potential of cells induced by 1 mM AAPH and 20 nM rotenone. Using liquid chromatography-mass spectrometry, we showed that a 10-min incubation of neuronal cultures with 2 mM carnosine leads to a 14.5-fold increase in carnosine content in cell lysates. Thus, carnosine is able to penetrate neurons and exerts an antioxidant effect. Western blot analysis revealed the presence of the peptide transporter PEPT2 in rat cerebellar cells, which suggests the possibility of carnosine transport into the cells. At the same time, Western blot analysis showed no carnosine-induced changes in the level of apoptosis regulating proteins of the Bcl-2 family and in the phosphorylation of MAP kinases, which suggests that carnosine could have minimal or no side effects on proliferation and apoptosis control systems in normal cells.

  5. Simulating spinal border cells and cerebellar granule cells under locomotion--a case study of spinocerebellar information processing.

    Directory of Open Access Journals (Sweden)

    Anton Spanne

    Full Text Available The spinocerebellar systems are essential for the brain in the performance of coordinated movements, but our knowledge about the spinocerebellar interactions is very limited. Recently, several crucial pieces of information have been acquired for the spinal border cell (SBC component of the ventral spinocerebellar tract (VSCT, as well as the effects of SBC mossy fiber activation in granule cells of the cerebellar cortex. SBCs receive monosynaptic input from the reticulospinal tract (RST, which is an important driving system under locomotion, and disynaptic inhibition from Ib muscle afferents. The patterns of activity of RST neurons and Ib afferents under locomotion are known. The activity of VSCT neurons under fictive locomotion, i.e. without sensory feedback, is also known, but there is little information on how these neurons behave under actual locomotion and for cerebellar granule cells receiving SBC input this is completely unknown. But the available information makes it possible to simulate the interactions between the spinal and cerebellar neuronal circuitries with a relatively large set of biological constraints. Using a model of the various neuronal elements and the network they compose, we simulated the modulation of the SBCs and their target granule cells under locomotion and hence generated testable predictions of their general pattern of modulation under this condition. This particular system offers a unique opportunity to simulate these interactions with a limited number of assumptions, which helps making the model biologically plausible. Similar principles of information processing may be expected to apply to all spinocerebellar systems.

  6. Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

    Science.gov (United States)

    Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

    2016-01-01

    Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

  7. The survival of cultured mouse cerebellar granule cells is not dependent on elevated potassium-ion concentration

    DEFF Research Database (Denmark)

    Mogensen, Helle Smidt; Hack, N; Balázs, R

    1994-01-01

    The effects of K(+)-induced membrane depolarization were studied on the survival and biochemical parameters in mouse and rat cerebellar granule cells grown in micro-well cultures. Cell numbers were determined by estimating DNA content using the Hoechst 33258 fluorochrome binding assay. DNA from d...

  8. Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells

    Directory of Open Access Journals (Sweden)

    Wu Kong-Yan

    2010-06-01

    Full Text Available Abstract Background During cerebellar development, Purkinje cells (PCs form the most elaborate dendritic trees among neurons in the brain, but the mechanism regulating PC arborization remains largely unknown. Geranylgeranyltransferase I (GGT is a prenyltransferase that is responsible for lipid modification of several signaling proteins, such as Rho family small GTPase Rac1, which has been shown to be involved in neuronal morphogenesis. Here we show that GGT plays an important role in dendritic development of PCs. Results We found that GGT was abundantly expressed in the developing rat cerebellum, in particular molecular layer (ML, the region enriched with PC dendrites. Inhibition or down-regulation of GGT using small interference RNA (siRNA inhibited dendritic development of PCs. In contrast, up-regulation of GGT promoted dendritic arborization of PCs. Furthermore, neuronal depolarization induced by high K+ or treatment with brain-derived neurotrophic factor (BDNF promoted membrane association of Rac1 and dendritic development of PCs in cultured cerebellar slices. The effect of BDNF or high K+ was inhibited by inhibition or down-regulation of GGT. Conclusion Our results indicate that GGT plays an important role in Purkinje cell development, and suggest a novel role of GGT in neuronal morphogenesis in vivo.

  9. Plasticity of Cerebellar Purkinje Cells in Behavioral Training of Body Balance Control

    Directory of Open Access Journals (Sweden)

    Ray X. Lee

    2015-08-01

    Full Text Available Neural responses to sensory inputs caused by self-generated movements (reafference and external passive stimulation (exafference differ in various brain regions. The ability to differentiate such sensory information can lead to movement execution with better accuracy. However, how sensory responses are adjusted in regard to this distinguishability during motor learning is still poorly understood. The cerebellum has been hypothesized to analyze the functional significance of sensory information during motor learning, and is thought to be a key region of reafference computation in the vestibular system. In this study, we investigated Purkinje cell (PC spike trains as cerebellar cortical output when rats learned to balance on a suspended dowel. Rats progressively reduced the amplitude of body swing and made fewer foot slips during a 5-min balancing task. Both PC simple (SSs; 17 of 26 and complex spikes (CSs; 7 of 12 were found to code initially on the angle of the heads with respect to a fixed reference. Using periods with comparable degrees of movement, we found that such SS coding of information in most PCs (10 of 17 decreased rapidly during balance learning. In response to unexpected perturbations and under anesthesia, SS coding capability of these PCs recovered. By plotting SS and CS firing frequencies over 15-s time windows in double-logarithmic plots, a negative correlation between SS and CS was found in awake, but not anesthetized, rats. PCs with prominent SS coding attenuation during motor learning showed weaker SS-CS correlation. Hence, we demonstrate that neural plasticity for filtering out sensory reafference from active motion occurs in the cerebellar cortex in rats during balance learning. SS-CS interaction may contribute to this rapid plasticity as a form of receptive field plasticity in the cerebellar cortex between two receptive maps of sensory inputs from the external world and of efference copies from the will center for

  10. Bmi1 overexpression in the cerebellar granule cell lineage of mice affects cell proliferation and survival without initiating medulloblastoma formation

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    Hourinaz Behesti

    2013-01-01

    BMI1 is a potent inducer of neural stem cell self-renewal and neural progenitor cell proliferation during development and in adult tissue homeostasis. It is overexpressed in numerous human cancers – including medulloblastomas, in which its functional role is unclear. We generated transgenic mouse lines with targeted overexpression of Bmi1 in the cerebellar granule cell lineage, a cell type that has been shown to act as a cell of origin for medulloblastomas. Overexpression of Bmi1 in granule cell progenitors (GCPs led to a decrease in cerebellar size due to decreased GCP proliferation and repression of the expression of cyclin genes, whereas Bmi1 overexpression in postmitotic granule cells improved cell survival in response to stress by altering the expression of genes in the mitochondrial cell death pathway and of Myc and Lef-1. Although no medulloblastomas developed in ageing cohorts of transgenic mice, crosses with Trp53−/− mice resulted in a low incidence of medulloblastoma formation. Furthermore, analysis of a large collection of primary human medulloblastomas revealed that tumours with a BMI1high TP53low molecular profile are significantly enriched in Group 4 human medulloblastomas. Our data suggest that different levels and timing of Bmi1 overexpression yield distinct cellular outcomes within the same cellular lineage. Importantly, Bmi1 overexpression at the GCP stage does not induce tumour formation, suggesting that BMI1 overexpression in GCP-derived human medulloblastomas probably occurs during later stages of oncogenesis and might serve to enhance tumour cell survival.

  11. Gradual nerve elongation affects nerve cell bodies and neuro-muscular junctions.

    Science.gov (United States)

    Kazuo Ikeda, K I; Masaki Matsuda, M M; Daisuke Yamauchi, D Y; Katsuro Tomita, K T; Shigenori Tanaka, S T

    2005-07-01

    The purpose of this study is to clarify the reactions of the neuro-muscular junction and nerve cell body to gradual nerve elongation. The sciatic nerves of Japanese white rabbits were lengthened by 30 mm in increments of 0.8 mm/day, 2.0 mm/day and 4.0 mm/day. A scanning electron microscopic examination showed no degenerative change at the neuro-muscular junction, even eight weeks after elongation in the 4-mm group. Hence, neuro-muscular junction is not critical for predicting damage from gradual nerve elongation. There were no axon reaction cells in the 0.8-mm group, a small amount in the 2-mm group, and a large amount in the 4-mm group. The rate of growth associated protein-43 positive nerve cells was significant in the 4-mm group. Hence, the safe speed for nerve cells appeared to be 0.8-mm/day, critical speed to be 2.0-mm/day, and dangerous speed to be 4.0-mm/day in this elongation model.

  12. Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

    Science.gov (United States)

    Boecker, Arne Hendrik; van Neerven, Sabien Geraldine Antonia; Scheffel, Juliane; Tank, Julian; Altinova, Haktan; Seidensticker, Katrin; Deumens, Ronald; Tolba, Rene; Weis, Joachim; Brook, Gary Anthony; Pallua, Norbert; Bozkurt, Ahmet

    2016-02-01

    Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Fear conditioning-related changes in cerebellar Purkinje cell activities in goldfish

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    Yoshida Masayuki

    2012-10-01

    Full Text Available Abstract Background Fear conditioning-induced changes in cerebellar Purkinje cell responses to a conditioned stimulus have been reported in rabbits. It has been suggested that synaptic long-term potentiation and the resulting increases in firing rates of Purkinje cells are related to the acquisition of conditioned fear in mammals. However, Purkinje cell activities during acquisition of conditioned fear have not been analysed, and changes in Purkinje cell activities throughout the development of conditioned fear have not yet been investigated. In the present study, we tracked Purkinje cell activities throughout a fear conditioning procedure and aimed to elucidate further how cerebellar circuits function during the acquisition and expression of conditioned fear. Methods Activities of single Purkinje cells in the corpus cerebelli were tracked throughout a classical fear conditioning procedure in goldfish. A delayed conditioning paradigm was used with cardiac deceleration as the conditioned response. Conditioning-related changes of Purkinje cell responses to a conditioned stimulus and unconditioned stimulus were examined. Results The majority of Purkinje cells sampled responded to the conditioned stimulus by either increasing or decreasing their firing rates before training. Although there were various types of conditioning-related changes in Purkinje cells, more than half of the cells showed suppressed activities in response to the conditioned stimulus after acquisition of conditioned fear. Purkinje cells that showed unconditioned stimulus-coupled complex-spike firings also exhibited conditioning-related suppression of simple-spike responses to the conditioned stimulus. A small number of Purkinje cells showed increased excitatory responses in the acquisition sessions. We found that the magnitudes of changes in the firing frequencies of some Purkinje cells in response to the conditioned stimulus correlated with the magnitudes of the conditioned

  14. Reappraisal of Bergmann glial cells as modulators of cerebellar circuit function

    Directory of Open Access Journals (Sweden)

    Chris I De Zeeuw

    2015-07-01

    Full Text Available Just as there is a huge morphological and functional diversity of neuron types specialized for specific aspects of information processing in the brain, astrocytes have equally distinct morphologies and functions that aid optimal functioning of the circuits in which they are embedded. One type of astrocyte, the Bergmann glial cell of the cerebellum, is a prime example of a highly diversified astrocyte type, the architecture of which is adapted to the cerebellar circuit and facilitates an impressive range of functions that optimize information processing in the adult brain. In this review we expand on the function of the Bergmann glial cell in the cerebellum to highlight the importance of astrocytes not only in housekeeping functions, but also in contributing to plasticity and information processing in the cerebellum.

  15. Regularity, variability and bi-stability in the activity of cerebellar purkinje cells.

    Science.gov (United States)

    Rokni, Dan; Tal, Zohar; Byk, Hananel; Yarom, Yosef

    2009-01-01

    Recent studies have demonstrated that the membrane potential of Purkinje cells is bi-stable and that this phenomenon underlies bi-modal simple spike firing. Membrane potential alternates between a depolarized state, that is associated with spontaneous simple spike firing (up state), and a quiescent hyperpolarized state (down state). A controversy has emerged regarding the relevance of bi-stability to the awake animal, yet recordings made from behaving cat Purkinje cells have demonstrated that at least 50% of the cells exhibit bi-modal firing. The robustness of the phenomenon in vitro or in anaesthetized systems on the one hand, and the controversy regarding its expression in behaving animals on the other hand suggest that state transitions are under neuronal control. Indeed, we have recently demonstrated that synaptic inputs can induce transitions between the states and suggested that the role of granule cell input is to control the states of Purkinje cells rather than increase or decrease firing rate gradually. We have also shown that the state of a Purkinje cell does not only affect its firing but also the waveform of climbing fiber-driven complex spikes and the associated calcium influx. These findings call for a reconsideration of the role of Purkinje cells in cerebellar function. In this manuscript we review the recent findings on Purkinje cell bi-stability and add some analyses of its effect on the regularity and variability of Purkinje cell activity.

  16. Regularity, variabilty and bi-stability in the activity of cerebellar Purkinje cells

    Directory of Open Access Journals (Sweden)

    Dan Rokni

    2009-11-01

    Full Text Available Recent studies have demonstrated that the membrane potential of Purkinje cells is bi-stable and that this phenomenon underlies bi-modal simple spike firing. Membrane potential alternates between a depolarized state, that is associated with spontaneous simple spike firing (up state, and a quiescent hyperpolarized state (down state. A controversy has emerged regarding the relevance of bi-stability to the awake animal, yet recordings made from behaving cat Purkinje cells have demonstrated that at least 50% of the cells exhibit bi-modal firing. The robustness of the phenomenon in-vitro or in anaesthetized systems on the one hand, and the controversy regarding its expression in behaving animals on the other hand suggest that state transitions are under neuronal control. Indeed, we have recently demonstrated that synaptic inputs can induce transitions between the states and suggested that the role of granule cell input is to control the states of Purkinje cells rather than increase or decrease firing rate gradually. We have also shown that the state of a Purkinje cell does not only affect its firing but also the waveform of climbing fiber-driven complex spikes and the associated calcium influx. These findings call for a reconsideration of the role of Purkinje cells in cerebellar function. In this manuscript we review the recent findings on Purkinje cell bi-stability and add some analyses of its effect on the regularity and variability of Purkinje cell activity.

  17. Gastric diffuse large B cell lymphoma presenting as para neoplastic cerebellar degeneration: Case report and review of literature

    International Nuclear Information System (INIS)

    Lakshmaiah, K.C.; Viveka, B.K.; Kumar, N.A.; Saini, M.L.; Sinha, S.; Saini, K.S.

    2013-01-01

    Para neoplastic cerebellar degeneration (PCD) is a type of para neoplastic neurological disorder (PND) that is associated with many solid tumors, Hodgkins lymphoma (HL) and very rarely with non-Hodgkin lymphoma (NHL). We report a case of PCD associated with gastric diffuse large B-cell lymphoma (DLBCL) in a patient who presented with acute onset of giddiness and double vision and had complete remission of the gastric lesion and marked improvement of cerebellar syndrome with rituximab-based combination chemotherapy. A brief review of the literature is also presented.

  18. Nerve growth factor reduces apoptotic cell death in rat facial motor neurons after facial nerve injury.

    Science.gov (United States)

    Hui, Lian; Yuan, Jing; Ren, Zhong; Jiang, Xuejun

    2015-01-01

    To assess the effects of nerve growth factor (NGF) on motor neurons after induction of a facial nerve lesion, and to compare the effects of different routes of NGF injection on motor neuron survival. This study was carried out in the Department of Otolaryngology Head & Neck Surgery, China Medical University, Liaoning, China from October 2012 to March 2013. Male Wistar rats (n = 65) were randomly assigned into 4 groups: A) healthy controls; B) facial nerve lesion model + normal saline injection; C) facial nerve lesion model + NGF injection through the stylomastoid foramen; D) facial nerve lesion model + intraperitoneal injection of NGF. Apoptotic cell death was detected using the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. Expression of caspase-3 and p53 up-regulated modulator of apoptosis (PUMA) was determined by immunohistochemistry. Injection of NGF significantly reduced cell apoptosis, and also greatly decreased caspase-3 and PUMA expression in injured motor neurons. Group C exhibited better efficacy for preventing cellular apoptosis and decreasing caspase-3 and PUMA expression compared with group D (pfacial nerve injury in rats. The NGF injected through the stylomastoid foramen demonstrated better protective efficacy than when injected intraperitoneally.

  19. Stimulation of the N-methyl-D-aspartate receptor has a trophic effect on differentiating cerebellar granule cells

    DEFF Research Database (Denmark)

    Balázs, R; Hack, N; Jørgensen, Ole Steen

    1988-01-01

    N-methyl-D-aspartate (NMDA) supplementation of cerebellar cultures enriched in granule neurones (about 90%) prevented the extensive cell loss which occurs when cultivation takes place, in serum containing media, in the presence of 'low' K+ (5-15 mM). Estimation of tetanus toxin receptors and N-CA...

  20. Gamma-radiation produces abnormal Bergmann fibers and ectopic granule cells in mouse cerebellar cortex

    International Nuclear Information System (INIS)

    Inouye, Minoru; Hayasaka, Shizu; Funahashi, Atsushi; Yamamura, Hideki

    1992-01-01

    Morphological changes in Bergmann glial fibers in the developing cerebellar cortex produced by exposure to gamma-rays were investigated in association with ectopic granule cells. Six-day-old mice that had been exposed to 3 Gy of gamma-radiation were killed 6 hours after exposure or at 7 through 30 days of age. Their cerebella were examined histologically and immunohistochemically for glial fibrillary acidic protein in Bergmann fibers. Extensive cell death took place in the external granular layer (EGL) of the cerebellum from 6 through 24 hours after exposure. This led to the thinning of the EGL and a decrease in the number of migrating cells in the molecular layer. The number of Bergmann cells was not decreased, but the fibers in the molecular layer were distorted; whereas, in the control these fibers were straight and perpendicular to the pial surface. The EGL began to recover 2 days after exposure, and abnormally oriented migrating cells were seen. At 17 days of age, some cell clustering was observed in the molecular layer of the irradiated cerebellum. Distortion of the Bergmann fibers was marked in regions where ectopic granule cells appeared at 30 days of age. These findings suggest that the distortion of Bergmann fibers leads to the production of ectopic granule cells after exposure to gamma-radiation. (author)

  1. Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models.

    Science.gov (United States)

    Yokoi, Fumiaki; Dang, Mai T; Yang, Guang; Li, Jindong; Doroodchi, Atbin; Zhou, Tong; Li, Yuqing

    2012-02-01

    Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for ɛ-sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M-D. We developed a mouse model of DYT11 M-D using paternally inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since ɛ-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of ɛ-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that ɛ-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of ɛ-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

    Science.gov (United States)

    2017-07-01

    with autologous mesenchymal stem cells . Exp Neurol. 2007 Apr; 204(2):658-66. 19. Dezawa M., et al., Sciatic nerve regeneration in rats induced by...36 23. Mimura T., et al., Peripheral nerve regeneration by transplantation of bone marrow stromal cell -derived Schwann cells in adult rats. J...AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve

  3. Anoxia increases potassium conductance in hippocampal nerve cells.

    Science.gov (United States)

    Hansen, A J; Hounsgaard, J; Jahnsen, H

    1982-07-01

    The effect of anoxia on nerve cell function was studied by intra- and extracellular microelectrode recordings from the CA1 and CA3 region in guinea pig hippocampal slices. Hyperpolarization and concomitant reduction of the nerve cell input resistance was observed early during anoxia. During this period the spontaneous activity first disappeared, then the evoked activity gradually disappeared. The hyperpolarization was followed by depolarization and an absence of a measurable input resistance. All the induced changes were reversed when the slice was reoxygenated. Reversal of the electro-chemical gradient for Cl- across the nerve cell membrane did not affect the course of events during anoxia. Aminopyridines blocked the anoxic hyperpolarization and attenuated the decrease of membrane resistance, but had no effect on the later depolarization. Blockers of synaptic transmission. Mn++, Mg++ and of Na+-channels (TTX) were without effect on the nerve cell changes during anoxia. It is suggested that the reduction of nerve cell excitability in anoxia is primarily due to increased K+-conductance. Thus, the nerve cells are hyperpolarized and the input resistance reduced, causing higher threshold and reduction of synaptic potentials. The mechanism of the K+-conductance activation is unknown at present.

  4. Electron microscopic study of the myelinated nerve fibres and the perineurial cell basement membrane in the diabetic human peripheral nerves

    International Nuclear Information System (INIS)

    ElBarrany, Wagih G.; Hamdy, Raid M.; AlHayani, Abdulmonem A.; Jalalah, Sawsan M.

    2009-01-01

    To study the quantitative and ultrastructural changes in myelinated nerve fibers and the basement membranes of the perineurial cells in diabetic nerves. The study was performed at the Department of Anatomy, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia from 2003 to 2005. Human sural nerves were obtained from 15 lower limbs and 5 diabetic nerve biopsies. The total mean and density of myelinated nerve fibers per fascicle were calculated, with density of microtubules and mitochondria in the axoplasm. The number of the perineurial cell basement membrane layers was counted, and thickness of the basement membrane was measured. Among the 15 diabetic and 5 normal human sural nerves, the average diameters, number and surface area of myelinated nerve fibers and axonal microtubules density were found to be less in diabetic nerves. Mitochondrial density was higher in diabetic axons. Thickness of the perineurial cell basement membrane had a greater mean, but the number of perineurial cell layers was less than that of the diabetic group. The inner cellular layer of the perineurium of the diabetic nerves contained large vacuoles containing electron-dense degenerated myelin. A few specimens showed degenerated myelinated nerve fibers, while others showed recovering ones. Retracted axoplasms were encountered with albumin extravasation. Diabetes caused an increase in perineurial permeability. The diabetic sural nerve showed marked decrease in the myelinated nerve fibres, increase degenerated mitochondria, and decreased microtubules. (author)

  5. Cerebellar interaction with the acoustic reflex.

    Science.gov (United States)

    Jastreboff, P J

    1981-01-01

    The involvement of the cerebellar vermis in the acoustic reflex was analyzed in 12 cats, decerebrated or in pentobarbital anesthesia. Anatomical data suggested the existence of a connection of lobules VIII with the ventral cochlear nucleus. Single cell recording and evoked potential techniques demonstrated the existence of the acoustic projection to lobulus VIII. Electrical stimulation of this area changed the tension of the middle ear muscle and caused evoked potential responses in the caudal part of the ventral cochlear nucleus. Electrical stimulation of the motor nucleus of the facial nerve evoked a slow wave in the recording taken from the surrounding of the cochlear round window. A hypothesis is proposed which postulates the involvement of the acoustic reflex in space localization of acoustic stimuli and the action of cerebellar vermis in order to assure the stability and plasticity of the acoustic reflex arc.

  6. Infantile onset progressive cerebellar atrophy and anterior horn cell degeneration--a late onset variant of PCH-1?

    Science.gov (United States)

    Lev, Dorit; Michelson-Kerman, Marina; Vinkler, Chana; Blumkin, Lubov; Shalev, Stavit A; Lerman-Sagie, Tally

    2008-03-01

    Despite major recent advances in our understanding of developmental cerebellar disorders, classification and delineation of these disorders remains difficult. The term pontocerebellar hypoplasia is used when there is a structural defect, originating in utero of both pons and cerebellar hemispheres. The term olivopontocerebellar atrophy is used when the disorder starts later in life and the process is a primary degeneration of cerebellar neurons. Pontocerebellar hypoplasia type 1 is associated with spinal anterior horn cell degeneration, congenital contractures, microcephaly, polyhydramnion and respiratory insufficiency leading to early death. However, anterior horn cell degeneration has also been described in cases with later onset pontocerebellar atrophy and recently the spectrum has even been further extended to include the association of anterior horn cell degeneration and cerebellar atrophy without pontine involvement. We describe two siblings from a consanguineous Moslem Arabic family who presented with progressive degeneration of both the cerebellum and the anterior horn cells. The patients presented after 1 year of age with a slow neurodegenerative course that included both cognitive and motor functions. There is considerable phenotypic variability; the sister shows a much milder course. Both children are still alive at 6 and 9 years. The sister could still crawl and speak two word sentences at the age of 3 years while the brother was bedridden and only uttered guttural sounds at the same age. Our cases further extend the phenotype of the cerebellar syndromes with anterior horn cell involvement to include a childhood onset and protracted course and further prove that this neurodegenerative disorder may start in utero or later in life.

  7. Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury

    Directory of Open Access Journals (Sweden)

    Xinhua Zhou

    2015-01-01

    Full Text Available Edaravone (EDA is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA- induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA-induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities.

  8. Adrenergic nerve fibres and mast cells: correlation in rat thymus.

    Science.gov (United States)

    Artico, Marco; Cavallotti, Carlo; Cavallotti, Daniela

    2002-10-21

    The interactions between adrenergic nerve fibres and mast cells (MCs) were studied in the thymus of adult and old rats by morphological methods and by quantitative analysis of images (QAIs). The whole thymus was drawn in adult (12 months old) rats: normal, sympathectomized or electrostimulated. Thymuses from the above-mentioned animals were weighed, measured and dissected. Thymic slices were stained with eosin orange for detection of microanatomical details and with Bodian's method for identification of the whole nerve fibres. Thymic MCs were stained with Astrablau. Histofluorescence microscopy was used for staining of adrenergic nerve fibres. Finally, all morphological results were submitted to the QAIs and statistical analysis of data. Our results suggest that after surgical sympathectomy, the greater part of adrenergic nerve fibres disappear while related MCs appear to show less evident fluorescence and few granules. On the contrary, electrostimulation of the cervical superior ganglion induced an increase in the fluorescence of adrenergic nerve fibres and of related MCs.

  9. Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor.

    Science.gov (United States)

    Zanin, Juan Pablo; Abercrombie, Elizabeth; Friedman, Wilma J

    2016-07-19

    Cerebellar granule cell progenitors (GCP) proliferate extensively in the external granule layer (EGL) of the developing cerebellum prior to differentiating and migrating. Mechanisms that regulate the appropriate timing of cell cycle withdrawal of these neuronal progenitors during brain development are not well defined. The p75 neurotrophin receptor (p75(NTR)) is highly expressed in the proliferating GCPs, but is downregulated once the cells leave the cell cycle. This receptor has primarily been characterized as a death receptor for its ability to induce neuronal apoptosis following injury. Here we demonstrate a novel function for p75(NTR) in regulating proper cell cycle exit of neuronal progenitors in the developing rat and mouse EGL, which is stimulated by proNT3. In the absence of p75(NTR), GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits.

  10. Mast Cells and Nerve Signal Conduction in Acupuncture

    Directory of Open Access Journals (Sweden)

    Na Yin

    2018-01-01

    Full Text Available Nerve and mast cells are densely distributed around acupoints in connective tissue. To explore the internal relations between them in acupuncture effect, we examined dorsal root potential (DRP response to acupuncture at Zusanli (ST36 under sodium cromoglicate (DSCG, a mast cell stabilizer intervention in anesthetized Sprague-Dawley (SD rats. We used single unit nerve recording techniques to collect nerve signals from DRP afferent nerves for a 45-minute period that includes 4 stages, that is, base, drug absorption, acupuncture, and recovery stages. We analyzed the recorded signals from time-domain and frequency-domain perspectives. The results showed that once acupuncture needle was inserted, twisting needle excited more nerves discharges than those at base discharges in ACU (from 35.1 ± 7.2 to 47 ± 9.2 Hz, P=0.004, and there existed the same trend in Saline + ACU group (from 23.8 ± 2.6 to 29.8 ± 4.2 Hz, P=0.059. There was no change of nerve discharges under twisting needle with injection of DSCG (from 34.8 ± 5.3 to 34.7 ± 4.4 Hz, P=0.480. We conclude that acupuncture manipulation promotes neural signal production and DSCG could partly inhibit nerve discharges.

  11. Relevance of mast cell-nerve interactions in intestinal nociception

    NARCIS (Netherlands)

    van Diest, Sophie A.; Stanisor, Oana I.; Boeckxstaens, Guy E.; de Jonge, Wouter J.; van den Wijngaard, René M.

    2012-01-01

    Cross-talk between the immune- and nervous-system is considered an important biological process in health and disease. Because mast cells are often strategically placed between nerves and surrounding (immune)cells they may function as important intermediate cells. This review summarizes the current

  12. Paraneoplastic cerebellar degeneration and lambert-eaton myasthenia in a patient with merkel cell carcinoma and voltage-gated calcium channel antibodies.

    Science.gov (United States)

    Pavolucci, Lucia; Giannini, Giulia; Giannoccaro, Maria Pia; Foschini, Maria Pia; Lang, Bethan; Avoni, Patrizia; Tinuper, Paolo; Vincent, Angela; Liguori, Rocco

    2017-11-01

    Merkel cell carcinoma is a rare cutaneous, aggressive tumor. Although it shares many neuroendocrine features with small cell lung carcinoma, it has only occasionally been reported with paraneoplastic neurological syndromes. A healthy 67-year-old man developed acute ataxia, vertigo, and nausea. Subsequently he also developed dysarthria, diplopia, xerostomia, fatigability and progressive anorexia. He underwent a full diagnostic workup and was found to have a high titer of voltage-gated calcium channel antibodies in serum and cerebrospinal fluid, neurophysiological findings compatible with Lambert-Eaton myasthenia and neurological signs compatible with cerebellar degeneration. A positron emission tomography study revealed a hypermetabolic lesion in the axilla, subsequently biopsied and consistent with Merkel cell carcinoma. In most previous reports, neurological symptoms preceded the Merkel cell carcinoma diagnosis, and the primary localization was in lymph nodes. This tumor should be considered in patients with paraneoplastic syndrome, and particularly Lambert-Eaton myasthenia after exclusion of small cell lung carcinoma. Muscle Nerve 56: 998-1000, 2017. © 2016 Wiley Periodicals, Inc.

  13. Axotomy induces MHC class I antigen expression on rat nerve cells

    DEFF Research Database (Denmark)

    Maehlen, J; Schröder, H D; Klareskog, L

    1988-01-01

    Immunomorphological staining demonstrates that class I major histocompatibility complex (MHC)-coded antigen expression can be selectively induced on otherwise class I-negative rat nerve cells by peripheral axotomy. Induction of class I as well as class II antigen expression was simultaneously seen...... on non-neural cells in the immediate vicinity of the injured nerve cells. As nerve regeneration after axotomy includes growth of new nerve cell processes and formation of new nerve cell contacts, the present findings raise the question of a role for MHC-coded molecules in cell-cell interactions during...... nerve cell growth....

  14. Neural stem cells promote nerve regeneration through IL12-induced Schwann cell differentiation.

    Science.gov (United States)

    Lee, Don-Ching; Chen, Jong-Hang; Hsu, Tai-Yu; Chang, Li-Hsun; Chang, Hsu; Chi, Ya-Hui; Chiu, Ing-Ming

    2017-03-01

    Regeneration of injured peripheral nerves is a slow, complicated process that could be improved by implantation of neural stem cells (NSCs) or nerve conduit. Implantation of NSCs along with conduits promotes the regeneration of damaged nerve, likely because (i) conduit supports and guides axonal growth from one nerve stump to the other, while preventing fibrous tissue ingrowth and retaining neurotrophic factors; and (ii) implanted NSCs differentiate into Schwann cells and maintain a growth factor enriched microenvironment, which promotes nerve regeneration. In this study, we identified IL12p80 (homodimer of IL12p40) in the cell extracts of implanted nerve conduit combined with NSCs by using protein antibody array and Western blotting. Levels of IL12p80 in these conduits are 1.6-fold higher than those in conduits without NSCs. In the sciatic nerve injury mouse model, implantation of NSCs combined with nerve conduit and IL12p80 improves motor recovery and increases the diameter up to 4.5-fold, at the medial site of the regenerated nerve. In vitro study further revealed that IL12p80 stimulates the Schwann cell differentiation of mouse NSCs through the phosphorylation of signal transducer and activator of transcription 3 (Stat3). These results suggest that IL12p80 can trigger Schwann cell differentiation of mouse NSCs through Stat3 phosphorylation and enhance the functional recovery and the diameter of regenerated nerves in a mouse sciatic nerve injury model. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Nerve Growth Factor in Cancer Cell Death and Survival

    Energy Technology Data Exchange (ETDEWEB)

    Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M., E-mail: adrienne.gorman@nuigalway.ie [Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway (Ireland)

    2011-02-01

    One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75{sup NTR}, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75{sup NTR}. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75{sup NTR}. This latter signaling through p75{sup NTR} promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75{sup NTR} mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer.

  16. Nerve Growth Factor in Cancer Cell Death and Survival

    International Nuclear Information System (INIS)

    Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M.

    2011-01-01

    One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75 NTR , a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75 NTR . For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75 NTR . This latter signaling through p75 NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75 NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer

  17. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves

    NARCIS (Netherlands)

    Gomez-Sanchez, Jose A.; Carty, Lucy; Iruarrizaga-Lejarreta, Marta; Palomo-Irigoyen, Marta; Varela-Rey, Marta; Griffith, Megan; Hantke, Janina; Macias-Camara, Nuria; Azkargorta, Mikel; Aurrekoetxea, Igor; de Juan, Virginia Gutiérrez; Jefferies, Harold B. J.; Aspichueta, Patricia; Elortza, Félix; Aransay, Ana M.; Martínez-Chantar, María L.; Baas, Frank; Mato, José M.; Mirsky, Rhona; Woodhoo, Ashwin; Jessen, Kristján R.

    2015-01-01

    Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell-mediated myelin digestion possible have not been established. We report that

  18. Cell proliferation and apoptosis in optic nerve and brain integration centers of adult trout Oncorhynchus mykiss after optic nerve injury

    Science.gov (United States)

    Pushchina, Evgeniya V.; Shukla, Sachin; Varaksin, Anatoly A.; Obukhov, Dmitry K.

    2016-01-01

    Fishes have remarkable ability to effectively rebuild the structure of nerve cells and nerve fibers after central nervous system injury. However, the underlying mechanism is poorly understood. In order to address this issue, we investigated the proliferation and apoptosis of cells in contralateral and ipsilateral optic nerves, after stab wound injury to the eye of an adult trout Oncorhynchus mykiss. Heterogenous population of proliferating cells was investigated at 1 week after injury. TUNEL labeling gave a qualitative and quantitative assessment of apoptosis in the cells of optic nerve of trout 2 days after injury. After optic nerve injury, apoptotic response was investigated, and mass patterns of cell migration were found. The maximal concentration of apoptotic bodies was detected in the areas of mass clumps of cells. It is probably indicative of massive cell death in the area of high phagocytic activity of macrophages/microglia. At 1 week after optic nerve injury, we observed nerve cell proliferation in the trout brain integration centers: the cerebellum and the optic tectum. In the optic tectum, proliferating cell nuclear antigen (PCNA)-immunopositive radial glia-like cells were identified. Proliferative activity of nerve cells was detected in the dorsal proliferative (matrix) area of the cerebellum and in parenchymal cells of the molecular and granular layers whereas local clusters of undifferentiated cells which formed neurogenic niches were observed in both the optic tectum and cerebellum after optic nerve injury. In vitro analysis of brain cells of trout showed that suspension cells compared with monolayer cells retain higher proliferative activity, as evidenced by PCNA immunolabeling. Phase contrast observation showed mitosis in individual cells and the formation of neurospheres which gradually increased during 1–4 days of culture. The present findings suggest that trout can be used as a novel model for studying neuronal regeneration. PMID:27212918

  19. Neurotoxicity of amphetamine derivatives is mediated by caspase pathway activation in rat cerebellar granule cells

    International Nuclear Information System (INIS)

    Jimenez, Andres; Jorda, Elvira G.; Verdaguer, Ester; Pubill, David; Sureda, Francesc X.; Canudas, Anna M.; Escubedo, Elena; Camarasa, Jordi; Camins, Antoni; Pallas, Merce

    2004-01-01

    The neurotoxic action of the abuse drugs methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) on cerebellar granule neurones (CGNs) culture was examined. Treatment for 48 h with METH or MDMA (1-5 mM) induced a higher decrease in viability than 24 h treatment. z.VAD.fmk (100 μM) but not MK-801 nor NBQX recovered control viability values. In both cases, cell death was characterised as apoptotic rather than necrotic by morphology cell observation. Apoptosis measured by flow cytometry indicated an increase in the hypodiploid population after 48 h treatment with METH and MDMA. Apoptosis was reverted by the presence of z.VAD.fmk (100 μM) but not by 10 μM MK-801 or NBQX. Similar results were obtained by analysing nuclear chromatine condensation. These results ruled out excitotoxic participation in amphetamine derivative-induced neurotoxicity in CGNs. Participation of radical oxygen species (ROS) was evaluated using α-tocopherol (1-15 μM) and cytometric studies. The co-treatment with 4 mM METH or MDMA for 48 h partially reverted neurotoxic action and apoptotic features, indicating ROS implication in CGNs death by amphetamine derivatives. Alteration of mitochondrial function induced cytochrome C (Cyt C) release after 48-h treatment with METH and MDMA (4 mM). There was also indication of caspase-3-like activation, measured by immunoanalysis and biochemically. Finally, neurodegenerative action caused by amphetamine derivatives may be prevented by using caspase inhibitors

  20. Cerebellar Degeneration

    Science.gov (United States)

    ... FARA) National Ataxia Foundation (NAF) National Multiple Sclerosis Society See all related organizations Publications Degeneración cerebelosa Order NINDS Publications Definition Cerebellar degeneration is a process in which neurons ( ...

  1. Selective loss of Purkinje cells in a patient with anti-gliadin-antibody-positive autoimmune cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Hasegawa Akira

    2011-02-01

    Full Text Available Abstract The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. IgA anti-gliadin antibody, IgG anti-gliadin antibody, anti-SS-A/Ro antibody, anti-SS-B/La antibody and anti-TPO antibody were positive. A conventional brain MRI did not show obvious cerebellar atrophy. However, MRI voxel based morphometry (VBM and SPECT-eZIS revealed cortical cerebellar atrophy and reduced cerebellar blood flow. IVIg treatment was performed and was moderately effective. After her death at age 85, the patient was autopsied. Neuropathological findings were as follows: selective loss of Purkinje cells; no apparent degenerative change in the efferent pathways, such as the dentate nuclei or vestibular nuclei; no prominent inflammatory reaction. From these findings, we diagnosed this case as autoimmune cerebellar atrophy associated with gluten ataxia. All 3 autopsies previously reported on gluten ataxia have noted infiltration of inflammatory cells in the cerebellum. In this case, we postulated that the infiltration of inflammatory cells was not found because the patient's condition was based on humoral immunity. The clinical conditions of gluten ataxia have not yet been properly elucidated, but are expected to be revealed as the number of autopsied cases increases.

  2. Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps

    KAUST Repository

    Takaku, Yasuharu; Hwang, Jung Shan; Wolf, Alexander; Bö ttger, Angelika; Shimizu, Hiroshi; David, Charles N.; Gojobori, Takashi

    2014-01-01

    Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential

  3. Electroactive biocompatible materials for nerve cell stimulation

    International Nuclear Information System (INIS)

    Yang, Mei; Liang, Youlong; Gui, Qingyuan; Liu, Yong; Chen, Jun

    2015-01-01

    In the past decades, great efforts have been developed for neurobiologists and neurologists to restore nervous system functions. Recently much attention has been paid to electrical stimulation (ES) of the nervous system as a potential way to repair it. Various conductive biocompatible materials with good electrical conductivity, biocompatibility, and long-term ES or electrical stability have been developed as the substrates for ES. In this review, we summarized different types of materials developed in the purpose for ES of nervous system, including conducting polymers, carbon nanomaterials and composites from conducting polymer/carbon nanomaterials. The present review will give our perspective on the future research directions for further investigation on development of ES particularly on the nerve system. (topical review)

  4. LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

    Energy Technology Data Exchange (ETDEWEB)

    Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang, E-mail: fanxiaotang2005@163.com

    2016-09-02

    Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.

  5. LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

    International Nuclear Information System (INIS)

    Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang

    2016-01-01

    Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.

  6. Axon-Schwann cell interaction in the squid nerve fibre.

    Science.gov (United States)

    Villegas, J

    1972-09-01

    The electrical properties of Schwann cells and the effects of neuronal impulses on their membrane potential have been studied in the giant nerve fibre of the squid.1. The behaviour of the Schwann cell membrane to current injection into the cell was ohmic. No impulse-like responses were observed with displacements of 35 mV in the membrane potential. The resistance of the Schwann cell membrane was found to be approximately 10(3) Omega cm(2).2. A long-lasting hyperpolarization is observed in the Schwann cells following the conduction of impulse trains by the axon. Whereas the propagation of a single impulse had little effect, prolonged stimulation of the fibre at 250 impulses/sec was followed by a hyperpolarization of the Schwann cell that gradually declined over a period of several minutes.3. The prolonged effects of nerve impulse trains on the Schwann cell were similar to those produced by depolarizing current pulses applied to the axon by the voltage-clamp technique. Thus, a series of depolarizing pulses in the axon was followed by a long-lasting hyperpolarization of the Schwann cells. In contrast, the application of a series of hyperpolarizing 100 mV pulses at a frequency of 1/sec had no apparent effects.4. Changes in the external potassium concentration did not reproduce the long-lasting effects of nerve excitation.5. The hyperpolarizing effects of impulse trains were abolished by the incubation of the nerve fibre in a sea-water solution containing trypsin.6. These findings are discussed in relation to the possible mechanisms that might be responsible for the long-lasting hyperpolarizations of the Schwann cells.

  7. Inositol Hexakisphosphate Kinase-3 Regulates the Morphology and Synapse Formation of Cerebellar Purkinje Cells via Spectrin/Adducin

    Science.gov (United States)

    Fu, Chenglai; Xu, Jing; Li, Ruo-Jing; Crawford, Joshua A.; Khan, A. Basit; Ma, Ting Martin; Cha, Jiyoung Y.; Snowman, Adele M.; Pletnikov, Mikhail V.

    2015-01-01

    The inositol hexakisphosphate kinases (IP6Ks) are the principal enzymes that generate inositol pyrophosphates. There are three IP6Ks (IP6K1, 2, and 3). Functions of IP6K1 and IP6K2 have been substantially delineated, but little is known of IP6K3's role in normal physiology, especially in the brain. To elucidate functions of IP6K3, we generated mice with targeted deletion of IP6K3. We demonstrate that IP6K3 is highly concentrated in the brain in cerebellar Purkinje cells. IP6K3 physiologically binds to the cytoskeletal proteins adducin and spectrin, whose mutual interactions are perturbed in IP6K3-null mutants. Consequently, IP6K3 knock-out cerebella manifest abnormalities in Purkinje cell structure and synapse number, and the mutant mice display deficits in motor learning and coordination. Thus, IP6K3 is a major determinant of cytoskeletal disposition and function of cerebellar Purkinje cells. SIGNIFICANCE STATEMENT We identified and cloned a family of three inositol hexakisphosphate kinases (IP6Ks) that generate the inositol pyrophosphates, most notably 5-diphosphoinositol pentakisphosphate (IP7). Of these, IP6K3 has been least characterized. In the present study we generated IP6K3 knock-out mice and show that IP6K3 is highly expressed in cerebellar Purkinje cells. IP6K3-deleted mice display defects of motor learning and coordination. IP6K3-null mice manifest aberrations of Purkinje cells with a diminished number of synapses. IP6K3 interacts with the cytoskeletal proteins spectrin and adducin whose altered disposition in IP6K3 knock-out mice may mediate phenotypic features of the mutant mice. These findings afford molecular/cytoskeletal mechanisms by which the inositol polyphosphate system impacts brain function. PMID:26245967

  8. Mast Cells Synthesize, Store, and Release Nerve Growth Factor

    Science.gov (United States)

    Leon, A.; Buriani, A.; dal Toso, R.; Fabris, M.; Romanello, S.; Aloe, L.; Levi-Montalcini, R.

    1994-04-01

    Mast cells and nerve growth factor (NGF) have both been reported to be involved in neuroimmune interactions and tissue inflammation. In many peripheral tissues, mast cells interact with the innervating fibers. Changes in the behaviors of both of these elements occur after tissue injury/inflammation. As such conditions are typically associated with rapid mast cell activation and NGF accumulation in inflammatory exudates, we hypothesized that mast cells may be capable of producing NGF. Here we report that (i) NGF mRNA is expressed in adult rat peritoneal mast cells; (ii) anti-NGF antibodies clearly stain vesicular compartments of purified mast cells and mast cells in histological sections of adult rodent mesenchymal tissues; and (iii) medium conditioned by peritoneal mast cells contains biologically active NGF. Mast cells thus represent a newly recognized source of NGF. The known actions of NGF on peripheral nerve fibers and immune cells suggest that mast cell-derived NGF may control adaptive/reactive responses of the nervous and immune systems toward noxious tissue perturbations. Conversely, alterations in normal mast cell behaviors may provoke maladaptive neuroimmune tissue responses whose consequences could have profound implications in inflammatory disease states, including those of an autoimmune nature.

  9. Sensorimotor-correlated discharge recorded from ensembles of cerebellar Purkinje cells varies across the estrous cycle of the rat.

    Science.gov (United States)

    Smith, S S

    1995-09-01

    1. In the present study, locomotor-correlated activity of cerebellar Purkinje cells, recorded using arrays of microwires chronically implanted in adult female rats, was examined across estrous-cycle-associated fluctuations in endogenous sex steroids. Ongoing studies from this laboratory have shown that systemic and local administration of the sex steroid 17 beta-estradiol (E2) augments excitatory responses of cerebellar Purkinje cells to iontophoretically applied glutamate, recorded in vivo from anesthetized female rats. In addition, this steroid potentiated discharge correlated with limb movement. For the present study, extracellular single-unit activity was recorded from as many as 5-11 Purkinje cells simultaneously during treadmill locomotion paradigms. Motor modulation of activity was recorded across three to five consecutive estrous cycles from behaviorally identified cohorts of neurons to test the hypothesis that fluctuations in endogenous sex steroids alter motor modulation of Purkinje cell discharge. 2. Locomotor-associated discharge correlated with treadmill locomotion was increased by a mean of 47% on proestrus, when E2 levels are elevated, relative to diestrus 1. These changes in discharge rate during treadmill locomotion were of significantly greater magnitude than corresponding cyclic alterations in discharge during stationary periods. 3. Correlations with the circadian cycle were also significant, because peak levels of locomotor-associated discharge on the night of behavioral estrus, following elevations in circulating E2, were on average 67% greater than corresponding discharge recorded during the light (proestrus). 4. Alterations in the step cycle were also observed across the estrous cycle: significant decreases in the duration of the flexion phase (by 265 ms, P estrus compared with diestrus. 5. When recorded on estrus, Purkinje cell discharge correlated with the stance or flexion phase of the step cycle was greater in magnitude and preceded the

  10. Human amniotic epithelial cell transplantation for the repair of injured brachial plexus nerve: evaluation of nerve viscoelastic properties

    Directory of Open Access Journals (Sweden)

    Hua Jin

    2015-01-01

    Full Text Available The transplantation of embryonic stem cells can effectively improve the creeping strength of nerves near an injury site in animals. Amniotic epithelial cells have similar biological properties as embryonic stem cells; therefore, we hypothesized that transplantation of amniotic epithelial cells can repair peripheral nerve injury and recover the creeping strength of the brachial plexus nerve. In the present study, a brachial plexus injury model was established in rabbits using the C 6 root avulsion method. A suspension of human amniotic epithelial cells was repeatedly injected over an area 4.0 mm lateral to the cephal and caudal ends of the C 6 brachial plexus injury site (1 × 10 6 cells/mL, 3 μL/injection, 25 injections immediately after the injury. The results showed that the decrease in stress and increase in strain at 7,200 seconds in the injured rabbit C 6 brachial plexus nerve were mitigated by the cell transplantation, restoring the viscoelastic stress relaxation and creep properties of the brachial plexus nerve. The forepaw functions were also significantly improved at 26 weeks after injury. These data indicate that transplantation of human amniotic epithelial cells can effectively restore the mechanical properties of the brachial plexus nerve after injury in rabbits and that viscoelasticity may be an important index for the evaluation of brachial plexus injury in animals.

  11. Sensorimotor Representations in Cerebellar Granule Cells in Larval Zebrafish Are Dense, Spatially Organized, and Non-temporally Patterned.

    Science.gov (United States)

    Knogler, Laura D; Markov, Daniil A; Dragomir, Elena I; Štih, Vilim; Portugues, Ruben

    2017-05-08

    A fundamental question in neurobiology is how animals integrate external sensory information from their environment with self-generated motor and sensory signals in order to guide motor behavior and adaptation. The cerebellum is a vertebrate hindbrain region where all of these signals converge and that has been implicated in the acquisition, coordination, and calibration of motor activity. Theories of cerebellar function postulate that granule cells encode a variety of sensorimotor signals in the cerebellar input layer. These models suggest that representations should be high-dimensional, sparse, and temporally patterned. However, in vivo physiological recordings addressing these points have been limited and in particular have been unable to measure the spatiotemporal dynamics of population-wide activity. In this study, we use both calcium imaging and electrophysiology in the awake larval zebrafish to investigate how cerebellar granule cells encode three types of sensory stimuli as well as stimulus-evoked motor behaviors. We find that a large fraction of all granule cells are active in response to these stimuli, such that representations are not sparse at the population level. We find instead that most responses belong to only one of a small number of distinct activity profiles, which are temporally homogeneous and anatomically clustered. We furthermore identify granule cells that are active during swimming behaviors and others that are multimodal for sensory and motor variables. When we pharmacologically change the threshold of a stimulus-evoked behavior, we observe correlated changes in these representations. Finally, electrophysiological data show no evidence for temporal patterning in the coding of different stimulus durations. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. gamma-Aminobutyric acid- and benzodiazepine-induced modulation of [35S]-t-butylbicyclophosphorothionate binding to cerebellar granule cells

    International Nuclear Information System (INIS)

    Gallo, V.; Wise, B.C.; Vaccarino, F.; Guidotti, A.

    1985-01-01

    t-Butylbicyclophosphorothionate (TBPS) is a bicyclophosphate derivative with potent picrotoxin-like convulsant activity that binds with high affinity and specificity to a Cl- channel-modulatory site of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. Using intact cerebellar granule cells maintained in primary culture, the authors have studied the modifications induced by GABA and diazepam on the ion channel-modulatory binding site labeled by [ 35 S]TBPS. At 25 degrees C, and in a modified Locke solution, the [ 35 S]TBPS specific binding, determined by displacing the radioligand with an excess (10(-4) M) of picrotoxin, was approximately 70% of the total radioactivity bound to the cells. [ 35 S]TBPS specific binding was saturable with a Kd of approximately 100 nM, a Bmax of approximately 440 fmol/mg of protein, and a Hill coefficient of 1.18. Neither cerebellar astrocytes maintained in culture for 2 weeks nor a neuroblastoma cell line (NB-2A) exhibited any specific [ 35 S]TBPS binding. Muscimol (0.3 to 5 microM) enhanced and bicuculline (0.1 to 5 microM) inhibited [ 35 S]TBPS specific binding to intact cerebellar granule cells. The effect of muscimol and bicuculline on [ 35 S]TBPS binding was noncompetitive. Muscimol (0.1 to 5 microM) reversed bicuculline inhibition in a dose-dependent fashion but failed to reverse picrotoxin-induced inhibition. [ 35 S]TBPS binding was also modulated by benzodiazepine receptor ligands. The binding was increased by diazepam and decreased by 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methylester. Muscimol (0.05 microM) failed to reverse bicuculline inhibition in the absence of diazepam, but it became effective in the presence of 0.1 to 1 microM diazepam

  13. Casein Kinase 1δ Is an APC/CCdh1 Substrate that Regulates Cerebellar Granule Cell Neurogenesis

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    Clara Penas

    2015-04-01

    Full Text Available Although casein kinase 1δ (CK1δ is at the center of multiple signaling pathways, its role in the expansion of CNS progenitor cells is unknown. Using mouse cerebellar granule cell progenitors (GCPs as a model for brain neurogenesis, we demonstrate that the loss of CK1δ or treatment of GCPs with a highly selective small molecule inhibits GCP expansion. In contrast, CK1δ overexpression increases GCP proliferation. Thus, CK1δ appears to regulate GCP neurogenesis. CK1δ is targeted for proteolysis via the anaphase-promoting complex/cyclosome (APC/CCdh1 ubiquitin ligase, and conditional deletion of the APC/CCdh1 activator Cdh1 in cerebellar GCPs results in higher levels of CK1δ. APC/CCdh1 also downregulates CK1δ during cell-cycle exit. Therefore, we conclude that APC/CCdh1 controls CK1δ levels to balance proliferation and cell-cycle exit in the developing CNS. Similar studies in medulloblastoma cells showed that CK1δ holds promise as a therapeutic target.

  14. Alcohol impairs long-term depression at the cerebellar parallel fiber-Purkinje cell synapse

    NARCIS (Netherlands)

    A. Belmeguenai (Amor); P. Botta (Paolo); J.T. Weber (John); M. Carta (Mario); M.M. de Ruiter (Martijn); C.I. de Zeeuw (Chris); C.F. Valenzuela (Fernando); C.R.W. Hansel (Christian)

    2008-01-01

    textabstractAcute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the

  15. Forced expression of platelet-derived growth factor B in the mouse cerebellar primordium changes cell migration during midline fusion and causes cerebellar ectopia

    NARCIS (Netherlands)

    Andrae, Johanna; Afink, Gijs; Zhang, Xiao-Qun; Wurst, Wolfgang; Nistér, Monica

    2004-01-01

    The platelet-derived growth factor (PDGF) and receptors are expressed in the developing central nervous system and in brain tumors. To investigate the role of PDGF during normal cerebellar development, we created transgenic mice where PDGF-B was introduced into the endogenous Engrailed1 locus (En1).

  16. Poly (ADP-ribose polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells

    Directory of Open Access Journals (Sweden)

    Chiu Sheng-Chun

    2012-03-01

    Full Text Available Abstract Background Episodic cessation of airflow during sleep in patients with sleep apnea syndrome results in intermittent hypoxia (IH. Our aim was to investigate the effects of IH on cerebellar granule cells and to identify the mechanism of IH-induced cell death. Methods Cerebellar granule cells were freshly prepared from neonatal Sprague-Dawley rats. IH was created by culturing the cerebellar granule cells in the incubators with oscillating O2 concentration at 20% and 5% every 30 min for 1-4 days. The results of this study are based on image analysis using a confocal microscope and associated software. Cellular oxidative stress increased with increase in IH. In addition, the occurrence of cell death (apoptosis and necrosis increased as the duration of IH increased, but decreased in the presence of an iron chelator (phenanthroline or poly (ADP-ribose polymerase (PARP inhibitors [3-aminobenzamide (3-AB and DPQ]. The fluorescence of caspase-3 remained the same regardless of the duration of IH, and Western blots did not detect activation of caspase-3. However, IH increased the ratio of apoptosis-inducing factor (AIF translocation to the nucleus, while PARP inhibitors (3-AB reduced this ratio. Results According to our findings, IH increased oxidative stress and subsequently leading to cell death. This effect was at least partially mediated by PARP activation, resulting in ATP depletion, calpain activation leading to AIF translocation to the nucleus. Conclusions We suggest that IH induces cell death in rat primary cerebellar granule cells by stimulating oxidative stress PARP-mediated calpain and AIF activation.

  17. Membrane phosphorylation and nerve cell function

    International Nuclear Information System (INIS)

    Baer, P.R.

    1982-01-01

    This thesis deals with the phosphorylation of membrane components. In part I a series of experiments is described using the hippocampal slice as a model system. In part II a different model system - cultured hybrid cells - is used to study protein and lipid phosphorylation, influenced by incubation with neuropeptides. In part III in vivo and in vitro studies are combined to study protein phosphorylation after neuroanatomical lesions. In a section of part II (Page 81-90) labelling experiments of the membrane inositol-phospholipids are described. 32 P-ATP was used to label phospholipids in intact hybrid cells, and short incubations were found to be the most favourable. (C.F.)

  18. Side-To-Side Nerve Bridges Support Donor Axon Regeneration Into Chronically Denervated Nerves and Are Associated With Characteristic Changes in Schwann Cell Phenotype.

    Science.gov (United States)

    Hendry, J Michael; Alvarez-Veronesi, M Cecilia; Snyder-Warwick, Alison; Gordon, Tessa; Borschel, Gregory H

    2015-11-01

    Chronic denervation resulting from long nerve regeneration times and distances contributes greatly to suboptimal outcomes following nerve injuries. Recent studies showed that multiple nerve grafts inserted between an intact donor nerve and a denervated distal recipient nerve stump (termed "side-to-side nerve bridges") enhanced regeneration after delayed nerve repair. To examine the cellular aspects of axon growth across these bridges to explore the "protective" mechanism of donor axons on chronically denervated Schwann cells. In Sprague Dawley rats, 3 side-to-side nerve bridges were placed over a 10-mm distance between an intact donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) distal nerve stump. Green fluorescent protein-expressing TIB axons grew across the bridges and were counted in cross section after 4 weeks. Immunofluorescent axons and Schwann cells were imaged over a 4-month period. Denervated Schwann cells dedifferentiated to a proliferative, nonmyelinating phenotype within the bridges and the recipient denervated CP nerve stump. As donor TIB axons grew across the 3 side-to-side nerve bridges and into the denervated CP nerve, the Schwann cells redifferentiated to the myelinating phenotype. Bridge placement led to an increased mass of hind limb anterior compartment muscles after 4 months of denervation compared with muscles whose CP nerve was not "protected" by bridges. This study describes patterns of donor axon regeneration and myelination in the denervated recipient nerve stump and supports a mechanism where these donor axons sustain a proregenerative state to prevent deterioration in the face of chronic denervation.

  19. Synaptic responses evoked by tactile stimuli in Purkinje cells in mouse cerebellar cortex Crus II in vivo.

    Directory of Open Access Journals (Sweden)

    Chun-Ping Chu

    Full Text Available Sensory stimuli evoke responses in cerebellar Purkinje cells (PCs via the mossy fiber-granule cell pathway. However, the properties of synaptic responses evoked by tactile stimulation in cerebellar PCs are unknown. The present study investigated the synaptic responses of PCs in response to an air-puff stimulation on the ipsilateral whisker pad in urethane-anesthetized mice.Thirty-three PCs were recorded from 48 urethane-anesthetized adult (6-8-week-old HA/ICR mice by somatic or dendritic patch-clamp recording and pharmacological methods. Tactile stimulation to the ipsilateral whisker pad was delivered by an air-puff through a 12-gauge stainless steel tube connected with a pressurized injection system. Under current-clamp conditions (I = 0, the air-puff stimulation evoked strong inhibitory postsynaptic potentials (IPSPs in the somata of PCs. Application of SR95531, a specific GABA(A receptor antagonist, blocked IPSPs and revealed stimulation-evoked simple spike firing. Under voltage-clamp conditions, tactile stimulation evoked a sequence of transient inward currents followed by strong outward currents in the somata and dendrites in PCs. Application of SR95531 blocked outward currents and revealed excitatory postsynaptic currents (EPSCs in somata and a temporal summation of parallel fiber EPSCs in PC dendrites. We also demonstrated that PCs respond to both the onset and offset of the air-puff stimulation.These findings indicated that tactile stimulation induced asynchronous parallel fiber excitatory inputs onto the dendrites of PCs, and failed to evoke strong EPSCs and spike firing in PCs, but induced the rapid activation of strong GABA(A receptor-mediated inhibitory postsynaptic currents in the somata and dendrites of PCs in the cerebellar cortex Crus II in urethane-anesthetized mice.

  20. Alkylation induced cerebellar degeneration dependent on Aag and Parp1 does not occur via previously established cell death mechanisms.

    Directory of Open Access Journals (Sweden)

    Carrie M Margulies

    Full Text Available Alkylating agents are ubiquitous in our internal and external environments, causing DNA damage that contributes to mutations and cell death that can result in aging, tissue degeneration and cancer. Repair of methylated DNA bases occurs primarily through the base excision repair (BER pathway, a multi-enzyme pathway initiated by the alkyladenine DNA glycosylase (Aag, also known as Mpg. Previous work demonstrated that mice treated with the alkylating agent methyl methanesulfonate (MMS undergo cerebellar degeneration in an Aag-dependent manner, whereby increased BER initiation by Aag causes increased tissue damage that is dependent on activation of poly (ADP-ribose polymerase 1 (Parp1. Here, we dissect the molecular mechanism of cerebellar granule neuron (CGN sensitivity to MMS using primary ex vivo neuronal cultures. We first established a high-throughput fluorescent imaging method to assess primary neuron sensitivity to treatment with DNA damaging agents. Next, we verified that the alkylation sensitivity of CGNs is an intrinsic phenotype that accurately recapitulates the in vivo dependency of alkylation-induced CGN cell death on Aag and Parp1 activity. Finally, we show that MMS-induced CGN toxicity is independent of all the cellular events that have previously been associated with Parp-mediated toxicity, including mitochondrial depolarization, AIF translocation, calcium fluxes, and NAD+ consumption. We therefore believe that further investigation is needed to adequately describe all varieties of Parp-mediated cell death.

  1. Alkylation induced cerebellar degeneration dependent on Aag and Parp1 does not occur via previously established cell death mechanisms.

    Science.gov (United States)

    Margulies, Carrie M; Chaim, Isaac Alexander; Mazumder, Aprotim; Criscione, June; Samson, Leona D

    2017-01-01

    Alkylating agents are ubiquitous in our internal and external environments, causing DNA damage that contributes to mutations and cell death that can result in aging, tissue degeneration and cancer. Repair of methylated DNA bases occurs primarily through the base excision repair (BER) pathway, a multi-enzyme pathway initiated by the alkyladenine DNA glycosylase (Aag, also known as Mpg). Previous work demonstrated that mice treated with the alkylating agent methyl methanesulfonate (MMS) undergo cerebellar degeneration in an Aag-dependent manner, whereby increased BER initiation by Aag causes increased tissue damage that is dependent on activation of poly (ADP-ribose) polymerase 1 (Parp1). Here, we dissect the molecular mechanism of cerebellar granule neuron (CGN) sensitivity to MMS using primary ex vivo neuronal cultures. We first established a high-throughput fluorescent imaging method to assess primary neuron sensitivity to treatment with DNA damaging agents. Next, we verified that the alkylation sensitivity of CGNs is an intrinsic phenotype that accurately recapitulates the in vivo dependency of alkylation-induced CGN cell death on Aag and Parp1 activity. Finally, we show that MMS-induced CGN toxicity is independent of all the cellular events that have previously been associated with Parp-mediated toxicity, including mitochondrial depolarization, AIF translocation, calcium fluxes, and NAD+ consumption. We therefore believe that further investigation is needed to adequately describe all varieties of Parp-mediated cell death.

  2. Schwann cell seeded guidance tubes restore erectile function after ablation of cavernous nerves in rats.

    Science.gov (United States)

    May, F; Weidner, N; Matiasek, K; Caspers, C; Mrva, T; Vroemen, M; Henke, J; Lehmer, A; Schwaibold, H; Erhardt, W; Gänsbacher, B; Hartung, R

    2004-07-01

    Dissection of the cavernous nerves eliminates spontaneous erections. We evaluated the ability of Schwann cell seeded nerve guidance tubes to restore erections after bilateral cavernous nerve resection in rats. Sections (5 mm) of the cavernous nerve were excised bilaterally, followed by immediate bilateral microsurgical reconstruction. In 10 animals per group (20 study nerves) reconstruction was performed by genitofemoral nerve interposition, interposition of silicone tubes or interposition of silicone tubes seeded with homologous Schwann cells. As the control 10 animals (20 study nerves) underwent sham operation (positive control) and bilateral nerve ablation (without reconstruction) was performed in a further 10 (negative control). Erectile function was evaluated 3 months postoperatively by relaparotomy, electrical nerve stimulation and intracavernous pressure recording. After 3 months neurostimulation resulted in an intact erectile response in 90% (18 of 20) of Schwann cell grafts, while treatment with autologous nerves (30% or 6 of 20) or tubes only (50% or 10 of 20) was less successful (p Schwann cell grafts compared to results in the other treatment groups (p Schwann cell grafts. Schwann cell seeded guidance tubes restore erectile function after the ablation of cavernous nerves in rats and they are superior to autologous nerve grafts.

  3. Immune cell distribution and immunoglobulin levels change following sciatic nerve injury in a rat model

    Directory of Open Access Journals (Sweden)

    Wei Yuan

    2016-07-01

    Full Text Available Objective(s: To investigate the systemic and local immune status of two surgical rat models of sciatic nerve injury, a crushed sciatic nerve, and a sciatic nerve transection Materials and Methods:Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group, sciatic nerve crush, and sciatic nerve transaction. Sciatic nerve surgery was performed. The percentage of CD4+ cells and the CD4+/CD8+ratio were determined by flow cytometry. Serum IgM and IgG levels were analyzed by ELISA. T-cells (CD3 and macrophages (CD68 in sciatic nerve tissue sections were identified through immunohistochemistry. Results: Compared to sham-operated controls, in rats that underwent nerve injury, the percentage of CD4+ cells and the CD4+/CD8+ ratio in the peripheral blood were significantly  decreased 7 days after surgery, serum IgM levels were increased 14 days after surgery, and serum IgG levels were increased 21 days after surgery. There were a large number of CD3+ cells and a small number of CD68+ cells in sciatic nerve tissue sections 21 days after surgery, indicating T-cell and macrophage activation and infiltration. Local IgG deposition was also detected at the nerve injury site 21 days after surgery. Conclusion: Rat humoral and cellular immune status changed following sciatic nerve injury, particularly with regard to the cellular immune response at the nerve injury site.

  4. Hydroxylated polychlorinated biphenyls increase reactive oxygen species formation and induce cell death in cultured cerebellar granule cells

    International Nuclear Information System (INIS)

    Dreiem, Anne; Rykken, Sidsel; Lehmler, Hans-Joachim; Robertson, Larry W.; Fonnum, Frode

    2009-01-01

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants that bioaccumulate in the body, however, they can be metabolized to more water-soluble products. Although they are more readily excreted than the parent compounds, some of the metabolites are still hydrophobic and may be more available to target tissues, such as the brain. They can also cross the placenta and reach a developing foetus. Much less is known about the toxicity of PCB metabolites than about the parent compounds. In the present study, we have investigated the effects of eight hydroxylated (OH) PCB congeners (2'-OH PCB 3, 4-OH PCB 14, 4-OH PCB 34, 4'-OH PCB 35, 4-OH PCB 36, 4'-OH PCB 36, 4-OH PCB 39, and 4'-OH PCB 68) on reactive oxygen species (ROS) formation and cell viability in rat cerebellar granule cells. We found that, similar to their parent compounds, OH-PCBs are potent ROS inducers with potency 4-OH PCB 14 < 4-OH PCB 36 < 4-OH PCB 34 < 4'-OH PCB 36 < 4'-OH PCB 68 < 4-OH PCB 39 < 4'-OH PCB 35. 4-OH PCB 36 was the most potent cell death inducer, and caused apoptotic or necrotic morphology depending on concentration. Inhibition of ERK1/2 kinase with U0126 reduced both cell death and ROS formation, suggesting that ERK1/2 activation is involved in OH-PCB toxicity. The results indicate that the hydroxylation of PCBs may not constitute a detoxification reaction. Since OH-PCBs like their parent compounds are retained in the body and may be more widely distributed to sensitive tissues, it is important that not only the levels of the parent compounds but also the levels of their metabolites are taken into account during risk assessment of PCBs and related compounds.

  5. Synchronization in primate cerebellar granule cell layer local field potentials: Basic anisotropy and dynamic changes during active expectancy

    Directory of Open Access Journals (Sweden)

    Richard Courtemanche

    2009-07-01

    Full Text Available The cerebellar cortex is remarkable for its organizational regularity, out of which task-related neural networks should emerge. So, in Purkinje cells, both complex and simple spike network patterns are evident in sensorimotor behavior. However, task-related patterns of activity in the granule cell layer (GCL have been less studied. We recorded local field potential (LFP activity simultaneously in pairs of GCL sites in monkeys performing an active expectancy (lever-press task, in passive expectancy, and at rest. LFP sites were selected when they showed strong 10-25 Hz oscillations; pair orientation was in stereotaxic sagittal and coronal (mainly, and diagonal. As shown previously, LFP oscillations at each site were modulated during the lever-press task. Synchronization across LFP pairs showed an evident basic anisotropy at rest: sagittal pairs of LFPs were better synchronized (more than double the cross-correlation coefficients than coronal pairs, and more than diagonal pairs. On the other hand, this basic anisotropy was modifiable: during the active expectancy condition, where sagittal and coronal orientations were tested, synchronization of LFP pairs would increase just preceding movement, most notably for the coronal pairs. This lateral extension of synchronization was not observed in passive expectancy. The basic pattern of synchronization at rest, favoring sagittal synchrony, thus seemed to adapt in a dynamic fashion, potentially extending laterally to include more cerebellar cortex elements. This dynamic anisotropy in LFP synchronization could underlie GCL network organization in the context of sensorimotor tasks.

  6. Acceleration of Regeneration of Large Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS)

    Science.gov (United States)

    2016-09-01

    AWARD NUMBER: W811XWH-13-1-0310 TITLE: Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts...plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Zhongyu Li, MD, PhD RECIPIENT: Wake Forest University Health Sciences...REPORT DATE September 2016 2. REPORT TYPE Annual 3. DATES COVERED 1Sep2015 - 31Aug2016 4. TITLE AND SUBTITLE Acceleration of Regeneration of Large

  7. Transplantation of bone-marrow-derived cells into a nerve guide resulted in transdifferentiation into Schwann cells and effective regeneration of transected mouse sciatic nerve.

    Science.gov (United States)

    Pereira Lopes, Fátima Rosalina; Frattini, Flávia; Marques, Suelen Adriani; Almeida, Fernanda Martins de; de Moura Campos, Lenira Camargo; Langone, Francesco; Lora, Silvano; Borojevic, Radovan; Martinez, Ana Maria Blanco

    2010-10-01

    Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Nevertheless, the functional outcome after peripheral-nerve regeneration is often poor, especially if the nerve injuries occur far from their targets. Aiming to optimize axon regeneration, we grafted bone-marrow-derived cells (BMDCs) into a collagen-tube nerve guide after transection of the mouse sciatic nerve. The control group received only the culture medium. Motor function was tested at 2, 4, and 6 weeks after surgery, using the sciatic functional index (SFI), and showed that functional recovery was significantly improved in animals that received the cell grafts. After 6 weeks, the mice were anesthetized, perfused transcardially, and the sciatic nerves were dissected and processed for transmission electron microscopy and light microscopy. The proximal and distal segments of the nerves were compared, to address the question of improvement in growth rate; the results revealed a maintenance and increase of nerve regeneration for both myelinated and non-myelinated fibers in distal segments of the experimental group. Also, quantitative analysis of the distal region of the regenerating nerves showed that the numbers of myelinated fibers, Schwann cells (SCs) and g-ratio were significantly increased in the experimental group compared to the control group. The transdifferentiation of BMDCs into Schwann cells was confirmed by double labeling with S100/and Hoechst staining. Our data suggest that BMDCs transplanted into a nerve guide can differentiate into SCs, and improve the growth rate of nerve fibers and motor function in a transected sciatic-nerve model.

  8. GDNF-transduced Schwann cell grafts enhance regeneration of erectile nerves.

    Science.gov (United States)

    May, Florian; Matiasek, Kaspar; Vroemen, Maurice; Caspers, Christiane; Mrva, Thomas; Arndt, Christian; Schlenker, Boris; Gais, Peter; Brill, Thomas; Buchner, Alexander; Blesch, Armin; Hartung, Rudolf; Stief, Christian; Gansbacher, Bernd; Weidner, Norbert

    2008-11-01

    Schwann cell-seeded guidance tubes have been shown to promote cavernous nerve regeneration, and the local delivery of neurotrophic factors may additionally enhance nerve regenerative capacity. The present study evaluates whether the transplantation of GDNF-overexpressing Schwann cells may enhance regeneration of bilaterally transected erectile nerves in rats. Silicon tubes seeded with either GDNF-overexpressing or GFP-expressing Schwann cells were implanted into the gaps between transected cavernous nerve endings. Six (10 study nerves) or 12 wk (20 study nerves) postoperatively, erectile function was evaluated by relaparotomy, electrical nerve stimulation, and intracavernous pressure recording, followed by ultrastructural evaluation of reconstructed nerves employing bright-field and electron microscopy. Additional animals were either sham-operated (positive control; 20 study nerves) or received bilateral nerve transection without nerve reconstruction (negative control; 20 study nerves). The combination of GDNF delivery and Schwann cell application promoted an intact erectile response in 90% (9 of 10) of grafted nerves after 6 wk and in 95% (19 of 20) after 12 wk, versus 50% (5 of 10) and 80% (16 of 20) of GFP-expressing Schwann cell grafts (p=0.02). The functional recovery was paralleled by enhanced axonal regeneration in GDNF-overexpressing Schwann cell grafts, as indicated by larger cross-sectional areas and a significantly higher percentage of neural tissue compared with GFP-transduced controls. These findings demonstrate that the time required to elicit functional recovery of erectile nerves can be reduced by local delivery of GDNF. In terms of clinical application, this enhanced nerve repair might be critical for timely reinnervation of the corpus cavernosum as a prerequisite for functional recovery in men.

  9. Demonstration of immunochemical identity between the nerve growth factor-inducible large external (NILE) glycoprotein and the cell adhesion molecule L1

    DEFF Research Database (Denmark)

    Bock, E; Richter-Landsberg, C; Faissner, A

    1985-01-01

    The nerve growth factor-inducible large external (NILE) glycoprotein and the neural cell adhesion molecule L1 were shown to be immunochemically identical. Immunoprecipitation with L1 and NILE antibodies of [3H]fucose-labeled material from culture supernatants and detergent extracts of NGF......-treated rat PC12 pheochromocytoma cells yielded comigrating bands by SDS-PAGE. NILE antibodies reacted with immunopurified L1 antigen, but not with N-CAM and other L2 epitope-bearing glycoproteins from adult mouse brain. Finally, by sequential immunoprecipitation from detergent extracts of [35S......]methionine-labeled early post-natal cerebellar cell cultures or [3H]fucose-labeled NGF-treated PC12 cells, all immunoreactivity for NILE antibody could be removed by pre-clearing with L1 antibody and vice versa....

  10. Antioxidant supplementation upregulates calbindin expression in cerebellar Purkinje cells of rat pups subjected to post natal exposure to sodium arsenite.

    Science.gov (United States)

    Dhar, Pushpa; Kaushal, Parul; Kumar, Pavan

    2018-07-01

    Optimal cytoplasmic calcium (Ca 2+ ) levels have been associated with adequate cell functioning and neuronal survival. Altered intracellular Ca 2+ levels following impaired Ca 2+ homeostasis could induce neuronal degeneration or even cell death. There are reports of arsenite induced oxidative stress and the associated disturbances in intracellular calcium homeostasis. The present study focused on determining the strategies that would modulate tissue redox status and calcium binding protein (CaBP) (Calbindin D28k-CB) expression affected adversely by sodium arsenite (NaAsO 2 ) exposure (postnatal) of rat pups. NaAsO 2 alone or along with antioxidants (AOXs) (alpha lipoic acid or curcumin) was administered by intraperitoneal (i.p.) route from postnatal day (PND) 1-21 (covering rapid brain growth period - RBGP) to experimental groups and animals receiving sterile water by the same route served as the controls. At the end of the experimental period, the animals were subjected to euthanasia and the cerebellar tissue obtained therefrom was processed for immunohistochemical localization and western blot analysis of CB protein. CB was diffusely expressed in cell body as well as dendritic processes of Purkinje cells (PCs) along the PC Layer (PCL) in all cerebellar folia of the control and the experimental animals. The multilayered pattern of CB +ve cells along with their downregulated expression and low packing density was significantly evident in the arsenic (iAs) alone exposed group as against the controls and AOX supplemented groups. The observations are suggestive of AOX induced restoration of CaBP expression in rat cerebellum following early postnatal exposure to NaAsO 2 . Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Subacute Cerebellar Degeneration due to a Paraneoplastic Phenomenon Associated with Metastatic Merkel Cell Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Angelos Sharobeam

    2017-08-01

    Full Text Available Purpose: The aim of this article is to illustrate the diagnostic challenges and management of paraneoplastic neurological syndromes in Merkel cell carcinoma. Materials and Methods: We describe a previously functionally independent 85-year-old woman who presented with subacute onset of dizziness and gait ataxia in the setting of metastatic Merkel cell carcinoma. Results: Diagnosis was made on biopsy after positron emission tomography imaging revealed increased metabolic activity in 2 left inguinofemoral lymph nodes. Cerebrospinal fluid analysis was positive for anti-Hu on subsequent admission. Her functional status improved with methylprednisolone treatment and radiotherapy. Conclusion: The case highlights the challenge of the evaluation of patients who present with progressive cerebellar signs and the need to consider a paraneoplastic syndrome, especially in the setting of previous malignancy.

  12. In vitro evaluation of cell-seeded chitosan films for peripheral nerve tissue engineering

    OpenAIRE

    Wrobel, Sandra; Serra, Sofia Cristina; Samy, S. M.; Sousa, Nuno; Heimann, Claudia; Barwig, Christina; Grothe, Claudia; Salgado, A. J.; Talini, Kirsten Haastert

    2014-01-01

    Natural biomaterials have attracted an increasing interest in the field of tissue-engineered nerve grafts, representing a possible alternative to autologous nerve transplantation. With the prospect of developing a novel entubulation strategy for transected nerves with cell-seeded chitosan films, we examined the biocompatibility of such films in vitro. Different types of rat Schwann cells (SCs)-immortalized, neonatal, and adult-as well as rat bone-marrow-derived mesenchymal stromal cells (BMSC...

  13. Selective stimulation of excitatory amino acid receptor subtypes and the survival of cerebellar granule cells in culture: effect of kainic acid

    DEFF Research Database (Denmark)

    Balázs, R; Hack, N; Jørgensen, Ole Steen

    1990-01-01

    Our previous studies showed that the survival of cerebellar granule cells in culture is promoted by treatment with N-methyl-D-aspartate. Here we report on the influence of another glutamate analogue, kainic acid, which, in contrast to N-methyl-D-aspartate, is believed to stimulate transmitter rec...

  14. Hydroxyurea Treatment and Development of the Rat Cerebellum: Effects on the Neurogenetic Profiles and Settled Patterns of Purkinje Cells and Deep Cerebellar Nuclei Neurons.

    Science.gov (United States)

    Martí, Joaquín; Santa-Cruz, M C; Serra, Roger; Hervás, José P

    2016-11-01

    The current paper analyzes the development of the male and female rat cerebellum exposed to hydroxyurea (HU) (300 or 600 mg/kg) as embryo and collected at postnatal day 90. Our study reveals that the administration of this drug compromises neither the cytoarchitecture of the cerebellar cortex nor deep nuclei (DCN). However, in comparison with the saline group, we observed that several cerebellar parameters were lower in the HU injected groups. These parameters included area of the cerebellum, cerebellar cortex length, molecular layer area, Purkinje cell number, granule cell counts, internal granular layer, white matter and cerebellar nuclei areas, and number of deep cerebellar nuclei neurons. These features were larger in the rats injected with saline, smaller in those exposed to 300 mg/kg of HU and smallest in the group receiving 600 mg/kg of this agent. No sex differences in the effect of the HU were observed. In addition, we infer the neurogenetic timetables and the neurogenetic gradients of PCs and DCN neurons in rats exposed to either saline or HU as embryos. For this purpose, 5-bromo-2'-deoxyuridine was injected into pregnant rats previously administered with saline or HU. This thymidine analog was administered following a progressively delayed cumulative labeling method. The data presented here show that systematic differences exist in the pattern of neurogenesis and in the spatial location of cerebellar neurons between rats injected with saline or HU. No sex differences in the effect of the HU were observed. These findings have implications for the administration of this compound to women in gestation as the effects of HU on the development of the cerebellum might persist throughout their offsprings' life.

  15. Adult Stem Cell-Based Enhancement of Nerve Conduit for Peripheral Nerve Repair

    Science.gov (United States)

    2017-10-01

    acceptable donor nerves are often not available for this purpose, particularly in patients suffering multiple extremity injuries or faced with traumatic...amputations. Alternatives include the use of a blood vessel graft or a synthetic nerve guide, although these devices are only effective over distances less...of combat-related orthopaedic trauma. Given the severity of the orthopaedic injuries sustained during battlefield trauma, an acceptable donor nerve is

  16. Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves.

    Science.gov (United States)

    Amoh, Yasuyuki; Li, Lingna; Campillo, Raul; Kawahara, Katsumasa; Katsuoka, Kensei; Penman, Sheldon; Hoffman, Robert M

    2005-12-06

    The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, also is expressed in follicle stem cells and their immediate, differentiated progeny. The fluorescent protein GFP, whose expression is driven by the nestin regulatory element in transgenic mice, served to mark the follicle cell fate. The pluripotent nestin-driven GFP stem cells are positive for the stem cell marker CD34 but negative for keratinocyte marker keratin 15, suggesting their relatively undifferentiated state. These cells can differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In vivo studies show the nestin-driven GFP hair follicle stem cells can differentiate into blood vessels and neural tissue after transplantation to the subcutis of nude mice. Equivalent hair follicle stem cells derived from transgenic mice with beta-actin-driven GFP implanted into the gap region of a severed sciatic nerve greatly enhance the rate of nerve regeneration and the restoration of nerve function. The follicle cells transdifferentiate largely into Schwann cells, which are known to support neuron regrowth. Function of the rejoined sciatic nerve was measured by contraction of the gastrocnemius muscle upon electrical stimulation. After severing the tibial nerve and subsequent transplantation of hair follicle stem cells, walking print length and intermediate toe spread significantly recovered, indicating that the transplanted mice recovered the ability to walk normally. These results suggest that hair follicle stem cells provide an important, accessible, autologous source of adult stem cells for regenerative medicine.

  17. Photodynamic damage of glial cells in crayfish ventral nerve cord

    Science.gov (United States)

    Kolosov, M. S.; Duz, E.; Uzdensky, A. B.

    2011-03-01

    Photodynamic therapy (PDT) is a promising method for treatment of brain tumors, the most of which are of glial origin. In the present work we studied PDT-mediated injury of glial cells in nerve tissue, specifically, in abdominal connectives in the crayfish ventral nerve cord. The preparation was photosensitized with alumophthalocyanine Photosens and irradiated 30 min with the diode laser (670 nm, 0.1 or 0.15 W/cm2). After following incubation in the darkness during 1- 10 hours it was fluorochromed with Hoechst 33342 and propidium iodide to reveal nuclei of living, necrotic and apoptotic cells. The chain-like location of the glial nuclei allowed visualization of those enveloping giant axons and blood vessels. The level of glial necrosis in control preparations was about 2-5 %. Apoptosis was not observed in control preparations. PDT significantly increased necrosis of glial cells to 52 or 67 % just after irradiation with 0.1 or 0.15 W/cm2, respectively. Apoptosis of glial cells was observed only at 10 hours after light exposure. Upper layers of the glial envelope of the connectives were injured stronger comparing to deep ones: the level of glial necrosis decreased from 100 to 30 % upon moving from the connective surface to the plane of the giant axon inside the connective. Survival of glial cells was also high in the vicinity of blood vessels. One can suggest that giant axons and blood vessels protect neighboring glial cells from photodynamic damage. The mechanism of such protective action remains to be elucidated.

  18. Intravenous Transplantation of Mesenchymal Stromal Cells to Enhance Peripheral Nerve Regeneration

    Directory of Open Access Journals (Sweden)

    Stella M. Matthes

    2013-01-01

    Full Text Available Peripheral nerve injury is a common and devastating complication after trauma and can cause irreversible impairment or even complete functional loss of the affected limb. While peripheral nerve repair results in some axonal regeneration and functional recovery, the clinical outcome is not optimal and research continues to optimize functional recovery after nerve repair. Cell transplantation approaches are being used experimentally to enhance regeneration. Intravenous infusion of mesenchymal stromal cells (MSCs into spinal cord injury and stroke was shown to improve functional outcome. However, the repair potential of intravenously transplanted MSCs in peripheral nerve injury has not been addressed yet. Here we describe the impact of intravenously infused MSCs on functional outcome in a peripheral nerve injury model. Rat sciatic nerves were transected followed, by intravenous MSCs transplantation. Footprint analysis was carried out and 21 days after transplantation, the nerves were removed for histology. Labelled MSCs were found in the sciatic nerve lesion site after intravenous injection and regeneration was improved. Intravenously infused MSCs after acute peripheral nerve target the lesion site and survive within the nerve and the MSC treated group showed greater functional improvement. The results of study suggest that nerve repair with cell transplantation could lead to greater functional outcome.

  19. Mycolactone cytotoxicity in Schwann cells could explain nerve damage in Buruli ulcer.

    Directory of Open Access Journals (Sweden)

    Junichiro En

    2017-08-01

    Full Text Available Buruli ulcer is a chronic painless skin disease caused by Mycobacterium ulcerans. The local nerve damage induced by M. ulcerans invasion is similar to the nerve damage evoked by the injection of mycolactone in a Buruli ulcer mouse model. In order to elucidate the mechanism of this nerve damage, we tested and compared the cytotoxic effect of synthetic mycolactone A/B on cultured Schwann cells, fibroblasts and macrophages. Mycolactone induced much higher cell death and apoptosis in Schwann cell line SW10 than in fibroblast line L929. These results suggest that mycolactone is a key substance in the production of nerve damage of Buruli ulcer.

  20. Characterization and Schwann Cell Seeding of up to 15.0 cm Long Spider Silk Nerve Conduits for Reconstruction of Peripheral Nerve Defects

    Directory of Open Access Journals (Sweden)

    Tim Kornfeld

    2016-11-01

    Full Text Available Nerve reconstruction of extended nerve defect injuries still remains challenging with respect to therapeutic options. The gold standard in nerve surgery is the autologous nerve graft. Due to the limitation of adequate donor nerves, surgical alternatives are needed. Nerve grafts made out of either natural or artificial materials represent this alternative. Several biomaterials are being explored and preclinical and clinical applications are ongoing. Unfortunately, nerve conduits with successful enhancement of axonal regeneration for nerve defects measuring over 4.0 cm are sparse and no conduits are available for nerve defects extending to 10.0 cm. In this study, spider silk nerve conduits seeded with Schwann cells were investigated for in vitro regeneration on defects measuring 4.0 cm, 10.0 cm and 15.0 cm in length. Schwann cells (SCs were isolated, cultured and purified. Cell purity was determined by immunofluorescence. Nerve grafts were constructed out of spider silk from Nephila edulis and decellularized ovine vessels. Finally, spider silk implants were seeded with purified Schwann cells. Cell attachment was observed within the first hour. After 7 and 21 days of culture, immunofluorescence for viability and determination of Schwann cell proliferation and migration throughout the conduits was performed. Analyses revealed that SCs maintained viable (>95% throughout the conduits independent of construct length. SC proliferation on the spider silk was determined from day 7 to day 21 with a proliferation index of 49.42% arithmetically averaged over all conduits. This indicates that spider silk nerve conduits represent a favorable environment for SC attachment, proliferation and distribution over a distance of least 15.0 cm in vitro. Thus spider silk nerve implants are a highly adequate biomaterial for nerve reconstruction.

  1. A forgotten facial nerve tumour: granular cell tumour of the parotid and its implications for treatment.

    Science.gov (United States)

    Lerut, B; Vosbeck, J; Linder, T E

    2011-04-01

    We present a rare case of a facial nerve granular cell tumour in the right parotid gland, in a 10-year-old boy. A parotid or neurogenic tumour was suspected, based on magnetic resonance imaging. Intra-operatively, strong adhesions to surrounding structures were found, and a midfacial nerve branch had to be sacrificed for complete tumour removal. Recent reports verify that granular cell tumours arise from Schwann cells of peripheral nerve branches. The rarity of this tumour within the parotid gland, its origin from peripheral nerves, its sometimes misleading imaging characteristics, and its rare presentation with facial weakness and pain all have considerable implications on the surgical strategy and pre-operative counselling. Fine needle aspiration cytology may confirm the neurogenic origin of this lesion. When resecting the tumour, the surgeon must anticipate strong adherence to the facial nerve and be prepared to graft, or sacrifice, certain branches of this nerve.

  2. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Lihua [Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Center of Molecular Medicine, School of Medicine, Hubei University of Arts and Sciences, Xiangyang 441053 (China); Gan, Li; Liu, Yongming; Tian, Weiqun; Tong, Zan [Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Wang, Xiong; Huselstein, Celine [Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), UMR 7365 CNRS – Université de Lorraine, Biopôle, 54500 Vandoeuvre-lès-Nancy (France); Chen, Yun, E-mail: yunchen@whu.edu.cn [Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-02-20

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide

  3. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect.

    Science.gov (United States)

    Luo, Lihua; Gan, Li; Liu, Yongming; Tian, Weiqun; Tong, Zan; Wang, Xiong; Huselstein, Celine; Chen, Yun

    2015-02-20

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide

  4. Developmental expression and differentiation-related neuron-specific splicing of metastasis suppressor 1 (Mtss1 in normal and transformed cerebellar cells

    Directory of Open Access Journals (Sweden)

    Baader Stephan L

    2007-10-01

    Full Text Available Abstract Background Mtss1 encodes an actin-binding protein, dysregulated in a variety of tumors, that interacts with sonic hedgehog/Gli signaling in epidermal cells. Given the prime importance of this pathway for cerebellar development and tumorigenesis, we assessed expression of Mtss1 in the developing murine cerebellum and human medulloblastoma specimens. Results During development, Mtss1 is transiently expressed in granule cells, from the time point they cease to proliferate to their synaptic integration. It is also expressed by granule cell precursor-derived medulloblastomas. In the adult CNS, Mtss1 is found exclusively in cerebellar Purkinje cells. Neuronal differentiation is accompanied by a switch in Mtss1 splicing. Whereas immature granule cells express a Mtss1 variant observed also in peripheral tissues and comprising exon 12, this exon is replaced by a CNS-specific exon, 12a, in more mature granule cells and in adult Purkinje cells. Bioinformatic analysis of Mtss1 suggests that differential exon usage may affect interaction with Fyn and Src, two tyrosine kinases previously recognized as critical for cerebellar cell migration and histogenesis. Further, this approach led to the identification of two evolutionary conserved nuclear localization sequences. These overlap with the actin filament binding site of Mtss1, and one also harbors a potential PKA and PKC phosphorylation site. Conclusion Both the pattern of expression and splicing of Mtss1 is developmentally regulated in the murine cerebellum. These findings are discussed with a view on the potential role of Mtss1 for cytoskeletal dynamics in developing and mature cerebellar neurons.

  5. Characterization of muscarinic receptor subtypes in primary cultures of cerebellar granule cells using specific muscarinic receptor antagonists

    International Nuclear Information System (INIS)

    McLeskey, S.W.

    1989-01-01

    In cerebellar granule cell cultures, two muscarinic receptor mediated responses were observed: inhibition of adenylate cyclase (M-AC) and stimulation of phosphoinositide hydrolysis (M-PI). These responses were antagonized by three purported specific muscarinic antagonists: pirenzipine and (-)QNX (specific for M-PI) and methoctramine (specific for M-AC). However, the specificity for the three antagonists in blocking these responses is not comparable to the specificity observed in binding studies on these cells or to that quoted in the literature. Two peaks of molecular sizes were found in these cells corresponding to the two molecular sizes of muscarinic receptive proteins reported in the literature. Muscarinic receptive proteins were alkylated with 3 H-propylbenzilylcholine mustard followed by sodium dodecylsulfate polyacrylamide gel electrophoresis. Pirenzipine and (-)QNX were able to block alkylation of the high molecular size peak, which corresponds to the receptive protein m 3 reported in the literature. Methoctramine was able to block alkylation of a portion of the lower molecular size peak, possibly corresponding to the m 2 and/or m 4 receptive proteins reported in the literature. Studies attempting to show the presence of receptor reserve for either of the two biochemical responses present in these cells by alkylation of the receptive protein with nonradiolabeled propylbenzilylcholine mustard (PBCM) were confounded by specificity of this agent for the lower molecular weight peak of muscarinic receptive protein. Thus the muscarinic receptive proteins coupled to M-AC were alkylated preferentially over the ones coupled to M-PI

  6. Endothelin-1 stimulates the release of preloaded [3H]D-aspartate from cultured cerebellar granule cells

    International Nuclear Information System (INIS)

    Lin, W.W.; Lee, C.Y.; Chuang, D.M.

    1990-01-01

    We have recently reported that endothelin-1 (ET) induces phosphoinositide hydrolysis in primary cultures of rat cerebellar granule cells. Here we found that ET in a dose-dependent manner (1-30 nM) stimulated the release of preloaded [ 3 H]D-aspartate from granule cells. The ET-induced aspartate release was completely blocked in the absence of extracellular Ca 2+ , but was unaffected by 1 mM Co 2+ or 1 microM dihydropyridine derivatives (nisoldipine and nimodipine). At higher concentration (10 microM) of nisoldipine and nimodipine, the release was partially inhibited. Short-term pretreatment of cells with phorbol 12,13-dibutyrate (PDBu) potentiated the ET-induced aspartate release, while long-term pretreatment with PDBu attenuated the release. Long-term exposure of cells to pertussis toxin (PTX), on the other hand, potentiated the ET-induced effects. Our results suggest that ET has a neuromodulatory function in the central nervous system

  7. Endothelin-1 stimulates the release of preloaded ( sup 3 H)D-aspartate from cultured cerebellar granule cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, W.W.; Lee, C.Y.; Chuang, D.M. (NIMH Neuroscience Center, Washington, DC (USA))

    1990-03-16

    We have recently reported that endothelin-1 (ET) induces phosphoinositide hydrolysis in primary cultures of rat cerebellar granule cells. Here we found that ET in a dose-dependent manner (1-30 nM) stimulated the release of preloaded ({sup 3}H)D-aspartate from granule cells. The ET-induced aspartate release was completely blocked in the absence of extracellular Ca{sup 2+}, but was unaffected by 1 mM Co{sup 2+} or 1 microM dihydropyridine derivatives (nisoldipine and nimodipine). At higher concentration (10 microM) of nisoldipine and nimodipine, the release was partially inhibited. Short-term pretreatment of cells with phorbol 12,13-dibutyrate (PDBu) potentiated the ET-induced aspartate release, while long-term pretreatment with PDBu attenuated the release. Long-term exposure of cells to pertussis toxin (PTX), on the other hand, potentiated the ET-induced effects. Our results suggest that ET has a neuromodulatory function in the central nervous system.

  8. Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps

    KAUST Repository

    Takaku, Yasuharu

    2014-01-07

    Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential for this behavior, although nerve cells in Hydra are organized in a diffuse network and do not form ganglia. Here we show that the gap junction protein innexin-2 is expressed in a small group of nerve cells in the lower body column of Hydra and that an anti-innexin-2 antibody binds to gap junctions in the same region. Treatment of live animals with innexin-2 antibody eliminates gap junction staining and reduces spontaneous body column contractions. We conclude that a small subset of nerve cells, connected by gap junctions and capable of synchronous firing, act as a pacemaker to coordinate the contraction of the body column in the absence of ganglia.

  9. Transplantation of olfactory ensheathing cells as adjunct cell therapy for peripheral nerve injury.

    Science.gov (United States)

    Radtke, Christine; Wewetzer, Konstantin; Reimers, Kerstin; Vogt, Peter M

    2011-01-01

    Traumatic events, such as work place trauma or motor vehicle accident violence, result in a significant number of severe peripheral nerve lesions, including nerve crush and nerve disruption defects. Transplantation of myelin-forming cells, such as Schwann cells (SCs) or olfactory ensheathing cells (OECs), may be beneficial to the regenerative process because the applied cells could mediate neurotrophic and neuroprotective effects by secretion of chemokines. Moreover, myelin-forming cells are capable of bridging the repair site by establishing an environment permissive to axonal regeneration. The cell types that are subject to intense investigation include SCs and OECs either derived from the olfactory bulb or the olfactory mucosa, stromal cells from bone marrow (mesenchymal stem cells, MSCs), and adipose tissue-derived cells. OECs reside in the peripheral and central nervous system and have been suggested to display unique regenerative properties. However, so far OECs were mainly used in experimental studies to foster central regeneration and it was not until recently that their regeneration-promoting activity for the peripheral nervous system was recognized. In the present review, we summarize recent experimental evidence regarding the regenerative effects of OECs applied to the peripheral nervous system that may be relevant to design novel autologous cell transplantation therapies. © 2011 Cognizant Comm. Corp.

  10. The role of undifferentiated adipose-derived stem cells in peripheral nerve repair.

    Science.gov (United States)

    Zhang, Rui; Rosen, Joseph M

    2018-05-01

    Peripheral nerve injuries impose significant health and economic consequences, yet no surgical repair can deliver a complete recovery of sensory or motor function. Traditional methods of repair are less than ideal: direct coaptation can only be performed when tension-free repair is possible, and transplantation of nerve autograft can cause donor-site morbidity and neuroma formation. Cell-based therapy delivered via nerve conduits has thus been explored as an alternative method of nerve repair in recent years. Stem cells are promising sources of the regenerative core material in a nerve conduit because stem cells are multipotent in function, abundant in supply, and more accessible than the myelinating Schwann cells. Among different types of stem cells, undifferentiated adipose-derived stem cell (uASC), which can be processed from adipose tissue in less than two hours, is a promising yet underexplored cell type. Studies of uASC have emerged in the past decade and have shown that autologous uASCs are non-immunogenic, easy to access, abundant in supply, and efficacious at promoting nerve regeneration. Two theories have been proposed as the primary regenerative mechanisms of uASC: in situ trans-differentiation towards Schwann cells, and secretion of trophic and anti-inflammatory factors. Future studies need to fully elucidate the mechanisms, side effects, and efficacy of uASC-based nerve regeneration so that uASCs can be utilized in clinical settings.

  11. Origin, lineage and function of cerebellar glia.

    Science.gov (United States)

    Buffo, Annalisa; Rossi, Ferdinando

    2013-10-01

    The glial cells of the cerebellum, and particularly astrocytes and oligodendrocytes, are characterized by a remarkable phenotypic variety, in which highly peculiar morphological features are associated with specific functional features, unique among the glial cells of the entire CNS. Here, we provide a critical report about the present knowledge of the development of cerebellar glia, including lineage relationships between cerebellar neurons, astrocytes and oligodendrocytes, the origins and the genesis of the repertoire of glial types, and the processes underlying their acquisition of mature morphological and functional traits. In parallel, we describe and discuss some fundamental roles played by specific categories of glial cells during cerebellar development. In particular, we propose that Bergmann glia exerts a crucial scaffolding activity that, together with the organizing function of Purkinje cells, is necessary to achieve the normal pattern of foliation and layering of the cerebellar cortex. Moreover, we discuss some of the functional tasks of cerebellar astrocytes and oligodendrocytes that are distinctive of cerebellar glia throughout the CNS. Notably, we report about the regulation of synaptic signalling in the molecular and granular layer mediated by Bergmann glia and parenchymal astrocytes, and the functional interaction between oligodendrocyte precursor cells and neurons. On the whole, this review provides an extensive overview of the available literature and some novel insights about the origin and differentiation of the variety of cerebellar glial cells and their function in the developing and mature cerebellum. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Nanoparticles carrying neurotrophin-3-modified Schwann cells promote repair of sciatic nerve defects.

    Science.gov (United States)

    Zong, Haibin; Zhao, Hongxing; Zhao, Yilei; Jia, Jingling; Yang, Libin; Ma, Chao; Zhang, Yang; Dong, Yuzhen

    2013-05-15

    Schwann cells and neurotrophin-3 play an important role in neural regeneration, but the secretion of neurotrophin-3 from Schwann cells is limited, and exogenous neurotrophin-3 is inactived easily in vivo. In this study, we have transfected neurotrophin-3 into Schwann cells cultured in vitro using nanoparticle liposomes. Results showed that neurotrophin-3 was successfully transfected into Schwann cells, where it was expressed effectively and steadily. A composite of Schwann cells transfected with neurotrophin-3 and poly(lactic-co-glycolic acid) biodegradable conduits was transplanted into rats to repair 10-mm sciatic nerve defects. Transplantation of the composite scaffold could restore the myoelectricity and wave amplitude of the sciatic nerve by electrophysiological examination, promote nerve axonal and myelin regeneration, and delay apoptosis of spinal motor neurons. Experimental findings indicate that neurotrophin-3 transfected Schwann cells combined with bridge grafting can promote neural regeneration and functional recovery after nerve injury.

  13. The beneficial effect of genetically engineered Schwann cells with enhanced motility in peripheral nerve regeneration: review.

    Science.gov (United States)

    Gravvanis, A I; Lavdas, A A; Papalois, A; Tsoutsos, D A; Matsas, R

    2007-01-01

    The importance of Schwann cells in promoting nerve regeneration across a conduit has been extensively reported in the literature, and Schwann cell motility has been acknowledged as a prerequisite for myelination of the peripheral nervous system during regeneration after injury. Review of recent literature and retrospective analysis of our studies with genetically modified Schwann Cells with increased motility in order to identify the underlying mechanism of action and outline the future trends in peripheral nerve repair. Schwann cell transduction with the pREV-retrovirus, for expression of Sialyl-Transferase-X, resulting in conferring Polysialyl-residues (PSA) on NCAM, increases their motility in-vitro and ensures nerve regeneration through silicone tubes after end-to-side neurorraphy in the rat sciatic nerve model, thus significantly promoting fiber maturation and functional outcome. An artificial nerve graft consisting of a type I collagen tube lined with the genetically modified Schwann cells with increased motility, used to bridge a defect in end-to-end fashion in the rat sciatic nerve model, was shown to promote nerve regeneration to a level equal to that of a nerve autograft. The use of genetically engineered Schwann cells with enhanced motility for grafting endoneural tubes promotes axonal regeneration, by virtue of the interaction of the transplanted cells with regenerating axonal growth cones as well as via the recruitment of endogenous Schwann cells. It is envisaged that mixed populations of Schwann cells, expressing PSA and one or more trophic factors, might further enhance the regenerating and remyelinating potential of the lesioned nerves.

  14. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor restores erectile function after cavernous nerve injury.

    Science.gov (United States)

    May, Florian; Buchner, Alexander; Schlenker, Boris; Gratzke, Christian; Arndt, Christian; Stief, Christian; Weidner, Norbert; Matiasek, Kaspar

    2013-03-01

    To evaluate the time-course of functional recovery after cavernous nerve injury using glial cell line-derived neurotrophic factor-transduced Schwann cell-seeded silicon tubes. Sections of the cavernous nerves were excised bilaterally (5 mm), followed by immediate bilateral surgical repair. A total of 20 study nerves per group were reconstructed by interposition of empty silicon tubes and silicon tubes seeded with either glial cell line-derived neurotrophic factor-overexpressing or green fluorescent protein-expressing Schwann cells. Control groups were either sham-operated or received bilateral nerve transection without nerve reconstruction. Erectile function was evaluated by relaparotomy, electrical nerve stimulation and intracavernous pressure recording after 2, 4, 6, 8 and 10 weeks. The animals underwent re-exploration only once, and were killed afterwards. The nerve grafts were investigated for the maturation state of regenerating nerve fibers and the fascular composition. Recovery of erectile function took at least 4 weeks in the current model. Glial cell line-derived neurotrophic factor-transduced Schwann cell grafts restored erectile function better than green fluorescent protein-transduced controls and unseeded conduits. Glial cell line-derived neurotrophic factor-transduced grafts promoted an intact erectile response (4/4) at 4, 6, 8 and 10 weeks that was overall significantly superior to negative controls (P cell line-derived neurotrophic factor-transduced grafts compared with negative controls (P = 0.018) and unseeded tubes (P = 0.034). Return of function was associated with the electron microscopic evidence of preganglionic myelinated nerve fibers and postganglionic unmyelinated axons. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor presents a viable approach for the treatment of erectile dysfunction after cavernous nerve injury. © 2013 The Japanese Urological Association.

  15. Tyrosine hydroxylase positive nerves and mast cells in the porcine gallbladder

    Directory of Open Access Journals (Sweden)

    I. Stefanov

    2017-03-01

    Full Text Available The aim of this study was to detect the localisation of tyrosine hydroxylase (TH positive nerve fibres (THN and distribution of tyrosine hydroxylase positive mast cells (THMC in the wall of porcine gallbladder. THN were observed as single fibres, nerve fibres forming perivascular plexuses and nerve fibres grouped within the nerve fascicles. In the gallbladder`s fundus, body and neck, the TH+ fibres formed mucosal, muscular and serosal nonganglionated nerve plexuses. Toluidine blue (TB staining was used to confirm that the TH positive cells were mast cells. The number of THMC in the propria of gallbladder`s fundus, body and neck was significantly higher than in the muscular and serosal layers in both genders. The number of mast cells in the musculature was higher than in the serosa. The density and location of the THMC were similar to the TB positive (with gamma meta-chromasia mast cells in both males and females, and statistically significant difference was not established. In conclusion, original data concerning the existence and localisation of catecholaminergic nerves and THMC distribution in the porcine gallbladder’s wall are presented. The results could con-tribute to the body of knowledge of functional communication between autonomic nerves and mast cells in the gallbladder.

  16. Conditional induction of Math1 specifies embryonic stem cells to cerebellar granule neuron lineage and promotes differentiation into mature granule neurons.

    Science.gov (United States)

    Srivastava, Rupali; Kumar, Manoj; Peineau, Stéphane; Csaba, Zsolt; Mani, Shyamala; Gressens, Pierre; El Ghouzzi, Vincent

    2013-04-01

    Directing differentiation of embryonic stem cells (ESCs) to specific neuronal subtype is critical for modeling disease pathology in vitro. An attractive means of action would be to combine regulatory differentiation factors and extrinsic inductive signals added to the culture medium. In this study, we have generated mature cerebellar granule neurons by combining a temporally controlled transient expression of Math1, a master gene in granule neuron differentiation, with inductive extrinsic factors involved in cerebellar development. Using a Tetracyclin-On transactivation system, we overexpressed Math1 at various stages of ESCs differentiation and found that the yield of progenitors was considerably increased when Math1 was induced during embryonic body stage. Math1 triggered expression of Mbh1 and Mbh2, two target genes directly involved in granule neuron precursor formation and strong expression of early cerebellar territory markers En1 and NeuroD1. Three weeks after induction, we observed a decrease in the number of glial cells and an increase in that of neurons albeit still immature. Combining Math1 induction with extrinsic factors specifically increased the number of neurons that expressed Pde1c, Zic1, and GABAα6R characteristic of mature granule neurons, formed "T-shaped" axons typical of granule neurons, and generated synaptic contacts and action potentials in vitro. Finally, in vivo implantation of Math1-induced progenitors into young adult mice resulted in cell migration and settling of newly generated neurons in the cerebellum. These results show that conditional induction of Math1 drives ESCs toward the cerebellar fate and indicate that acting on both intrinsic and extrinsic factors is a powerful means to modulate ESCs differentiation and maturation into a specific neuronal lineage. Copyright © 2012 AlphaMed Press.

  17. Roles of neural stem cells in the repair of peripheral nerve injury.

    Science.gov (United States)

    Wang, Chong; Lu, Chang-Feng; Peng, Jiang; Hu, Cheng-Dong; Wang, Yu

    2017-12-01

    Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

  18. A note on the definition and the development of cerebellar purkinje cell zones

    NARCIS (Netherlands)

    J. Voogd (Jan)

    2012-01-01

    textabstractThe definition of Purkinje cell zones by their white matter comprtments, their physiological properties, and their molecular identity and the birthdate of their Purkinje cells will be reviewed.

  19. A Note on the Definition and the Development of Cerebellar Purkinje Cell Zones

    OpenAIRE

    Voogd, J.

    2012-01-01

    textabstractThe definition of Purkinje cell zones by their white matter comprtments, their physiological properties, and their molecular identity and the birthdate of their Purkinje cells will be reviewed.

  20. G-CSF prevents caspase 3 activation in Schwann cells after sciatic nerve transection, but does not improve nerve regeneration.

    Science.gov (United States)

    Frost, Hanna K; Kodama, Akira; Ekström, Per; Dahlin, Lars B

    2016-10-15

    Exogenous granulocyte-colony stimulating factor (G-CSF) has emerged as a drug candidate for improving the outcome after peripheral nerve injuries. We raised the question if exogenous G-CSF can improve nerve regeneration following a clinically relevant model - nerve transection and repair - in healthy and diabetic rats. In short-term experiments, distance of axonal regeneration and extent of injury-induced Schwann cell death was quantified by staining for neurofilaments and cleaved caspase 3, respectively, seven days after repair. There was no difference in axonal outgrowth between G-CSF-treated and non-treated rats, regardless if healthy Wistar or diabetic Goto-Kakizaki (GK) rats were examined. However, G-CSF treatment caused a significant 13% decrease of cleaved caspase 3-positive Schwann cells at the lesion site in healthy rats, but only a trend in diabetic rats. In the distal nerve segments of healthy rats a similar trend was observed. In long-term experiments of healthy rats, regeneration outcome was evaluated at 90days after repair by presence of neurofilaments, wet weight of gastrocnemius muscle, and perception of touch (von Frey monofilament testing weekly). The presence of neurofilaments distal to the suture line was similar in G-CSF-treated and non-treated rats. The weight ratio of ipsi-over contralateral gastrocnemius muscles, and perception of touch at any time point, were likewise not affected by G-CSF treatment. In addition, the inflammatory response in short- and long-term experiments was studied by analyzing ED1 stainable macrophages in healthy rats, but in neither case was any attenuation seen at the injury site or distal to it. G-CSF can prevent caspase 3 activation in Schwann cells in the short-term, but does not detectably affect the inflammatory response, nor improve early or late axonal outgrowth or functional recovery. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Early increase and late decrease of purkinje cell dendritic spine density in prion-infected organotypic mouse cerebellar cultures.

    Science.gov (United States)

    Campeau, Jody L; Wu, Gengshu; Bell, John R; Rasmussen, Jay; Sim, Valerie L

    2013-01-01

    Prion diseases are infectious neurodegenerative diseases associated with the accumulation of protease-resistant prion protein, neuronal loss, spongiform change and astrogliosis. In the mouse model, the loss of dendritic spines is one of the earliest pathological changes observed in vivo, occurring 4-5 weeks after the first detection of protease-resistant prion protein in the brain. While there are cell culture models of prion infection, most do not recapitulate the neuropathology seen in vivo. Only the recently developed prion organotypic slice culture assay has been reported to undergo neuronal loss and the development of some aspects of prion pathology, namely small vacuolar degeneration and tubulovesicular bodies. Given the rapid replication of prions in this system, with protease-resistant prion protein detectable by 21 days, we investigated whether the dendritic spine loss and altered dendritic morphology seen in prion disease might also develop within the lifetime of this culture system. Indeed, six weeks after first detection of protease-resistant prion protein in tga20 mouse cerebellar slice cultures infected with RML prion strain, we found a statistically significant loss of Purkinje cell dendritic spines and altered dendritic morphology in infected cultures, analogous to that seen in vivo. In addition, we found a transient but statistically significant increase in Purkinje cell dendritic spine density during infection, at the time when protease-resistant prion protein was first detectable in culture. Our findings support the use of this slice culture system as one which recapitulates prion disease pathology and one which may facilitate study of the earliest stages of prion disease pathogenesis.

  2. Exposure to nerve growth factor worsens nephrotoxic effect induced by Cyclosporine A in HK-2 cells.

    Directory of Open Access Journals (Sweden)

    Donatella Vizza

    Full Text Available Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkA(NTR and p75(NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells combined treatment with Cyclosporine A + nerve growth factor induced a significant reduction in cell vitality concomitant with a down-regulation of Cyclin D1 and up-regulation of p21 levels respect to cells treated with Cyclosporine A alone. Moreover functional experiments showed that the co-treatment significantly up-regulated human p21promoter activity by involvement of the Sp1 transcription factor, whose nuclear content was negatively regulated by activated NFATc1. In addition we observed that the combined exposure to Cyclosporine A + nerve growth factor promoted an up-regulation of p75 (NTR and its target genes, p53 and BAD leading to the activation of intrinsic apoptosis. Finally, the chemical inhibition of p75(NTR down-regulated the intrinsic apoptotic signal. We describe two new mechanisms by which nerve growth factor promotes growth arrest and apoptosis in tubular renal cells exposed to Cyclosporine A.

  3. Neuroprotective effects of thymoquinone against cerebellar ...

    African Journals Online (AJOL)

    cerebellum mainly functions to coordinate motor functions and control ... development of the brain and life-long cognitive function [2]. ... and serial equidistant sections of the right cerebellar ... Cells outside of the left vertical and bottom bars ...

  4. Cerebellar leukoencephalopathy: most likely histiocytosis-related

    NARCIS (Netherlands)

    van der Knaap, M.S.; Arts, W.F.M.; Garbern, J.Y.; Hedlund, G.; Winkler, F.; Barbosa, C.; King, M.D.; Bjornstad, A.; Hussain, N.; Beyer, M.K.; Gomez, C.; Patterson, M.C.; Grattan-Smith, P.; Timmons, M.; van der Valk, P.

    2008-01-01

    Background: Histiocytosis, both Langerhans and non-Langerhans cell type, can be associated with cerebellar white matter abnormalities, thought to be paraneoplastic. The associated clinical picture consists of ataxia, spasticity, and cognitive decline. Hormonal dysfunction is frequent. MRI shows

  5. An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival

    Science.gov (United States)

    Tang, Zhongshu; Zhang, Shuihua; Lee, Chunsik; Kumar, Anil; Arjunan, Pachiappan; Li, Yang; Zhang, Fan; Li, Xuri

    2011-01-01

    Injury to the optic nerve can lead to axonal degeneration, followed by a gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. Examples of such diseases in human include traumatic optic neuropathy and optic nerve degeneration in glaucoma. It is characterized by typical changes in the optic nerve head, progressive optic nerve degeneration, and loss of retinal ganglion cells, if uncontrolled, leading to vision loss and blindness. The optic nerve crush (ONC) injury mouse model is an important experimental disease model for traumatic optic neuropathy, glaucoma, etc. In this model, the crush injury to the optic nerve leads to gradual retinal ganglion cells apoptosis. This disease model can be used to study the general processes and mechanisms of neuronal death and survival, which is essential for the development of therapeutic measures. In addition, pharmacological and molecular approaches can be used in this model to identify and test potential therapeutic reagents to treat different types of optic neuropathy. Here, we provide a step by step demonstration of (I) Baseline retrograde labeling of retinal ganglion cells (RGCs) at day 1, (II) Optic nerve crush injury at day 4, (III) Harvest the retinae and analyze RGC survival at day 11, and (IV) Representative result. PMID:21540827

  6. Trigeminal nerve involvement in T-cell acute lymphoblastic leukemia: value of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Karadag, Demet; Karaguelle, Ayse Tuba; Erden, Ilhan; Erden, Ayse E-mail: erden@ada.net.tr

    2002-10-01

    A 30-year-old male with T-cell acute lymphoblastic leukemia presented with facial numbness. Neurological examination revealed paresthesia of the left trigeminal nerve. Cerebrospinal fluid (CSF) cytology showed no atypical cells. Gadolinium-enhanced magnetic resonance (MR) imaging demonstrated enlargement and enhancement of intracranial portions of the left trigeminal nerve. The abnormal MR imaging findings almost completely resolved after the chemotherapy. Gadolinium-enhanced MR imaging is not only a useful procedure for the early diagnosis of cranial nerve invasion by leukemia but it might be helpful to follow the changes after the treatment.

  7. Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation

    Science.gov (United States)

    2012-02-01

    10-1-0927 TITLE: Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation...immunosuppression. Bone Marrow Derived Mesenchymal stem cells (BM-MSCs) are pluripotent cells, capable of differentiation along multiple mesenchymal lineages into...As part of implemented transition from University of Pittsburgh to Johns Hopkins University, we optimized our mesenchymal stem cell (MSC) isolation

  8. Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth.

    Science.gov (United States)

    Sugimura-Wakayama, Yukiko; Katagiri, Wataru; Osugi, Masashi; Kawai, Takamasa; Ogata, Kenichi; Sakaguchi, Kohei; Hibi, Hideharu

    2015-11-15

    Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

  9. Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS)

    Science.gov (United States)

    2017-09-01

    cells (AFS) to promote and accelerate nerve regeneration . The presence of the AFS will provide support for the regenerating axons without the...plus AFS cells . Cross sections of the distal part of the regenerated nerves were evaluated by light and electronic microscopy. ANA plus AFS group...and myelin thickness in ANA plus AFS cells treated group (Figure 2.1.1), indicating enhanced regenerating ability of the axons. Neuromuscular

  10. Bone marrow-derived mesenchymal stem cells versus adipose-derived mesenchymal stem cells for peripheral nerve regeneration

    Directory of Open Access Journals (Sweden)

    Marcela Fernandes

    2018-01-01

    Full Text Available Studies have confirmed that bone marrow-derived mesenchymal stem cells (MSCs can be used for treatment of several nervous system diseases. However, isolation of bone marrow-derived MSCs (BMSCs is an invasive and painful process and the yield is very low. Therefore, there is a need to search for other alterative stem cell sources. Adipose-derived MSCs (ADSCs have phenotypic and gene expression profiles similar to those of BMSCs. The production of ADSCs is greater than that of BMSCs, and ADSCs proliferate faster than BMSCs. To compare the effects of venous grafts containing BMSCs or ADSCs on sciatic nerve injury, in this study, rats were randomly divided into four groups: sham (only sciatic nerve exposed, Matrigel (MG; sciatic nerve injury + intravenous transplantation of MG vehicle, ADSCs (sciatic nerve injury + intravenous MG containing ADSCs, and BMSCs (sciatic nerve injury + intravenous MG containing BMSCs groups. Sciatic functional index was calculated to evaluate the function of injured sciatic nerve. Morphologic characteristics of nerves distal to the lesion were observed by toluidine blue staining. Spinal motor neurons labeled with Fluoro-Gold were quantitatively assessed. Compared with sham-operated rats, sciatic functional index was lower, the density of small-diameter fibers was significantly increased, and the number of motor neurons significantly decreased in rats with sciatic nerve injury. Neither ADSCs nor BMSCs significantly improved the sciatic nerve function of rats with sciatic nerve injury, increased fiber density, fiber diameters, axonal diameters, myelin sheath thickness, and G ratios (axonal diameter/fiber diameter ratios in the sciatic nerve distal to the lesion site. There was no significant difference in the number of spinal motor neurons among ADSCs, BMSCs and MG groups. These results suggest that neither BMSCs nor ADSCs provide satisfactory results for peripheral nerve repair when using MG as the conductor for

  11. Mice deficient in carbonic anhydrase type 8 exhibit motor dysfunctions and abnormal calcium dynamics in the somatic region of cerebellar granule cells.

    Science.gov (United States)

    Lamont, Matthew G; Weber, John T

    2015-06-01

    The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Macrophage polarization in nerve injury: do Schwann cells play a role?

    Directory of Open Access Journals (Sweden)

    Jo Anne Stratton

    2016-01-01

    Full Text Available In response to peripheral nerve injury, the inflammatory response is almost entirely comprised of infiltrating macrophages. Macrophages are a highly plastic, heterogenic immune cell, playing an indispensable role in peripheral nerve injury, clearing debris and regulating the microenvironment to allow for efficient regeneration. There are several cells within the microenvironment that likely interact with macrophages to support their function - most notably the Schwann cell, the glial cell of the peripheral nervous system. Schwann cells express several ligands that are known to interact with receptors expressed by macrophages, yet the effects of Schwann cells in regulating macrophage phenotype remains largely unexplored. This review discusses macrophages in peripheral nerve injury and how Schwann cells may regulate their behavior.

  13. Sodium channels in axons and glial cells of the optic nerve of Necturus maculosa.

    Science.gov (United States)

    Tang, C M; Strichartz, G R; Orkand, R K

    1979-11-01

    Experiments investigating both the binding of radioactively labelled saxitoxin (STX) and the electrophysiological response to drugs that increase the sodium permeability of excitable membranes were conducted in an effort to detect sodium channels in glial cells of the optic nerve of Necturus maculosa, the mudpuppy. Glial cells in nerves from chronically enucleated animals, which lack optic nerve axons, show no saturable uptake of STX whereas a saturable uptake is clearly present in normal optic nerves. The normal nerve is depolarized by aconitine, batrachotoxin, and veratridine (10(-6)-10(-5) M), whereas the all-glial preparation is only depolarized by veratridine and at concentrations greater than 10(-3) M. Unlike the depolarization caused by veratridine in normal nerves, the response in the all-glial tissue is not blocked by tetrodotoxin nor enhanced by scorpion venom (Leiurus quinquestriatus). In glial cells of the normal nerve, where axons are also present, the addition of 10(-5) M veratridine does lead to a transient depolarization; however, it is much briefer than the axonal response to veratridine in this same tissue. This glial response to veratridine could be caused by the efflux of K+ from the drug-depolarized axons, and is similar to the glial response to extracellular K+ accumulation resulting from action potentials in the axon.

  14. Trophic Effects of Dental Pulp Stem Cells on Schwann Cells in Peripheral Nerve Regeneration.

    Science.gov (United States)

    Yamamoto, Tsubasa; Osako, Yohei; Ito, Masataka; Murakami, Masashi; Hayashi, Yuki; Horibe, Hiroshi; Iohara, Koichiro; Takeuchi, Norio; Okui, Nobuyuki; Hirata, Hitoshi; Nakayama, Hidenori; Kurita, Kenichi; Nakashima, Misako

    2016-01-01

    Recently, mesenchymal stem cells have demonstrated a potential for neurotrophy and neurodifferentiation. We have recently isolated mobilized dental pulp stem cells (MDPSCs) using granulocyte-colony stimulating factor (G-CSF) gradient, which has high neurotrophic/angiogenic potential. The aim of this study is to investigate the effects of MDPSC transplantation on peripheral nerve regeneration. Effects of MDPSC transplantation were examined in a rat sciatic nerve defect model and compared with autografts and control conduits containing collagen scaffold. Effects of conditioned medium of MDPSCs were also evaluated in vitro. Transplantation of MDPSCs in the defect demonstrated regeneration of myelinated fibers, whose axons were significantly higher in density compared with those in autografts and control conduits only. Enhanced revascularization was also observed in the MDPSC transplants. The MDPSCs did not directly differentiate into Schwann cell phenotype; localization of these cells near Schwann cells induced several neurotrophic factors. Immunofluorescence labeling demonstrated reduced apoptosis and increased proliferation in resident Schwann cells in the MDPSC transplant compared with control conduits. These trophic effects of MDPSCs on proliferation, migration, and antiapoptosis in Schwann cells were further elucidated in vitro. The results demonstrate that MDPSCs promote axon regeneration through trophic functions, acting on Schwann cells, and promoting angiogenesis.

  15. ATP secretion from nerve trunks and Schwann cells mediated by glutamate.

    Science.gov (United States)

    Liu, Guo Jun; Bennett, Max R

    2003-11-14

    ATP release from rat sciatic nerves and from cultured Schwann cells isolated from the nerves was investigated using an online bioluminescence technique. ATP was released in relatively large amounts from rat sciatic nerve trunks during electrical stimulation. This release was blocked by the sodium channel inhibitor tetrodotoxin and the non-NMDA glutamate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Schwann cells isolated from the nerve trunks did not release ATP when electrically stimulated but did in response to glutamate in a concentration-dependent manner. Glutamate-stimulated ATP release was inhibited by specific non-competitive AMPA receptor antagonist GYKI 52466 and competitive non-NMDA receptor antagonist CNQX. Glutamate-stimulated ATP release was decreased by inhibition of anion transporter inhibitors by furosemide, cystic fibrosis transmembrane conductance regulator by glibenclamide and exocytosis by botulinum toxin A, indicating that anion transporters and exocytosis provide the main secretion mechanisms for ATP release from the Schwann cells.

  16. Posterior cerebellar Purkinje cells in an SCA5/SPARCA1 mouse model are especially vulnerable to the synergistic effect of loss of β-III spectrin and GLAST.

    Science.gov (United States)

    Perkins, Emma M; Suminaite, Daumante; Clarkson, Yvonne L; Lee, Sin Kwan; Lyndon, Alastair R; Rothstein, Jeffrey D; Wyllie, David J A; Tanaka, Kohichi; Jackson, Mandy

    2016-10-15

    Clinical phenotypes of spinocerebellar ataxia type-5 (SCA5) and spectrin-associated autosomal recessive cerebellar ataxia type-1 (SPARCA1) are mirrored in mice lacking β-III spectrin (β-III-/-). One function of β-III spectrin is the stabilization of the Purkinje cell-specific glutamate transporter EAAT4 at the plasma membrane. In β-III-/- mice EAAT4 levels are reduced from an early age. In contrast levels of the predominant cerebellar glutamate transporter GLAST, expressed in Bergmann glia, only fall progressively from 3 months onwards. Here we elucidated the roles of these two glutamate transporters in cerebellar pathogenesis mediated through loss of β-III spectrin function by studying EAAT4 and GLAST knockout mice as well as crosses of both with β-III-/- mice. Our data demonstrate that EAAT4 loss, but not abnormal AMPA receptor composition, in young β-III-/- mice underlies early Purkinje cell hyper-excitability and that subsequent loss of GLAST, superimposed on the earlier deficiency of EAAT4, is responsible for Purkinje cell loss and progression of motor deficits. Yet the loss of GLAST appears to be independent of EAAT4 loss, highlighting that other aspects of Purkinje cell dysfunction underpin the pathogenic loss of GLAST. Finally, our results demonstrate that Purkinje cells in the posterior cerebellum of β-III-/- mice are most susceptible to the combined loss of EAAT4 and GLAST, with degeneration of proximal dendrites, the site of climbing fibre innervation, most pronounced. This highlights the necessity for efficient glutamate clearance from these regions and identifies dysregulation of glutamatergic neurotransmission particularly within the posterior cerebellum as a key mechanism in SCA5 and SPARCA1 pathogenesis.

  17. Improved motor performance in Dyt1 ΔGAG heterozygous knock-in mice by cerebellar Purkinje-cell specific Dyt1 conditional knocking-out.

    Science.gov (United States)

    Yokoi, Fumiaki; Dang, Mai Tu; Li, Yuqing

    2012-05-01

    Early-onset generalized torsion dystonia (dystonia 1) is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most patients have a 3-base pair deletion (ΔGAG) in one allele of DYT1, corresponding to a loss of a glutamic acid residue (ΔE) in the C-terminal region of the protein. Functional alterations in basal ganglia circuits and the cerebellum have been reported in dystonia. Pharmacological manipulations or mutations in genes that result in functional alterations of the cerebellum have been reported to have dystonic symptoms and have been used as phenotypic rodent models. Additionally, structural lesions in the abnormal cerebellar circuits, such as cerebellectomy, have therapeutic effects in these models. A previous study has shown that the Dyt1 ΔGAG heterozygous knock-in (KI) mice exhibit motor deficits in the beam-walking test. Both Dyt1 ΔGAG heterozygous knock-in (KI) and Dyt1 Purkinje cell-specific knockout (Dyt1 pKO) mice exhibit dendritic alterations of cerebellar Purkinje cells. Here, Dyt1 pKO mice exhibited significantly less slip numbers in the beam-walking test, suggesting better motor performance than control littermates, and normal gait. Furthermore, Dyt1 ΔGAG KI/Dyt1 pKO double mutant mice exhibited significantly lower numbers of slips than Dyt1 ΔGAG heterozygous KI mice, suggesting Purkinje-cell specific knockout of Dyt1 wild-type (WT) allele in Dyt1 ΔGAG heterozygous KI mice rescued the motor deficits. The results suggest that molecular lesions of torsinA in Purkinje cells by gene therapy or intervening in the signaling pathway downstream of the cerebellar Purkinje cells may rescue motor symptoms in dystonia 1. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. DNA synthesis during development and proliferation of glial cells in organotypic rat cerebellar culture

    International Nuclear Information System (INIS)

    Renkawek, K.

    1977-01-01

    DNA synthesis was investigated in glial cells in vitro with 3 H thymidine in concentration 1 μCi/ml medium. Incorporation of isotope into the glial nuclei has been found both in the explant (7-21%) and in the outgrowth (22-56%). DNA synthesis was dependent on the age of culture and due to the contact inhibition in the outgrowth. Results point out that marked DNA synthesis is a characteristic feature of glia differentiation and of reactive character of glial cells in vitro. (author)

  19. The Effect of Salvia Rhytidea Extract on the Number of Cells of Different Layers of Cerebellar Cortex Following Ischemia Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    M Farahmand

    2016-09-01

    Full Text Available Background & aim: Salvia has anti-oxidant oxygen free radicals which are generated during the interruption and reestablishment of ischemia reperfusion.  The aim of study was to investigate the effect of Salvia Rhytidea extract on the number of cells of different layers of cerebellar cortex following ischemia reperfusion in rats. Methods: In the present experimental study, 35 adult male rats were randomly divided into 7 groups of 5: Group 1 (control-: Sampling without ischemia. Group 2 (control +: Cerebellar ischemia with administration of normal saline. Group 3(sham: Manipulation without ischemia with normal saline administration. Group 4   received (3.2 mg/kg aqueous and alcoholic Salvia extract 2 hours after ischemia. Group 5 received 50 mg/kg silymarin drug, 2 hours after ischemia. Group 6 received 3.2 mg/kg aqueous and alcoholic Salvia extract 72, 48, 24 and 0 h before ischemia and group 7 received silymarin drug (50 mg/kg, 0, 24, 48, and 72, hrs. before ischemia. 24 hrs. following reperfusion, the rats were euthanized and samples of the cerebellum were obtained. By using routine histological technique, the sections were stained by H&E. The measurement of cell count in cerebellar cortex were accomplished. Data were evaluated with One-Way ANOVA and Tukey diagnostic tests. Results: A significant decrease was observed in the number of neural cells in granular layer in the non-treated ischemia group and in the groups which received Salvia extract and silymarin, two hours after the ischemia (p< 0.05. No significant decrease was observed in the number of cells of this layer in the groups which received salvia extract before ischemia. But regarding the cell number of molecular and purkinje layers in above groups, no significant difference was observed compared to the control group (P˃0.05. However, no significant differences was seen in the number of cells layers compared to the control group (P˃0.05. Conclusion: Finally, administration of

  20. Stereological estimation of total cell numbers in the human cerebral and cerebellar cortex

    DEFF Research Database (Denmark)

    Walløe, Solveig; Pakkenberg, Bente; Fabricius, Katrine

    2014-01-01

    estimates and were often very time-consuming. Within the last 20-30 years, it has become possible to rely on more advanced and unbiased methods. These methods have provided us with information about fetal brain development, differences in cell numbers between men and women, the effect of age on selected...

  1. Stem cells and related factors involved in facial nerve function regeneration

    Directory of Open Access Journals (Sweden)

    Kamil H. Nelke

    2015-09-01

    Full Text Available The facial nerve (VII is one of the most important cranial nerves for head and neck surgeons. Its function is closely related to facial expressions that are individual for every person. After its injury or palsy, its functions can be either impaired or absent. Because of the presence of motor, sensory and parasympathetic fibers, the biology of its repair and function restoration depends on many factors. In order to achieve good outcome, many different therapies can be performed in order to restore as much of the nerve function as possible. When rehabilitation and physiotherapy are not sufficient, additional surgical procedures and therapies are taken into serious consideration. The final outcome of many of them is discussable, depending on nerve damage etiology. Stem cells in facial nerve repair are used, but long-term outcomes and results are still not fully known. In order to understand this therapeutic approach, clinicians and surgeons should understand the immunobiology of nerve repair and regeneration. In this review, potential stem cell usage in facial nerve regeneration procedures is discussed.

  2. The natural scorpion peptide, BmK NT1 activates voltage-gated sodium channels and produces neurotoxicity in primary cultured cerebellar granule cells.

    Science.gov (United States)

    Zou, Xiaohan; He, Yuwei; Qiao, Jinping; Zhang, Chunlei; Cao, Zhengyu

    2016-01-01

    The scorpion Buthus martensii Karsch has been used in Traditional Chinese Medicine to treat neuronal diseases such as neuropathic pain, paralysis and epilepsy for thousands of years. Studies have demonstrated that scorpion venom is the primary active component. Although scorpion venom can effectively attenuate pain in the clinic, it also produces neurotoxic response. In this study, toxicity guided purification led to identify a mammalian toxin termed BmK NT1 comprising of 65 amino acid residues and an amidated C-terminus, a mature peptide encoded by the nucleotide sequence (GenBank No. AF464898). In contract to the recombinant product of the same nucleotide sequence, BmK AGAP, which displayed analgesic and anti-tumor effect, intravenous injection (i.v.) of BmK NT1 produced acute toxicity in mice with an LD50 value of 1.36 mg/kg. In primary cultured cerebellar granule cells, BmK NT1 produced a concentration-dependent cell death with an IC50 value of 0.65 μM (0.41-1.03 μM, 95% Confidence Intervals, 95% CI) which was abolished by TTX, a voltage-gated sodium channel (VGSC) blocker. We also demonstrated that BmK NT1 produced modest sodium influx in cerebellar granule cell cultures with an EC50 value of 2.19 μM (0.76-6.40 μM, 95% CI), an effect similar to VGSC agonist, veratridine. The sodium influx response was abolished by TTX suggesting that BmK NT1-induced sodium influx is solely through activation of VGSC. Considered these data together, we demonstrated that BmK NT1 activated VGSC and produced neurotoxicity in cerebellar granule cell cultures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Effects of cholinergic compounds on the axon-Schwann cell relationship in the squid nerve fiber.

    Science.gov (United States)

    Villegas, J

    1975-04-01

    The effects of acetylcholine, carbamylcholine, D-tubocurarine, eserine, and alpha-bungarotoxin on the Schwann cell electrical potential of resting and stimulated squid nerve fibers were studied. Acetylcholine (10-7 M) and barbamylcholine (10-6 M) induce a prolonged hyper polarization in the Schwann cells of the unstimulated nerve fiber. In the presence of carbamylcholine (10-6 M) the behavior of the Schwann cell membrane to changes in the external potassium concentration approximates the behavior of an ideal potassium electrode. D-Tubocurarine (10-9 M) blocks the hyperpolarizing effects of nerve impulse trains and carbamylcholine (10-6 M), whereas at the same concentration eserine prolongs the Schwann cell hyperpolarizations induced by axon stimulation or by acetylcholine (10-7 M). alpha-Bungarotoxin (10-9M) also blocks the hyperpolarizing effect of nerve impulse trains and of carbamylcholine. D-Tubocurarine (10-5M) protects the Schwann cells against the irreversible action of alpha-bungarotoxin. These results show the existence of acetylcholine receptors in the Schwann cell membrane. Preliminary measurements of the binding of 125I-alpha bungarotoxin to the plasma membranes isolated from squid nerves also indicate the presence of acetylcholine receptors. These findings support the involvement of cholinergic mechanisms in the axon-Schwann cell relationship previously described.

  4. Adult Stem Cell-Based Enhancement of Nerve Conduit for Peripheral Nerve Repair

    Science.gov (United States)

    2017-10-01

    neurotrophically activated cell types and conditioned media (via RT-PCR and ELISA of neurotrophic factors), followed by cell storage Specific objective 9...Mesenchymal Progenitor Cells (NI-MiMPCs) and Mesenchymal Stem Cells (MSCs), quantified via ELISA . MiMPCs and MSCs were cultured in neurotrophic induction...LIF, (E) osteonectin, and (F) clusterin. All ELISA results are expressed in pg/ml or ng/ml produced per million cells. Medium taken from NI-MiMPC

  5. Effect on pancreatic beta cells and nerve cells by low let x-ray

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kwang Hun [Dept. of Nuclear Medicine, Kyungbuk National University Hospital, Daegu (Korea, Republic of); Kim, Kgu Hwan [Dept. of Radiological Technology, Daegu health College, Daegu (Korea, Republic of)

    2014-03-15

    Cultured pancreatic beta cells and nerve cells, it is given normal condition of 10% FBS (fetal bovine serum), 11.1 mM glucose and hyperglycemia condition of 1% FBS, 30 mM glucose. For low LET X-ray irradiated with 0.5 Gy/hr dose-rate(total dose: 0.5 to 5 Gy). Survival rates were measured by MTT assay. When non irradiated, differentiated in the pancreatic beta cells experiment is hyperglycemia conditions survival rate compared to normal conditions survival rate seemed a small reduction. However increasing the total dose of X-ray, the survival rate of normal conditions decreased slightly compared to the survival rate of hyperglycemia conditions, the synergistic effect was drastically reduced. When non irradiated, undifferentiated in the nerve cells experiment is hyperglycemia conditions survival rate compared to normal conditions survival rate seemed a large reduction. As the cumulative dose of X-ray normal conditions and hyperglycemia were all relatively rapid cell death. But the rate of decreased survivals by almost parallel to the reduction proceed and it didn't show synergistic effect.

  6. Characterization of two novel nuclear BTB/POZ domain zinc finger isoforms. Association with differentiation of hippocampal neurons, cerebellar granule cells, and macroglia

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Kjaerulff, Karen M; Pedersen, Hans C

    2002-01-01

    BTB/POZ (broad complex tramtrack bric-a-brac/poxvirus and zinc finger) zinc finger factors are a class of nuclear DNA-binding proteins involved in development, chromatin remodeling, and cancer. However, BTB/POZ domain zinc finger factors linked to development of the mammalian cerebral cortex......, cerebellum, and macroglia have not been described previously. We report here the isolation and characterization of two novel nuclear BTB/POZ domain zinc finger isoforms, designated HOF(L) and HOF(S), that are specifically expressed in early hippocampal neurons, cerebellar granule cells, and gliogenic...

  7. Delivery of adipose-derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration.

    Science.gov (United States)

    Allbright, Kassandra O; Bliley, Jacqueline M; Havis, Emmanuelle; Kim, Deok-Yeol; Dibernardo, Gabriella A; Grybowski, Damian; Waldner, Matthias; James, Isaac B; Sivak, Wesley N; Rubin, J Peter; Marra, Kacey G

    2018-02-06

    Peripheral nerve damage is associated with high long-term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose-derived stem cells (ASC) represents a promising therapeutic modality. Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical-sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

  8. Dendrites of cerebellar granule cells correctly recognize their target axons for synaptogenesis in vitro.

    Science.gov (United States)

    Ito, Shoko; Takeichi, Masatoshi

    2009-08-04

    Neural circuits are generated by precisely ordered synaptic connections among neurons, and this process is thought to rely on the ability of neurons to recognize specific partners. However, it is also known that neurons promiscuously form synapses with nonspecific partners, in particular when cultured in vitro, causing controversies about neural recognition mechanisms. Here we reexamined whether neurons can or cannot select particular partners in vitro. In the cerebellum, granule cell (GC) dendrites form synaptic connections specifically with mossy fibers, but not with climbing fibers. We cocultured GC neurons with pontine or inferior olivary axons, the major sources for mossy and climbing fibers, respectively, as well as with hippocampal axons as a control. The GC neurons formed synapses with pontine axons predominantly at the distal ends of their dendrites, reproducing the characteristic morphology of their synapses observed in vivo, whereas they failed to do so when combined with other axons. In the latter case, synaptic proteins could accumulate between axons and dendrites, but these synapses were randomly distributed throughout the contact sites, and also their synaptic vesicle recycling was anomalous. These observations suggest that GC dendrites can select their authentic partners for synaptogenesis even in vitro, forming the synapses with a GC-specific nature only with them.

  9. Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network

    Directory of Open Access Journals (Sweden)

    Jean-Marc Good

    2017-11-01

    Full Text Available Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the climbing fiber (CF to Purkinje cell (PC network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity.

  10. Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases

    Science.gov (United States)

    Lin, Chi-Ying; Wang, Jie; Sims, Peter A.; Pan, Ming-Kai; Liou, Jyun-you; Lee, Danielle; Tate, William J.; Kelly, Geoffrey C.; Louis, Elan D.; Faust, Phyllis L.

    2017-01-01

    Changes in climbing fiber-Purkinje cell (CF-PC) synaptic connections have been found in the essential tremor (ET) cerebellum, and these changes are correlated with tremor severity. Whether these postmortem changes are specific to ET remains to be investigated. We assessed CF-PC synaptic pathology in the postmortem cerebellum across a range of degenerative movement disorders [10 Parkinson’s disease (PD) cases, 10 multiple system atrophy (MSA) cases, 10 spinocerebellar ataxia type 1 (SCA1) cases, and 20 ET cases] and 25 controls. We observed differences in terms of CF pathological features across these disorders. Specifically, PD cases and ET cases both had more CFs extending into the parallel fiber (PF) territory, but ET cases had more complex branching and increased length of CFs in the PF territory along with decreased CF synaptic density compared to PD cases. MSA cases and SCA1 cases had the most severely reduced CF synaptic density and a marked paucity of CFs extending into the PF territory. Furthermore, CFs in a subset of MSA cases formed collateral branches parallel to the PC layer, a feature not seen in other diagnostic groups. Using unsupervised cluster analysis, the cases and controls could all be categorized into four clusters based on the CF pathology and features of PC pathology, including counts of PCs and their axonal torpedoes. ET cases and PD cases co-segregated into two clusters, whereas SCA1 cases and MSA cases formed another cluster, separate from the control cluster. Interestingly, the presence of resting tremor seemed to be the clinical feature that separated the cases into the two ET-PD clusters. In conclusion, our study demonstrates that these degenerative movement disorders seem to differ with respect to the pattern of CF synaptic pathology they exhibit. It remains to be determined how these differences contribute to the clinical presentations of these diseases. PMID:27704282

  11. Critical periods during the in situ repair of radiation-induced DNA damage in rat cerebellar neurons and 9L brain tumor cells

    International Nuclear Information System (INIS)

    Wierowski, J.V.; Thomas, R.R.; Ritter, P.; Wheeler, K.T.

    1982-01-01

    The consequences of delivering a second 1250-rad dose at various times during and after the repair of DNA damage produced by an initial 1250-rad dose were assessed in intracerebral 9L tumor cells and rat cerebellar neurons by measuring the sedimentation properties of their DNA through alkaline sucrose gradients in zonal rotors with slow gradient reorienting capabilities.In cerebellar neurons, separating the two doses by 15 min resulted in an accumulation of DNA damage as expressed by an increase in the amount of DNA sedimenting >250 S over that obtained from unirradiated controls. Although not statistically different from unirradiated controls, a slight increase in the amount of fast-sedimenting neuronal DNA also occurred when a 1-hr interval between the two doses was investigated. At intervals of 2 hr or more, no such increase in fast-sedimenting neuronal DNA was observed. None of the periods between doses resulted in an accumulation of DNA damage in intracerebral 9L tumor cells. The accumulation of this type of DNA damage in neurons but not in tumor cells suggests that avoidance of a critical period in neuronal DNA repair may someday be an important concept in the design of brain tumor therapy schedules

  12. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2015-01-01

    Full Text Available The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better

  13. Role of Schwann cells in the regeneration of penile and peripheral nerves

    Directory of Open Access Journals (Sweden)

    Lin Wang

    2015-01-01

    Full Text Available Schwann cells (SCs are the principal glia of the peripheral nervous system. The end point of SC development is the formation of myelinating and nonmyelinating cells which ensheath large and small diameter axons, respectively. They play an important role in axon regeneration after injury, including cavernous nerve injury that leads to erectile dysfunction (ED. Despite improvement in radical prostatectomy surgical techniques, many patients still suffer from ED postoperatively as surgical trauma causes traction injuries and local inflammatory changes in the neuronal microenvironment of the autonomic fibers innervating the penis resulting in pathophysiological alterations in the end organ. The aim of this review is to summarize contemporary evidence regarding: (1 the origin and development of SCs in the peripheral and penile nerve system; (2 Wallerian degeneration and SC plastic change following peripheral and penile nerve injury; (3 how SCs promote peripheral and penile nerve regeneration by secreting neurotrophic factors; (4 and strategies targeting SCs to accelerate peripheral nerve regeneration. We searched PubMed for articles related to these topics in both animal models and human research and found numerous studies suggesting that SCs could be a novel target for treatment of nerve injury-induced ED.

  14. Cerebellar medulloblastoma presenting with skeletal metastasis

    Directory of Open Access Journals (Sweden)

    Barai Sukanta

    2004-04-01

    Full Text Available Medulloblastomas are highly malignant brain tumours, but only rarely produce skeletal metastases. No case of medulloblastoma has been documented to have produced skeletal metastases prior to craniotomy or shunt surgery. A 21-year-old male presented with pain in the hip and lower back with difficulty in walking of 3 months′ duration. Signs of cerebellar dysfunction were present hence a diagnosis of cerebellar neoplasm or skeletal tuberculosis with cerebellar abscess formation was considered. MRI of brain revealed a lesion in the cerebellum suggestive of medulloblastoma. Bone scan revealed multiple sites of skeletal metastases excluding the lumbar vertebrae. MRI of lumbar spine and hip revealed metastases to all lumbar vertebrae and both hips. Computed tomography-guided biopsy was obtained from the L3 vertebra, which revealed metastatic deposits from medulloblastoma. Cerebrospinal fluid cytology showed the presence of medulloblastoma cells. A final diagnosis of cerebellar medulloblastoma with skeletal metastases was made. He underwent craniotomy and histopathology confirmed medulloblastoma.

  15. Adipose-derived mesenchymal stem cells accelerate nerve regeneration and functional recovery in a rat model of recurrent laryngeal nerve injury

    Directory of Open Access Journals (Sweden)

    Yun Li

    2017-01-01

    Full Text Available Medialization thyroplasty or injection laryngoplasty for unilateral vocal fold paralysis cannot restore mobility of the vocal fold. Recent studies have shown that transplantation of mesenchymal stem cells is effective in the repair of nerve injuries. This study investigated whether adipose-derived stem cell transplantation could repair recurrent laryngeal nerve injury. Rat models of recurrent laryngeal nerve injury were established by crushing with micro forceps. Adipose-derived mesenchymal stem cells (ADSCs; 8 × 105 or differentiated Schwann-like adipose-derived mesenchymal stem cells (dADSCs; 8 × 105 or extracellular matrix were injected at the site of injury. At 2, 4 and 6 weeks post-surgery, a higher density of myelinated nerve fiber, thicker myelin sheath, improved vocal fold movement, better recovery of nerve conduction capacity and reduced thyroarytenoid muscle atrophy were found in ADSCs and dADSCs groups compared with the extracellular matrix group. The effects were more pronounced in the ADSCs group than in the dADSCs group. These experimental results indicated that ADSCs transplantation could be an early interventional strategy to promote regeneration after recurrent laryngeal nerve injury.

  16. Early regenerative effects of NGF-transduced Schwann cells in peripheral nerve repair

    NARCIS (Netherlands)

    Shakhbazau, A.; Kawasoe, J.; Hoyng, S.A.; Kumar, R.; van Minnen, J.; Verhaagen, J.; Midha, R.

    2012-01-01

    Peripheral nerve injury leads to a rapid and robust increase in the synthesis of neurotrophins which guide and support regenerating axons. To further optimize neurotrophin supply at the earliest stages of regeneration, we over-expressed NGF in Schwann cells (SCs) by transducing these cells with a

  17. Distributed Cerebellar Motor Learning; a Spike-Timing-Dependent Plasticity Model

    Directory of Open Access Journals (Sweden)

    Niceto Rafael Luque

    2016-03-01

    Full Text Available Deep cerebellar nuclei neurons receive both inhibitory (GABAergic synaptic currents from Purkinje cells (within the cerebellar cortex and excitatory (glutamatergic synaptic currents from mossy fibres. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP located at different cerebellar sites (parallel fibres to Purkinje cells, mossy fibres to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibres to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP and inhibitory (i-STDP mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibres to Purkinje cells synapses and then transferred to mossy fibres to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation towards optimising its working range.

  18. Study of the damage induced by radiations with different linear energy transfer in the nerve cells of the rat cerebellum

    International Nuclear Information System (INIS)

    Krasavin, E.A.; Mashinskaya, T.E.; Ryzhov, N.I.

    1978-01-01

    The increase in space flight duration suggests the study of damage induced by high-fluxes of ionizing radiations in the tissues of the nervous system of the man. The quantitative and qualitative changes in the cerebellar granular cells of the rats of early postnatal period, affected by 25 and 50 MeV protons, 180 kV X-rays and Co 60 gamma-rays have been studied. It has been found that the radiosensitivity of neurons in different compartments of the cerebellar cortex varies significantly. Radiosensitivity of the inner and outer granular layers of the cerebellum to irradiation with 25 MeV protons was similar

  19. Landolphia owariensis Attenuates Alcohol-induced Cerebellar Neurodegeneration: Significance of Neurofilament Protein Alteration in the Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Oyinbo Charles A.

    2016-12-01

    Full Text Available Background: Alcohol-induced cerebellar neurodegeneration is a neuroadaptation that is associated with chronic alcohol abuse. Conventional drugs have been largely unsatisfactory in preventing neurodegeneration. Yet, multimodal neuro-protective therapeutic agents have been hypothesised to have high therapeutic potential for the treatment of CNS conditions; there is yet a dilemma of how this would be achieved. Contrarily, medicinal botanicals are naturally multimodal in their mechanism of action.

  20. Calcium Imaging of Nerve-Mast Cell Signaling in the Human Intestine

    Directory of Open Access Journals (Sweden)

    Sabine Buhner

    2017-11-01

    Full Text Available Introduction: It is suggested that an altered microenvironment in the gut wall alters communication along a mast cell nerve axis. We aimed to record for the first time signaling between mast cells and neurons in intact human submucous preparations.Methods: We used the Ca2+ sensitive dye Fluo-4 AM to simultaneously image changes in intracellular calcium [Ca+2]i (%ΔF/F in neurons and mast cells. Data are presented as median with interquartile ranges (25/75%.Results: We recorded nerve responses in 29 samples upon selective activation of 223 mast cells by IgE receptor cross linking with the antibody mAb22E7. Mast cells responded to mAb22E7 with a median [Ca+2]i increase of 20% (11/39 peaking 90 s (64/144 after the application. Only very few neurons responded and the median percentage of responding neuronal area was 0% (0/5.9. Mast cell activation remained in the presence of the fast sodium channel blocker tetrodotoxin. Specific neuronal activation by transmural electrical field stimulation (EFS in 34 samples evoked instantaneously [Ca+2]i signals in submucous neurons. This was followed by a [Ca+2]i peak response of 8%ΔF/F (4/15 in 33% of 168 mast cells in the field of view. The mast cell response was abolished by the nerve blocker tetrododoxin, reduced by the Calcitonin Gene-Related Peptide receptor 1 antagonist BIBN-4096 and the Vasoactive Intestinal Peptide receptor antagonist PG97-269, but not by blockade of the neurokinin receptors 1–3.Conclusion: The findings revealed bidirectional signaling between mast cells and submucous neurons in human gut. In our macroscopically normal preparations a nerve to mast cell signaling was very prominent whereas a mast cell to nerve signaling was rather rare.

  1. Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis

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    Aleksandra Somogyi

    2018-02-01

    Full Text Available Juvenile neuronal ceroid lipofuscinosis (JNCL is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model (Cln3Δex7/8 mice for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3Δex7/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both biochemical and cytochemical methods. However, quantitative high-performance liquid chromatography analysis revealed a highly significant increase in GM3, suggesting a metabolic blockade in the conversion of GM3 to more complex gangliosides. Quantitative real-time PCR analysis revealed a significant reduction in the transcripts of the interconverting enzymes, especially of β-1,4-N-acetyl-galactosaminyl transferase 1 (GM2 synthase, which is the enzyme converting GM3 to GM2. Thus, our data suggest that the complex a-series gangliosides are reduced in Cln3Δex7/8 mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis.

  2. Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis

    Science.gov (United States)

    Somogyi, Aleksandra; Petcherski, Anton; Beckert, Benedikt; Huebecker, Mylene; Priestman, David A.; Banning, Antje; Cotman, Susan L.; Platt, Frances M.; Ruonala, Mika O.

    2018-01-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model (Cln3Δex7/8 mice) for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3Δex7/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both biochemical and cytochemical methods. However, quantitative high-performance liquid chromatography analysis revealed a highly significant increase in GM3, suggesting a metabolic blockade in the conversion of GM3 to more complex gangliosides. Quantitative real-time PCR analysis revealed a significant reduction in the transcripts of the interconverting enzymes, especially of β-1,4-N-acetyl-galactosaminyl transferase 1 (GM2 synthase), which is the enzyme converting GM3 to GM2. Thus, our data suggest that the complex a-series gangliosides are reduced in Cln3Δex7/8 mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis. PMID:29470438

  3. Chicken HOXA3 Gene: Its Expression Pattern and Role in Branchial Nerve Precursor Cell Migration

    Science.gov (United States)

    Watari-Goshima, Natsuko; Chisaka, Osamu

    2011-01-01

    In vertebrates, the proximal and distal sensory ganglia of the branchial nerves are derived from neural crest cells (NCCs) and placodes, respectively. We previously reported that in Hoxa3 knockout mouse embryos, NCCs and placode-derived cells of the glossopharyngeal nerve were defective in their migration. In this report, to determine the cell-type origin for this Hoxa3 knockout phenotype, we blocked the expression of the gene with antisense morpholino oligonucleotides (MO) specifically in either NCCs/neural tube or placodal cells of chicken embryos. Our results showed that HOXA3 function was required for the migration of the epibranchial placode-derived cells and that HOXA3 regulated this cell migration in both NCCs/neural tube and placodal cells. We also report that the expression pattern of chicken HOXA3 was slightly different from that of mouse Hoxa3. PMID:21278919

  4. Investigation of cell adhesion in chitosan membranes for peripheral nerve regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Cristiana R.; López-Cebral, Rita; Silva-Correia, Joana; Silva, Joana M.; Mano, João F.; Silva, Tiago H. [3B' s Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark – Parque de Ciência e Tecnologia, 4805-017, Barco, Guimarães (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Braga, Guimarães (Portugal); Freier, Thomas [MEDOVENT GmbH, Friedrich-Koenig-Str. 3, D-55129 Mainz (Germany); Reis, Rui L. [3B' s Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark – Parque de Ciência e Tecnologia, 4805-017, Barco, Guimarães (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Braga, Guimarães (Portugal); Oliveira, Joaquim M., E-mail: miguel.oliveira@dep.uminho.pt [3B' s Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark – Parque de Ciência e Tecnologia, 4805-017, Barco, Guimarães (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Braga, Guimarães (Portugal)

    2017-02-01

    Peripheral nerve injuries have produced major concerns in regenerative medicine for several years, as the recovery of normal nerve function continues to be a significant clinical challenge. Chitosan (CHT), because of its good biocompatibility, biodegradability and physicochemical properties, has been widely used as a biomaterial in tissue engineering scaffolding. In this study, CHT membranes were produced with three different Degrees of Acetylation (DA), envisioning its application in peripheral nerve regeneration. The three CHT membranes (DA I: 1%, DA II: 2%, DA III: 5%) were extensively characterized and were found to have a smooth and flat surface, with DA III membrane having slightly higher roughness and surface energy. All the membranes presented suitable mechanical properties and did not show any signs of calcification after SBF test. Biodegradability was similar for all samples, and adequate to physically support neurite outgrowth. The in vitro cell culture results indicate selective cell adhesion. The CHT membranes favoured Schwann cells invasion and proliferation, with a display of appropriate cytoskeletal morphology. At the same time they presented low fibroblast infiltration. This fact may be greatly beneficial for the prevention of fibrotic tissue formation, a common phenomenon impairing peripheral nerve regeneration. The great deal of results obtained during this work permitted to select the formulation with the greatest potential for further biological tests. - Highlights: • Three chitosan membranes were produced with very specific degrees of acetylation (DA I: 1%, DA II: 2%, DA III: 5%). • Physicochemical characterization of the membranes showed their suitability for peripheral nerve regeneration purposes. • In vitro cellular tests confirmed the potential of the membranes as peripheral nerve regeneration systems. • The results indicated that DA III membrane should be the one considered for further peripheral nerve regeneration studies.

  5. Investigation of cell adhesion in chitosan membranes for peripheral nerve regeneration

    International Nuclear Information System (INIS)

    Carvalho, Cristiana R.; López-Cebral, Rita; Silva-Correia, Joana; Silva, Joana M.; Mano, João F.; Silva, Tiago H.; Freier, Thomas; Reis, Rui L.; Oliveira, Joaquim M.

    2017-01-01

    Peripheral nerve injuries have produced major concerns in regenerative medicine for several years, as the recovery of normal nerve function continues to be a significant clinical challenge. Chitosan (CHT), because of its good biocompatibility, biodegradability and physicochemical properties, has been widely used as a biomaterial in tissue engineering scaffolding. In this study, CHT membranes were produced with three different Degrees of Acetylation (DA), envisioning its application in peripheral nerve regeneration. The three CHT membranes (DA I: 1%, DA II: 2%, DA III: 5%) were extensively characterized and were found to have a smooth and flat surface, with DA III membrane having slightly higher roughness and surface energy. All the membranes presented suitable mechanical properties and did not show any signs of calcification after SBF test. Biodegradability was similar for all samples, and adequate to physically support neurite outgrowth. The in vitro cell culture results indicate selective cell adhesion. The CHT membranes favoured Schwann cells invasion and proliferation, with a display of appropriate cytoskeletal morphology. At the same time they presented low fibroblast infiltration. This fact may be greatly beneficial for the prevention of fibrotic tissue formation, a common phenomenon impairing peripheral nerve regeneration. The great deal of results obtained during this work permitted to select the formulation with the greatest potential for further biological tests. - Highlights: • Three chitosan membranes were produced with very specific degrees of acetylation (DA I: 1%, DA II: 2%, DA III: 5%). • Physicochemical characterization of the membranes showed their suitability for peripheral nerve regeneration purposes. • In vitro cellular tests confirmed the potential of the membranes as peripheral nerve regeneration systems. • The results indicated that DA III membrane should be the one considered for further peripheral nerve regeneration studies.

  6. Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

    Science.gov (United States)

    2017-09-01

    repair in the upper extremity using processed nerve allograft. J Hand Surg Am 2012 Nov;37(11):2340-9. (9) Joo S, Ko IK, Atala A, Yoo JJ , Lee SJ. Amniotic...nerve grafts implanted with autologous mesenchymal stem cells.Exp Neurol. 2007 Apr;204(2):658-66. (18) Kim BS, Chun SY, Atala A, Soker S, Yoo JJ , Kwon TG...wounds. Stem Cells Transl Med. 2012 ;1(11):792-802 4. Joo S, Ko IK, Atala A, Yoo JJ , Lee SJ. Amniotic fluid-derived stem cells in regenerative

  7. Production and in vitro evaluation of macroporous, cell-encapsulating alginate fibres for nerve repair

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Sharon Chien-Yu, E-mail: sharonlin114@gmail.com [The University of Queensland, Pharmacy Australia Centre of Excellence, 20 Cornwall Street, Woolloongabba, Brisbane QLD 4102 (Australia); Wang, Yiwei, E-mail: yiweiwang@anzac.edu.au [The University of Queensland, Pharmacy Australia Centre of Excellence, 20 Cornwall Street, Woolloongabba, Brisbane QLD 4102 (Australia); Wertheim, David F., E-mail: d.wertheim@kingston.ac.uk [Faculty of Science, Engineering and Computing, Kingston University, Kingston upon Thames, Surrey KT1 2EE (United Kingdom); Coombes, Allan G.A., E-mail: allancoombes@pharmacy.psu.ac.th [Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112 (Thailand)

    2017-04-01

    The prospects for successful peripheral nerve repair using fibre guides are considered to be enhanced by the use of a scaffold material, which promotes attachment and proliferation of glial cells and axonal regeneration. Macroporous alginate fibres were produced by extraction of gelatin particle porogens from wet spun fibres produced using a suspension of gelatin particles in 1.5% w/v alginate solution. Gelatin loading of the starting suspension of 40.0, 57.0, and 62.5% w/w resulted in gelatin loading of the dried alginate fibres of 16, 21, and 24% w/w respectively. Between 45 and 60% of the gelatin content of hydrated fibres was released in 1 h in distilled water at 37 °C, leading to rapid formation of a macroporous structure. Confocal laser scanning microscopy (CLSM) and image processing provided qualitative and quantitative analysis of mean equivalent macropore diameter (48–69 μm), pore size distribution, estimates of maximum porosity (14.6%) and pore connectivity. CLSM also revealed that gelatin residues lined the macropore cavities and infiltrated into the body of the alginate scaffolds, thus, providing cell adhesion molecules, which are potentially advantageous for promoting growth of glial cells and axonal extension. Macroporous alginate fibres encapsulating nerve cells [primary rat dorsal root ganglia (DRGs)] were produced by wet spinning alginate solution containing dispersed gelatin particles and DRGs. Marked outgrowth was evident over a distance of 150 μm at day 11 in cell culture, indicating that pores and channels created within the alginate hydrogel were providing a favourable environment for neurite development. These findings indicate that macroporous alginate fibres encapsulating nerve cells may provide the basis of a useful strategy for nerve repair. - Highlights: • Nerve cells were encapsulated in macroporous alginate fibres for use in nerve repair. • Fibres were produced from alginate solution containing gelatin porogens and cells.

  8. Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms

    Directory of Open Access Journals (Sweden)

    Zhi-yuan Guo

    2015-01-01

    Full Text Available Human umbilical cord-derived mesenchymal stem cells (hUCMSCs represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the paracrine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These findings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.

  9. [Facial nerve injuries cause changes in central nervous system microglial cells].

    Science.gov (United States)

    Cerón, Jeimmy; Troncoso, Julieta

    2016-12-01

    Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.

  10. Somato-synaptic variation of GABA(A) receptors in cultured murine cerebellar granule cells: investigation of the role of the alpha6 subunit.

    Science.gov (United States)

    Mellor, J R; Wisden, W; Randall, A D

    2000-07-10

    Electrophysiological investigation of cultured cerebellar murine granule cells revealed differences between the GABA(A) receptors at inhibitory synapses and those on the cell body. Specifically, mIPSCs decayed more rapidly than cell body receptors deactivated, the mean single channel conductance at the synapse (32 pS) was greater than that at cell body (21 pS) and only cell body receptors were sensitive to Zn(2+) (150 microM), which depressed response amplitude by 82+/-5% and almost doubled the rate of channel deactivation. The GABA(A) receptor alpha6 subunit is selectively expressed in cerebellar granule cells. Although concentrated at synapses, it is also found on extrasynaptic membranes. Using a mouse line (Deltaalpha6lacZ) lacking this subunit, we investigated its role in the somato-synaptic differences in GABA(A) receptor function. All differences between cell body and synaptic GABA(A) receptors observed in wild-type (WT) granule cells persisted in Deltaalpha6lacZ cells, thus demonstrating that they are not specifically due to the cellular distribution of the alpha6 subunit. However, mIPSCs from WT and Deltaalpha6lacZ cells differed in both their kinetics (faster decay in WT cells) and underlying single channel conductance (32 pS WT, 25 pS Deltaalpha6lacZ). This provides good evidence for a functional contribution of the alpha6 subunit to postsynaptic GABA(A) receptors in these cells. Despite this, deactivation kinetics of mIPSCs in WT and Deltaalpha6lacZ granule cells exhibited similar benzodiazepene (BDZ) sensitivity. This suggests that the enhanced BDZ-induced ataxia seen in Deltaalpha6lacZ mice may reflect physiological activity at extrasynaptic receptors which, unlike those at synapses, display differential BDZ-sensitivity in WT and Deltaalpha6lacZ granule cells (Jones, A.M., Korpi, E.R., McKernan, R.M., Nusser, Z., Pelz, R., Makela, R., Mellor, J.R., Pollard, S., Bahn, S., Stephenson, F.A., Randall, A.D., Sieghart, W., Somogyi, P., Smith, A.J.H., Wisden

  11. Posterior fossa gangliocytoma with facial nerve invasion: case report

    Directory of Open Access Journals (Sweden)

    Koerbel Andrei

    2003-01-01

    Full Text Available A 5 year-old boy with a cerebellar gangliocytoma with a peripheral right facial paresis and ataxia is presented. His MRI showed a heterogenous, diffuse lesion, isointense on T1 and hyperintense on T2-weigthed sequences, involving the right cerebellar hemisphere with direct extension into the right facial nerve. The present case is the first description of a gangliocytoma with direct facial nerve invasion, as demonstrated for the facial nerve paresis and supported by MRI and surgical inspection.

  12. The Wound Microenvironment Reprograms Schwann Cells to Invasive Mesenchymal-like Cells to Drive Peripheral Nerve Regeneration.

    Science.gov (United States)

    Clements, Melanie P; Byrne, Elizabeth; Camarillo Guerrero, Luis F; Cattin, Anne-Laure; Zakka, Leila; Ashraf, Azhaar; Burden, Jemima J; Khadayate, Sanjay; Lloyd, Alison C; Marguerat, Samuel; Parrinello, Simona

    2017-09-27

    Schwann cell dedifferentiation from a myelinating to a progenitor-like cell underlies the remarkable ability of peripheral nerves to regenerate following injury. However, the molecular identity of the differentiated and dedifferentiated states in vivo has been elusive. Here, we profiled Schwann cells acutely purified from intact nerves and from the wound and distal regions of severed nerves. Our analysis reveals novel facets of the dedifferentiation response, including acquisition of mesenchymal traits and a Myc module. Furthermore, wound and distal dedifferentiated Schwann cells constitute different populations, with wound cells displaying increased mesenchymal character induced by localized TGFβ signaling. TGFβ promotes invasion and crosstalks with Eph signaling via N-cadherin to drive collective migration of the Schwann cells across the wound. Consistently, Tgfbr2 deletion in Schwann cells resulted in misdirected and delayed reinnervation. Thus, the wound microenvironment is a key determinant of Schwann cell identity, and it promotes nerve repair through integration of multiple concerted signals. VIDEO ABSTRACT. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Lipid raft localization of GABA A receptor and Na+, K+-ATPase in discrete microdomain clusters in rat cerebellar granule cells

    DEFF Research Database (Denmark)

    Dalskov, Stine-Mathilde; Immerdal, Lissi; Niels-Christiansen, Lise-Lotte W

    2005-01-01

    The microdomain localization of the GABA(A) receptor in rat cerebellar granule cells was studied by subcellular fractionation and fluorescence- and immunogold electron microscopy. The receptor resided in lipid rafts, prepared at 37 degrees C by extraction with the nonionic detergent Brij 98......, but the raft fraction, defined by the marker ganglioside GM(1) in the floating fractions following density gradient centrifugation, was heterogeneous in density and protein composition. Thus, another major raft-associated membrane protein, the Na(+), K(+)-ATPase, was found in discrete rafts of lower density......, reflecting clustering of the two proteins in separate membrane microdomains. Both proteins were observed in patchy "hot spots" at the cell surface as well as in isolated lipid rafts. Their insolubility in Brij 98 was only marginally affected by methyl-beta-cyclodextrin. In contrast, both the GABA(A) receptor...

  14. Bone Marrow-Derived, Neural-Like Cells Have the Characteristics of Neurons to Protect the Peripheral Nerve in Microenvironment

    Directory of Open Access Journals (Sweden)

    Shi-lei Guo

    2015-01-01

    Full Text Available Effective repair of peripheral nerve defects is difficult because of the slow growth of new axonal growth. We propose that “neural-like cells” may be useful for the protection of peripheral nerve destructions. Such cells should prolong the time for the disintegration of spinal nerves, reduce lesions, and improve recovery. But the mechanism of neural-like cells in the peripheral nerve is still unclear. In this study, bone marrow-derived neural-like cells were used as seed cells. The cells were injected into the distal end of severed rabbit peripheral nerves that were no longer integrated with the central nervous system. Electromyography (EMG, immunohistochemistry, and transmission electron microscopy (TEM were employed to analyze the development of the cells in the peripheral nerve environment. The CMAP amplitude appeared during the 5th week following surgery, at which time morphological characteristics of myelinated nerve fiber formation were observed. Bone marrow-derived neural-like cells could protect the disintegration and destruction of the injured peripheral nerve.

  15. Administration of memantine during ethanol withdrawal in neonatal rats: effects on long-term ethanol-induced motor incoordination and cerebellar Purkinje cell loss.

    Science.gov (United States)

    Idrus, Nirelia M; McGough, Nancy N H; Riley, Edward P; Thomas, Jennifer D

    2011-02-01

    Alcohol consumption during pregnancy can damage the developing fetus, illustrated by central nervous system dysfunction and deficits in motor and cognitive abilities. Binge drinking has been associated with an increased risk of fetal alcohol spectrum disorders, likely due to increased episodes of ethanol withdrawal. We hypothesized that overactivity of the N-methyl-D-aspartate (NMDA) receptor during ethanol withdrawal leads to excitotoxic cell death in the developing brain. Consistent with this, administration of NMDA receptor antagonists (e.g., MK-801) during withdrawal can attenuate ethanol's teratogenic effects. The aim of this study was to determine whether administration of memantine, an NMDA receptor antagonist, during ethanol withdrawal could effectively attenuate ethanol-related deficits, without the adverse side effects associated with other NMDA receptor antagonists. Sprague-Dawley pups were exposed to 6.0 g/kg ethanol or isocaloric maltose solution via intubation on postnatal day 6, a period of brain development equivalent to a portion of the 3rd trimester. Twenty-four and 36 hours after ethanol, subjects were injected with 0, 10, or 15 mg/kg memantine, totaling doses of 0, 20, or 30 mg/kg. Motor coordination was tested on a parallel bar task and the total number of cerebellar Purkinje cells was estimated using unbiased stereology. Alcohol exposure induced significant parallel bar motor incoordination and reduced Purkinje cell number. Memantine administration significantly attenuated both ethanol-associated motor deficits and cerebellar cell loss in a dose-dependent manner. Memantine was neuroprotective when administered during ethanol withdrawal. These data provide further support that ethanol withdrawal contributes to fetal alcohol spectrum disorders. Copyright © 2010 by the Research Society on Alcoholism.

  16. Methylmercury disrupts the balance between phosphorylated and non-phosphorylated cofilin in primary cultures of mice cerebellar granule cells A proteomic study

    International Nuclear Information System (INIS)

    Vendrell, Iolanda; Carrascal, Montserrat; Campos, Francisco; Abian, Joaquin; Sunol, Cristina

    2010-01-01

    Methylmercury is an environmental contaminant that is particularly toxic to the developing central nervous system; cerebellar granule neurons are especially vulnerable. Here, primary cultures of cerebellar granule cells (CGCs) were continuously exposed to methylmercury for up to 16 days in vitro (div). LC50 values were 508 ± 199, 345 ± 47, and 243 ± 45 nM after exposure for 6, 11, and 16 div, respectively. Proteins from cultured mouse CGCs were separated by 2DE. Seventy-one protein spots were identified by MALDI-TOF PMF and MALDI-TOF/TOF sequencing. Prolonged exposure to a subcytotoxic concentration of methylmercury significantly increased non-phosphorylated cofilin both in cell protein extracts (1.4-fold; p < 0.01) and in mitochondrial-enriched fractions (1.7-fold; p < 0.01). The decrease in P-cofilin induced by methylmercury was concentration-dependent and occurred after different exposure times. The percentage of P-cofilin relative to total cofilin significantly decreased to 49 ± 13% vs. control cells after exposure to 300 nM methylmercury for 5 div. The balance between the phosphorylated and non-phosphorylated form of cofilin regulates actin dynamics and facilitates actin filament turnover. Filamentous actin dynamics and reorganization are responsible of neuron shape change, migration, polarity formation, regulation of synaptic structures and function, and cell apoptosis. An alteration of the complex regulation of the cofilin phosphorylation/dephosphorylation pathway could be envisaged as an underlying mechanism compatible with reported signs of methylmercury-induced neurotoxicity.

  17. The effects of early hypo- and hyperthyroidism on the development of rat cerebellar cortex. III. Kinetics of cell proliferation in the external granular layer.

    Science.gov (United States)

    Lauder, J M

    1977-04-22

    The effects of early hypo- and hyperthyroidism on the rates of cell acquisition and proliferation have been studied in the external granular layer (EGL) of the developing rat cerebellar cortex at 10 days of age using quantitative autoradiographic methods. Both altered thyroid states reduce the rate of cell acquisition in the EGL, but appear to do so for different reasons. Hyperthyroidism shortens the average length of the cell cycle by decreasing the duration of the pre-DNA synthetic phase (G1), indicating that excess thyroxine may exert a direct effect on the EGL. This action involves the early onset of neuronal differentiation (cessation of proliferation)46 which presumably leads to the observed decrease in the rate of cell acquisition (increased doubling time). Such differentiating cells do not, however, leave the proliferative zone or the EGL prematurely, resulting in a reduced labeling index, mitotic index, and growth fraction as non-dividing cells dilute the proliferating cell population. Hypothyroidism, on the other hand, leads to no significant change in the length of the cell cycle or in the mitotic index, but causes a decreased labeling index and growth fraction, as well as a reduced rate of cell acquisition (increased doubling time). No significant change in the amount of cell death in the EGL could be found to explain this apparent discrepancy between the rate of cell proliferation (cell cycle length) and cell acqusiition. The answer to this puzzle appears to lie in the mitotic index, which is not affected to the same extent as the labeling index, although it is also slightly reduced. If cells were to remain longer in mitosis, this could result in a decreased labeling index and growth fraction but nearly normal mitotic index and cell cycle length (as measured using the % labeled mitoses method), since those cells dropping out of the cycling population would be counted as mitoses...

  18. Effect of neural-induced mesenchymal stem cells and platelet-rich plasma on facial nerve regeneration in an acute nerve injury model.

    Science.gov (United States)

    Cho, Hyong-Ho; Jang, Sujeong; Lee, Sang-Chul; Jeong, Han-Seong; Park, Jong-Seong; Han, Jae-Young; Lee, Kyung-Hwa; Cho, Yong-Bum

    2010-05-01

    The purpose of this study was to investigate the effects of platelet-rich plasma (PRP) and neural-induced human mesenchymal stem cells (nMSCs) on axonal regeneration from a facial nerve axotomy injury in a guinea pig model. Prospective, controlled animal study. Experiments involved the transection and repair of the facial nerve in 24 albino guinea pigs. Four groups were created based on the method of repair: suture only (group I, control group); PRP with suture (group II); nMSCs with suture (group III); and PRP and nMSCs with suture (group IV). Each method of repair was applied immediately after nerve transection. The outcomes measured were: 1) functional outcome measurement (vibrissae and eyelid closure movements); 2) electrophysiologic evaluation; 3) neurotrophic factors assay; and 4) histologic evaluation. With respect to the functional outcome measurement, the functional outcomes improved after transection and reanastomosis in all groups. The control group was the slowest to demonstrate recovery of movement after transection and reanastomosis. The other three groups (groups II, III, and IV) had significant improvement in function compared to the control group 4 weeks after surgery (P facial nerve regeneration in an animal model of facial nerve axotomy. The use of nMSCs showed no benefit over the use of PRP in facial nerve regeneration, but the combined use of PRP and nMSCs showed a greater beneficial effect than use of either alone. This study provides evidence for the potential clinical application of PRP and nMSCs in peripheral nerve regeneration of an acute nerve injury. Laryngoscope, 2010.

  19. Generation of a Motor Nerve Organoid with Human Stem Cell-Derived Neurons

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    Jiro Kawada

    2017-11-01

    Full Text Available During development, axons spontaneously assemble into a fascicle to form nerves and tracts in the nervous system as they extend within a spatially constrained path. However, understanding of the axonal fascicle has been hampered by lack of an in vitro model system. Here, we report generation of a nerve organoid composed of a robust fascicle of axons extended from a spheroid of human stem cell-derived motor neurons within our custom-designed microdevice. The device is equipped with a narrow channel providing a microenvironment that facilitates the growing axons to spontaneously assemble into a unidirectional fascicle. The fascicle was specifically made with axons. We found that it was electrically active and elastic and could serve as a model to evaluate degeneration of axons in vitro. This nerve organoid model should facilitate future studies on the development of the axonal fascicle and drug screening for diseases affecting axon fascicles.

  20. Adipose-Derived Stem Cells Promote Peripheral Nerve Regeneration In Vivo without Differentiation into Schwann-Like Lineage.

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    Sowa, Yoshihiro; Kishida, Tsunao; Imura, Tetsuya; Numajiri, Toshiaki; Nishino, Kenichi; Tabata, Yasuhiko; Mazda, Osam

    2016-02-01

    During recent decades, multipotent stem cells were found to reside in the adipose tissue, and these adipose-derived stem cells were shown to play beneficial roles, like those of Schwann cells, in peripheral nerve regeneration. However, it has not been well established whether adipose-derived stem cells offer beneficial effects to peripheral nerve injuries in vivo as Schwann cells do. Furthermore, the in situ survival and differentiation of adipose-derived stem cells after transplantation at the injured peripheral nerve tissue remain to be fully elucidated. Adipose-derived stem cells and Schwann cells were transplanted with gelatin hydrogel tubes at the artificially blunted sciatic nerve lesion in mice. Neuroregenerative abilities of them were comparably estimated. Cre-loxP-mediated fate tracking was performed to visualize survival in vivo of transplanted adipose-derived stem cells and to investigate whether they differentiated into Schwann linage cells at the peripheral nerve injury site. The transplantation of adipose-derived stem cells promoted regeneration of axons, formation of myelin, and restoration of denervation muscle atrophy to levels comparable to those achieved by Schwann cell transplantation. The adipose-derived stem cells survived for at least 4 weeks after transplantation without differentiating into Schwann cells. Transplanted adipose-derived stem cells did not differentiate into Schwann cells but promoted peripheral nerve regeneration at the injured site. The neuroregenerative ability was comparable to that of Schwann cells. Adipose-derived stem cells at an undifferentiated stage may be used as an alternative cell source for autologous cell therapy for patients with peripheral nerve injury.

  1. Age-Dependent Schwann Cell Phenotype Regulation Following Peripheral Nerve Injury.

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    Chen, Wayne A; Luo, T David; Barnwell, Jonathan C; Smith, Thomas L; Li, Zhongyu

    2017-12-01

    Schwann cells are integral to the regenerative capacity of the peripheral nervous system, which declines after adolescence. The mechanisms underlying this decline are poorly understood. This study sought to compare the protein expression of Notch, c-Jun, and Krox-20 after nerve crush injury in adolescent and young adult rats. We hypothesized that these Schwann cell myelinating regulatory factors are down-regulated after nerve injury in an age-dependent fashion. Adolescent (2 months old) and young adult (12 months old) rats (n = 48) underwent sciatic nerve crush injury. Protein expression of Notch, c-Jun, and Krox-20 was quantified by Western blot analysis at 1, 3, and 7 days post-injury. Functional recovery was assessed in a separate group of animals (n = 8) by gait analysis (sciatic functional index) and electromyography (compound motor action potential) over an 8-week post-injury period. Young adult rats demonstrated a trend of delayed onset of the dedifferentiating regulatory factors, Notch and c-Jun, corresponding to the delayed functional recovery observed in young adult rats compared to adolescent rats. Compound motor action potential area was significantly greater in adolescent rats relative to young adult rats, while amplitude and velocity trended toward statistical significance. The process of Schwann cell dedifferentiation following peripheral nerve injury shows different trends with age. These trends of delayed onset of key regulatory factors responsible for Schwann cell myelination may be one of many possible factors mediating the significant differences in functional recovery between adolescent and young adult rats following peripheral nerve injury.

  2. Delayed nerve stimulation promotes axon-protective neurofilament phosphorylation, accelerates immune cell clearance and enhances remyelination in vivo in focally demyelinated nerves.

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    Nikki A McLean

    Full Text Available Rapid and efficient axon remyelination aids in restoring strong electrochemical communication with end organs and in preventing axonal degeneration often observed in demyelinating neuropathies. The signals from axons that can trigger more effective remyelination in vivo are still being elucidated. Here we report the remarkable effect of delayed brief electrical nerve stimulation (ES; 1 hour @ 20 Hz 5 days post-demyelination on ensuing reparative events in a focally demyelinated adult rat peripheral nerve. ES impacted many parameters underlying successful remyelination. It effected increased neurofilament expression and phosphorylation, both implicated in axon protection. ES increased expression of myelin basic protein (MBP and promoted node of Ranvier re-organization, both of which coincided with the early reappearance of remyelinated axons, effects not observed at the same time points in non-stimulated demyelinated nerves. The improved ES-associated remyelination was accompanied by enhanced clearance of ED-1 positive macrophages and attenuation of glial fibrillary acidic protein expression in accompanying Schwann cells, suggesting a more rapid clearance of myelin debris and return of Schwann cells to a nonreactive myelinating state. These benefits of ES correlated with increased levels of brain derived neurotrophic factor (BDNF in the acute demyelination zone, a key molecule in the initiation of the myelination program. In conclusion, the tremendous impact of delayed brief nerve stimulation on enhancement of the innate capacity of a focally demyelinated nerve to successfully remyelinate identifies manipulation of this axis as a novel therapeutic target for demyelinating pathologies.

  3. Delayed nerve stimulation promotes axon-protective neurofilament phosphorylation, accelerates immune cell clearance and enhances remyelination in vivo in focally demyelinated nerves.

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    McLean, Nikki A; Popescu, Bogdan F; Gordon, Tessa; Zochodne, Douglas W; Verge, Valerie M K

    2014-01-01

    Rapid and efficient axon remyelination aids in restoring strong electrochemical communication with end organs and in preventing axonal degeneration often observed in demyelinating neuropathies. The signals from axons that can trigger more effective remyelination in vivo are still being elucidated. Here we report the remarkable effect of delayed brief electrical nerve stimulation (ES; 1 hour @ 20 Hz 5 days post-demyelination) on ensuing reparative events in a focally demyelinated adult rat peripheral nerve. ES impacted many parameters underlying successful remyelination. It effected increased neurofilament expression and phosphorylation, both implicated in axon protection. ES increased expression of myelin basic protein (MBP) and promoted node of Ranvier re-organization, both of which coincided with the early reappearance of remyelinated axons, effects not observed at the same time points in non-stimulated demyelinated nerves. The improved ES-associated remyelination was accompanied by enhanced clearance of ED-1 positive macrophages and attenuation of glial fibrillary acidic protein expression in accompanying Schwann cells, suggesting a more rapid clearance of myelin debris and return of Schwann cells to a nonreactive myelinating state. These benefits of ES correlated with increased levels of brain derived neurotrophic factor (BDNF) in the acute demyelination zone, a key molecule in the initiation of the myelination program. In conclusion, the tremendous impact of delayed brief nerve stimulation on enhancement of the innate capacity of a focally demyelinated nerve to successfully remyelinate identifies manipulation of this axis as a novel therapeutic target for demyelinating pathologies.

  4. Dominant inheritance of retinal ganglion cell resistance to optic nerve crush in mice

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    Schlamp Cassandra L

    2007-03-01

    Full Text Available Abstract Background Several neurodegenerative diseases are influenced by complex genetics that affect an individual's susceptibility, disease severity, and rate of progression. One such disease is glaucoma, a chronic neurodegenerative condition of the eye that targets and stimulates apoptosis of CNS neurons called retinal ganglion cells. Since ganglion cell death is intrinsic, it is reasonable that the genes that control this process may contribute to the complex genetics that affect ganglion cell susceptibility to disease. To determine if genetic background influences susceptibility to optic nerve damage, leading to ganglion cell death, we performed optic nerve crush on 15 different inbred lines of mice and measured ganglion cell loss. Resistant and susceptible strains were used in a reciprocal breeding strategy to examine the inheritance pattern of the resistance phenotype. Because earlier studies had implicated Bax as a susceptibility allele for ganglion cell death in the chronic neurodegenerative disease glaucoma, we conducted allelic segregation analysis and mRNA quantification to assess this gene as a candidate for the cell death phenotype. Results Inbred lines showed varying levels of susceptibility to optic nerve crush. DBA/2J mice were most resistant and BALB/cByJ mice were most susceptible. F1 mice from these lines inherited the DBA/2J phenotype, while N2 backcross mice exhibited the BALB/cByJ phenotype. F2 mice exhibited an intermediate phenotype. A Wright Formula calculation suggested as few as 2 dominant loci were linked to the resistance phenotype, which was corroborated by a Punnett Square analysis of the distribution of the mean phenotype in each cross. The levels of latent Bax mRNA were the same in both lines, and Bax alleles did not segregate with phenotype in N2 and F2 mice. Conclusion Inbred mice show different levels of resistance to optic nerve crush. The resistance phenotype is heritable in a dominant fashion involving

  5. Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes.

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    Zagha, Edward; Manita, Satoshi; Ross, William N; Rudy, Bernardo

    2010-06-01

    Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca(2+) spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca(2+) spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca(2+)](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca(2+) signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca(2+) influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease.

  6. After Nerve Injury, Lineage Tracing Shows That Myelin and Remak Schwann Cells Elongate Extensively and Branch to Form Repair Schwann Cells, Which Shorten Radically on Remyelination.

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    Gomez-Sanchez, Jose A; Pilch, Kjara S; van der Lans, Milou; Fazal, Shaline V; Benito, Cristina; Wagstaff, Laura J; Mirsky, Rhona; Jessen, Kristjan R

    2017-09-13

    There is consensus that, distal to peripheral nerve injury, myelin and Remak cells reorganize to form cellular columns, Bungner's bands, which are indispensable for regeneration. However, knowledge of the structure of these regeneration tracks has not advanced for decades and the structure of the cells that form them, denervated or repair Schwann cells, remains obscure. Furthermore, the origin of these cells from myelin and Remak cells and their ability to give rise to myelin cells after regeneration has not been demonstrated directly, although these conversions are believed to be central to nerve repair. Using genetic lineage-tracing and scanning-block face electron microscopy, we show that injury of sciatic nerves from mice of either sex triggers extensive and unexpected Schwann cell elongation and branching to form long, parallel processes. Repair cells are 2- to 3-fold longer than myelin and Remak cells and 7- to 10-fold longer than immature Schwann cells. Remarkably, when repair cells transit back to myelinating cells, they shorten ∼7-fold to generate the typically short internodes of regenerated nerves. The present experiments define novel morphological transitions in injured nerves and show that repair Schwann cells have a cell-type-specific structure that differentiates them from other cells in the Schwann cell lineage. They also provide the first direct evidence using genetic lineage tracing for two basic assumptions in Schwann cell biology: that myelin and Remak cells generate the elongated cells that build Bungner bands in injured nerves and that such cells can transform to myelin cells after regeneration. SIGNIFICANCE STATEMENT After injury to peripheral nerves, the myelin and Remak Schwann cells distal to the injury site reorganize and modify their properties to form cells that support the survival of injured neurons, promote axon growth, remove myelin-associated growth inhibitors, and guide regenerating axons to their targets. We show that the

  7. Dynamic Quantification of Host Schwann Cell Migration into Peripheral Nerve Allografts

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    Whitlock, Elizabeth L.; Myckatyn, Terence M.; Tong, Alice Y.; Yee, Andrew; Yan, Ying; Magill, Christina K.; Johnson, Philip J.; Mackinnon, Susan E.

    2010-01-01

    Host Schwann cell (SC) migration into nerve allografts is the limiting factor in the duration of immunosuppression following peripheral nerve allotransplantation, and may be affected by different immunosuppressive regimens. Our objective was to compare SC migration patterns between clinical and experimental immunosuppression regimens both over time and at the harvest endpoint. Eighty mice that express GFP under the control of the Schwann cell specific S100 promoter were engrafted with allogeneic, nonfluorescent sciatic nerve grafts. Mice received immunosuppression with either tacrolimus (FK506), or experimental T-cell triple costimulation blockade (CSB), consisting of CTLA4-immunoglobulin fusion protein, anti-CD40 monoclonal antibody, and anti-inducible costimulator monoclonal antibody. Migration of GFP-expressing host SCs into wild-type allografts was assessed in vivo every 3 weeks until 15 weeks postoperatively, and explanted allografts were evaluated for immunohistochemical staining patterns to differentiate graft from host SCs. Immunosuppression with tacrolimus exhibited a plateau of SC migration, characterized by significant early migration (< 3 weeks) followed by a constant level of host SCs in the graft (15 weeks). At the endpoint, graft fluorescence was decreased relative to surrounding host nerve, and donor SCs persisted within the graft. CSB-treated mice displayed gradually increasing migration of host SCs into the graft, without the plateau noted in tacrolimus-treated mice, and also maintained a population of donor SCs at the 15-week endpoint. SC migration patterns are affected by immunosuppressant choice, particularly in the immediate postoperative period, and the use of a single treatment of CSB may allow for gradual population of nerve allografts with host SCs. PMID:20633557

  8. Local delivery of glial cell line-derived neurotrophic factor improves facial nerve regeneration after late repair.

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    Barras, Florian M; Kuntzer, Thierry; Zurn, Anne D; Pasche, Philippe

    2009-05-01

    Facial nerve regeneration is limited in some clinical situations: in long grafts, by aged patients, and when the delay between nerve lesion and repair is prolonged. This deficient regeneration is due to the limited number of regenerating nerve fibers, their immaturity and the unresponsiveness of Schwann cells after a long period of denervation. This study proposes to apply glial cell line-derived neurotrophic factor (GDNF) on facial nerve grafts via nerve guidance channels to improve the regeneration. Two situations were evaluated: immediate and delayed grafts (repair 7 months after the lesion). Each group contained three subgroups: a) graft without channel, b) graft with a channel without neurotrophic factor; and c) graft with a GDNF-releasing channel. A functional analysis was performed with clinical observation of facial nerve function, and nerve conduction study at 6 weeks. Histological analysis was performed with the count of number of myelinated fibers within the graft, and distally to the graft. Central evaluation was assessed with Fluoro-Ruby retrograde labeling and Nissl staining. This study showed that GDNF allowed an increase in the number and the maturation of nerve fibers, as well as the number of retrogradely labeled neurons in delayed anastomoses. On the contrary, after immediate repair, the regenerated nerves in the presence of GDNF showed inferior results compared to the other groups. GDNF is a potent neurotrophic factor to improve facial nerve regeneration in grafts performed several months after the nerve lesion. However, GDNF should not be used for immediate repair, as it possibly inhibits the nerve regeneration.

  9. Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis

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    Noriyuki Koibuchi

    2016-08-01

    Full Text Available Gadolinium (Gd-based contrast agents (GBCAs are used in diagnostic imaging to enhance the quality of magnetic resonance imaging or angiography. After intravenous injection, GBCAs can accumulate in the brain. Thyroid hormones (THs are critical to the development and functional maintenance of the central nervous system. TH actions in brain are mainly exerted through nuclear TH receptors (TRs. We examined the effects of GBCAs on TR-mediated transcription in CV-1 cells using transient transfection-based reporter assay and thyroid hormone-mediated cerebellar Purkinje cell morphogenesis in primary culture. We also measured the cellular accumulation and viability of Gd after representative GBCA treatments in cultured CV-1 cells. Both linear (Gd-diethylene triamine pentaacetic acid-bis methyl acid, Gd-DTPA-BMA and macrocyclic (Gd-tetraazacyclododecane tetraacetic acid, Gd-DOTA GBCAs were accumulated without inducing cell death in CV-1 cells. In contrast, Gd chloride (GdCl3 treatment induced approximately 100 times higher Gd accumulation and significantly reduced the number of cells. Low doses of Gd-DTPA-BMA (10−8–10−6 M augmented TR-mediated transcription, but the transcription was suppressed at higher dose (10−5 – 10−4 M, with decreased β-galactosidase activity indicating cellular toxicity. TR-mediated transcription was not altered by Gd-DOTA or GdCl3, but the latter induced a significant reduction in β-galactosidase activity at high doses, indicating cellular toxicity. In cerebellar cultures, the dendrite arborization of Purkinje cells induced by 10-9 M T4 was augmented by low-dose Gd-DTPA-BMA (10−7 M but was suppressed by higher dose (10−5 M. Such augmentation by low-dose Gd-DTPA-BMA was not observed with 10-9 M T3, probably because of the greater dendrite arborization by T3; however, the arborization by T3 was suppressed by a higher dose of Gd-DTPA-BMA (10-5 M as seen in T4 treatment. The effect of Gd-DOTA on dendrite arborization

  10. Direct Conversion of Human Fibroblasts into Schwann Cells that Facilitate Regeneration of Injured Peripheral Nerve In Vivo.

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    Sowa, Yoshihiro; Kishida, Tsunao; Tomita, Koichi; Yamamoto, Kenta; Numajiri, Toshiaki; Mazda, Osam

    2017-04-01

    Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs). The dSCs expressed SC-specific proteins, secreted neurotrophic factors, and induced neuronal cells to extend neurites. The dSCs also displayed myelin-forming capability both in vitro and in vivo. Moreover, transplantation of the dSCs into the transected sciatic nerve in mice resulted in significantly accelerated regeneration of the nerve and in improved motor function at a level comparable to that with transplantation of the SCs obtained from a peripheral nerve. The dSCs induced by our procedure may be applicable for novel regeneration therapy for not only peripheral nerve injury but also for central nerve damage and for neurodegenerative disorders related to SC dysfunction. Stem Cells Translational Medicine 2017;6:1207-1216. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  11. Cerebellar abiotrophy in a family of Border Collie dogs.

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    Sandy, J R; Slocombe, R E; Mitten, R W; Jedwab, D

    2002-11-01

    Cerebellar abiotrophies have a nonsex-linked, autosomal, recessively inherited basis in a number of species, and lesions typically reflect profound and progressive loss of Purkinje cells. In this report, an unusual form of abiotrophy is described for two sibling Border Collies. Extensive loss of the cerebellar granular cell layer was present with relative sparing of Purkinje cells of two female pups. The biochemical basis for this form of cerebellar abiotrophy is unknown, but the lack of disease in other siblings supports an autosomal recessive mode of inheritance.

  12. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization

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    Xue-man Lv

    2016-01-01

    Full Text Available The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 µg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

  13. Allotransplanted DRG neurons or Schwann cells affect functional recovery in a rodent model of sciatic nerve injury.

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    Dayawansa, Samantha; Wang, Ernest W; Liu, Weimin; Markman, John D; Gelbard, Harris A; Huang, Jason H

    2014-11-01

    In this study, the functional recoveries of Sprague-Dawley rats following repair of a complete sciatic nerve transection using allotransplanted dorsal root ganglion (DRG) neurons or Schwann cells were examined using a number of outcome measures. Four groups were compared: (1) repair with a nerve guide conduit seeded with allotransplanted Schwann cells harvested from Wistar rats, (2) repair with a nerve guide conduit seeded with DRG neurons, (3) repair with solely a nerve guide conduit, and (4) sham-surgery animals where the sciatic nerve was left intact. The results corroborated our previous reported histology findings and measures of immunogenicity. The Wistar-DRG-treated group achieved the best recovery, significantly outperforming both the Wistar-Schwann group and the nerve guide conduit group in the Von Frey assay of touch response (P DRG and Wistar-Schwann seeded repairs showed lower frequency and severity in an autotomy measure of the self-mutilation of the injured leg because of neuralgia. These results suggest that in complete peripheral nerve transections, surgical repair using nerve guide conduits with allotransplanted DRG and Schwann cells may improve recovery, especially DRG neurons, which elicit less of an immune response.

  14. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells

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    Louise A. Mesentier-Louro

    2017-01-01

    Full Text Available Nerve growth factor (NGF is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC degenerate following optic-nerve crush (ONC, even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75NTR, TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

  15. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells.

    Science.gov (United States)

    Mesentier-Louro, Louise A; De Nicolò, Sara; Rosso, Pamela; De Vitis, Luigi A; Castoldi, Valerio; Leocani, Letizia; Mendez-Otero, Rosalia; Santiago, Marcelo F; Tirassa, Paola; Rama, Paolo; Lambiase, Alessandro

    2017-01-05

    Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75 NTR , TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75 NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75 NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

  16. Ex Vivo Assay of Electrical Stimulation to Rat Sciatic Nerves: Cell Behaviors and Growth Factor Expression.

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    Du, Zhiyong; Bondarenko, Olexandr; Wang, Dingkun; Rouabhia, Mahmoud; Zhang, Ze

    2016-06-01

    Neurite outgrowth and axon regeneration are known to benefit from electrical stimulation. However, how neuritis and their surroundings react to electrical field is difficult to replicate by monolayer cell culture. In this work freshly harvested rat sciatic nerves were cultured and exposed to two types of electrical field, after which time the nerve tissues were immunohistologically stained and the expression of neurotrophic factors and cytokines were evaluated. ELISA assay was used to confirm the production of specific proteins. All cell populations survived the 48 h culture with little necrosis. Electrical stimulation was found to accelerate Wallerian degeneration and help Schwann cells to switch into migratory phenotype. Inductive electrical stimulation was shown to upregulate the secretion of multiple neurotrophic factors. Cellular distribution in nerve tissue was altered upon the application of an electrical field. This work thus presents an ex vivo model to study denervated axon in well controlled electrical field, bridging monolayer cell culture and animal experiment. It also demonstrated the critical role of electrical field distribution in regulating cellular activities. © 2015 Wiley Periodicals, Inc.

  17. Early regenerative effects of NGF-transduced Schwann cells in peripheral nerve repair.

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    Shakhbazau, Antos; Kawasoe, Jean; Hoyng, Stefan A; Kumar, Ranjan; van Minnen, Jan; Verhaagen, Joost; Midha, Rajiv

    2012-05-01

    Peripheral nerve injury leads to a rapid and robust increase in the synthesis of neurotrophins which guide and support regenerating axons. To further optimize neurotrophin supply at the earliest stages of regeneration, we over-expressed NGF in Schwann cells (SCs) by transducing these cells with a lentiviral vector encoding NGF (NGF-SCs). Transplantation of NGF-SCs in a rat sciatic nerve transection/repair model led to significant increase of NGF levels 2weeks after injury and correspondingly to substantial improvement in axonal regeneration. Numbers of NF200, ChAT and CGRP-positive axon profiles, as well as the gastrocnemius muscle weights, were significantly higher in the NGF-Schwann cell group compared to the animals that received control SCs transduced with a lentiviral vector encoding GFP (GFP-SCs). Comparison with other models of NGF application signifies the important role of this neurotrophin during the early stages of regeneration, and supports the importance of developing combined gene and cell therapy for peripheral nerve repair. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Effects of Schwann cell alignment along the oriented electrospun chitosan nanofibers on nerve regeneration.

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    Wang, Wei; Itoh, Soichiro; Konno, Katsumi; Kikkawa, Takeshi; Ichinose, Shizuko; Sakai, Katsuyoshi; Ohkuma, Tsuneo; Watabe, Kazuhiko

    2009-12-15

    We have constructed a chitosan nonwoven nanofiber mesh tube consisting of oriented fibers by the electrospinning method. The efficacy of oriented nanofibers on Schwann cell alignment and positive effect of this tube on peripheral nerve regeneration were confirmed. The physical properties of the chitosan nanofiber mesh sheets prepared by electrospinning with or without fiber orientation were characterized. Then, immortalized Schwann cells were cultured on these sheets. Furthermore, the chitosan nanofiber mesh tubes with or without orientation, and bilayered chitosan mesh tube with an inner layer of oriented nanofibers and an outer layer of randomized nanofibers were bridgegrafted into rat sciatic nerve defect. As a result of fiber orientation, the tensile strength along the axis of the sheet increased. Because Schwann cells aligned along the nanofibers, oriented fibrous sheets could exhibit a Schwann cell column. Functional recovery and electrophysiological recovery occurred in time in the oriented group as well as in the bilayered group, and approximately matched those in the isograft. Furthermore, histological analysis revealed that the sprouting of myelinated axons occurred vigorously followed by axonal maturation in the isograft, oriented, and bilayered group in the order. The oriented chitosan nanofiber mesh tube may be a promising substitute for autogenous nerve graft.

  19. Peripheral Nerve Injuries and Transplantation of Olfactory Ensheathing Cells for Axonal Regeneration and Remyelination: Fact or Fiction?

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    Christine Radtke

    2012-10-01

    Full Text Available Successful nerve regeneration after nerve trauma is not only important for the restoration of motor and sensory functions, but also to reduce the potential for abnormal sensory impulse generation that can occur following neuroma formation. Satisfying functional results after severe lesions are difficult to achieve and the development of interventional methods to achieve optimal functional recovery after peripheral nerve injury is of increasing clinical interest. Olfactory ensheathing cells (OECs have been used to improve axonal regeneration and functional outcome in a number of studies in spinal cord injury models. The rationale is that the OECs may provide trophic support and a permissive environment for axonal regeneration. The experimental transplantation of OECs to support and enhance peripheral nerve regeneration is much more limited. This chapter reviews studies using OECs as an experimental cell therapy to improve peripheral nerve regeneration.

  20. Neural-differentiated mesenchymal stem cells incorporated into muscle stuffed vein scaffold forms a stable living nerve conduit.

    Science.gov (United States)

    Hassan, Nur Hidayah; Sulong, Ahmad Fadzli; Ng, Min-Hwei; Htwe, Ohnmar; Idrus, Ruszymah B H; Roohi, Sharifah; Naicker, Amaramalar S; Abdullah, Shalimar

    2012-10-01

    Autologous nerve grafts to bridge nerve gaps have donor site morbidity and possible neuroma formation resulting in development of various methods of bridging nerve gaps without using autologous nerve grafts. We have fabricated an acellular muscle stuffed vein seeded with differentiated mesenchymal stem cells (MSCs) as a substitute for nerve autografts. Human vein and muscle were both decellularized by liquid nitrogen immersion with subsequent hydrolysis in hydrochloric acid. Human MSCs were subjected to a series of treatments with a reducing agent, retinoic acid, and a combination of trophic factors. The differentiated MSCs were seeded on the surface of acellular muscle tissue and then stuffed into the vein. Our study showed that 35-75% of the cells expressed neural markers such as S100b, glial fibrillary acidic protein (GFAP), p75 NGF receptor, and Nestin after differentiation. Histological and ultra structural analyses of muscle stuffed veins showed attachment of cells onto the surface of the acellular muscle and penetration of the cells into the hydrolyzed fraction of muscle fibers. We implanted these muscle stuffed veins into athymic mice and at 8 weeks post-implantation, the acellular muscle tissue had fully degraded and replaced with new matrix produced by the seeded cells. The vein was still intact and no inflammatory reactions were observed proving the biocompatibility and biodegradability of the conduit. In conclusion, we have successfully formed a stable living nerve conduit which may serve as a substitute for autologous nerves. Copyright © 2012 Orthopaedic Research Society.

  1. Fractional cable equation models for anomalous electrodiffusion in nerve cells: infinite domain solutions.

    Science.gov (United States)

    Langlands, T A M; Henry, B I; Wearne, S L

    2009-12-01

    We introduce fractional Nernst-Planck equations and derive fractional cable equations as macroscopic models for electrodiffusion of ions in nerve cells when molecular diffusion is anomalous subdiffusion due to binding, crowding or trapping. The anomalous subdiffusion is modelled by replacing diffusion constants with time dependent operators parameterized by fractional order exponents. Solutions are obtained as functions of the scaling parameters for infinite cables and semi-infinite cables with instantaneous current injections. Voltage attenuation along dendrites in response to alpha function synaptic inputs is computed. Action potential firing rates are also derived based on simple integrate and fire versions of the models. Our results show that electrotonic properties and firing rates of nerve cells are altered by anomalous subdiffusion in these models. We have suggested electrophysiological experiments to calibrate and validate the models.

  2. Local Xenotransplantation of Bone Marrow Derived Mast Cells (BMMCs) Improves Functional Recovery of Transected Sciatic Nerve in Cat: A Novel Approach in Cell Therapy.

    Science.gov (United States)

    Mohammadi, Rahim; Anousheh, Dana; Alaei, Mohammad-Hazhir; Nikpasand, Amin; Rostami, Hawdam; Shahrooz, Rasoul

    2018-04-01

    To determine the effects of bone marrow derived mast cells (BMMCs) on functional recovery of transected sciatic nerve in animal model of cat. A 20-mm sciatic nerve defect was bridged using a silicone nerve guide filled with BMMCs in BMMC group. In Sham-surgery group (SHAM), the sciatic nerve was only exposed and manipulated. In control group (SILOCONE) the gap was repaired with a silicone nerve guide and both ends were sealed using sterile Vaseline to avoid leakage and the nerve guide was filled with 100 μL of phosphate-buffered saline alone. In cell treated group ([SILOCONE/BMMC) the nerve guide was filled with 100 μL BMMCs (2× 106 cells/100 μL). The regenerated nerve fibers were studied, biomechanically, histologically and immunohiscochemically 6 months later. Biomechanical studies confirmed faster recovery of regenerated axons in BMMCs transplanted animals compared to control group ( p <0.05). Morphometric indices of the regenerated fibers showed that the number and diameter of the myelinated fibers were significantly higher in BMMCs transplanted animals than in control group ( p <0.05). In immunohistochemistry, location of reactions to S-100 in BMMCs transplanted animals was clearly more positive than that in control group. BMMCs xenotransplantation could be considered as a readily accessible source of cells that could improve recovery of transected sciatic nerve.

  3. Cerebellar anatomy as applied to cerebellar microsurgical resections

    Directory of Open Access Journals (Sweden)

    Alejandro Ramos

    2012-06-01

    Full Text Available OBJECTIVE: To define the anatomy of dentate nucleus and cerebellar peduncles, demonstrating the surgical application of anatomic landmarks in cerebellar resections. METHODS: Twenty cerebellar hemispheres were studied. RESULTS: The majority of dentate nucleus and cerebellar peduncles had demonstrated constant relationship to other cerebellar structures, which provided landmarks for surgical approaching. The lateral border is separated from the midline by 19.5 mm in both hemispheres. The posterior border of the cortex is separated 23.3 mm from the posterior segment of the dentate nucleus; the lateral one is separated 26 mm from the lateral border of the nucleus; and the posterior segment of the dentate nucleus is separated 25.4 mm from the posterolateral angle formed by the junction of lateral and posterior borders of cerebellar hemisphere. CONCLUSIONS: Microsurgical anatomy has provided important landmarks that could be applied to cerebellar surgical resections.

  4. Functional collagen conduits combined with human mesenchymal stem cells promote regeneration after sciatic nerve transection in dogs.

    Science.gov (United States)

    Cui, Yi; Yao, Yao; Zhao, Yannan; Xiao, Zhifeng; Cao, Zongfu; Han, Sufang; Li, Xing; Huan, Yong; Pan, Juli; Dai, Jianwu

    2018-05-01

    Numerous studies have focused on the development of novel and innovative approaches for the treatment of peripheral nerve injury using artificial nerve guide conduits. In this study, we attempted to bridge 3.5-cm defects of the sciatic nerve with a longitudinally oriented collagen conduit (LOCC) loaded with human umbilical cord mesenchymal stem cells (hUC-MSCs). The LOCC contains a bundle of longitudinally aligned collagenous fibres enclosed in a hollow collagen tube. Our previous studies showed that an LOCC combined with neurotrophic factors enhances peripheral nerve regeneration. However, it remained unknown whether an LOCC seeded with hUC-MSCs could also promote regeneration. In this study, using various histological and electrophysiological analyses, we found that an LOCC provides mechanical support to newly growing nerves and functions as a structural scaffold for cells, thereby stimulating sciatic nerve regeneration. The LOCC and hUC-MSCs synergistically promoted regeneration and improved the functional recovery in a dog model of sciatic nerve injury. Therefore, the combined use of an LOCC and hUC-MSCs might have therapeutic potential for the treatment of peripheral nerve injury. Copyright © 2018 John Wiley & Sons, Ltd.

  5. Novel Adult Stem Cells for Peripheral Nerve Regeneration

    Science.gov (United States)

    2013-09-01

    presentations related to this project o Days of Molecular Medicine-Regenerative Medicine, Hong Kong . 11/2011 Figure 4. Differentiation of MVSCs into...School, Boston. 10/2012 o Distinguished Seminar Series, Mechanical and Industrial Engineering, University of Toronto, Canada. 11/2012 o International...10% of the cells in the carotid arterial tunica media of SM-MHC-Cre/LoxP- EGFP mice were not labelled with EGFP, indicating the existence of a small

  6. Comparison of Individual and Combined Effects of Four Endocrine Disruptors on Estrogen Receptor Beta Transcription in Cerebellar Cell Culture: The Modulatory Role of Estradiol and Triiodo-Thyronine

    Science.gov (United States)

    Jocsak, Gergely; Kiss, David Sandor; Toth, Istvan; Goszleth, Greta; Bartha, Tibor; Frenyo, Laszlo V.; Horvath, Tamas L.; Zsarnovszky, Attila

    2016-01-01

    Background: Humans and animals are continuously exposed to a number of environmental substances that act as endocrine disruptors (EDs). While a growing body of evidence is available to prove their adverse health effects, very little is known about the consequences of simultaneous exposure to a combination of such chemicals; Methods: Here, we used an in vitro model to demonstrate how exposure to bisphenol A, zearalenone, arsenic, and 4-methylbenzylidene camphor, alone or in combination, affect estrogen receptor β (ERβ) mRNA expression in primary cerebellar cell cultures. Additionally, we also show the modulatory role of intrinsic biological factors, such as estradiol (E2), triiodo-thyronine (T3), and glial cells, as potential effect modulators; Results: Results show a wide diversity in ED effects on ERβ mRNA expression, and that the magnitude of these ED effects highly depends on the presence or absence of E2, T3, and glial cells; Conclusion: The observed potency of the EDs to influence ERβ mRNA expression, and the modulatory role of E2, T3, and the glia suggests that environmental ED effects may be masked as long as the hormonal milieu is physiological, but may tend to turn additive or superadditive in case of hormone deficiency. PMID:27338438

  7. Fast transdifferentiation of human Wharton's jelly mesenchymal stem cells into neurospheres and nerve-like cells.

    Science.gov (United States)

    Bonilla-Porras, A R; Velez-Pardo, C; Jimenez-Del-Rio, M

    2017-04-15

    The human mesenchymal stem cells derived from Wharton's jelly tissue (hWJ-MSCs) represent a tool for cell-based therapies and regenerative medicine. hWJ-MSCs form neurospheres (NSs) within 3-7 days. No data is available to establish the neuro-phenotypic markers and time of formation of nerve-like (NLCs) and glial cells from NSs derived from hWJ-MSCs. NEW METHOD: hWJ-MSCs were incubated with Fast-N-Spheres medium for 24 and 72h. The new formed NSs were in turn incubated with forskolin in neurogenic NeuroForsk medium for 1-7days. hWJ-MSCs cultured with Fast-N-Spheres medium trans-differentiated into NSs in just 24h compared to 72h for hWJ-MSCs cultured with classic growth factor medium. The NSs generated from the Fast-N-Spheres medium expressed reduced levels SOX2, OCT4 and NANOG, as markers of pluripotency compared to undifferentiated hWJ-MSCs. The formed NSs exposed to NeuroForsk medium differentiated into NLCs in 4days as evidenced by high levels of protein expression of the neuronal markers, and no expression of the glial marker GFAP. Currently, the formation and harvest of NSs is expensive and time consuming. Published protocols require 3-7days to form NSs from whole human umbilical cord MSCs. We report for the first time, to our knowledge, the differentiation of NSs-derived from hWJ-MSCs into NLCs. The fastest method to obtain NSs and NLCs from hWJ-MSCs takes only five days using the two-step incubation media Fast-N-Spheres and NeuroForsk. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Enhancement of Median Nerve Regeneration by Mesenchymal Stem Cells Engraftment in an Absorbable Conduit: Improvement of Peripheral Nerve Morphology with Enlargement of Somatosensory Cortical Representation.

    Directory of Open Access Journals (Sweden)

    Julia Teixeira Oliveira

    2014-10-01

    Full Text Available We studied the morphology and the cortical representation of the median nerve (MN, 10 weeks after a transection immediately followed by treatment with tubulization using a polycaprolactone (PCL conduit with or without bone marrow-derived mesenchymal stem cell (MSC transplant. In order to characterize the cutaneous representation of MN inputs in primary somatosensory cortex (S1, electrophysiological cortical mapping of the somatosensory representation of the forepaw and adjacent body parts was performed after acute lesion of all brachial plexus nerves, except for the MN. This was performed in ten adult male Wistar rats randomly assigned in 3 groups: MN Intact (n=4, PCL-Only (n=3 and PCL+MSC (n=3. Ten weeks before mapping procedures in animals from PCL-Only and PCL+MSC groups, animal were subjected to MN transection with removal of a 4-mm-long segment, immediately followed by suturing a PCL conduit to the nerve stumps with (PCL+MSC group or without (PCL-Only group injection of MSC into the conduit. After mapping the representation of the MN in S1, animals had a segment of the regenerated nerve processed for light and transmission electron microscopy. For histomorphometric analysis of the nerve segment, sample size was increased to 5 animals per experimental group. The PCL+MSC group presented a higher number of myelinated fibers and a larger cortical representation of MN inputs in S1 (3,383±390 fibers; 2.3 mm2, respectively than the PCL-Only group (2,226±575 fibers; 1.6 mm2. In conclusion, MSC-based therapy associated with PCL conduits can improve MN regeneration. This treatment seems to rescue the nerve representation in S1, thus minimizing the stabilization of new representations of adjacent body parts in regions previously responsive to the MN.

  9. Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases

    Directory of Open Access Journals (Sweden)

    Louise A. Mesentier-Louro

    2016-01-01

    Full Text Available Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow-derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized.

  10. Contribution of cerebellar sensorimotor adaptation to hippocampal spatial memory.

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Passot

    Full Text Available Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation.

  11. rhEPO Enhances Cellular Anti-oxidant Capacity to Protect Long-Term Cultured Aging Primary Nerve Cells.

    Science.gov (United States)

    Wang, Huqing; Fan, Jiaxin; Chen, Mengyi; Yao, Qingling; Gao, Zhen; Zhang, Guilian; Wu, Haiqin; Yu, Xiaorui

    2017-08-01

    Erythropoietin (EPO) may protect the nervous system of animals against aging damage, making it a potential anti-aging drug for the nervous system. However, experimental evidence from natural aging nerve cell models is lacking, and the efficacy of EPO and underlying mechanism of this effect warrant further study. Thus, the present study used long-term cultured primary nerve cells to successfully mimic the natural aging process of nerve cells. Starting on the 11th day of culture, cells were treated with different concentrations of recombinant human erythropoietin (rhEPO). Using double immunofluorescence labeling, we found that rhEPO significantly improved the morphology of long-term cultured primary nerve cells and increased the total number of long-term cultured primary cells. However, rhEPO did not improve the ratio of nerve cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure nerve cell activity and showed that rhEPO significantly improved the activity of long-term cultured primary nerve cells. Moreover, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double immunofluorescence labeling flow cytometry revealed that rhEPO reduced the apoptotic rate of long-term cultured primary nerve cells. Senescence-associated β-galactosidase (SA-β-gal) immunohistochemistry staining showed that rhEPO significantly reduced the aging rate of long-term cultured primary nerve cells. Immunochemistry revealed that rhEPO enhanced intracellular superoxide dismutase (SOD) activity and glutathione (GSH) abundance and reduced the intracellular malondialdehyde (MDA) level. In addition, this effect depended on the dose, was maximized at a dose of 100 U/ml and was more pronounced than that of vitamin E. In summary, this study finds that rhEPO protects long-term cultured primary nerve cells from aging in a dose-dependent manner. The mechanism of this effect may be associated with the enhancement of the intracellular anti

  12. Electrical stimulation promotes nerve cell differentiation on polypyrrole/poly (2-methoxy-5 aniline sulfonic acid) composites.

    Science.gov (United States)

    Liu, Xiao; Gilmore, Kerry J; Moulton, Simon E; Wallace, Gordon G

    2009-12-01

    The purpose of this work was to investigate for the first time the potential biomedical applications of novel polypyrrole (PPy) composites incorporating a large polyelectrolyte dopant, poly (2-methoxy-5 aniline sulfonic acid) (PMAS). The physical and electrochemical properties were characterized. The PPy/PMAS composites were found to be smooth and hydrophilic and have low electrical impedance. We demonstrate that PPy/PMAS supports nerve cell (PC12) differentiation, and that clinically relevant 250 Hz biphasic current pulses delivered via PPy/PMAS films significantly promote nerve cell differentiation in the presence of nerve growth factor (NGF). The capacity of PPy/PMAS composites to support and enhance nerve cell differentiation via electrical stimulation renders them valuable for medical implants for neurological applications.

  13. A magnetically responsive nanocomposite scaffold combined with Schwann cells promotes sciatic nerve regeneration upon exposure to magnetic field

    Directory of Open Access Journals (Sweden)

    Liu ZY

    2017-10-01

    Full Text Available Zhongyang Liu,1,* Shu Zhu,1,* Liang Liu,2,* Jun Ge,3,4,* Liangliang Huang,1 Zhen Sun,1 Wen Zeng,5 Jinghui Huang,1 Zhuojing Luo1 1Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 2Department of Orthopedics, No 161 Hospital of PLA, Wuhan, Hubei, 3Department of Orthopedics, No 323 Hospital of PLA, Xi’an, Shaanxi, 4Department of Anatomy, Fourth Military Medical University, Xi’an, Shaanxi, 5Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Abstract: Peripheral nerve repair is still challenging for surgeons. Autologous nerve transplantation is the acknowledged therapy; however, its application is limited by the scarcity of available donor nerves, donor area morbidity, and neuroma formation. Biomaterials for engineering artificial nerves, particularly materials combined with supportive cells, display remarkable promising prospects. Schwann cells (SCs are the absorbing seeding cells in peripheral nerve engineering repair; however, the attenuated biologic activity restricts their application. In this study, a magnetic nanocomposite scaffold fabricated from magnetic nanoparticles and a biodegradable chitosan–glycerophosphate polymer was made. Its structure was evaluated and characterized. The combined effects of magnetic scaffold (MG with an applied magnetic field (MF on the viability of SCs and peripheral nerve injury repair were investigated. The magnetic nanocomposite scaffold showed tunable magnetization and degradation rate. The MGs synergized with the applied MF to enhance the viability of SCs after transplantation. Furthermore, nerve regeneration and functional recovery were promoted by the synergism of SCs-loaded MGs and MF. Based on the current findings, the combined application of MGs and SCs with applied MF is a promising therapy for the engineering of peripheral

  14. Unusual Spread of Renal Cell Carcinoma to the Clivus with Cranial Nerve Deficit

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    Jerome Okudo

    2016-01-01

    Full Text Available Renal cell carcinoma (RCC has unusual presentation affecting elderly males with a smoking history. The incidence of RCC varies while the incidence of spread of RCC to the clivus is rare. The typicality of RCC presentation includes hematuria, flank pain, and a palpable flank mass; however, RCC can also present with clival metastasis. The unique path of the abducens nerve in the clivus makes it susceptible to damage in metastasis. We report a case of a 54-year-old African American female that was evaluated for back pain, weakness, numbness, and tingling of bilateral lower extremities and subsequently disconjugate gaze and diplopia. Brain MRI confirmed metastasis to the clivus. She was started on radiotherapy and was planned for chemotherapy and transfer to a nursing home. When a patient presents with sudden unusual cranial nerve pathology, the possibility of metastatic RCC should be sought.

  15. Unusual Spread of Renal Cell Carcinoma to the Clivus with Cranial Nerve Deficit.

    Science.gov (United States)

    Okudo, Jerome; Anusim, Nwabundo

    2016-01-01

    Renal cell carcinoma (RCC) has unusual presentation affecting elderly males with a smoking history. The incidence of RCC varies while the incidence of spread of RCC to the clivus is rare. The typicality of RCC presentation includes hematuria, flank pain, and a palpable flank mass; however, RCC can also present with clival metastasis. The unique path of the abducens nerve in the clivus makes it susceptible to damage in metastasis. We report a case of a 54-year-old African American female that was evaluated for back pain, weakness, numbness, and tingling of bilateral lower extremities and subsequently disconjugate gaze and diplopia. Brain MRI confirmed metastasis to the clivus. She was started on radiotherapy and was planned for chemotherapy and transfer to a nursing home. When a patient presents with sudden unusual cranial nerve pathology, the possibility of metastatic RCC should be sought.

  16. Neuroprotection comparison of chlorogenic acid and its metabolites against mechanistically distinct cell death-inducing agents in cultured cerebellar granule neurons.

    Science.gov (United States)

    Taram, Faten; Winter, Aimee N; Linseman, Daniel A

    2016-10-01

    While the number of patients diagnosed with neurodegenerative disorders like Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease is increasing, there are currently no effective treatments that significantly limit the neuronal cell death underlying these diseases. Chlorogenic acid (CGA), a polyphenolic compound found in high concentration in coffee, is known to possess antioxidant and free radical scavenging activity. In this study, we investigated the neuroprotective effects of CGA and its major metabolites in primary cultures of rat cerebellar granule neurons. We show that CGA and caffeic acid displayed a dramatic protective effect against the nitric oxide donor, sodium nitroprusside. In marked contrast, ferulic acid and quinic acid had no protective effect against this nitrosative stress. While CGA and quinic acid had no protective effect against glutamate-induced cell death, caffeic acid and ferulic acid significantly protected neurons from excitotoxicity. Finally, caffeic acid was the only compound to display significant protective activity against hydrogen peroxide, proteasome inhibition, caspase-dependent intrinsic apoptosis, and endoplasmic reticulum stress. These results indicate that caffeic acid displays a much broader profile of neuroprotection against a diverse range of stressors than its parent polyphenol, CGA, or the other major metabolites, ferulic acid and quinic acid. We conclude that caffeic acid is a promising candidate for testing in pre-clinical models of neurodegeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Human primordial germ cells migrate along nerve fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge

    DEFF Research Database (Denmark)

    Møllgård, Kjeld; Jespersen, Åse; Lutterodt, Melissa Catherine

    2010-01-01

    The aim of this study was to investigate the spatiotemporal development of autonomic nerve fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic nerve...... arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic nerve fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine nerve plexus....

  18. Repair of facial nerve defects with decellularized artery allografts containing autologous adipose-derived stem cells in a rat model.

    Science.gov (United States)

    Sun, Fei; Zhou, Ke; Mi, Wen-Juan; Qiu, Jian-Hua

    2011-07-20

    The purpose of this study was to investigate the effects of a decellularized artery allograft containing autologous adipose-derived stem cells (ADSCs) on an 8-mm facial nerve branch lesion in a rat model. At 8 weeks postoperatively, functional evaluation of unilateral vibrissae movements, morphological analysis of regenerated nerve segments and retrograde labeling of facial motoneurons were all analyzed. Better regenerative outcomes associated with functional improvement, great axonal growth, and improved target reinnervation were achieved in the artery-ADSCs group (2), whereas the cut nerves sutured with artery conduits alone (group 1) achieved inferior restoration. Furthermore, transected nerves repaired with nerve autografts (group 3) resulted in significant recovery of whisking, maturation of myelinated fibers and increased number of labeled facial neurons, and the latter two parameters were significantly different from those of group 2. Collectively, though our combined use of a decellularized artery allograft with autologous ADSCs achieved regenerative outcomes inferior to a nerve autograft, it certainly showed a beneficial effect on promoting nerve regeneration and thus represents an alternative approach for the reconstruction of peripheral facial nerve defects. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Macrophage-derived microvesicles promote proliferation and migration of Schwann cell on peripheral nerve repair

    Energy Technology Data Exchange (ETDEWEB)

    Zhan, Chuan, E-mail: zhchuansy@163.com; Ma, Cheng-bin; Yuan, Hong-mou; Cao, Bao-yuan; Zhu, Jia-jun

    2015-12-04

    Background: Macrophages have been implicated in peripheral nerve regeneration. However, whether macrophages-derived microvesicles (MVs) are involved in this process remains unknown. In the present study, the effects of macrophages-derived MVs on proliferation and migration of Schwann cells (SCs) were evaluated in both in vitro and in vivo. Methods: Human monocytic leukaemia cell line (THP-1) was successfully driven to M1 and M2 phenotypes by delivery of either IFN-γ or IL-4, respectively. SCs incubated with M1 or M2 macrophages-derived MVs, the cell migration and proliferation were assessed, and expression levels of nerve growth factor (NGF) and Laminin were measured. A rat model of sciatic nerve was established and the effects of macrophages-derived MVs on nerve regeneration were investigated. Results: M2-derived MVs elevated migration, proliferation, NFG and Laminin protein levels of SCs compared with M1-or M0-derived MVs. The relative expression levels of miR-223 were also increased in M2 macrophages and M2-derived MVs. Transfected M2 macrophages with miR-223 inhibitor then co-incubated with SCs, an inhibition of cell migration and proliferation and a down-regulated levels of NFG and Laminin protein expression were observed. In vivo, M2-derived MVs significantly increased the infiltration and axon number of SCs. Conclusion: M2-derived MVs promoted proliferation and migration of SCs in vitro and in vivo, which provided a therapeutic strategy for nerve regeneration. - Highlights: • M2 macrophages-derived MVs elevated migration and proliferation of SCs. • M2 macrophages-derived MVs up-regulated NFG and Laminin expression of SCs. • MiR-223 expression was increased in M2 macrophages-derived MVs. • MiR-223 inhibitor reduced migration and proliferation of SCs co-incubated with MVs. • MiR-223 inhibitor down-regulated NFG and Laminin levels of SCs co-incubated with MVs.

  20. Primate Cerebellar Granule Cells Exhibit a Tonic GABAAR Conductance that is not Affected by Alcohol: A Possible Cellular Substrate of the Low Level of Response Phenotype.

    Directory of Open Access Journals (Sweden)

    Claudia eMohr

    2013-11-01

    Full Text Available In many rodent brain regions, alcohol increases vesicular release of GABA, resulting in an increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs and the magnitude of tonic GABAA receptor (GABAAR currents. A neglected issue in translating the rodent literature to humans is the possibility that phylogenetic differences alter the actions of alcohol. To address this issue we made voltage-clamp recordings from granule cells (GCs in cerebellar slices from the non-human primate, Macaca fascicularis. We found that similar to Sprague Dawley rats (SDRs, non-human primate (NHP GCs exhibit a tonic conductance generated by 6 subunit containing GABAARs, as evidenced by its blockade by the broad spectrum GABAAR antagonist, GABAzine (10M, inhibition by 6 selective antagonist, furosemide (100M, and enhancement by THDOC (10-20nM and THIP (500nM. In contrast to SDR GCs, in most NHP GCs (~60%, application of EtOH (25-105mM did not increase sIPSC frequency or the tonic GABAAR current. In a minority of cells (~40%, EtOH did increase sIPSC frequency and the tonic current. The relative lack of response to EtOH was associated with reduced expression of neuronal nitric oxide synthase (nNOS, which we recently reported mediates EtOH-induced enhancement of vesicular GABA release in rats. The EtOH-induced increase in tonic GABAAR current was significantly smaller in NHPs than in SDRs, presumably due to less GABA release, because there were no obvious differences in the density of GABAARs or GABA transporters between SDR and NHP GCs. Thus, EtOH does not directly modulate 6 subunit GABAARs in NHPs. Instead, EtOH enhanced GABAergic transmission is mediated by enhanced GABA release. Further, SDR GC responses to alcohol are only representative of a subpopulation of NHP GCs. This suggests that the impact of EtOH on NHP cerebellar physiology will be reduced compared to SDRs, and will likely have different computational and behavioral

  1. [Progression of nerve fiber layer defects in retrobulbar optic neuritis by the macular ganglion cell complex].

    Science.gov (United States)

    Hong, D; Bosc, C; Chiambaretta, F

    2017-11-01

    Recent studies with SD OCT had shown early axonal damage to the macular ganglion cell complex (which consists of the three innermost layers of the retina: Inner Plexiform Layer [IPL], Ganglion Cell Layer [GCL], Retinal Nerve Fibre layer [RNFL]) in optic nerve pathology. Retrobulbar optic neuritis (RBON), occurring frequently in demyelinating diseases, leads to atrophy of the optic nerve fibers at the level of the ganglion cell axons, previously described in the literature. The goal of this study is to evaluate the progression of optic nerve fiber defects and macular ganglion cell complex defects with the SPECTRALIS OCT via a reproducible method by calculating a mean thickness in each quadrant after an episode of retrobulbar optic neuritis. This is a prospective monocentric observational study including 8 patients at the Clermont-Ferrand university medical center. All patients underwent ocular examination with macular and disc OCT analysis and a Goldmann visual field at the time of inclusion (onset or recurrence of RBON), at 3 months and at 6 months. Patients were 40-years-old on average at the time of inclusion. After 6 months of follow-up, there was progression of the atrophy of the macular ganglion cell complex in the affected eye on (11.5% or 11μm) predominantly inferonasally (13.9% or 16μm) and superonasally (12.9% or 14μm) while the other eye remained stable. The decrease in thickness occurred mainly in the most internal 3 layers of the retina. On average, the loss in thickness of the peripapillary RNFL was predominantly inferotemporal (24.9% or 39μm) and superotemporal (21.8% or 28μm). In 3 months of progression, the loss of optic nerve fibers is already seen on macular and disc OCT after an episode of RBON, especially in inferior quadrants in spite of the improvement in the Goldmann visual field and visual acuity. Segmentation by quadrant was used here to compare the progression of the defect by region compared to the fovea in a global and reproducible

  2. Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury

    Science.gov (United States)

    Tashima, Ryoichi; Mikuriya, Satsuki; Tomiyama, Daisuke; Shiratori-Hayashi, Miho; Yamashita, Tomohiro; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID:27005516

  3. Nerve Blocks

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Nerve Blocks A nerve block is an injection to ... the limitations of Nerve Block? What is a Nerve Block? A nerve block is an anesthetic and/ ...

  4. Flow cytometry analysis of inflammatory cells isolated from the sciatic nerve and DRG after chronic constriction injury in mice.

    Science.gov (United States)

    Liu, Liping; Yin, Yan; Li, Fei; Malhotra, Charvi; Cheng, Jianguo

    2017-06-01

    Cellular responses to nerve injury play a central role in the pathogenesis of neuropathic pain. However, the analysis of site specific cellular responses to nerve injury and neuropathic pain is limited to immunohistochemistry staining with numerous limitations. We proposed to apply flow cytometry to overcome some of the limitations and developed two protocols for isolation of cells from small specimens of the sciatic nerve and dorsal root ganglion (DRG) in mice. RESULTS AND COMPARASION WITH EXISTING: methods We found that both the non-enzymatic and enzymatic approaches were highly effective in harvesting a sufficient number of cells for flow cytometry analysis in normal and pathological conditions. The total number of cells in the injury site of the sciatic and its DRGs increased significantly 14days after chronic constriction injury (CCI) of the sciatic nerve, compared to sham surgery control or the contralateral control. The enzymatic approach yielded a significantly higher total number of cells and CD45 negative cells, suggesting that this approach allows for harvest of more resident cells, compared to the non-enzymatic method. The percentage of CD45 + /CD11b + cells was significantly increased in the sciatic nerve but not in the DRG. These results were consistent with both protocols. We thus offer two simple and effective protocols that allow for application of flow cytometry to the investigation of cellular and molecular mechanisms of neuropathic pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Effect of duration and severity of migraine on retinal nerve fiber layer, ganglion cell layer, and choroidal thickness.

    Science.gov (United States)

    Abdellatif, Mona K; Fouad, Mohamed M

    2018-03-01

    To investigate the factors in migraine that have the highest significance on retinal and choroidal layers' thickness. Ninety patients with migraine and 40 age-matched healthy participants were enrolled in this observational, cross-sectional study. After full ophthalmological examination, spectral domain-optical coherence tomography was done for all patients measuring the thickness of ganglion cell layer and retinal nerve fiber layer. Enhanced depth imaging technique was used to measure the choroidal thickness. There was significant thinning in the superior and inferior ganglion cell layers, all retinal nerve fiber layer quadrants, and all choroidal quadrants (except for the central subfield) in migraineurs compared to controls. The duration of migraine was significantly correlated with ganglion cell layer, retinal nerve fiber layer, and all choroidal quadrants, while the severity of migraine was significantly correlated with ganglion cell layer and retinal nerve fiber layer only. Multiregression analysis showed that the duration of migraine is the most important determinant factor of the superior retinal nerve fiber layer quadrant (β = -0.375, p = 0.001) and in all the choroidal quadrants (β = -0.531, -0.692, -0.503, -0.461, -0.564, respectively, p  layer quadrants (β = -0.256, -0.335, -0.308; p  = 0.036, 0.005, 0.009, respectively) and the inferior ganglion cell layer hemisphere (β = -0.377 and p = 0.001). Ganglion cell layer, retinal nerve fiber layer, and choroidal thickness are significantly thinner in patients with migraine. The severity of migraine has more significant influence in the thinning of ganglion cell layer and retinal nerve fiber layer, while the duration of the disease affected the choroidal thickness more.

  6. Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

    Energy Technology Data Exchange (ETDEWEB)

    Weingart, Oliver G., E-mail: Oliver.Weingart@hest.ethz.ch; Loessner, Martin J.

    2016-12-15

    Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocation of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.

  7. Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

    International Nuclear Information System (INIS)

    Weingart, Oliver G.; Loessner, Martin J.

    2016-01-01

    Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocation of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.

  8. Schwann cells promote post-traumatic nerve inflammation and neuropathic pain through MHC class II.

    Science.gov (United States)

    Hartlehnert, Maike; Derksen, Angelika; Hagenacker, Tim; Kindermann, David; Schäfers, Maria; Pawlak, Mathias; Kieseier, Bernd C; Meyer Zu Horste, Gerd

    2017-10-02

    The activation of T helper cells requires antigens to be exposed on the surface of antigen presenting cells (APCs) via MHC class II (MHC-II) molecules. Expression of MHC-II is generally limited to professional APCs, but other cell types can express MHC-II under inflammatory conditions. However, the importance of these conditional APCs is unknown. We and others have previously shown that Schwann cells are potentially conditional APCs, but the functional relevance of MHC-II expression by Schwann cells has not been studied in vivo. Here, we conditionally deleted the MHC-II β-chain from myelinating Schwann cells in mice and investigated how this influenced post-traumatic intraneural inflammation and neuropathic pain using the chronic constriction injury (CCI) model. We demonstrate that deletion of MHC-II in myelinating Schwann cells reduces thermal hyperalgesia and, to a lesser extent, also diminishes mechanical allodynia in CCI in female mice. This was accompanied by a reduction of intraneural CD4+ T cells and greater preservation of preferentially large-caliber axons. Activation of T helper cells by MHC-II on Schwann cells thus promotes post-traumatic axonal loss and neuropathic pain. Hence, we provide experimental evidence that Schwann cells gain antigen-presenting function in vivo and modulate local immune responses and diseases in the peripheral nerves.

  9. The Secreted Protein C1QL1 and Its Receptor BAI3 Control the Synaptic Connectivity of Excitatory Inputs Converging on Cerebellar Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Séverine M. Sigoillot

    2015-02-01

    Full Text Available Precise patterns of connectivity are established by different types of afferents on a given target neuron, leading to well-defined and non-overlapping synaptic territories. What regulates the specific characteristics of each type of synapse, in terms of number, morphology, and subcellular localization, remains to be understood. Here, we show that the signaling pathway formed by the secreted complement C1Q-related protein C1QL1 and its receptor, the adhesion-GPCR brain angiogenesis inhibitor 3 (BAI3, controls the stereotyped pattern of connectivity established by excitatory afferents on cerebellar Purkinje cells. The BAI3 receptor modulates synaptogenesis of both parallel fiber and climbing fiber afferents. The restricted and timely expression of its ligand C1QL1 in inferior olivary neurons ensures the establishment of the proper synaptic territory for climbing fibers. Given the broad expression of C1QL and BAI proteins in the developing mouse brain, our study reveals a general mechanism contributing to the formation of a functional brain.

  10. Microvascular anatomy of the cerebellar parafloccular perforating space.

    Science.gov (United States)

    Sosa, Pablo; Dujovny, Manuel; Onyekachi, Ibe; Sockwell, Noressia; Cremaschi, Fabián; Savastano, Luis E

    2016-02-01

    The cerebellopontine angle is a common site for tumor growth and vascular pathologies requiring surgical manipulations that jeopardize cranial nerve integrity and cerebellar and brainstem perfusion. To date, a detailed study of vessels perforating the cisternal surface of the middle cerebellar peduncle-namely, the paraflocculus or parafloccular perforating space-has yet to be published. In this report, the perforating vessels of the anterior inferior cerebellar artery (AICA) in the parafloccular space, or on the cisternal surface of the middle cerebellar peduncle, are described to elucidate their relevance pertaining to microsurgery and the different pathologies that occur at the cerebellopontine angle. Fourteen cadaveric cerebellopontine cisterns (CPCs) were studied. Anatomical dissections and analysis of the perforating arteries of the AICA and posterior inferior cerebellar artery at the parafloccular space were recorded using direct visualization by surgical microscope, optical histology, and scanning electron microscope. A comprehensive review of the English-language and Spanish-language literature was also performed, and findings related to anatomy, histology, physiology, neurology, neuroradiology, microsurgery, and endovascular surgery pertaining to the cerebellar flocculus or parafloccular spaces are summarized. A total of 298 perforating arteries were found in the dissected specimens, with a minimum of 15 to a maximum of 26 vessels per parafloccular perforating space. The average outer diameter of the cisternal portion of the perforating arteries was 0.11 ± 0.042 mm (mean ± SD) and the average length was 2.84 ± 1.2 mm. Detailed schematics and the surgical anatomy of the perforating vessels at the CPC and their clinical relevance are reported. The parafloccular space is a key entry point for many perforating vessels toward the middle cerebellar peduncle and lateral brainstem, and it must be respected and protected during surgical approaches to the

  11. Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells

    Science.gov (United States)

    Dombrowski, Mary A.; Sasaki, Masanori; Lankford, Karen L.; Kocsis, Jeffery D.; Radtke, Christine

    2009-01-01

    Transplantation of olfactory ensheathing cells (OECs) into injured spinal cord results in improved functional outcome. Mechanisms suggested to account for this functional improvement include axonal regeneration, remyelination and neuroprotection. OECs transplanted into transected peripheral nerve have been shown to modify peripheral axonal regeneration and functional outcome. However, little is known of the detailed integration of OECs at the transplantation site in peripheral nerve. To address this issue cells populations enriched in OECs were isolated from the olfactory bulbs of adult green fluorescent protein (GFP)-expressing transgenic rats and transplanted into a sciatic nerve crush lesion which transects all axons. Five weeks to six months after transplantation the nerves were studied histologically. GFP-expressing OECs survived in the lesion and distributed longitudinally across the lesion zone. The internodal regions of individual teased fibers distal to the transection site were characterized by GFP expression in the cytoplasmic and nuclear compartments of cells surrounding the axons. Immuno-electron microscopy for GFP indicated that the transplanted OECs formed peripheral type myelin. Immunostaining for sodium channel and Caspr revealed a high density of Nav1.6 at the newly formed nodes of Ranvier which were flanked by paranodal Caspr staining. These results indicate that transplanted OECs extensively integrate into transected peripheral nerve and form myelin on regenerated peripheral nerve fibers, and that nodes of Ranvier of these axons display proper sodium channel organization. PMID:17112480

  12. Falls and cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    I. V. Damulin

    2015-01-01

    Full Text Available The paper considers the main causes of falls. Whatever their cause is, falls may lead to severe maladjustment in everyday life. In nearly 1 out of 10 cases, they are accompanied by severe injuries, including fractures (most commonly those of the proximal femur and humerus, hands, pelvic bones, and vertebrae, subdural hematoma, and severe soft tissue and head injuries. This process is emphasized to be multifactorial. Particular emphasis is laid on the involvement of the cerebellum and its associations, which may be accompanied by falls. This is clinically manifested mainly by gait disorders. Walking is a result of an interaction of three related functions (locomotion, maintenance of balance and adaptive reactions. In addition to synergies related to locomotion and balance maintenance, standing at rest and walking are influenced bythe following factors: postural and environmental information (proprioceptive, vestibular, and visual, the capacity to interpret and integrate this information, the ability of the musculoskeletal system to make movements, and the capability to optimally modulate these movements in view of the specific situation and the ability to choose and adapt synergy in terms of external factors and the capacities and purposes of an individual. The clinical signs of damage to the cerebellum and its associations are considered in detail. These structures are emphasized to be involved not only in movements, but also in cognitive functions. The major symptoms that permit cerebellar dysfunction to be diagnosed are given. Symptoms in cerebellar injuries are generally most pronounced when suddenly changing the direction of movements or attempting to start walking immediately after a dramatic rise. The magnitude of ataxia also increases in a patient who tries to decrease the step size. Falling tendencies or bending to one side (in other symptoms characteristic of cerebellar diseases suggest injury of the corresponding

  13. Curcumin accelerates the repair of sciatic nerve injury in rats through reducing Schwann cells apoptosis and promoting myelinization.

    Science.gov (United States)

    Zhao, Zhiwei; Li, Xiaoling; Li, Qing

    2017-08-01

    Schwann cells (SCs) play an indispensable role in the repair and regeneration of injured peripheral nerve. Curcumin can reduce SCs apoptosis, and promote the regeneration and functional recovery of injured peripheral nerves. However, the corresponding mechanisms are not clear. The article was aimed to explore the effect and corresponding mechanisms of curcumin on the repair of sciatic nerve injury in rats. After surgery induced sciatic nerve injury, the model rats were divided into three groups and treated with curcumin, curcumin+PD98059 and curcumin+IGF-1 respectively for 4days. The phosphorylation of Erk1/2 and Akt, and the expression of LC3-II, Beclin 1 and p62 were measured using western blotting. After treatment for 60days, myelination of the injured sciatic nerve was evaluated by MBP immunohistochemical staining and the expression of PMP22, Fibrin and S100 were determined using qRT-PCR and western blotting. In vitro, RSC96 cells were starved for 12h to induce autophagy, and received DMSO, curcumin, PD98059+curcumin, IGF-1+curcumin and BFA1 respectively. The phosphorylation of Erk1/2、Akt and the expression of LC3-II, Beclin 1, p62, PMP22, Fibrin and S100 were measured using western blotting, and the cell apoptosis was detected by flow cytometry. Curcumin could promote injury-induced cell autophagy, remyelination and axon regeneration in sciatic nerve of rats. In vitro, curcumin could accelerate cell autophagy through regulating autophagy related Erk1/2 and Akt pathway, prevent cell apoptosis and promote expression of PMP22 and S100, and reduced deposition of Fibrin in cultured RSC96 SCs. Curcumin could accelerate injured sciatic nerve repair in rats through reducing SCs apoptosis and promoting myelinization. Copyright © 2017. Published by Elsevier Masson SAS.

  14. Unusual Spread of Renal Cell Carcinoma to the Clivus with Cranial Nerve Deficit

    OpenAIRE

    Okudo, Jerome; Anusim, Nwabundo

    2016-01-01

    Renal cell carcinoma (RCC) has unusual presentation affecting elderly males with a smoking history. The incidence of RCC varies while the incidence of spread of RCC to the clivus is rare. The typicality of RCC presentation includes hematuria, flank pain, and a palpable flank mass; however, RCC can also present with clival metastasis. The unique path of the abducens nerve in the clivus makes it susceptible to damage in metastasis. We report a case of a 54-year-old African American female that ...

  15. Facial Nerve Palsy: An Unusual Presenting Feature of Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ozcan Yildiz

    2011-01-01

    Full Text Available Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in men and women; it is responsible for 1.3 million deaths annually worldwide. It can metastasize to any organ. The most common site of metastasis in the head and neck region is the brain; however, it can also metastasize to the oral cavity, gingiva, tongue, parotid gland and lymph nodes. This article reports a case of small cell lung cancer presenting with metastasis to the facial nerve.

  16. HLA-DR-expressing cells and T-lymphocytes in sural nerve biopsies

    DEFF Research Database (Denmark)

    Schrøder, H D; Olsson, T; Solders, G

    1988-01-01

    was confirmed. HLA-DR expression was found in all biopsies and thus was not restricted to any particular type of neuropathy. The HLA-DR expression appeared to correlate with severity and activity of the neuropathy. HLA-DR-expressing macrophages wrapping myelinated fibers were prominent in primary demyelinating......Thirty-five sural nerve biopsies were stained immunohistochemically for HLA-DR antigen. HLA-DR was expressed on nonmyelinating Schwann cells, macrophages, vascular endothelium, and perineurium. By means of double immunofluorescence staining the identity of the HLA-DR presenting structures...

  17. Cerebellar abiotrophy in a miniature schnauzer

    OpenAIRE

    Berry, Michelle L.; Blas-Machado, Uriel

    2003-01-01

    A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.

  18. Cerebellar abiotrophy in a miniature schnauzer.

    Science.gov (United States)

    Berry, Michelle L; Blas-Machado, Uriel

    2003-08-01

    A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.

  19. Evidence for a intimate relationship between mast cells and nerve fibers in the tongue of the frog, Rana esculenta

    Energy Technology Data Exchange (ETDEWEB)

    Chieffi Baccari, Gabriella; Minucci, Sergio [Naples, II Univ. (Italy). Dipt. di Fisiologia Umana e Funzioni Biologiche Integrate `Filippo Bottazzi`

    1997-12-31

    Morphological and ultrastructural association of mast cells and nerve fibers were studied in the tongue of the frog Rana esculenta. The number of mast cells in the tongue (253 {+-} 45 / mm{sup 2}) is far the highest of the frog tissue as far as people know. They are distributed throughout the connective tissue among the muscular fibers, near arterioles and venules but predominantly in close association and within the nerves. They are often embedded in the endoneurium within a nerve bundle near to myelinic or unmyelinic fibers and in membrane-to-membrane contact with axonlike processes. Just for the richness of mast cells, the tongue of the frog could represent an useful model to study the relationship between these cells and the peripheral nervous system.

  20. Evidence for a intimate relationship between mast cells and nerve fibers in the tongue of the frog, Rana esculenta

    Energy Technology Data Exchange (ETDEWEB)

    Chieffi Baccari, Gabriella; Minucci, Sergio [Naples, II Univ. (Italy). Dipt. di Fisiologia Umana e Funzioni Biologiche Integrate ` Filippo Bottazzi`

    1998-12-31

    Morphological and ultrastructural association of mast cells and nerve fibers were studied in the tongue of the frog Rana esculenta. The number of mast cells in the tongue (253 {+-} 45 / mm{sup 2}) is far the highest of the frog tissue as far as people know. They are distributed throughout the connective tissue among the muscular fibers, near arterioles and venules but predominantly in close association and within the nerves. They are often embedded in the endoneurium within a nerve bundle near to myelinic or unmyelinic fibers and in membrane-to-membrane contact with axonlike processes. Just for the richness of mast cells, the tongue of the frog could represent an useful model to study the relationship between these cells and the peripheral nervous system.

  1. Distribution of elements in rat peripheral axons and nerve cell bodies determined by x-ray microprobe analysis

    Energy Technology Data Exchange (ETDEWEB)

    LoPachin, R.M. Jr.; Lowery, J.; Eichberg, J.; Kirkpatrick, J.B.; Cartwright, J. Jr.; Saubermann, A.J.

    1988-09-01

    X-ray microprobe analysis was used to determine concentrations (millimoles of element per kilogram dry weight) of Na, P, Cl, K, and Ca in cellular compartments of frozen, unfixed sections of rat sciatic and tibial nerves and dorsal root ganglion (DRG). Five compartments were examined in peripheral nerve (axoplasm, mitochondria, myelin, extraaxonal space, and Schwann cell cytoplasm), and four were analyzed in DRG nerve cell bodies (cytoplasm, mitochondria, nucleus, and nucleolus). Each morphological compartment exhibited characteristic concentrations of elements. The extraaxonal space contained high concentrations of Na, Cl, and Ca, whereas intraaxonal compartments exhibited lower concentrations of these elements but relatively high K contents. Nerve axoplasm and axonal mitochondria had similar elemental profiles, and both compartments displayed proximodistal gradients of decreasing levels of K, Cl, and, to some extent, Na. Myelin had a selectively high P concentration with low levels of other elements. The elemental concentrations of Schwann cell cytoplasm and DRG were similar, but both were different from that of axoplasm, in that K and Cl were markedly lower whereas P was higher. DRG cell nuclei contained substantially higher K levels than cytoplasm. The subcellular distribution of elements was clearly shown by color-coded images generated by computer-directed digital x-ray imaging. The results of this study demonstrate characteristic elemental distributions for each anatomical compartment, which doubtless reflect nerve cell structure and function.

  2. Binding and internalization of nerve growth factor by PC12 cells

    International Nuclear Information System (INIS)

    Kasaian, M.T.

    1987-01-01

    The interaction of nerve growth factor (NGF) with its cell surface receptors has been studied using both fluorescent- and radio-labelled NGF. The fluorescence studies were done by flow cytometry, and gave information about the concentration dependence and time course of NGF binding to rat pheochromocytoma cells (PC12) and human melanoma cells (A875). 125 I-NGF was used to study the fate of NGF in PC12 cells following its association with cell surface receptors. Variations of the PC12 binding assay were used to distinguish ligand bound to fast and slowly dissociating receptors at the cell surface, internalized ligand, and cytoskeletally-associated NGF. Ligand uptake into each of these pools was followed in untreated cells, as well as in cells exposed to colchicine and/or cytochalasin B to disrupt the cytoskeleton. NGF degradation was also followed in these cells, and chloroquine was used to inhibit this process. In a separate project, NGF activity was assayed in samples of human amniotic fluid and cerebrospinal fluid (CSF). A range of activities was found in these samples, with the CSF samples containing somewhat more activity than the amniotic fluid samples

  3. Magnetic resonance imaging of cerebellar Schistosomiasis mansoni

    International Nuclear Information System (INIS)

    Braga, Bruno Perocco; Costa Junior, Leodante Batista da; Lambertucci, Jose Roberto

    2003-01-01

    A 15-year-old boy was admitted to hospital with a history of headache, dizziness, vomiting and double vision that started two weeks before. His parents denied any previous disease. During clinical examination he presented diplopia on lateral gaze to the left and horizontal nystagmus. No major neurological dysfunction was detected. He was well built, mentally responsive and perceptive. Laboratory findings revealed a leukocyte count of 10,000/mL, a normal red blood cell count and no eosinophilia. The magnetic resonance images (MRI) of the brain showed a left cerebellar lesion with mass effect compressing the surrounding tissues. Contrast-enhanced images showed a mass like structure and punctate nodules (Figures A and B: axial and coronal contrast-enhanced T1-weighted MR images showed the nodular - yellow arrows - enhancement pattern of a left cerebellar intraxial lesion). The lesion extended to the vermis and brachium pons and compressed the medulla. There was no hydrocephalus. He was taken to the operating room with the presumptive diagnosis of a neuroglial tumor, and submitted to a lateral suboccipital craniectomy. A brown, brittle tumoral mass without a clearly defined margin with the cerebellar tissue was removed. Microscopic examination revealed schistosomal granulomas in the productive phase in the cerebellum (Figure C). After surgery, treatment with praziquantel (50 mg/kg/dia, single dose) and prednisone (1 mg/kg/day) was offered and the patient improved quickly. Thirty days later he was seen again at the outpatient clinic: he was asymptomatic and with no neurological impairment. This is the eighth case of cerebellar involvement in schistosomiasis mansoni and the second report of a tumoral form of cerebellar schistosomiasis documented by magnetic resonance images. (author)

  4. Activation of sodium channels by α-scorpion toxin, BmK NT1, produced neurotoxicity in cerebellar granule cells: an association with intracellular Ca2+ overloading.

    Science.gov (United States)

    He, Yuwei; Zou, Xiaohan; Li, Xichun; Chen, Juan; Jin, Liang; Zhang, Fan; Yu, Boyang; Cao, Zhengyu

    2017-02-01

    Voltage-gated sodium channels (VGSCs) are responsible for the action potential generation in excitable cells including neurons and involved in many physiological and pathological processes. Scorpion toxins are invaluable tools to explore the structure and function of ion channels. BmK NT1, a scorpion toxin from Buthus martensii Karsch, stimulates sodium influx in cerebellar granule cells (CGCs). In this study, we characterized the mode of action of BmK NT1 on the VGSCs and explored the cellular response in CGC cultures. BmK NT1 delayed the fast inactivation of VGSCs, increased the Na + currents, and shifted the steady-state activation and inactivation to more hyperpolarized membrane potential, which was similar to the mode of action of α-scorpion toxins. BmK NT1 stimulated neuron death (EC 50  = 0.68 µM) and produced massive intracellular Ca 2+ overloading (EC 50  = 0.98 µM). TTX abrogated these responses, suggesting that both responses were subsequent to the activation of VGSCs. The Ca 2+ response of BmK NT1 was primary through extracellular Ca 2+ influx since reducing the extracellular Ca 2+ concentration suppressed the Ca 2+ response. Further pharmacological evaluation demonstrated that BmK NT1-induced Ca 2+ influx and neurotoxicity were partially blocked either by MK-801, an NMDA receptor blocker, or by KB-R7943, an inhibitor of Na + /Ca 2+ exchangers. Nifedipine, an L-type Ca 2+ channel inhibitor, slightly suppressed both Ca 2+ response and neurotoxicity. A combination of these three inhibitors abrogated both responses. Considered together, these data ambiguously demonstrated that activation of VGSCs by an α-scorpion toxin was sufficient to produce neurotoxicity which was associated with intracellular Ca 2+ overloading through both NMDA receptor- and Na + /Ca 2+ exchanger-mediated Ca 2+ influx.

  5. Development of a Functional Schwann Cell Phenotype from Autologous Porcine Bone Marrow Mononuclear Cells for Nerve Repair

    Directory of Open Access Journals (Sweden)

    Michael J. Rutten

    2012-01-01

    Full Text Available Adult bone marrow mononuclear cells (BM-MNCs are a potential resource for making Schwann cells to repair damaged peripheral nerves. However, many methods of producing Schwann-like cells can be laborious with the cells lacking a functional phenotype. The objective of this study was to develop a simple and rapid method using autologous BM-MNCs to produce a phenotypic and functional Schwann-like cell. Adult porcine bone marrow was collected and enriched for BM-MNCs using a SEPAX device, then cells cultured in Neurobasal media, 4 mM L-glutamine and 20% serum. After 6–8 days, the cultures expressed Schwann cell markers, S-100, O4, GFAP, were FluoroMyelin positive, but had low p75(NGF expression. Addition of neuregulin (1–25 nM increased p75(NGF levels at 24–48 hrs. We found ATP dose-dependently increased intracellular calcium [Ca2+]i, with nucleotide potency being UTP=ATP>ADP>AMP>adenosine. Suramin blocked the ATP-induced [Ca2+]i but α, β,-methylene-ATP had little effect suggesting an ATP purinergic P2Y2 G-protein-coupled receptor is present. Both the Schwann cell markers and ATP-induced [Ca2+]i sensitivity decreased in cells passaged >20 times. Our studies indicate that autologous BM-MNCs can be induced to form a phenotypic and functional Schwann-like cell which could be used for peripheral nerve repair.

  6. Protection by imidazol(ine) drugs and agmatine of glutamate-induced neurotoxicity in cultured cerebellar granule cells through blockade of NMDA receptor.

    Science.gov (United States)

    Olmos, G; DeGregorio-Rocasolano, N; Paz Regalado, M; Gasull, T; Assumpció Boronat, M; Trullas, R; Villarroel, A; Lerma, J; García-Sevilla, J A

    1999-07-01

    This study was designed to assess the potential neuroprotective effect of several imidazol(ine) drugs and agmatine on glutamate-induced necrosis and on apoptosis induced by low extracellular K+ in cultured cerebellar granule cells. Exposure (30 min) of energy deprived cells to L-glutamate (1-100 microM) caused a concentration-dependent neurotoxicity, as determined 24 h later by a decrease in the ability of the cells to metabolize 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) into a reduced formazan product. L-glutamate-induced neurotoxicity (EC50=5 microM) was blocked by the specific NMDA receptor antagonist MK-801 (dizocilpine). Imidazol(ine) drugs and agmatine fully prevented neurotoxicity induced by 20 microM (EC100) L-glutamate with the rank order (EC50 in microM): antazoline (13)>cirazoline (44)>LSL 61122 [2-styryl-2-imidazoline] (54)>LSL 60101 [2-(2-benzofuranyl) imidazole] (75)>idazoxan (90)>LSL 60129 [2-(1,4-benzodioxan-6-yl)-4,5-dihydroimidazole](101)>RX82 1002 (2-methoxy idazoxan) (106)>agmatine (196). No neuroprotective effect of these drugs was observed in a model of apoptotic neuronal cell death (reduction of extracellular K+) which does not involve stimulation of NMDA receptors. Imidazol(ine) drugs and agmatine fully inhibited [3H]-(+)-MK-801 binding to the phencyclidine site of NMDA receptors in rat brain. The profile of drug potency protecting against L-glutamate neurotoxicity correlated well (r=0.90) with the potency of the same compounds competing against [3H]-(+)-MK-801 binding. In HEK-293 cells transfected to express the NR1-1a and NR2C subunits of the NMDA receptor, antazoline and agmatine produced a voltage- and concentration-dependent block of glutamate-induced currents. Analysis of the voltage dependence of the block was consistent with the presence of a binding site for antazoline located within the NMDA channel pore with an IC50 of 10-12 microM at 0 mV. It is concluded that imidazol(ine) drugs and agmatine are

  7. The Effect of Plasma Treated PLGA/MWCNTs-COOH Composite Nanofibers on Nerve Cell Behavior

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    Jing Wang

    2017-12-01

    Full Text Available Electrospun nanofibrous scaffolds which can mimic the architecture of the natural extracellular matrix (ECM are potential candidates for peripheral nerve repair application. Multi-walled carbon nanotubes (MWCNTs are used in peripheral nerve repair due to their ability to promote neurite extension and support neural network formation. In this study, surface-modified nanofibrous scaffolds composed of poly(lactic-co-glycolic acid (PLGA and various ratios of carboxyl-modified MWCNTs (MWCNTs-COOH (PC0, PC2, PC4 and PC8 were fabricated by electrospinning. The effects of MWCNTs-COOH on the fibers’ morphology, diameter distribution, mechanical properties and surface hydrophilicity were characterized by Scanning Electron Microscopy (SEM, ImageJ software, tensile testing and water contact angle. Furthermore, air plasma treatment was applied to improve the surface hydrophilicity of the scaffolds, and the optimal treatment condition was determined in terms of surface morphology, water contact angle and PC12 cell adhesion. Plasma treated nanofibers (p-PC0, p-PC2, p-PC4 and p-PC8 under optimal treatment conditions were used for further study. PC12 cell proliferation and differentiation were both improved by the addition of MWCNTs-COOH in scaffolds. Additionally, the proliferation and maturation of Schwann cells were enhanced on scaffolds containing MWCNTs-COOH. The neurite outgrowth of rat dorsal root ganglia (DRG neurons was promoted on MWCNTs-COOH-containing scaffolds, and those cultured on p-PC8 scaffolds showed elongated neurites with a length up to 78.27 μm after 3 days culture. Our results suggested that plasma treated nanofibers under appropriate conditions were able to improve cell attachment. They also demonstrated that plasma treated scaffolds containing MWCNTs-COOH, especially the p-PC8 nanofibrous scaffold could support the proliferation, differentiation, maturation and neurite extension of PC12 cells, Schwann cells and DRG neurons. Therefore

  8. In vitro study of uptake and synthesis of creatine and its precursors by cerebellar granule cells and astrocytes suggests some hypotheses on the physiopathology of the inherited disorders of creatine metabolism

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    Carducci Claudia

    2012-04-01

    Full Text Available Abstract Background The discovery of the inherited disorders of creatine (Cr synthesis and transport in the last few years disclosed the importance of blood Cr supply for the normal functioning of the brain. These putatively rare diseases share a common pathogenetic mechanism (the depletion of brain Cr and similar phenotypes characterized by mental retardation, language disturbances, seizures and movement disorders. In the effort to improve our knowledge on the mechanisms regulating Cr pool inside the nervous tissue, Cr transport and synthesis and related gene transcripts were explored in primary cultures of rat cerebellar granule cells and astrocytes. Methods Cr uptake and synthesis were explored in vitro by incubating monotypic primary cultures of rat type I astrocytes and cerebellar granule cells with: a D3-Creatine (D3Cr and D3Cr plus β-guanidinopropionate (GPA, an inhibitor of Cr transporter, and b labelled precursors of Guanidinoacetate (GAA and Cr (Arginine, Arg; Glycine, Gly. Intracellular D3Cr and labelled GAA and Cr were assessed by ESI-MS/MS. Creatine transporter (CT1, L-arginine:glycine amidinotransferase (AGAT, and S-adenosylmethionine:guanidinoacetate N-methyltransferase (GAMT gene expression was assessed in the same cells by real time PCR. Results D3Cr signal was extremely high in cells incubated with this isotope (labelled/unlabelled Cr ratio reached about 10 and 122, respectively in cerebellar granule cells and astrocytes and was reduced by GPA. Labelled Arg and Gly were taken up by the cells and incorporated in GAA, whose concentration paralleled that of these precursors both in the extracellular medium and inside the cells (astrocytes. In contrast, the increase of labelled Cr was relatively much more limited since labelled Cr after precursors' supplementation did not exceed 2,7% (cerebellar granule cells and 21% (astrocytes of unlabelled Cr. Finally, AGAT, GAMT and SLC6A8 were expressed in both kind of cells. Conclusions Our

  9. 17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

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    Yan Chen

    2016-01-01

    Full Text Available Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2 on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation.

  10. 17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

    Science.gov (United States)

    Chen, Yan; Guo, Wenjie; Li, Wenjuan; Cheng, Meng; Hu, Ying; Xu, Wenming

    2016-01-01

    Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation. PMID:27872858

  11. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation

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    Zhong-jun Zhang

    2015-01-01

    Full Text Available Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10 6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

  12. Analysis of spatial relationships in three dimensions: tools for the study of nerve cell patterning

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    Raven Mary A

    2008-07-01

    Full Text Available Abstract Background Multiple technologies have been brought to bear on understanding the three-dimensional morphology of individual neurons and glia within the brain, but little progress has been made on understanding the rules controlling cellular patterning. We describe new matlab-based software tools, now available to the scientific community, permitting the calculation of spatial statistics associated with 3D point patterns. The analyses are largely derived from the Delaunay tessellation of the field, including the nearest neighbor and Voronoi domain analyses, and from the spatial autocorrelogram. Results Our tools enable the analysis of the spatial relationship between neurons within the central nervous system in 3D, and permit the modeling of these fields based on lattice-like simulations, and on simulations of minimal-distance spacing rules. Here we demonstrate the utility of our analysis methods to discriminate between two different simulated neuronal populations. Conclusion Together, these tools can be used to reveal the presence of nerve cell patterning and to model its foundation, in turn informing on the potential developmental mechanisms that govern its establishment. Furthermore, in conjunction with analyses of dendritic morphology, they can be used to determine the degree of dendritic coverage within a volume of tissue exhibited by mature nerve cells.

  13. Retinal ganglion cell survival and axon regeneration after optic nerve injury in naked mole-rats.

    Science.gov (United States)

    Park, Kevin K; Luo, Xueting; Mooney, Skyler J; Yungher, Benjamin J; Belin, Stephane; Wang, Chen; Holmes, Melissa M; He, Zhigang

    2017-02-01

    In the adult mammalian central nervous system (CNS), axonal damage often triggers neuronal cell death and glial activation, with very limited spontaneous axon regeneration. In this study, we performed optic nerve injury in adult naked mole-rats, the longest living rodent, with a maximum life span exceeding 30 years, and found that injury responses in this species are quite distinct from those in other mammalian species. In contrast to what is seen in other mammals, the majority of injured retinal ganglion cells (RGCs) survive with relatively high spontaneous axon regeneration. Furthermore, injured RGCs display activated signal transducer and activator of transcription-3 (STAT3), whereas astrocytes in the optic nerve robustly occupy and fill the lesion area days after injury. These neuron-intrinsic and -extrinsic injury responses are reminiscent of those in "cold-blooded" animals, such as fish and amphibians, suggesting that the naked mole-rat is a powerful model for exploring the mechanisms of neuronal injury responses and axon regeneration in mammals. J. Comp. Neurol. 525:380-388, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Toxic agents causing cerebellar ataxias.

    Science.gov (United States)

    Manto, Mario

    2012-01-01

    The cerebellum is particularly vulnerable to intoxication and poisoning, especially so the cerebellar cortex and Purkinje neurons. In humans, the most common cause of a toxic lesion to the cerebellar circuitry is alcohol related, but the cerebellum is also a main target of drug exposure (such as anticonvulsants, antineoplastics, lithium salts, calcineurin inhibitors), drug abuse and addiction (such as cocaine, heroin, phencyclidine), and environmental toxins (such as mercury, lead, manganese, toluene/benzene derivatives). Although data for the prevalence and incidence of cerebellar lesions related to intoxication and poisoning are still unknown in many cases, clinicians should keep in mind the list of agents that may cause cerebellar deficits, since toxin-induced cerebellar ataxias are not rare in daily practice. Moreover, the patient's status may require immediate therapies when the intoxication is life-threatening. 2012 Elsevier B.V. All rights reserved.

  15. STAT3 Controls the Long-Term Survival and Phenotype of Repair Schwann Cells during Nerve Regeneration.

    Science.gov (United States)

    Benito, Cristina; Davis, Catherine M; Gomez-Sanchez, Jose A; Turmaine, Mark; Meijer, Dies; Poli, Valeria; Mirsky, Rhona; Jessen, Kristjan R

    2017-04-19

    After nerve injury, Schwann cells convert to a phenotype specialized to promote repair. But during the slow process of axonal regrowth, these repair Schwann cells gradually lose their regeneration-supportive features and eventually die. Although this is a key reason for the frequent regeneration failures in humans, the transcriptional mechanisms that control long-term survival and phenotype of repair cells have not been studied, and the molecular signaling underlying their decline is obscure. We show, in mice, that Schwann cell STAT3 has a dual role. It supports the long-term survival of repair Schwann cells and is required for the maintenance of repair Schwann cell properties. In contrast, STAT3 is less important for the initial generation of repair Schwann cells after injury. In repair Schwann cells, we find that Schwann cell STAT3 activation by Tyr705 phosphorylation is sustained during long-term denervation. STAT3 is required for maintaining autocrine Schwann cell survival signaling, and inactivation of Schwann cell STAT3 results in a striking loss of repair cells from chronically denervated distal stumps. STAT3 inactivation also results in abnormal morphology of repair cells and regeneration tracks, and failure to sustain expression of repair cell markers, including Shh, GDNF, and BDNF. Because Schwann cell development proceeds normally without STAT3, the function of this factor appears restricted to Schwann cells after injury. This identification of transcriptional mechanisms that support long-term survival and differentiation of repair cells will help identify, and eventually correct, the failures that lead to the deterioration of this important cell population. SIGNIFICANCE STATEMENT Although injured peripheral nerves contain repair Schwann cells that provide signals and spatial clues for promoting regeneration, the clinical outcome after nerve damage is frequently poor. A key reason for this is that, during the slow growth of axons through the proximal

  16. From the Cover: Selective Enhancement of Domoic Acid Toxicity in Primary Cultures of Cerebellar Granule Cells by Lowering Extracellular Na+ Concentration.

    Science.gov (United States)

    Pérez-Gómez, Anabel; Cabrera-García, David; Warm, Davide; Marini, Ann M; Salas Puig, Javier; Fernández-Sánchez, Maria Teresa; Novelli, Antonello

    2018-01-01

    Domoic acid (DOM) is an excitatory amino acid analog of kainic acid (KA) that acts through glutamic acid (GLU) receptors, inducing a fast and potent neurotoxic response. Here, we present evidence for an enhancement of excitotoxicity following exposure of cultured cerebellar granule cells to DOM in the presence of lower than physiological Na+ concentrations. The concentration of DOM that reduced by 50% neuronal survival was approximately 3 µM in Na+-free conditions and 16 µM in presence of a physiological concentration of extracellular Na+. The enhanced neurotoxic effect of DOM was fully prevented by AMPA/KA receptor antagonist, while N-methyl-D-aspartate-receptor-mediated neurotoxicity did not seem to be involved, as the absence of extracellular Na+ failed to potentiate GLU excitotoxicity under the same experimental conditions. Lowering of extracellular Na+ concentration to 60 mM eliminated extracellular recording of spontaneous electrophysiological activity from cultured neurons grown on a multi electrode array and prevented DOM stimulation of the electrical activity. Although changes in the extracellular Na+ concentration did not alter the magnitude of the rapid increase in intracellular Ca2+ levels associated to DOM exposure, they did change significantly the contribution of voltage-sensitive calcium channels (VScaCs) and the recovery time to baseline. The prevention of Ca2+ influx via VSCaCs by nifedipine failed to prevent DOM toxicity at any extracellular Na+ concentration, while the reduction of extracellular Ca2+ concentration ameliorated DOM toxicity only in the absence of extracellular Na+, enhancing it in physiological conditions. Our data suggest a crucial role for extracellular Na+ concentration in determining excitotoxicity by DOM. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.

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    Marvin R Diaz

    Full Text Available Cerebellar granule cells (CGNs are one of many neurons that express phasic and tonic GABAergic conductances. Although it is well established that Golgi cells (GoCs mediate phasic GABAergic currents in CGNs, their role in mediating tonic currents in CGNs (CGN-I(tonic is controversial. Earlier studies suggested that GoCs mediate a component of CGN-I(tonic that is present only in preparations from immature rodents. However, more recent studies have detected a GoC-dependent component of CGN-I(tonic in preparations of mature rodents. In addition, acute exposure to ethanol was shown to potentiate the GoC component of CGN-I(tonic and to induce a parallel increase in spontaneous inhibitory postsynaptic current frequency at CGNs. Here, we tested the hypothesis that these effects of ethanol on GABAergic transmission in CGNs are mediated by inhibition of the Na(+/K(+-ATPase. We used whole-cell patch-clamp electrophysiology techniques in cerebellar slices of male rats (postnatal day 23-30. Under these conditions, we reliably detected a GoC-dependent component of CGN-I(tonic that could be blocked with tetrodotoxin. Further analysis revealed a positive correlation between basal sIPSC frequency and the magnitude of the GoC-dependent component of CGN-I(tonic. Inhibition of the Na(+/K(+-ATPase with a submaximal concentration of ouabain partially mimicked the ethanol-induced potentiation of both phasic and tonic GABAergic currents in CGNs. Modeling studies suggest that selective inhibition of the Na(+/K(+-ATPase in GoCs can, in part, explain these effects of ethanol. These findings establish a novel mechanism of action of ethanol on GABAergic transmission in the central nervous system.

  18. A polymer foam conduit seeded with Schwann cells promotes guided peripheral nerve regeneration.

    Science.gov (United States)

    Hadlock, T; Sundback, C; Hunter, D; Cheney, M; Vacanti, J P

    2000-04-01

    Alternatives to autografts have long been sought for use in bridging neural gaps. Many entubulation materials have been studied, although with generally disappointing results in comparison with autografts. The purpose of this study was to design a more effective neural guidance conduit, to introduce Schwann cells into the conduit, and to determine regenerative capability through it in an in vivo model. A novel, fully biodegradable polymer conduit was designed and fabricated for use in peripheral nerve repair, which approximates the macro- and microarchitecture of native peripheral nerves. It comprised a series of longitudinally aligned channels, with diameters ranging from 60 to 550 microns. The lumenal surfaces promoted the adherence of Schwann cells, whose presence is known to play a key role in nerve regeneration. This unique channel architecture increased the surface area available for Schwann cell adherence up to five-fold over that available through a simple hollow conduit. The conduit was composed of a high-molecular-weight copolymer of lactic and glycolic acids (PLGA) (MW 130,000) in an 85:15 monomer ratio. A novel foam-processing technique, employing low-pressure injection molding, was used to create highly porous conduits (approximately 90% pore volume) with continuous longitudinal channels. Using this technique, conduits were constructed containing 1, 5, 16, 45, or more longitudinally aligned channels. Prior to cellular seeding of these conduits, the foams were prewet with 50% ethanol, flushed with physiologic saline, and coated with laminin solution (10 microg/mL). A Schwann cell suspension was dynamically introduced into these processed foams at a concentration of 5 X 10(5) cells/mL, using a simple bioreactor flow loop. In vivo regeneration studies were carried out in which cell-laden five-channel polymer conduits (individual channel ID 500 microm, total conduit OD 2.3 mm) were implanted across a 7-mm gap in the rat sciatic nerve (n = 4), and midgraft

  19. Interactive effects involving different classes of excitatory amino acid receptors and the survival of cerebellar granule cells in culture

    DEFF Research Database (Denmark)

    Balázs, R; Hack, N; Jørgensen, Ole Steen

    1990-01-01

    Differentiating granule cells develop survival requirements in culture which can be met by treatment with high K+ or N-methyl-D-aspartate (NMDA) and, according to our recent findings, also with low concentrations of kainic acid (KA, 50 microM). We have now attempted to elucidate the mechanism(s) ...

  20. Association of nerve growth factor receptors with the triton X-100 cytoskeleton of PC12 cells

    International Nuclear Information System (INIS)

    Vale, R.D.; Ignatius, M.J.; Shooter, E.M.

    1985-01-01

    Triton X-100 solubilizes membranes of PC12 cells and leaves behind a nucleus and an array of cytoskeletal filaments. Nerve growth factor (NGF) receptors are associated with this Triton X-100-insoluble residue. Two classes of NGF receptors are found on PC12 cells which display rapid and slow dissociating kinetics. Although rapidly dissociating binding is predominant (greater than 75%) in intact cells, the majority of binding to the Triton X-100 cytoskeleton is slowly dissociating (greater than 75%). Rapidly dissociating NGF binding on intact cells can be converted to a slowly dissociating form by the plant lectin wheat germ agglutinin (WGA). This lectin also increases the number of receptors which associate with the Triton X-100 cytoskeleton by more than 10-fold. 125 I-NGF bound to receptors can be visualized by light microscopy autoradiography in Triton X-100-insoluble residues of cell bodies, as well as growth cones and neurites. The WGA-induced association with the cytoskeleton, however, is not specific for the NGF receptor. Concentrations of WGA which change the Triton X-100 solubility of membrane glycoproteins are similar to those required to alter the kinetic state of the NGF receptor. Both events may be related to the crossbridging of cell surface proteins induced by this multivalent lectin

  1. Reconstruction of Multiple Facial Nerve Branches Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet-Pellet Transplantation.

    Science.gov (United States)

    Saito, Kosuke; Tamaki, Tetsuro; Hirata, Maki; Hashimoto, Hiroyuki; Nakazato, Kenei; Nakajima, Nobuyuki; Kazuno, Akihito; Sakai, Akihiro; Iida, Masahiro; Okami, Kenji

    2015-01-01

    Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL). We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs), which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk-MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST). Culture medium was transplanted as a control (NT). In the mouse experiment, facial-nerve-palsy (FNP) scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold) scores when compared to the NT-group after 2-8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP+ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks.

  2. Reconstruction of Multiple Facial Nerve Branches Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet-Pellet Transplantation.

    Directory of Open Access Journals (Sweden)

    Kosuke Saito

    Full Text Available Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL. We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs, which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk-MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST. Culture medium was transplanted as a control (NT. In the mouse experiment, facial-nerve-palsy (FNP scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold scores when compared to the NT-group after 2-8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP+ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks.

  3. Functional, electrophysiological recoveries of rats with sciatic nerve lesions following transplantation of elongated DRG cells.

    Science.gov (United States)

    Dayawansa, Samantha; Zhang, Jun; Shih, Chung-Hsuan; Tharakan, Binu; Huang, Jason H

    2016-04-01

    Functional data are essential when confirming the efficacy of elongated dorsal root ganglia (DRG) cells as a substitute for autografting. We present the quantitative functional motor, electrophysiological findings of engineered DRG recipients for the first time. Elongated DRG neurons and autografts were transplanted to bridge 1-cm sciatic nerve lesions of Sprague Dawley (SD) rats. Motor recoveries of elongated DRG recipients (n=9), autograft recipients (n=9), unrepaired rats (n=9) and intact rats (n=6) were investigated using the angle board challenge test following 16 weeks of recovery. Electrophysiology studies were conducted to assess the functional recovery at 16 weeks. In addition, elongated DRGs were subjected to histology assessments. At threshold levels (35° angle) of the angle board challenge test, the autograft recipients', DRG recipients' and unrepaired group's performances were equal to each other and were less than the intact group (pDRG recipients' performance was similar to both the intact group and the autograft nerve recipients, and was better (pDRG constructs had intact signal transmission when recorded over the lesion, while the unrepaired rats did not. It was observed that elongated DRG neurons closely resembled an autograft during histological assessments. Performances of autograft and elongated DRG construct recipients were similar. Elongated DRG neurons should be further investigated as a substitute for autografting.

  4. Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury: an advantageous alternative to ES and iPS cells.

    Science.gov (United States)

    Amoh, Yasuyuki; Kanoh, Maho; Niiyama, Shiro; Hamada, Yuko; Kawahara, Katsumasa; Sato, Yuichi; Hoffman, Robert M; Katsuoka, Kensei

    2009-08-01

    The optimal source of stem cells for regenerative medicine is a major question. Embryonic stem (ES) cells have shown promise for pluripotency but have ethical issues and potential to form teratomas. Pluripotent stem cells have been produced from skin cells by either viral-, plasmid- or transposon-mediated gene transfer. These stem cells have been termed induced pluripotent stem cells or iPS cells. iPS cells may also have malignant potential and are inefficiently produced. Embryonic stem cells may not be suited for individualized therapy, since they can undergo immunologic rejection. To address these fundamental problems, our group is developing hair follicle pluripotent stem (hfPS) cells. Our previous studies have shown that mouse hfPS cells can differentiate to neurons, glial cells in vitro, and other cell types, and can promote nerve and spinal cord regeneration in vivo. hfPS cells are located above the hair follicle bulge in what we have termed the hfPS cell area (hfPSA) and are nestin positive and keratin 15 (K-15) negative. Human hfPS cells can also differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In the present study, human hfPS cells were transplanted in the severed sciatic nerve of the mouse where they differentiated into glial fibrillary-acidic-protein (GFAP)-positive Schwann cells and promoted the recovery of pre-existing axons, leading to nerve generation. The regenerated nerve recovered function and, upon electrical stimulation, contracted the gastrocnemius muscle. The hfPS cells can be readily isolated from the human scalp, thereby providing an accessible, autologous and safe source of stem cells for regenerative medicine that have important advantages over ES or iPS cells. (c) 2009 Wiley-Liss, Inc.

  5. The Effects of Epidermal Neural Crest Stem Cells on Local Inflammation Microenvironment in the Defected Sciatic Nerve of Rats

    Directory of Open Access Journals (Sweden)

    Yue Li

    2017-05-01

    Full Text Available Cell-based therapy is a promising strategy for the repair of peripheral nerve injuries (PNIs. epidermal neural crest stems cells (EPI-NCSCs are thought to be important donor cells for repairing PNI in different animal models. Following PNI, inflammatory response is important to regulate the repair process. However, the effects of EPI-NCSCs on regulation of local inflammation microenviroment have not been investigated extensively. In the present study, these effects were studied by using 10 mm defected sciatic nerve, which was bridged with 15 mm artificial nerve composed of EPI-NCSCs, extracellular matrix (ECM and poly (lactide-co-glycolide (PLGA. Then the expression of pro- and anti-inflammatory cytokines, polarization of macrophages, regulation of fibroblasts and shwann cells (SCs were assessed by western blot, immunohistochemistry, immunofluorescence staining at 1, 3, 7 and 21 days after bridging. The structure and the function of the bridged nerve were determined by observation under light microscope and by examination of right lateral foot retraction time (LFRT, sciatic function index (SFI, gastrocnemius wet weight and electrophysiology at 9 weeks. After bridging with EPI-NCSCs, the expression of anti-inflammatory cytokines (IL-4 and IL-13 was increased, but decreased for pro-inflammatory cytokines (IL-6 and TNF-α compared to the control bridging, which was consistent with increase of M2 macrophages and decrease of M1 macrophages at 7 days after transplantation. Likewise, myelin-formed SCs were significantly increased, but decreased for the activated fibroblasts in their number at 21 days. The recovery of structure and function of nerve bridged with EPI-NCSCs was significantly superior to that of DMEM. These results indicated that EPI-NCSCs could be able to regulate and provide more suitable inflammation microenvironment for the repair of defected sciatic nerve.

  6. Protection by an oral disubstituted hydroxylamine derivative against loss of retinal ganglion cell differentiation following optic nerve crush.

    Directory of Open Access Journals (Sweden)

    James D Lindsey

    Full Text Available Thy-1 is a cell surface protein that is expressed during the differentiation of retinal ganglion cells (RGCs. Optic nerve injury induces progressive loss in the number of RGCs expressing Thy-1. The rate of this loss is fastest during the first week after optic nerve injury and slower in subsequent weeks. This study was undertaken to determine whether oral treatment with a water-soluble N-hydroxy-2,2,6,6-tetramethylpiperidine derivative (OT-440 protects against loss of Thy-1 promoter activation following optic nerve crush and whether this effect targets the earlier quick phase or the later slow phase. The retina of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice was imaged using a blue-light confocal scanning laser ophthalmoscope (bCSLO. These mice then received oral OT-440 prepared in cream cheese or dissolved in water, or plain vehicle, for two weeks and were imaged again prior to unilateral optic nerve crush. Treatments and weekly imaging continued for four more weeks. Fluorescent neurons were counted in the same defined retinal areas imaged at each time point in a masked fashion. When the counts at each time point were directly compared, the numbers of fluorescent cells at each time point were greater in the animals that received OT-440 in cream cheese by 8%, 27%, 52% and 60% than in corresponding control animals at 1, 2, 3 and 4 weeks after optic nerve crush. Similar results were obtained when the vehicle was water. Rate analysis indicated the protective effect of OT-440 was greatest during the first two weeks and was maintained in the second two weeks after crush for both the cream cheese vehicle study and water vehicle study. Because most of the fluorescent cells detected by bCSLO are RGCs, these findings suggest that oral OT-440 can either protect against or delay early degenerative responses occurring in RGCs following optic nerve injury.

  7. Protection by an oral disubstituted hydroxylamine derivative against loss of retinal ganglion cell differentiation following optic nerve crush.

    Science.gov (United States)

    Lindsey, James D; Duong-Polk, Karen X; Dai, Yi; Nguyen, Duy H; Leung, Christopher K; Weinreb, Robert N

    2013-01-01

    Thy-1 is a cell surface protein that is expressed during the differentiation of retinal ganglion cells (RGCs). Optic nerve injury induces progressive loss in the number of RGCs expressing Thy-1. The rate of this loss is fastest during the first week after optic nerve injury and slower in subsequent weeks. This study was undertaken to determine whether oral treatment with a water-soluble N-hydroxy-2,2,6,6-tetramethylpiperidine derivative (OT-440) protects against loss of Thy-1 promoter activation following optic nerve crush and whether this effect targets the earlier quick phase or the later slow phase. The retina of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) was imaged using a blue-light confocal scanning laser ophthalmoscope (bCSLO). These mice then received oral OT-440 prepared in cream cheese or dissolved in water, or plain vehicle, for two weeks and were imaged again prior to unilateral optic nerve crush. Treatments and weekly imaging continued for four more weeks. Fluorescent neurons were counted in the same defined retinal areas imaged at each time point in a masked fashion. When the counts at each time point were directly compared, the numbers of fluorescent cells at each time point were greater in the animals that received OT-440 in cream cheese by 8%, 27%, 52% and 60% than in corresponding control animals at 1, 2, 3 and 4 weeks after optic nerve crush. Similar results were obtained when the vehicle was water. Rate analysis indicated the protective effect of OT-440 was greatest during the first two weeks and was maintained in the second two weeks after crush for both the cream cheese vehicle study and water vehicle study. Because most of the fluorescent cells detected by bCSLO are RGCs, these findings suggest that oral OT-440 can either protect against or delay early degenerative responses occurring in RGCs following optic nerve injury.

  8. Sleep disorders in cerebellar ataxias

    Directory of Open Access Journals (Sweden)

    José L. Pedroso

    2011-04-01

    Full Text Available Cerebellar ataxias comprise a wide range of etiologies leading to central nervous system-related motor and non-motor symptoms. Recently, a large body of evidence has demonstrated a high frequency of non-motor manifestations in cerebellar ataxias, specially in autosomal dominant spinocerebellar ataxias (SCA. Among these non-motor dysfunctions, sleep disorders have been recognized, although still under or even misdiagnosed. In this review, we highlight the main sleep disorders related to cerebellar ataxias focusing on REM sleep behavior disorder (RBD, restless legs syndrome (RLS, periodic limb movement in sleep (PLMS, excessive daytime sleepiness (EDS, insomnia and sleep apnea.

  9. Study of the Peripheral Nerve Fibers Myelin Structure Changes during Activation of Schwann Cell Acetylcholine Receptors.

    Directory of Open Access Journals (Sweden)

    Ekaterina E Verdiyan

    Full Text Available In the present paper we consider a new type of mechanism by which neurotransmitter acetylcholine (ACh regulates the properties of peripheral nerve fibers myelin. Our data show the importance of the relationship between the changes in the number of Schwann cell (SC acetylcholine receptors (AChRs and the axon excitation (different intervals between action potentials (APs. Using Raman spectroscopy, an effect of activation of SC AChRs on the myelin membrane fluidity was investigated. It was found, that ACh stimulates an increase in lipid ordering degree of the myelin lipids, thus providing evidence for specific role of the "axon-SC" interactions at the axon excitation. It was proposed, that during the axon excitation, the SC membrane K+- depolarization and the Ca2+-influx led to phospholipase activation or exocytosis of intracellular membrane vesicles and myelin structure reorganization.

  10. Nerve Cells Decide to Orient inside an Injectable Hydrogel with Minimal Structural Guidance.

    Science.gov (United States)

    Rose, Jonas C; Cámara-Torres, María; Rahimi, Khosrow; Köhler, Jens; Möller, Martin; De Laporte, Laura

    2017-06-14

    Injectable biomaterials provide the advantage of a minimally invasive application but mostly lack the required structural complexity to regenerate aligned tissues. Here, we report a new class of tissue regenerative materials that can be injected and form an anisotropic matrix with controlled dimensions using rod-shaped, magnetoceptive microgel objects. Microgels are doped with small quantities of superparamagnetic iron oxide nanoparticles (0.0046 vol %), allowing alignment by external magnetic fields in the millitesla order. The microgels are dispersed in a biocompatible gel precursor and after injection and orientation are fixed inside the matrix hydrogel. Regardless of the low volume concentration of the microgels below 3%, at which the geometrical constrain for orientation is still minimum, the generated macroscopic unidirectional orientation is strongly sensed by the cells resulting in parallel nerve extension. This finding opens a new, minimal invasive route for therapy after spinal cord injury.

  11. Regenerative medicine for Parkinson's disease using differentiated nerve cells derived from human buccal fat pad stem cells.

    Science.gov (United States)

    Takahashi, Haruka; Ishikawa, Hiroshi; Tanaka, Akira

    2017-04-01

    The purpose of this study was to evaluate the utility of human adipose stem cells derived from the buccal fat pad (hBFP-ASCs) for nerve regeneration. Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons. PD is a candidate disease for cell replacement therapy because it has no fundamental therapeutic methods. We examined the properties of neural-related cells induced from hBFP-ASCs as a cell source for PD treatment. hBFP-ASCs were cultured in neurogenic differentiation medium for about 2 weeks. After the morphology of hBFP-ASCs changed to neural-like cells, the medium was replaced with neural maintenance medium. Cells differentiated from hBFP-ASCs showed neuron-like structures and expressed neuron markers (β3-tubulin, neurofilament 200, and microtubule-associated protein 2), an astrocyte marker (glial fibrillary acidic protein), or dopaminergic neuron-related marker (tyrosine hydroxylase). Induced neural cells were transplanted into a 6-hydroxydopamine (6-OHDA)-lesioned rat hemi-parkinsonian model. At 4 weeks after transplantation, 6-OHDA-lesioned rats were subjected to apomorphine-induced rotation analysis. The transplanted cells survived in the brain of rats as dopaminergic neural cells. No tumor formation was found after cell transplantation. We demonstrated differentiation of hBFP-ASCs into neural cells, and that transplantation of these neural cells improved the symptoms of model rats. Our results suggest that neurons differentiated from hBFP-ASCs would be applicable to cell replacement therapy of PD.

  12. Positive effects of bFGF modified rat amniotic epithelial cells transplantation on transected rat optic nerve.

    Directory of Open Access Journals (Sweden)

    Jia-Xin Xie

    Full Text Available Effective therapy for visual loss caused by optic nerve injury or diseases has not been achieved even though the optic nerve has the regeneration potential after injury. This study was designed to modify amniotic epithelial cells (AECs with basic fibroblast growth factor (bFGF gene, preliminarily investigating its effect on transected optic nerve.A human bFGF gene segment was delivered into rat AECs (AECs/hbFGF by lentiviral vector, and the gene expression was examined by RT-PCR and ELISA. The AECs/hbFGF and untransfected rat AECs were transplanted into the transected site of the rat optic nerve. At 28 days post transplantation, the survival and migration of the transplanted cells was observed by tracking labeled cells; meanwhile retinal ganglion cells (RGCs were observed and counted by employing biotin dextran amine (BDA and Nissl staining. Furthermore, the expression of growth associated protein 43 (GAP-43 within the injury site was examined with immunohistochemical staining.The AECs/hbFGF was proven to express bFGF gene and secrete bFGF peptide. Both AECs/hbFGF and AECs could survive and migrate after transplantation. RGCs counting implicated that RGCs numbers of the cell transplantation groups were significantly higher than that of the control group, and the AECs/hbFGF group was significantly higher than that of the AECs group. Moreover GAP-43 integral optical density value in the control group was significantly lower than that of the cell transplantation groups, and the value in the AECs/hbFGF group was significantly higher than that of the AECs group.AECs modified with bFGF could reduce RGCs loss and promote expression of GAP-43 in the rat optic nerve transected model, facilitating the process of neural restoration following injury.

  13. Expression patterns of cell cycle components in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors

    NARCIS (Netherlands)

    Agesen, Trude Holmeide; Florenes, Viva Ann; Molenaar, Willemina M.; Lind, Guro E.; Berner, Jeane-Marie; Plaat, Boudewijn E.C.; Komdeur, Rudy; Myklebost, Ola; van den Berg, Eva; Lothe, Ragnhild A.

    The molecular biology underlying the development of highly malignant peripheral nerve sheath tumors (MPNSTs) remains mostly unknown. In the present study, the expression pattern of 10 selected cell cycle components is investigated in a series of 15 MPNSTs from patients with (n = 9) or without (n =

  14. Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the Göttingen minipig basal forebrain

    DEFF Research Database (Denmark)

    Fjord-Larsen, L; Kusk, P; Tornøe, Jens

    2010-01-01

    Nerve growth factor (NGF) prevents cholinergic degeneration in Alzheimer's disease (AD) and improves memory in AD animal models. In humans, the safe delivery of therapeutic doses of NGF is challenging. For clinical use, we have therefore developed an encapsulated cell (EC) biodelivery device...

  15. Patterns of lipofuscin accumulation in ganglionic nerve cells of superior cervical ganglion in humans

    Directory of Open Access Journals (Sweden)

    Živković Vladimir

    2008-01-01

    Full Text Available Background/Aim. Considering available literature lipofuscin is a classical age pigment of postmitotic cells, and a consistently recognized phenomenon in humans and animals. Lipofuscin accumulation is characteristic for nerve cells that are postmitotic. This research was focused on lipofuscin accumulation in ganglionic cells (GC (postganglionic sympathetic cell bodies of superior cervical ganglion in humans during ageing. Methods. We analysed 30 ganglions from cadavers ranging from 20 to over 80 years of age. As material the tissue samples were used from the middle portion of the ganglion, which was separated from the surrounding tissue by the method of macrodissection. The tissue samples were routinely fixed in 10% neutral formalin and embedded in paraffin for classical histological analysis, then three consecutive (successive sections 5 μm thick were made and stained with hematoxylin and eosin method (HE, silver impregnation technique by Masson Fontana and trichrome stain by Florantin. Results. Immersion microscopy was used to analyse patterns of lipofuscin accumulation during ageing making possible to distinguish diffuse type (lipofuscin granules were irregularly distributed and non-confluent, unipolar type (lipofuscin granules were grouped at the end of the cell, bipolar type (lipofuscin granules were concentrated at the two opposite ends of a cell with the nucleus in between at the center of a cell, annular type (lipofuscin granules were in the shape of a complete or incomplete ring around the nucleus and a cell completely filled with lipofuscin (two subtypes distinguishing, one with visible a nucleus, and the other with invisible one. Even at the age of 20 there were cells with lipofuscin granules accumulated in diffuse way, but in smaller numbers; the GC without lipofuscin were dominant. Growing older, especially above 60 years, all of the above mentioned patterns of lipofuscin accumulation were present with the evident increase in cells

  16. Microcystic adnexal carcinoma (MAC)-like squamous cell carcinoma as a differential diagnosis to Bell´s palsy: review of guidelines for refractory facial nerve palsy.

    Science.gov (United States)

    Mueller, S K; Iro, H; Lell, M; Seifert, F; Bohr, C; Scherl, C; Agaimy, A; Traxdorf, M

    2017-01-05

    Bell´s palsy is the most common cause of facial paralysis worldwide and the most common disorder of the cranial nerves. It is a diagnosis of exclusion, accounting for 60-75% of all acquired peripheral facial nerve palsies. Our case shows the first case of a microcystic adnexal carcinoma-like squamous cell carcinoma as a cause of facial nerve palsy. The patient, a 70-year-old Caucasian male, experienced subsequent functional impairment of the trigeminal and the glossopharyngeal nerve about 1½ years after refractory facial nerve palsy. An extensive clinical work-up and tissue biopsy of the surrounding parotid gland tissue was not able to determine the cause of the paralysis. Primary infiltration of the facial nerve with subsequent spreading to the trigeminal and glossopharyngeal nerve via neuroanastomoses was suspected. After discussing options with the patient, the main stem of the facial nerve was resected to ascertain the diagnosis of MAC-like squamous cell carcinoma, and radiochemotherapy was subsequently started. This case report shows that even rare neoplastic etiologies should be considered as a cause of refractory facial nerve palsy and that it is necessary to perform an extended diagnostic work-up to ascertain the diagnosis. This includes high-resolution MRI imaging and, as perilesional parotid biopsies might be inadequate for rare cases like ours, consideration of a direct nerve biopsy to establish the right diagnosis.

  17. Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia.

    Science.gov (United States)

    Mittleman, Guy; Goldowitz, Daniel; Heck, Detlef H; Blaha, Charles D

    2008-07-01

    Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 muA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked prefrontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders.

  18. Combination of heterologous fibrin sealant and bioengineered human embryonic stem cells to improve regeneration following autogenous sciatic nerve grafting repair.

    Science.gov (United States)

    Mozafari, Roghayeh; Kyrylenko, Sergiy; Castro, Mateus Vidigal; Ferreira, Rui Seabra; Barraviera, Benedito; Oliveira, Alexandre Leite Rodrigues

    2018-01-01

    Peripheral nerve injury is a worldwide clinical problem, and the preferred surgical method for treating it is the end-to-end neurorrhaphy. When it is not possible due to a large nerve gap, autologous nerve grafting is used. However, these surgical techniques result in nerve regeneration at highly variable degrees. It is thus very important to seek complementary techniques to improve motor and sensory recovery. One promising approach could be cell therapy. Transplantation therapy with human embryonic stem cells (hESCs) is appealing because these cells are pluripotent and can differentiate into specialized cell types and have self-renewal ability. Therefore, the main objective of this study was to find conditions under which functional recovery is improved after sciatic nerve neurorrhaphy. We assumed that hESC, either alone or in combination with heterologous fibrin sealant scaffold, could be used to support regeneration in a mouse model of sciatic nerve injury and repair via autografting with end-to-end neurorrhaphy. Five millimeters of the sciatic nerve of C57BL/6 J mice were transected off and rotated 180 degrees to simulate an injury, and then stumps were sutured. Next, we applied heterologous fibrin sealant and/or human embryonic stem cells genetically altered to overexpress fibroblast growth factor 2 (FGF2) at the site of the injury. The study was designed to include six experimental groups comprising neurorrhaphy (N), neurorrhaphy + heterologous fibrin sealant (N + F), neurorrhaphy + heterologous fibrin sealant + doxycycline (N + F + D), neurorrhaphy + heterologous fibrin sealant + wild-type hESC (N + F + W), neurorrhaphy + heterologous fibrin sealant + hESC off (N + F + T), and neurorrhaphy + heterologous fibrin sealant + hESC on via doxycycline (N + F + D + T). We evaluated the recovery rate using Catwalk and von Frey functional recovery tests, as well as immunohistochemistry analysis. The experiments indicated that

  19. Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves

    OpenAIRE

    Amoh, Yasuyuki; Li, Lingna; Campillo, Raul; Kawahara, Katsumasa; Katsuoka, Kensei; Penman, Sheldon; Hoffman, Robert M.

    2005-01-01

    The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, also is expressed in follicle stem cells and their immediate, differentiated progeny. The fluorescent protein GFP, whose expression is driven by the nestin regulatory element in transgenic mice, served to mark the follicle cell fate. The pluripotent nestin-driven GFP stem cells are positive for the stem cell marker CD34 but ne...

  20. Autophagy is involved in the reduction of myelinating Schwann cell cytoplasm during myelin maturation of the peripheral nerve.

    Directory of Open Access Journals (Sweden)

    So Young Jang

    Full Text Available Peripheral nerve myelination involves dynamic changes in Schwann cell morphology and membrane structure. Recent studies have demonstrated that autophagy regulates organelle biogenesis and plasma membrane dynamics. In the present study, we investigated the role of autophagy in the development and differentiation of myelinating Schwann cells during sciatic nerve myelination. Electron microscopy and biochemical assays have shown that Schwann cells remove excess cytoplasmic organelles during myelination through macroautophagy. Inhibition of autophagy via Schwann cell-specific removal of ATG7, an essential molecule for macroautophagy, using a conditional knockout strategy, resulted in abnormally enlarged abaxonal cytoplasm in myelinating Schwann cells that contained a large number of ribosomes and an atypically expanded endoplasmic reticulum. Small fiber hypermyelination and minor anomalous peripheral nerve functions are observed in this mutant. Rapamycin-induced suppression of mTOR activity during the early postnatal period enhanced not only autophagy but also developmental reduction of myelinating Schwann cells cytoplasm in vivo. Together, our findings suggest that autophagy is a regulatory mechanism of Schwann cells structural plasticity during myelination.

  1. Combined use of decellularized allogeneic artery conduits with autologous transdifferentiated adipose-derived stem cells for facial nerve regeneration in rats.

    Science.gov (United States)

    Sun, Fei; Zhou, Ke; Mi, Wen-juan; Qiu, Jian-hua

    2011-11-01

    Natural biological conduits containing seed cells have been widely used as an alternative strategy for nerve gap reconstruction to replace traditional nerve autograft techniques. The purpose of this study was to investigate the effects of a decellularized allogeneic artery conduit containing autologous transdifferentiated adipose-derived stem cells (dADSCs) on an 8-mm facial nerve branch lesion in a rat model. After 8 weeks, functional evaluation of vibrissae movements and electrophysiological assessment, retrograde labeling of facial motoneurons and morphological analysis of regenerated nerves were performed to assess nerve regeneration. The transected nerves reconstructed with dADSC-seeded artery conduits achieved satisfying regenerative outcomes associated with morphological and functional improvements which approached those achieved with Schwann cell (SC)-seeded artery conduits, and superior to those achieved with artery conduits alone or ADSC-seeded artery conduits, but inferior to those achieved with nerve autografts. Besides, numerous transplanted PKH26-labeled dADSCs maintained their acquired SC-phenotype and myelin sheath-forming capacity inside decellularized artery conduits and were involved in the process of axonal regeneration and remyelination. Collectively, our combined use of decellularized allogeneic artery conduits with autologous dADSCs certainly showed beneficial effects on nerve regeneration and functional restoration, and thus represents an alternative approach for the reconstruction of peripheral facial nerve defects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Stem Cell Ophthalmology Treatment Study (SCOTS for retinal and optic nerve diseases: a preliminary report

    Directory of Open Access Journals (Sweden)

    Jeffrey N Weiss

    2015-01-01

    Full Text Available In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS. SCOTS is an Institutional Review Board approved clinical trial and is the largest ophthalmology stem cell study registered at the National Institutes of Health to date- www.clinicaltrials.gov Identifier NCT 01920867. SCOTS utilizes autologous bone marrow-derived stem cells in the treatment of optic nerve and retinal diseases. Pre- and post-treatment comprehensive eye exams were independently performed at the Wilmer Eye Institute at the Johns Hopkins Hospital, USA. A 27 year old female patient had lost vision approximately 5 years prior to enrollment in SCOTS. Pre-treatment best-corrected visual acuity at the Wilmer Eye Institute was 20/800 Right Eye (OD and 20/4,000 Left Eye (OS. Four months following treatment in SCOTS, the central visual acuity had improved to 20/100 OD and 20/40 OS.

  3. Targeting of liposomes to cells bearing nerve growth factor receptors mediated by biotinylated NGF

    International Nuclear Information System (INIS)

    Rosenberg, M.B.

    1986-01-01

    Previous studies of liposome targeting have concentrated on immunological systems, the use of ligand-receptor interactions has received little attention. The protein hormone beta-nerve growth factor (NGF) was modified by biotinylation via carboxyl group substitution (C-bio-NGF) under reaction conditions that yielded an average of 3 biotin additions per NGF subunit. NGF was also biotinylated through amino group substitution to produce derivatives with ratios of 1, 2 and 4 biotin moieties per NGF subunit (N-bio-NGF). These derivatives were compared with native NGF for their ability to compete with 125 I-NGF for binding to NGF receptors on rat pheochromocytoma (PC 12) cells at 4 0 C. C-bio-NGF was as effective as native NGF in binding to NGF receptors, while N-bio-NGF containing 1 biotin per NGF subunit was only 28% as active in binding as native NGF. C-bio-NGF, but not N-bio-NGF, mediated the specific binding of 125 I-streptavidin to PC12 cells. Biocytin-NGF, a derivative of C-bio-NGF with an extended spacer chain, was also synthesized and retained full biological and receptor binding activities. C-bio-NGF and biocytin-NGF were as effective as native NGF in a bioassay involving induction of neurite outgrowth from PC12 cells

  4. Complex partial seizures: cerebellar metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Theodore, W.H.; Fishbein, D.; Deitz, M.; Baldwin, P.

    1987-07-01

    We used positron emission tomography (PET) with (/sup 18/F)2-deoxyglucose to study cerebellar glucose metabolism (LCMRglu) and the effect of phenytoin (PHT) in 42 patients with complex partial seizures (CPS), and 12 normal controls. Mean +/- SD patient LCMRglu was 6.9 +/- 1.8 mg glucose/100 g/min (left = right), significantly lower than control values of 8.5 +/- 1.8 (left, p less than 0.006), and 8.3 +/- 1.6 (right, p less than 0.02). Only four patients had cerebellar atrophy on CT/MRI; cerebellar LCMRglu in these was 5.5 +/- 1.5 (p = 0.054 vs. total patient sample). Patients with unilateral temporal hypometabolism or EEG foci did not have lateralized cerebellar hypometabolism. Patients receiving phenytoin (PHT) at the time of scan and patients with less than 5 years total PHT exposure had lower LCMRglu, but the differences were not significant. There were weak inverse correlations between PHT level and cerebellar LCMRglu in patients receiving PHT (r = -0.36; 0.05 less than p less than 0.1), as well as between length of illness and LCMRglu (r = -0.22; 0.05 less than p less than 0.1). Patients with complex partial seizures have cerebellar hypometabolism that is bilateral and due only in part to the effect of PHT.

  5. Intravenous mesenchymal stem cell therapy after recurrent laryngeal nerve injury: a preliminary study.

    Science.gov (United States)

    Lerner, Michael Z; Matsushita, Takashi; Lankford, Karen L; Radtke, Christine; Kocsis, Jeffery D; Young, Nwanmegha O

    2014-11-01

    Intravenous administration of mesenchymal stem cells (MSCs) has been recently shown to enhance functional recovery after stroke and spinal cord injury. The therapeutic properties of MSCs are attributed to their secretion of a variety of potent antiinflammatory and neurotrophic factors. We hypothesize that intravenous administration of MSCs after recurrent laryngeal nerve (RLN) injury in the rat may enhance functional recovery. Animal Research. Twelve 250-gram Sprague-Dawley rats underwent a controlled crush injury to the left RLN. After confirming postoperative vocal fold immobility, each rat was intravenously infused with either green fluorescent protein-expressing MSCs or control media in a randomized and blinded fashion. Videolaryngoscopy was performed weekly. The laryngoscopy video recordings were reviewed and rated by a fellowship-trained laryngologist who remained blinded to the intervention using a 0 to 3 scale. At 1 week postinjury, the MSC-infused group showed a trend for higher average functional recovery scores compared to the control group (2.2 vs 1.3), but it did not reach statistical significance (P value of 0.06). By 2 weeks, however, both groups exhibited complete return of function. These pilot data indicate that with complete nerve transection by crush injury of the RLN in rat, there is complete recovery of vocal fold mobility at 2 weeks. At 1 week postinjury, animals receiving intravenous infusion of MSCs showed a trend for greater functional recovery, suggesting a potential beneficial effect of MSCs; however, this did not reach statistical significance. Therefore, no definite conclusions can be drawn from these data and further study is required. N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  6. Endovascular treatment of the posterior inferior cerebellar artery aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Bradac, G.B.; Bergui, M. [Neuroradiology, Univ. di Torino, Turin (Italy)

    2004-12-01

    Aneurysms may arise at various locations along the course of the posterior inferior cerebellar artery. Brainstem and cranial nerves manipulation make the surgical approach to proximal aneurysms difficult, while the occlusion of the parent vessel is sometimes unavoidable in peripheral aneurysms. Endovascular treatment can be a good alternative, but also with this approach the location of the aneurysm is critical. If occlusion of the parent vessel is planned, anatomical variations and vascular territories of the brainstem should be considered. We report our experience with 18 consecutive aneurysms (12 proximal, 6 peripheral) treated by coils. Complete occlusion was achieved in 14 patients and subtotal in 4. In three patients the parent vessel had to be sacrificed. During treatment two perforations occurred; aneurysms were completely occluded without clinical consequences. Two small asymptomatic cerebellar infarctions were seen on postoperative computed tomography. Clinical outcome was good in 16 patients. (orig.)

  7. Functional and regenerative effects of local administration of autologous mononuclear bone marrow cells combined with silicone conduit on transected femoral nerve of rabbits.

    Science.gov (United States)

    Trindade, Anelise Bonilla; Schestatsky, Pedro; Torres, Vítor Félix; Gomes, Cristiano; Gianotti, Giordano Cabral; Paz, Ana Helena da Rosa; Terraciano, Paula Barros; Marques, Janete Maria Volpato; Guimarães, Karina Magano; Graça, Dominguita Lühers; Cirne-Lima, Elizabeth Obino; Contesini, Emerson Antonio

    2015-10-01

    The inoculation of cells into injury sites can accelerate and improve the quality of nerve regeneration. This study aimed to evaluate the functional and regenerative effects of mononuclear autologous bone marrow cells (MABMC) combined with silicon conduit grafting in rabbit femoral nerves. Twenty-eight animals were allocated to one of two groups: treatment group (TG) or control group (CG), divided according to the time of evaluation, at either 50 or 75 days. After neurotmesis of the femoral nerve, surgical repair was performed with nerve autografts in silicon conduits, leaving a 5mm gap in both groups. The TG received MABMC in silicon conduits, and CG received a sham saline inoculum. Histological, clinical and electrophysiological analyses detected no differences between groups, but analysis of leg diameter showed that TG diameters were larger. This cell therapy did not improve regeneration of the femoral nerve, but there was a tendency for better functional recovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Pinched Nerve

    Science.gov (United States)

    ... You are here Home » Disorders » All Disorders Pinched Nerve Information Page Pinched Nerve Information Page What research is being done? Within the NINDS research programs, pinched nerves are addressed primarily through studies associated with pain ...

  9. Intercellular K⁺ accumulation depolarizes Type I vestibular hair cells and their associated afferent nerve calyx.

    Science.gov (United States)

    Contini, D; Zampini, V; Tavazzani, E; Magistretti, J; Russo, G; Prigioni, I; Masetto, S

    2012-12-27

    Mammalian vestibular organs contain two types of sensory receptors, named Type I and Type II hair cells. While Type II hair cells are contacted by several small afferent nerve terminals, the basolateral surface of Type I hair cells is almost entirely enveloped by a single large afferent nerve terminal, called calyx. Moreover Type I, but not Type II hair cells, express a low-voltage-activated outward K(+) current, I(K,L), which is responsible for their much lower input resistance (Rm) at rest as compared to Type II hair cells. The functional meaning of I(K,L) and associated calyx is still enigmatic. By combining the patch-clamp whole-cell technique with the mouse whole crista preparation, we have recorded the current- and voltage responses of in situ hair cells. Outward K(+) current activation resulted in K(+) accumulation around Type I hair cells, since it induced a rightward shift of the K(+) reversal potential the magnitude of which depended on the amplitude and duration of K(+) current flow. Since this phenomenon was never observed for Type II hair cells, we ascribed it to the presence of a residual calyx limiting K(+) efflux from the synaptic cleft. Intercellular K(+) accumulation added a slow (τ>100ms) depolarizing component to the cell voltage response. In a few cases we were able to record from the calyx and found evidence for intercellular K(+) accumulation as well. The resulting depolarization could trigger a discharge of action potentials in the afferent nerve fiber. Present results support a model where pre- and postsynaptic depolarization produced by intercellular K(+) accumulation cooperates with neurotransmitter exocytosis in sustaining afferent transmission arising from Type I hair cells. While vesicular transmission together with the low Rm of Type I hair cells appears best suited for signaling fast head movements, depolarization produced by intercellular K(+) accumulation could enhance signal transmission during slow head movements. Copyright

  10. Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

    Science.gov (United States)

    Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

    2016-05-01

    Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Skin derived precursor Schwann cell-generated acellular matrix modified chitosan/silk scaffolds for bridging rat sciatic nerve gap.

    Science.gov (United States)

    Zhu, Changlai; Huang, Jing; Xue, Chengbin; Wang, Yaxian; Wang, Shengran; Bao, Shuangxi; Chen, Ruyue; Li, Yuan; Gu, Yun

    2017-12-27

    Extracellular/acellular matrix has been attracted much research interests for its unique biological characteristics, and ACM modified neural scaffolds shows the remarkable role of promoting peripheral nerve regeneration. In this study, skin-derived precursors pre-differentiated into Schwann cells (SKP-SCs) were used as parent cells to generate acellular(ACM) for constructing a ACM-modified neural scaffold. SKP-SCs were co-cultured with chitosan nerve guidance conduits (NGC) and silk fibroin filamentous fillers, followed by decellularization to stimulate ACM deposition. This NGC-based, SKP-SC-derived ACM-modified neural scaffold was used for bridging a 10 mm long rat sciatic nerve gap. Histological and functional evaluation after grafting demonstrated that regenerative outcomes achieved by this engineered neural scaffold were better than those achieved by a plain chitosan-silk fibroin scaffold, and suggested the benefits of SKP-SC-derived ACM for peripheral nerve repair. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  12. [Cerebellar cognitive affective syndrome secondary to a cerebellar tumour].

    Science.gov (United States)

    Domínguez-Carral, J; Carreras-Sáez, I; García-Peñas, J J; Fournier-Del Castillo, C; Villalobos-Reales, J

    2015-01-01

    Cerebellar cognitive affective syndrome is characterized by disturbances of executive function, impaired spatial cognition, linguistic difficulties, and personality change. The case of an 11 year old boy is presented, with behavior problems, learning difficulties and social interaction problems. In the physical examination he had poor visual contact, immature behavior, reduced expressive language and global motor disability with gait dyspraxia, with no defined cerebellar motor signs. In the neuropsychological evaluation he has a full scale overall intellectual quotient of 84, with signs of cerebellar cognitive affective syndrome. A tumour affecting inferior cerebellar vermis was observed in the magnetic resonance imaging, which had not significantly grown during 5 years of follow up. The cerebellum participates in controlling cognitive and affective functions. Cerebellar pathology must be considered in the differential diagnosis of children with cognitive or learning disorder with associated behavioral and emotional components. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  13. Cerebellar and pontine tegmental hypermetabolism in miller-fisher syndrome

    International Nuclear Information System (INIS)

    Kim, Yu Kyrong; Kim, Ji Soo; Lee, Won Woo; Kim, Sang Eun

    2007-01-01

    Miller Fisher syndrome (MFS) has been considered as a variant of Guillain-Barre syndrome (GBS), a type of acute immune neuropathies involving peripheral nerve system. Unlike GBS, presence of cerebellar type ataxia and supranuclear ophthalmioplesia in MFS suggests additional involvement of the central nervous system. To determine involvement of the central nervous system in MFS, we investigated the cerebral metabolic abnormalities in patients with MFS using FDG PET. Nine patients who were diagnosed as MFS based on acute ophthalmoplegia, ataxia, and areflexia without other identifiable causes participated in this study. In six patients, serum antibodies possibly related with symptom of MFS (anti- GQ1b or anti-GM1) were detected at the time of the study. With the interval of 25 26 days (range: 3-83 days) from the symptom on set, brain FDG PET were underwent in patients and compared with those from healthy controls. In group analysis comparing with healthy controls, FDG PET of patients revealed increased metabolism in the bilateral cerebellar hemispheres and vermis, and the thalamus. In contrast, the occipital cortex showed decreased metabolism. Individual analyses disclosed hypermetabolism in the cerebellar vermis or hemispheres in 5, and in the pontine tegmentum in 2 of the 9 patients. We also found that the cerebellar vermian hypermetabolism was inversely correlated with the interval between from the symptom on set to PET study. Moreover, follow-up PET of a patient demonstrated that cerebellar hypermetabolism decreased markedly with an improvement of the ophthalmoplegia and ataxia. These findings indicate an involvement of the central nervous system in MFS and suggest an antibody-associated acute inflammatory process as a mechanism of this disorder

  14. Cerebellar and pontine tegmental hypermetabolism in miller-fisher syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyrong; Kim, Ji Soo; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Miller Fisher syndrome (MFS) has been considered as a variant of Guillain-Barre syndrome (GBS), a type of acute immune neuropathies involving peripheral nerve system. Unlike GBS, presence of cerebellar type ataxia and supranuclear ophthalmioplesia in MFS suggests additional involvement of the central nervous system. To determine involvement of the central nervous system in MFS, we investigated the cerebral metabolic abnormalities in patients with MFS using FDG PET. Nine patients who were diagnosed as MFS based on acute ophthalmoplegia, ataxia, and areflexia without other identifiable causes participated in this study. In six patients, serum antibodies possibly related with symptom of MFS (anti- GQ1b or anti-GM1) were detected at the time of the study. With the interval of 25 26 days (range: 3-83 days) from the symptom on set, brain FDG PET were underwent in patients and compared with those from healthy controls. In group analysis comparing with healthy controls, FDG PET of patients revealed increased metabolism in the bilateral cerebellar hemispheres and vermis, and the thalamus. In contrast, the occipital cortex showed decreased metabolism. Individual analyses disclosed hypermetabolism in the cerebellar vermis or hemispheres in 5, and in the pontine tegmentum in 2 of the 9 patients. We also found that the cerebellar vermian hypermetabolism was inversely correlated with the interval between from the symptom on set to PET study. Moreover, follow-up PET of a patient demonstrated that cerebellar hypermetabolism decreased markedly with an improvement of the ophthalmoplegia and ataxia. These findings indicate an involvement of the central nervous system in MFS and suggest an antibody-associated acute inflammatory process as a mechanism of this disorder.

  15. Ultrasound-Guided Phrenic Nerve Block for Intractable Hiccups following Placement of Esophageal Stent for Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Arsanious, David; Khoury, Spiro; Martinez, Edgar; Nawras, Ali; Filatoff, Gregory; Ajabnoor, Hossam; Darr, Umar; Atallah, Joseph

    2016-05-01

    Hiccups are actions consisting of sudden contractions of the diaphragm and intercostals followed by a sudden inspiration and transient closure of the vocal cords. They are generally short lived and benign; however, in extreme and rare cases, such as esophageal carcinoma, they can become persistent or intractable, up to and involving significant pain, dramatically impacting the patient's quality of life. This case involves a 60-year-old man with a known history of squamous cell carcinoma of the esophagus. He was considered to have high surgical risk, and therefore he received palliative care through the use of fully covered metallic esophageal self-expandable stents due to a spontaneous perforated esophagus, after which he developed intractable hiccups and associated mediastinal pain. Conservative treatment, including baclofen, chlorpromazine, metoclopramide, and omeprazole, provided no relief for his symptoms. The patient was referred to pain management from gastroenterology for consultation on pain control. He ultimately received an ultrasound-guided left phrenic nerve block with bupivacaine and depomedrol, and 3 days later underwent the identical procedure on the right phrenic nerve. This led to complete resolution of his hiccups and associated mediastinal pain. At follow-up, 2 and 4 weeks after the left phrenic nerve block, the patient was found to maintain complete alleviation of the hiccups. Esophageal dilatation and/or phrenic or vagal afferent fiber irritation can be suspected in cases of intractable hiccups secondary to esophageal stenting. Regional anesthesia of the phrenic nerve through ultrasound guidance offers a long-term therapeutic option for intractable hiccups and associated mediastinal pain in selected patients with esophageal carcinoma after stent placement. Esophageal stent, esophageal stenting, intractable hiccups, intractable singultus, phrenic nerve block, phrenic nerve, ultrasound, palliative care, esophageal carcinoma.

  16. Uptake of 3H-thymidine by the receptor cell populations after injury of the sensory nerve fibres

    International Nuclear Information System (INIS)

    Chuchkov, Ch.N.

    1978-01-01

    The material of the study was the skin from the beak of two-day ducklings. The investigation was carried out on the 2nd, 5th, 20th and 45th day after the crushing of the sensory nerve fibres entering the capsulated Herbst receptors. Twenty four hours before the biopsy, the ducklings were injected at 6 hours intervals with 3 H-thymidine. The number of labelled index in the three cell pupulations, participating in the receptor development was determined. The cells of the subcapsular space of all control animals (with intacted suborbital nerves) have shown the highest labelled index. The index of the capsular perineural cells is about 12 times lower, while the labelled index of the Schwann receptor cells is about 10 times lower. Following the denervation, the labelled index in increasing and reaches its maximum on the 5th postoperative day. The Schwann receptor cells in comparison to the two other cell populations show the most significant deviation during the regeneration (45th day after the intervention). The investigations show that all three cell populations pass through a miotic cycle of innovation. The low labelled index of the Schwann receptors (1-2 labelled cells in 1000) is an indication of a high differentiation. One can assume that their regeneration takes place at the expense of the proper proliferation activity as well as of the differentiation of the Schwann cells from the distal section of the regenerating sensory nerve fibres. Taking into consideration the high labelled index of the other populations, it seems most probable that their regeneration takes place for the expense of their own cell populations. (A.B.)

  17. Retinal nerve fiber layer and ganglion cell complex thickness in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mehmet Demir

    2014-01-01

    Full Text Available Aim: The aim of the following study is to evaluate the retinal nerve fiber layer (RNFL and ganglion cell complex (GCC thickness in patients with type 2 diabetes mellitus (DM. Materials and Methods: Average, inferior, and superior values of RNFL and GCC thickness were measured in 123 patients using spectral domain optical coherence tomography. The values of participants with DM were compared to controls. Diabetic patients were collected in Groups 1, 2 and 3. Group 1 = 33 participants who had no diabetic retinopathy (DR; Group 2 = 30 participants who had mild nonproliferative DR and Group 3 = 30 participants who had moderate non-proliferative DR. The 30 healthy participants collected in Group 4. Analysis of variance test and a multiple linear regression analysis were used for statistical analysis. Results: The values of RNFL and GCC in the type 2 diabetes were thinner than controls, but this difference was not statistically significant. Conclusions: This study showed that there is a nonsignificant loss of RNFL and GCC in patients with type 2 diabetes.

  18. Microencapsulation improves inhibitory effects of transplanted olfactory ensheathing cells on pain after sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Hao Zhao

    2015-01-01

    Full Text Available Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells (OECs remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L 4-5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L 4-5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.

  19. Neuron-Derived ADAM10 Production Stimulates Peripheral Nerve Injury-Induced Neuropathic Pain by Cleavage of E-Cadherin in Satellite Glial Cells.

    Science.gov (United States)

    Li, Jian; Ouyang, Qing; Chen, Cheng-Wen; Chen, Qian-Bo; Li, Xiang-Nan; Xiang, Zheng-Hua; Yuan, Hong-Bin

    2017-09-01

    Increasing evidence suggests the potential involvement of metalloproteinase family proteins in the pathogenesis of neuropathic pain, although the underlying mechanisms remain elusive. Using the spinal nerve ligation model, we investigated whether ADAM10 proteins participate in pain regulation. By implementing invitro methods, we produced a purified culture of satellite glial cells to study the underlying mechanisms of ADAM10 in regulating neuropathic pain. Results showed that the ADAM10 protein was expressed in calcitonin gene-related peptide (CGRP)-containing neurons of the dorsal root ganglia, and expression was upregulated following spinal nerve ligation surgery invivo. Intrathecal administration of GI254023X, an ADAM10 selective inhibitor, to the rats one to three days after spinal nerve ligation surgery attenuated the spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia. Intrathecal injection of ADAM10 recombinant protein simulated pain behavior in normal rats to a similar extent as those treated by spinal nerve ligation surgery. These results raised a question about the relative contribution of ADAM10 in pain regulation. Further results showed that ADAM10 might act by cleaving E-cadherin, which is mainly expressed in satellite glial cells. GI254023X reversed spinal nerve ligation-induced downregulation of E-cadherin and activation of cyclooxygenase 2 after spinal nerve ligation. β-catenin, which creates a complex with E-cadherin in the membranes of satellite glial cells, was also downregulated by spinal nerve ligation surgery in satellite glial cells. Finally, knockdown expression of β-catenin by lentiviral infection in purified satellite glial cells increased expression of inducible nitric oxide synthase and cyclooxygenase 2. Our findings indicate that neuron-derived ADAM10 production stimulates peripheral nerve injury-induced neuropathic pain by cleaving E-cadherin in satellite glial cells. © 2017 American Academy of Pain Medicine

  20. Engrafted human induced pluripotent stem cell-derived anterior specified neural progenitors protect the rat crushed optic nerve.

    Directory of Open Access Journals (Sweden)

    Leila Satarian

    Full Text Available BACKGROUND: Degeneration of retinal ganglion cells (RGCs is a common occurrence in several eye diseases. This study examined the functional improvement and protection of host RGCs in addition to the survival, integration and neuronal differentiation capabilities of anterior specified neural progenitors (NPs following intravitreal transplantation. METHODOLOGY/PRINCIPAL FINDINGS: NPs were produced under defined conditions from human induced pluripotent stem cells (hiPSCs and transplanted into rats whose optic nerves have been crushed (ONC. hiPSCs were induced to differentiate into anterior specified NPs by the use of Noggin and retinoic acid. The hiPSC-NPs were labeled by green fluorescent protein or a fluorescent tracer 1,1' -dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI and injected two days after induction of ONC in hooded rats. Functional analysis according to visual evoked potential recordings showed significant amplitude recovery in animals transplanted with hiPSC-NPs. Retrograde labeling by an intra-collicular DiI injection showed significantly higher numbers of RGCs and spared axons in ONC rats treated with hiPSC-NPs or their conditioned medium (CM. The analysis of CM of hiPSC-NPs showed the secretion of ciliary neurotrophic factor, basic fibroblast growth factor, and insulin-like growth factor. Optic nerve of cell transplanted groups also had increased GAP43 immunoreactivity and myelin staining by FluoroMyelin™ which imply for protection of axons and myelin. At 60 days post-transplantation hiPSC-NPs were integrated into the ganglion cell layer of the retina and expressed neuronal markers. CONCLUSIONS/SIGNIFICANCE: The transplantation of anterior specified NPs may improve optic nerve injury through neuroprotection and differentiation into neuronal lineages. These NPs possibly provide a promising new therapeutic approach for traumatic optic nerve injuries and loss of RGCs caused by other diseases.

  1. Intravenous Infusion of Bone Marrow–Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats

    OpenAIRE

    Yohei Matsuda, MD; Masanori Sasaki, MD, PhD; Yuko Kataoka-Sasaki, MD, PhD; Akio Takayanagi, MD, PhD; Ko Kobayashi, MD, PhD; Shinichi Oka, MD, PhD; Masahito Nakazaki, MD, PhD; Naoya Masumori, MD, PhD; Jeffery D. Kocsis, PhD; Osamu Honmou, MD, PhD

    2018-01-01

    Introduction: Intravenous preload (delivered before cavernous nerve [CN] injury) of bone marrow–derived mesenchymal stem cells (MSCs) can prevent or decrease postoperative erectile dysfunction (J Sex Med 2015;12:1713–1721). In the present study, the potential therapeutic effects of intravenously administered MSCs on postoperative erectile dysfunction were evaluated in a rat model of CN injury. Methods: Male Sprague-Dawley rats were randomized into 2 groups after electric CN injury. Intrave...

  2. Uptake and metabolism of fructose by rat neocortical cells in vivo and by isolated nerve terminals in vitro.

    Science.gov (United States)

    Hassel, Bjørnar; Elsais, Ahmed; Frøland, Anne-Sofie; Taubøll, Erik; Gjerstad, Leif; Quan, Yi; Dingledine, Raymond; Rise, Frode

    2015-05-01

    Fructose reacts spontaneously with proteins in the brain to form advanced glycation end products (AGE) that may elicit neuroinflammation and cause brain pathology, including Alzheimer's disease. We investigated whether fructose is eliminated by oxidative metabolism in neocortex. Injection of [(14) C]fructose or its AGE-prone metabolite [(14) C]glyceraldehyde into rat neocortex in vivo led to formation of (14) C-labeled alanine, glutamate, aspartate, GABA, and glutamine. In isolated neocortical nerve terminals, [(14) C]fructose-labeled glutamate, GABA, and aspartate, indicating uptake of fructose into nerve terminals and oxidative fructose metabolism in these structures. This was supported by high expression of hexokinase 1, which channels fructose into glycolysis, and whose activity was similar with fructose or glucose as substrates. By contrast, the fructose-specific ketohexokinase was weakly expressed. The fructose transporter Glut5 was expressed at only 4% of the level of neuronal glucose transporter Glut3, suggesting transport across plasma membranes of brain cells as the limiting factor in removal of extracellular fructose. The genes encoding aldose reductase and sorbitol dehydrogenase, enzymes of the polyol pathway that forms glucose from fructose, were expressed in rat neocortex. These results point to fructose being transported into neocortical cells, including nerve terminals, and that it is metabolized and thereby detoxified primarily through hexokinase activity. We asked how the brain handles fructose, which may react spontaneously with proteins to form 'advanced glycation end products' and trigger inflammation. Neocortical cells took up and metabolized extracellular fructose oxidatively in vivo, and isolated nerve terminals did so in vitro. The low expression of fructose transporter Glut5 limited uptake of extracellular fructose. Hexokinase was a main pathway for fructose metabolism, but ketohexokinase (which leads to glyceraldehyde formation) was

  3. Retinal ganglion cell-inner plexiform and nerve fiber layers in neuromyelitis optica.

    Science.gov (United States)

    Hu, Sai-Jing; Lu, Pei-Rong

    2018-01-01

    To determine the thickness of the retinal ganglion cell-inner plexiform layer (GCIPL) and the retinal nerve fiber layer (RNFL) in patients with neuromyelitis optica (NMO). We conducted a cross-sectional study that included 30 NMO patients with a total of 60 eyes. Based on the presence or absence of optic neuritis (ON), subjects were divided into either the NMO-ON group (30 eyes) or the NMO-ON contra group (10 eyes). A detailed ophthalmologic examination was performed for each group; subsequently, the GCIPL and the RNFL were measured using high-definition optical coherence tomography (OCT). In the NMO-ON group, the mean GCIPL thickness was 69.28±21.12 µm, the minimum GCIPL thickness was 66.02±10.02 µm, and the RNFL thickness were 109.33±11.23, 110.47±3.10, 64.92±12.71 and 71.21±50.22 µm in the superior, inferior, temporal and nasal quadrants, respectively. In the NMO-ON contra group, the mean GCIPL thickness was 85.12±17.09 µm, the minimum GCIPL thickness was 25.39±25.1 µm, and the RNFL thicknesses were 148.33±23.22, 126.36±23.45, 82.21±22.30 and 83.36±31.28 µm in the superior, inferior, temporal and nasal quadrants, respectively. In the control group, the mean GCIPL thickness was 86.98±22.37 µm, the minimum GCIPL thickness was 85.28±10.75 µm, and the RNFL thicknesses were 150.22±22.73, 154.79±60.23, 82.33±7.01 and 85.62±13.81 µm in the superior, inferior, temporal and nasal quadrants, respectively. The GCIPL and RNFL were thinner in the NMO-ON contra group than in the control group ( P deviation (MD) and corrected pattern standard deviation (PSD) in the NMO-ON group ( P <0.05). The thickness of the GCIPL and RNFL, as measured using OCT, may indicate optic nerve damage in patients with NMO.

  4. Transplantation of Human Dental Pulp-Derived Stem Cells or Differentiated Neuronal Cells from Human Dental Pulp-Derived Stem Cells Identically Enhances Regeneration of the Injured Peripheral Nerve.

    Science.gov (United States)

    Ullah, Imran; Park, Ju-Mi; Kang, Young-Hoon; Byun, June-Ho; Kim, Dae-Geon; Kim, Joo-Heon; Kang, Dong-Ho; Rho, Gyu-Jin; Park, Bong-Wook

    2017-09-01

    Human dental mesenchymal stem cells isolated from the dental follicle, pulp, and root apical papilla of extracted wisdom teeth have been known to exhibit successful and potent neurogenic differentiation capacity. In particular, human dental pulp-derived stem cells (hDPSCs) stand out as the most prominent source for in vitro neuronal differentiation. In this study, to evaluate the in vivo peripheral nerve regeneration potential of hDPSCs and differentiated neuronal cells from DPSCs (DF-DPSCs), a total of 1 × 10 6 hDPSCs or DF-hDPSCs labeled with PKH26 tracking dye and supplemented with fibrin glue scaffold and collagen tubulization were transplanted into the sciatic nerve resection (5-mm gap) of rat models. At 12 weeks after cell transplantation, both hDPSC and DF-hDPSC groups showed notably increased behavioral activities and higher muscle contraction forces compared with those in the non-cell transplanted control group. In immunohistochemical analysis of regenerated nerve specimens, specific markers for angiogenesis, axonal fiber, and myelin sheath increased in both the cell transplantation groups. Pretransplanted labeled PKH26 were also distinctly detected in the regenerated nerve tissues, indicating that transplanted cells were well-preserved and differentiated into nerve cells. Furthermore, no difference was observed in the nerve regeneration potential between the hDPSC and DF-hDPSC transplanted groups. These results demonstrate that dental pulp tissue is an excellent stem cell source for nerve regeneration, and in vivo transplantation of the undifferentiated hDPSCs could exhibit sufficient and excellent peripheral nerve regeneration potential.

  5. Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto.

    Science.gov (United States)

    Pan, Hung-Chuan; Yang, Dar-Yu; Ho, Shu-Peng; Sheu, Meei-Ling; Chen, Chung-Jung; Hwang, Shiaw-Min; Chang, Ming-Hong; Cheng, Fu-Chou

    2009-08-23

    Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days); Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits.

  6. Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto

    Directory of Open Access Journals (Sweden)

    Pan Hung-Chuan

    2009-08-01

    Full Text Available Abstract Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days; Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits.

  7. Gene expression as a sensitive endpoint to evaluate cell differentiation and maturation of the developing central nervous system in primary cultures of rat cerebellar granule cells (CGCs) exposed to pesticides

    International Nuclear Information System (INIS)

    Hogberg, Helena T.; Kinsner-Ovaskainen, Agnieszka; Hartung, Thomas; Coecke, Sandra; Bal-Price, Anna K.

    2009-01-01

    The major advantage of primary neuronal cultures for developmental neurotoxicity (DNT) testing is their ability to replicate the crucial stages of neurodevelopment. In our studies using primary culture of cerebellar granule cells (CGCs) we have evaluated whether the gene expression relevant to the most critical developmental processes such as neuronal differentiation (NF-68 and NF-200) and functional maturation (NMDA and GABA A receptors), proliferation and differentiation of astrocytes (GFAP and S100β) as well as the presence of neural precursor cells (nestin and Sox10) could be used as an endpoint for in vitro DNT. The expression of these genes was assessed after exposure to various pesticides (paraquat parathion, dichlorvos, pentachlorophenol and cycloheximide) that could induce developmental neurotoxicity through different mechanisms. All studied pesticides significantly modified the expression of selected genes, related to the different stages of neuronal and/or glial cell development and maturation. The most significant changes were observed after exposure to paraquat and parathion (i.e. down-regulation of mRNA expression of NF-68 and NF-200, NMDA and GABA A receptors). Similarly, dichlorvos affected mainly neurons (decreased mRNA expression of NF-68 and GABA A receptors) whereas cycloheximide had an effect on neurons and astrocytes, as significant decreases in the mRNA expression of both neurofilaments (NF-68 and NF-200) and the astrocyte marker (S100β) were observed. Our results suggest that toxicity induced by pesticides that target multiple pathways of neurodevelopment can be identified by studying expression of genes that are involved in different stages of cell development and maturation, and that gene expression could be used as a sensitive endpoint for initial screening to identify the compounds with the potential to cause developmental neurotoxicity

  8. Hypertensive cerebellar hemorrhage and cerebellar hemorrhage caused by cryptic angioma

    International Nuclear Information System (INIS)

    Yoshida, Shinichi; Sano, Keiji; Kwak, Suyong; Saito, Isamu.

    1981-01-01

    A series of 44 patients with hypertensive cerebellar hemorrhage and nine patients with cerebellar hemorrhage caused by small angiomas is described. Hypertensive hemorrhage occurred most frequently in the patients in their seventies, whereas the onset of angioma-caused hemorrhage was often seen below the age of 40. Clinical syndromes of cerebellar hemorrhages can be categorized into three basic types: the vertigo syndrome, cerebellar dysfunction syndrome and brain stem compression syndrome. Patients with small (>= 2 cm in diameter in CT scans) and medium-sized (2 cm = 3 cm) hematomas deteriorated into unresponsive conditions and developed signs of brain stem compression. Surgical mortality was 32% in the hypertensive group, while it was 0% in the angioma group. Mortality as well as morbidity in both groups was strongly influenced by the preoperative status of consciousness. Our results suggest that substantial improvement could be obtained in the overall outcome of this disease by emergency craniectomy and removal of hematomas in all patients with large hematomas regardless of the levels of consciousness and regardless of the causes of bleeding. Furthermore, when clinical information and CT findings are suggestive of a ''cryptic'' angioma as the causative lesion, posterior fossa surgery may be indicated to extirpate the lesion, even if the hematoma is small. (author)

  9. Cerebellar Codings for Control of Compensatory Eye Movements

    NARCIS (Netherlands)

    M. Schonewille (Martijn)

    2008-01-01

    textabstractThis thesis focuses on the control of the cerebellum on motor behaviour, and more specifically on the role of the cerebellar Purkinje cells in exerting this control. As the cerebellum is an online control system, we look at both motor performance and learning, trying to identify

  10. [The neuroprotective effect of erigeron breviscapus (vant) hand-mazz on retinal ganglion cells after optic nerve crush injury].

    Science.gov (United States)

    Jiang, Bing; Jiang, You-qin

    2003-08-01

    To investigate whether a Chinese herbal medicine, erigeron breviscapus (vant) hand-mazz (EBHM), can protect the retinal ganglion cells (RGC) damaged by calibrated optic nerve crush injury. Forty-two Sprague-Dawley rats were randomly divided into two groups. Calibrated optic nerve crush injury model was induced in the right eyes by a special designed optic nerve clip. The left eyes served as a control. All 42 rats were randomly divided into 2 groups. Group A consisted of the rats with calibrated optic nerve crush injury and group B consisted of rats with calibrated optic nerve crush injury treated with EBHM. In group B, EBHM solution was given once after the crush injury. According to the time interval between the optic nerve crush and the sacrifice, both groups A and B were further divided into three subgroups (day 4, day 14 and day 21). Therefore, there were 7 rats in each subgroup. Three days before sacrifice, 3% fast blue was injected into superior colliculi bilaterally. The eyes were enucleated after the rat was sacrificed, and flat mounts of the retina from both eyes were prepared on a slide and observed under a fluorescence microscope. Four photos with 400 x magnification were taken from each of the four quadrants of the retina 1 mm away from the optic disc. The labeled RGC were counted by a computerized image analyzer. The labeled RGC rate was used for statistical analysis (the labeled RGC rate = number of RGC in injured eye/control eye x 100%). In group A, the labeled RGC rate was (77.79 +/- 7.11)%, (63.76 +/- 3.79)% and (54.66 +/- 4.75)% on day 4, day 14 and day 21, respectively. In group B, the labeled RGC rate was (80.13 +/- 12.03)%, (78.17 +/- 9.19)% and (83.59 +/- 12.61)% on day 4, day 14 and day 21, respectively. In group B, which was treated with EBHM after injury, the labeled RGC rate was significantly higher than that of group A on day 14 and day 21. In the experimental optic nerve crush model in rats, EBHM therapy can increase the survival rate of

  11. Tumors of the optic nerve

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Heegaard, Steffen

    2009-01-01

    A variety of lesions may involve the optic nerve. Mainly, these lesions are inflammatory or vascular lesions that rarely necessitate surgery but may induce significant visual morbidity. Orbital tumors may induce proptosis, visual loss, relative afferent pupillary defect, disc edema and optic...... atrophy, but less than one-tenth of these tumors are confined to the optic nerve or its sheaths. No signs or symptoms are pathognomonic for tumors of the optic nerve. The tumors of the optic nerve may originate from the optic nerve itself (primary tumors) as a proliferation of cells normally present...... in the nerve (e.g., astrocytes and meningothelial cells). The optic nerve may also be invaded from tumors originating elsewhere (secondary tumors), invading the nerve from adjacent structures (e.g., choroidal melanoma and retinoblastoma) or from distant sites (e.g., lymphocytic infiltration and distant...

  12. Combined Ipsilateral Oculomotor Nerve Palsy and Contralateral Downbeat Nystagmus in a Case of Cerebral Infarction

    Directory of Open Access Journals (Sweden)

    Kosuke Matsuzono

    2014-04-01

    Full Text Available We report a patient with acute cerebral infarction of the left paramedian thalamus, upper mesencephalon and cerebellum who exhibited ipsilateral oculomotor nerve palsy and contralateral downbeat nystagmus. The site of the infarction was considered to be the paramedian thalamopeduncular and cerebellar regions, which are supplied by the superior cerebellar artery containing direct perforating branches or both the superior cerebellar artery and the superior mesencephalic and posterior thalamosubthalamic arteries. Contralateral and monocular downbeat nystagmus is very rare. Our case suggests that the present downbeat nystagmus was due to dysfunction of cerebellar-modulated crossed oculovestibular fibers of the superior cerebellar peduncle or bilateral downbeat nystagmus with one-sided oculomotor nerve palsy.

  13. Defects in the CAPN1 Gene Result in Alterations in Cerebellar Development and Cerebellar Ataxia in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Yubin Wang

    2016-06-01

    Full Text Available A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1, which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

  14. Cerebellar arteriovenous malformations in children

    Energy Technology Data Exchange (ETDEWEB)

    Griffiths, P.D. [Sheffield Univ. (United Kingdom). Acad. Dept. of Radiol.; Blaser, S.; Armstrong, D.; Chuang, S.; Harwood-Nash, D. [Division of Neuroradiology, The Hospital for Sick Children and University of Toronto, Toronto (Canada); Humphreys, R.P. [Division of Neurosurgery, The Hospital for Sick Children and University of Toronto, Toronto (Canada)

    1998-05-01

    We review the presentation, imaging findings and outcome in 18 children with cerebellar arteriovenous malformations (AVM). This group is of particular interest because of the reported poor outcome despite modern imaging and neurosurgical techniques. All children had CT and 15 underwent catheter angiography at presentation. Several of the children in the latter part of the study had MRI. Of the 18 children, 17 presented with a ruptured AVM producing intracranial haemorrhage. The remaining child presented with temporal lobe epilepsy and was shown to have temporal, vermian and cerebellar hemisphere AVM. This child had other stigmata of Osler-Weber-Rendu syndrome. Three other children had pre-existing abnormalities of possible relevance. One had a vascular malformation of the cheek and mandible, one a documented chromosomal abnormality and another a midline cleft upper lip and palate. Six of the 17 children with a ruptured cerebellar AVM died within 7 days of the ictus. Vascular pathology other than an AVM was found in 10 of the 14 children with a ruptured cerebellar AVM who had angiography: 4 intranidal aneurysms, 5 venous aneurysms and 2 cases of venous outflow obstruction (one child having both an aneurysm and obstruction). The severity of clinical presentation was directly related to the size of the acute haematoma, which was a reasonable predictor of outcome. (orig.) With 4 figs., 4 tabs., 23 refs.

  15. Language Impairment in Cerebellar Ataxia

    NARCIS (Netherlands)

    van Gaalen, Judith; de Swart, Bert J. M.; Oostveen, Judith; Knuijt, Simone; van de Warrenburg, Bart P. C.; Kremer, Berry (H. ) P. H.

    Background: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). Methods: We assessed speech and language in 29 SCA6 patients

  16. Cerebellar arteriovenous malformations in children

    International Nuclear Information System (INIS)

    Griffiths, P.D.; Humphreys, R.P.

    1998-01-01

    We review the presentation, imaging findings and outcome in 18 children with cerebellar arteriovenous malformations (AVM). This group is of particular interest because of the reported poor outcome despite modern imaging and neurosurgical techniques. All children had CT and 15 underwent catheter angiography at presentation. Several of the children in the latter part of the study had MRI. Of the 18 children, 17 presented with a ruptured AVM producing intracranial haemorrhage. The remaining child presented with temporal lobe epilepsy and was shown to have temporal, vermian and cerebellar hemisphere AVM. This child had other stigmata of Osler-Weber-Rendu syndrome. Three other children had pre-existing abnormalities of possible relevance. One had a vascular malformation of the cheek and mandible, one a documented chromosomal abnormality and another a midline cleft upper lip and palate. Six of the 17 children with a ruptured cerebellar AVM died within 7 days of the ictus. Vascular pathology other than an AVM was found in 10 of the 14 children with a ruptured cerebellar AVM who had angiography: 4 intranidal aneurysms, 5 venous aneurysms and 2 cases of venous outflow obstruction (one child having both an aneurysm and obstruction). The severity of clinical presentation was directly related to the size of the acute haematoma, which was a reasonable predictor of outcome. (orig.)

  17. Speech Prosody in Cerebellar Ataxia

    Science.gov (United States)

    Casper, Maureen A.; Raphael, Lawrence J.; Harris, Katherine S.; Geibel, Jennifer M.

    2007-01-01

    Persons with cerebellar ataxia exhibit changes in physical coordination and speech and voice production. Previously, these alterations of speech and voice production were described primarily via perceptual coordinates. In this study, the spatial-temporal properties of syllable production were examined in 12 speakers, six of whom were healthy…

  18. Transmitter release modulation in nerve terminals of rat neocortical pyramidal cells by intracellular calcium buffers

    Science.gov (United States)

    Ohana, Ora; Sakmann, Bert

    1998-01-01

    Dual whole-cell voltage recordings were made from synaptically connected layer 5 (L5) pyramidal neurones in slices of the young (P14-P16) rat neocortex. The Ca2+ buffers BAPTA or EGTA were loaded into the presynaptic neurone via the pipette recording from the presynaptic neurone to examine their effect on the mean and the coefficient of variation (c.v.) of single fibre EPSP amplitudes, referred to as unitary EPSPs. The fast Ca2+ buffer BAPTA reduced unitary EPSP amplitudes in a concentration dependent way. With 0.1 mm BAPTA in the pipette, the mean EPSP amplitude was reduced by 14 ± 2.8% (mean ±s.e.m., n = 7) compared with control pipette solution, whereas with 1.5 mm BAPTA, the mean EPSP amplitude was reduced by 72 ± 1.5% (n = 5). The concentration of BAPTA that reduced mean EPSP amplitudes to one-half of control was close to 0.7 mm. Saturation of BAPTA during evoked release was tested by comparing the effect of loading the presynaptic neurone with 0.1 mm BAPTA at 2 and 1 mm[Ca2+]o. Reducing [Ca2+]o from 2 to 1 mm, thereby reducing Ca2+ influx into the terminals, decreased the mean EPSP amplitude by 60 ± 2.2% with control pipette solution and by 62 ± 1.9% after loading with 0.1 mm BAPTA (n = 7). The slow Ca2+ buffer EGTA at 1 mm reduced mean EPSP amplitudes by 15 ± 2.5% (n = 5). With 10 mm EGTA mean EPSP amplitudes were reduced by 56 ± 2.3% (n = 4). With both Ca2+ buffers, the reduction in mean EPSP amplitudes was associated with an increase in the c.v. of peak EPSP amplitudes, consistent with a reduction of the transmitter release probability as the major mechanism underlying the reduction of the EPSP amplitude. The results suggest that in nerve terminals of thick tufted L5 pyramidal cells the endogenous mobile Ca2+ buffer is equivalent to less than 0.1 mm BAPTA and that at many release sites of pyramidal cell terminals the Ca2+ channel domains overlap, a situation comparable with that at large calyx-type terminals in the brainstem. PMID:9782165

  19. Activation of transglutaminase 2 by nerve growth factor in differentiating neuroblastoma cells: A role in cell survival and neurite outgrowth.

    Science.gov (United States)

    Algarni, Alanood S; Hargreaves, Alan J; Dickenson, John M

    2018-02-05

    NGF (nerve growth factor) and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 transamidase activity by NGF in retinoic acid-induced differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. The role of TG2 in NGF-induced cytoprotection and neurite outgrowth was investigated by monitoring hypoxia-induced cell death and appearance of axonal-like processes, respectively. The amine incorporation and protein crosslinking activity of TG2 increased in a time and concentration-dependent manner following stimulation with NGF in N2a and SH-SY5Y cells. NGF mediated increases in TG2 activity were abolished by the TG2 inhibitors Z-DON (Z-ZON-Val-Pro-Leu-OMe; Benzyloxycarbonyl-(6-Diazo-5-oxonorleucinyl)-l-valinyl-l-prolinyl-l-leucinmethylester) and R283 (1,3,dimethyl-2[2-oxo-propyl]thio)imidazole chloride) and by pharmacological inhibition of extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase B (PKB) and protein kinase C (PKC), and removal of extracellular Ca 2+ . Fluorescence microscopy demonstrated NGF induced in situ TG2 activity. TG2 inhibition blocked NGF-induced attenuation of hypoxia-induced cell death and neurite outgrowth in both cell lines. Together, these results demonstrate that NGF stimulates TG2 transamidase activity via a ERK1/2, PKB and PKC-dependent pathway in differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. Furthermore, NGF-induced cytoprotection and neurite outgrowth are dependent upon TG2. These results suggest a novel and important role of TG2 in the cellular functions of NGF. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury.

    Science.gov (United States)

    Bucan, Vesna; Vaslaitis, Desiree; Peck, Claas-Tido; Strauß, Sarah; Vogt, Peter M; Radtke, Christine

    2018-06-21

    Peripheral nerve injury requires optimal conditions in both macro-environment and microenvironment for promotion of axonal regeneration. However, most repair strategies of traumatic peripheral nerve injury often lead to dissatisfying results in clinical outcome. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the microenvironment provided by nerve conduit remains unclear. In this study, we evaluate the effects of from adipose-derived mesenchymal stem cells (adMSCs) originating exosomes with respect to sciatic nerve regeneration and neurite growth. Molecular and immunohistochemical techniques were used to investigate the presence of characteristic exosome markers. A co-culture system was established to determine the effect of exosomes on neurite elongation in vitro. The in vivo walking behaviour of rats was evaluated by footprint analysis, and the nerve regeneration was assessed by immunocytochemistry. adMSCs secrete nano-vesicles known as exosomes, which increase neurite outgrowth in vitro and enhance regeneration after sciatic nerve injury in vivo. Furthermore, we showed the presence of neural growth factors transcripts in adMSC exosomes for the first time. Our results demonstrate that exosomes, constitutively produced by adMSCs, are involved in peripheral nerve regeneration and have the potential to be utilised as a therapeutic tool for effective tissue-engineered nerves.

  1. Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit

    NARCIS (Netherlands)

    Zampini, Valeria; Liu, Jian K; Diana, Marco A; Maldonado, Paloma P; Brunel, Nicolas; Dieudonné, Stéphane

    2016-01-01

    Synaptic currents display a large degree of heterogeneity of their temporal characteristics, but the functional role of such heterogeneities remains unknown. We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells (UBCs), which generate intrinsic mossy fibers relaying

  2. Age-related changes of structures in cerebellar cortex of cat

    Indian Academy of Sciences (India)

    Madhu

    ness of the cerebellar cortex as well as loss of neurons, and hypertrophy and ... Purkinje cells. (PCs) in old cats showed much fewer NF-IR dendrites than those in young adults. ... diminution in motor control and motor learning) underlying.

  3. The efflux of choline from nerve cells: mediation by ionic gradients and functional exchange of choline from glia to neurons

    International Nuclear Information System (INIS)

    Hoffmann, D.; Ferret, B.; Massarelli, R.; Mykita, S.

    1986-01-01

    This paper analyzes the relationship between ions and the efflux of choline, and suggests the possibility of a balance effect for choline fluxes which is produced and maintained by ioinic gradients. It is also suggested that glial cells may actively exchange choline with neurons during nerve actively exchange choline with neurons during nerve activity, and that they may function as a choline reservoir for neuronal needs. The study shows that neurons and glial cells spontaneously discharge choline into the incubation medium. The exiting choline is essentially of free origin, as can be seen in an illustration provided. Neurons and glial cells had been prelabelled with ( 14 C) choline overnight, and labelled for 15 min with tritium-choline. The higher amount of tritium-choline exiting the cells indicates that it is the freshly labelled choline which is preferentially released. The remaining of ( 14 C) - choline exiting the cells corresponds to the free choline of phospholipid origin which amounts to about one third of the total free choline content

  4. Retinal ganglion cell-inner plexiform and nerve fiber layers in neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Sai-Jing Hu

    2018-01-01

    Full Text Available AIM: To determine the thickness of the retinal ganglion cell-inner plexiform layer (GCIPL and the retinal nerve fiber layer (RNFL in patients with neuromyelitis optica (NMO. METHODS: We conducted a cross-sectional study that included 30 NMO patients with a total of 60 eyes. Based on the presence or absence of optic neuritis (ON, subjects were divided into either the NMO-ON group (30 eyes or the NMO-ON contra group (10 eyes. A detailed ophthalmologic examination was performed for each group; subsequently, the GCIPL and the RNFL were measured using high-definition optical coherence tomography (OCT. RESULTS: In the NMO-ON group, the mean GCIPL thickness was 69.28±21.12 μm, the minimum GCIPL thickness was 66.02±10.02 μm, and the RNFL thickness were 109.33±11.23, 110.47±3.10, 64.92±12.71 and 71.21±50.22 μm in the superior, inferior, temporal and nasal quadrants, respectively. In the NMO-ON contra group, the mean GCIPL thickness was 85.12±17.09 μm, the minimum GCIPL thickness was 25.39±25.1 μm, and the RNFL thicknesses were 148.33±23.22, 126.36±23.45, 82.21±22.30 and 83.36±31.28 μm in the superior, inferior, temporal and nasal quadrants, respectively. In the control group, the mean GCIPL thickness was 86.98±22.37 μm, the minimum GCIPL thickness was 85.28±10.75 μm, and the RNFL thicknesses were 150.22±22.73, 154.79±60.23, 82.33±7.01 and 85.62±13.81 μm in the superior, inferior, temporal and nasal quadrants, respectively. The GCIPL and RNFL were thinner in the NMO-ON contra group than in the control group (P<0.05; additionally, the RNFL was thinner in the inferior quadrant in the NMO-ON group than in the control group (P<0.05. Significant correlations were observed between the GCIPL and RNFL thickness measurements as well as between thickness measurements and the two visual field parameters of mean deviation (MD and corrected pattern standard deviation (PSD in the NMO-ON group (P<0.05. CONCLUSION: The thickness of the GCIPL

  5. Late onset autosomal dominant cerebellar ataxia a family description and linkage analysis with the hla system

    Directory of Open Access Journals (Sweden)

    Walter O. Arruda

    1991-09-01

    Full Text Available A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1±5.4 years (27-47 years. The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem (and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded - 0==0,02, z=(-2,17 - and the overall analysis of the lod scores suggest another chromossomal location than chromosome 6.

  6. MR imaging of the cranial nerves and the intracranial vessels using 3D-SPGR

    International Nuclear Information System (INIS)

    Hosoya, Takaaki; Sato, Nami; Yamaguchi, Koichi; Sugai, Yukio; Ogushi, Masatoshi; Kubota, Hisashi

    1992-01-01

    MR angiography (MRA) has developed rapidly, but it is still insufficient to demonstrate the detail of the intracranial vascular anatomy. We found that original images of MRA render more information than MRA images about not only intracranial vessels but also cranial nerves. We have tried to demonstrate cranial nerves and intracranial vessels on 26 patients and evaluated using real time reformation of original images of MRA. MR images were obtained by SPGR (3DFT) after injection of Gd-DTPA. The optic nerve, the oculomotor nerve, the trigeminal nerve, the facial nerve and the vestibulocochlear nerve were visualized clearly on almost patients and detectabilities of these nerves were 100%, 98%, 100%, 94% and 100%, respectively. The abducent nerve was also detectable in 76%. The trochlear nerve, which could not be observed by any modality, was detected at prepontine cistern in 10%. Arteries around brain stem such as the superior cerebellar artery (SCA), the anterior inferior cerebellar artery (AICA), the posterior inferior cerebellar artery (PICA) and the posterior communicating artery (PcomA) were clearly visible, and branching of these arteries and anatomical detail were completely coincide with angiogram on 12 patients. The basal vein of Rosenthal and the petrosal vein were confirmed in 100% and their anastomose were demonstrated obviously. We concluded that this method was extremely useful to observe cranial nerves and intracranial small vessels. (author)

  7. Fabrication of bioactive conduits containing the fibroblast growth factor 1 and neural stem cells for peripheral nerve regeneration across a 15 mm critical gap

    International Nuclear Information System (INIS)

    Ni, Hsiao-Chiang; Tseng, Ting-Chen; Hsu, Shan-hui; Chen, Jeng-Rung; Chiu, Ing-Ming

    2013-01-01

    Nerve conduits are often used in combination with bioactive molecules and stem cells to enhance peripheral nerve regeneration. In this study, the acidic fibroblast growth factor 1 (FGF1) was immobilized onto the microporous/micropatterned poly (D, L-lactic acid) (PLA) nerve conduits after open air plasma treatment. PLA substrates grafted with chitosan in the presence of a small amount of gold nanoparticles (nano Au) showed a protective effect on the activity of the immobilized FGF1 in vitro. Different conduits were tested for their ability to bridge a 15 mm critical gap defect in a rat sciatic nerve injury model. Axon regeneration and functional recovery were evaluated by histology, walking track analysis and electrophysiology. Among different conduits, PLA conduits grafted with chitosan–nano Au and the FGF1 after plasma activation had the greatest regeneration capacity and functional recovery in the experimental animals. When the above conduit was seeded with aligned neural stem cells, the efficacy was further enhanced and it approached that of the autograft group. This work suggested that microporous/micropatterned nerve conduits containing bioactive growth factors may be successfully fabricated by micropatterning techniques, open plasma activation, and immobilization, which, combined with aligned stem cells, may synergistically contribute to the regeneration of the severely damaged peripheral nerve. (paper)

  8. Delayed peripheral nerve repair: methods, including surgical ?cross-bridging? to promote nerve regeneration

    OpenAIRE

    Gordon, Tessa; Eva, Placheta; Borschel, Gregory H.

    2015-01-01

    Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour per...

  9. Visuomotor learning in cerebellar patients.

    Science.gov (United States)

    Timmann, D; Shimansky, Y; Larson, P S; Wunderlich, D A; Stelmach, G E; Bloedel, J R

    1996-11-01

    The aim of the present study was to demonstrate that patients with pathology affecting substantial regions of the cerebellum can improve their performance in a series of two-dimensional tracing tasks, thus supporting the view that this type of motor behavior can be acquired even when the integrity of this structure is compromised. Eight patients with chronic, isolated cerebellar lesions and eight age- and sex-matched healthy controls were tested. Three patients had mild, five had moderate upper limb ataxia. The experiment was divided into two parts. In the first, subjects traced an irregularly shaped outline over 20 consecutive trials ('Trace 1' task). Next, subjects were asked to redraw the object without any underlying template as a guide ('Memory 1' task). In the second part of the study, subjects were asked to trace a different, irregularly shaped outline over 20 consecutive trials ('Trace 2' task). Next, they were required to redraw it by memory with its axis rotated 90 degrees ('Memory 2' task). In each of the memory tasks the template was placed over the drawn image after each trial and shown to the subjects. The error of performance was determined by calculating three different measurements, each focused on different aspects of the task. Based on these measurements, the cerebellar patients showed improvement in both memory tasks. In the 'Memory 1' task the calculated error decreased significantly for the patients with mild ataxia. In the 'Memory 2' task all cerebellar patients improved their performance substantially enough to reduce significantly the magnitude of all three error measurements. The experiments demonstrate that patients with cerebellar lesions are capable of improving substantially their performance of a complex motor task involving the recall of memorized shapes and the visuomotor control of a tracing movement.

  10. Collagen-coated polylactic-glycolic acid (PLGA) seeded with neural-differentiated human mesenchymal stem cells as a potential nerve conduit.

    Science.gov (United States)

    Sulong, Ahmad Fadzli; Hassan, Nur Hidayah; Hwei, Ng Min; Lokanathan, Yogeswaran; Naicker, Amaramalar Selvi; Abdullah, Shalimar; Yusof, Mohd Reusmaazran; Htwe, Ohnmar; Idrus, Ruszymah Bt Hj; Haflah, Nor Hazla Mohamed

    2014-01-01

    Autologous nerve grafts to bridge nerve gaps pose various drawbacks. Nerve tissue engineering to promote nerve regeneration using artificial neural conduits has emerged as a promising alternative. To develop an artificial nerve conduit using collagen-coated polylactic-glycolic acid (PLGA) and to analyse the survivability and propagating ability of the neuro-differentiated human mesenchymal stem cells in this conduit. The PLGA conduit was constructed by dip-molding method and coated with collagen by immersing the conduit in collagen bath. The ultra structure of the conduits were examined before they were seeded with neural-differentiated human mesenchymal stem cells (nMSC) and implanted sub-muscularly on nude mice thighs. The non-collagen-coated PLGA conduit seeded with nMSC and non-seeded non-collagen-coated PLGA conduit were also implanted for comparison purposes. The survivability and propagation ability of nMSC was studied by histological and immunohistochemical analysis. The collagen-coated conduits had a smooth inner wall and a highly porous outer wall. Conduits coated with collagen and seeded with nMSCs produced the most number of cells after 3 weeks. The best conduit based on the number of cells contained within it after 3 weeks was the collagen-coated PLGA conduit seeded with neuro-transdifferentiated cells. The collagen-coated PLGA conduit found to be suitable for attachment, survival and proliferation of the nMSC. Minimal cell infiltration was found in the implanted conduits where nearly all of the cells found in the cell seeded conduits are non-mouse origin and have neural cell markers, which exhibit the biocompatibility of the conduits. The collagen-coated PLGA conduit is biocompatible, non-cytotoxic and suitable for use as artificial nerve conduits.

  11. Radiosensitivity of glial progenitor cells of the perinatal and adult rat optic nerve studied by an in vitro clonogenic assay

    International Nuclear Information System (INIS)

    Maazen, R.W.M. van der; Verhagen, I.; Kleiboer, B.J.; Kogel, A.J. van der

    1991-01-01

    The cellular basis of radiation-induced demyelination and white matter necrosis of the central nervous system (CNS), is poorly understood. Glial cells responsible for myelination in the CNS might be the target cells of this type of damage. Glial cells with stem cell properties derived from the perinatal and adult rat CNS can be cultured in vitro. These cells are able to differentiate into oligodendrocytes or type-2 astrocytes (O-2A) depending on the culture conditions. Growth factors produced by monolayers of type-1 astrocytes inhibit premature differentiation of O-2A progenitor cells and allow colony formation. A method which employs these monolayers of type-1 astrocytes to culture O-2A progenitor cells has been adapted to allow the analysis of colonies of surviving cells after X-irradiation. In vitro survival curves were obtained for glial progenitor cells derived from perinatal and adult optic nerves. The intrinsic radiosensitivity of perinatal and adult O-2A progenitor cells showed a large difference. Perinatal O-2A progenitor cells are quite radiosensitive, in contrast to adult O-2A progenitor cells. For both cell types an inverse relationship was found between the dose and the size of colonies derived from surviving cells. Surviving O-2A progenitor cells maintain their ability to differentiate into oligo-dendrocytes or type-2 astrocytes. This system to assess radiation-induced damage to glial progenitor cells in vitro systems to have a great potential in unraveling the cellular basis of radiation-induced demyelinating syndromes of the CNS. (author). 28 refs.; 4 figs.; 1 tab

  12. Cerebellar ataxia of early onset

    International Nuclear Information System (INIS)

    Yamashita, Sumimasa; Miyake, Shota; Yamada, Michiko; Iwamoto, Hiroko; Yamada, Kazuhiko.

    1989-01-01

    Eight cases of childhood cerebellar ataxia were reported. All these cases showed chronic cerebellar ataxia with early onset, and the other diseases of cerebellum such as infections, neoplasms and storage diseases were excluded by clinical symptoms and laboratory findings including blood counts, blood chemistry, lactate, pyruvate, ceruloplasmine, urinalysis, serum immunoglobulins, amino acid analysis in blood and urine, CSF analysis, leukocyte lysosomal enzymes, MCV, EMG, EEG and brain X-CT. Two pairs of siblings were included in this study. The clinical diagnosis were cerebellar type (5), spinocerebellar type (1), one Marinesco-Sjoegren syndrome and undetermined type (1). The age of onset was 1 to 5 years. The chief complaint was motor developmental delay in 6 cases; among them 5 patients could walk alone at the ages of 2 to 3 years'. Mental retardation was observed in 7 cases and epilepsy in 2. TRH was effective in 5 cases. The MRI study revealed that the area of medial sagittal slice of the cerebellum was reduced significantly in all cases and also that of pons was reduced in 5 cases. Different from typical adult onset spinocerebellar degenerations, most of the present cases have achieved slow developmental milestones and the clinical course was not progressive. Genetic factors are suspected in the pathogenesis of this disease in some cases. (author)

  13. Cerebellar mutism--report of four cases.

    Science.gov (United States)

    Ozimek, A; Richter, S; Hein-Kropp, C; Schoch, B; Gorissen, B; Kaiser, O; Gizewski, E; Ziegler, W; Timmann, D

    2004-08-01

    The aim of the present study was to investigate the manifestations of mutism after surgery in children with cerebellar tumors. Speech impairment following cerebellar mutism in children was investigated based on standardized acoustic speech parameters and perceptual criteria. Mutistic and non-mutistic children after cerebellar surgery as well as orthopedic controls were tested pre-and postoperatively. Speech impairment was compared with the localization of cerebellar lesions (i. e. affected lobules and nuclei). Whereas both control groups showed no abnormalities in speech and behavior, the mutistic group could be divided into children with dysarthria in post mutistic phase and children with mainly behavioral disturbances. In the mutistic children involvement of dentate and fastigial nuclei tended to be more frequent and extended than in the nonmutistic cerebellar children. Cerebellar mutism is a complex phenomenon of at least two types. Dysarthric symptoms during resolution of mutism support the anarthria hypothesis, while mainly behavioral changes suggest an explanation independent from speech motor control.

  14. Adaptive robotic control driven by a versatile spiking cerebellar network.

    Directory of Open Access Journals (Sweden)

    Claudia Casellato

    Full Text Available The cerebellum is involved in a large number of different neural processes, especially in associative learning and in fine motor control. To develop a comprehensive theory of sensorimotor learning and control, it is crucial to determine the neural basis of coding and plasticity embedded into the cerebellar neural circuit and how they are translated into behavioral outcomes in learning paradigms. Learning has to be inferred from the interaction of an embodied system with its real environment, and the same cerebellar principles derived from cell physiology have to be able to drive a variety of tasks of different nature, calling for complex timing and movement patterns. We have coupled a realistic cerebellar spiking neural network (SNN with a real robot and challenged it in multiple diverse sensorimotor tasks. Encoding and decoding strategies based on neuronal firing rates were applied. Adaptive motor control protocols with acquisition and extinction phases have been designed and tested, including an associative Pavlovian task (Eye blinking classical conditioning, a vestibulo-ocular task and a perturbed arm reaching task operating in closed-loop. The SNN processed in real-time mossy fiber inputs as arbitrary contextual signals, irrespective of whether they conveyed a tone, a vestibular stimulus or the position of a limb. A bidirectional long-term plasticity rule implemented at parallel fibers-Purkinje cell synapses modulated the output activity in the deep cerebellar nuclei. In all tasks, the neurorobot learned to adjust timing and gain of the motor responses by tuning its output discharge. It succeeded in reproducing how human biological systems acquire, extinguish and express knowledge of a noisy and changing world. By varying stimuli and perturbations patterns, real-time control robustness and generalizability were validated. The implicit spiking dynamics of the cerebellar model fulfill timing, prediction and learning functions.

  15. Adaptive robotic control driven by a versatile spiking cerebellar network.

    Science.gov (United States)

    Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A; Carrillo, Richard R; Luque, Niceto R; Ros, Eduardo; Pedrocchi, Alessandra; D'Angelo, Egidio

    2014-01-01

    The cerebellum is involved in a large number of different neural processes, especially in associative learning and in fine motor control. To develop a comprehensive theory of sensorimotor learning and control, it is crucial to determine the neural basis of coding and plasticity embedded into the cerebellar neural circuit and how they are translated into behavioral outcomes in learning paradigms. Learning has to be inferred from the interaction of an embodied system with its real environment, and the same cerebellar principles derived from cell physiology have to be able to drive a variety of tasks of different nature, calling for complex timing and movement patterns. We have coupled a realistic cerebellar spiking neural network (SNN) with a real robot and challenged it in multiple diverse sensorimotor tasks. Encoding and decoding strategies based on neuronal firing rates were applied. Adaptive motor control protocols with acquisition and extinction phases have been designed and tested, including an associative Pavlovian task (Eye blinking classical conditioning), a vestibulo-ocular task and a perturbed arm reaching task operating in closed-loop. The SNN processed in real-time mossy fiber inputs as arbitrary contextual signals, irrespective of whether they conveyed a tone, a vestibular stimulus or the position of a limb. A bidirectional long-term plasticity rule implemented at parallel fibers-Purkinje cell synapses modulated the output activity in the deep cerebellar nuclei. In all tasks, the neurorobot learned to adjust timing and gain of the motor responses by tuning its output discharge. It succeeded in reproducing how human biological systems acquire, extinguish and express knowledge of a noisy and changing world. By varying stimuli and perturbations patterns, real-time control robustness and generalizability were validated. The implicit spiking dynamics of the cerebellar model fulfill timing, prediction and learning functions.

  16. The effects of functional magnetic nanotubes with incorporated nerve growth factor in neuronal differentiation of PC12 cells

    International Nuclear Information System (INIS)

    Xie Jining; Chen Linfeng; Varadan, Vijay K; Yancey, Justin; Srivatsan, Malathi

    2008-01-01

    In this in vitro study the efficiency of magnetic nanotubes to bind with nerve growth factor (NGF) and the ability of NGF-incorporated magnetic nanotubes to release the bound NGF are investigated using rat pheochromocytoma cells (PC12 cells). It is found that functional magnetic nanotubes with NGF incorporation enabled the differentiation of PC12 cells into neurons exhibiting growth cones and neurite outgrowth. Microscope observations show that filopodia extending from neuron growth cones were in close proximity to the NGF-incorporated magnetic nanotubes, at times appearing to extend towards or into them. These results show that magnetic nanotubes can be used as a delivery vehicle for NGF and thus may be exploited in attempts to treat neurodegenerative disorders such as Parkinson's disease with neurotrophins. Further neurite outgrowth can be controlled by manipulating magnetic nanotubes with external magnetic fields, thus helping in directed regeneration

  17. Regeneration of Optic Nerve

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    Kwok-Fai So

    2011-05-01

    Full Text Available The optic nerve is part of the central nervous system (CNS and has a structure similar to other CNS tracts. The axons that form the optic nerve originate in the ganglion cell layer of the retina and extend through the optic tract. As a tissue, the optic nerve has the same organization as the white matter of the brain in regard to its glia. There are three types of glial cells: Oligodendrocytes, astrocytes, and microglia. Little structural and functional regeneration of the CNS takes place spontaneously following injury in adult mammals. In contrast, the ability of the mammalian peripheral nervous system (PNS to regenerate axons after injury is well documented. A number of factors are involved in the lack of CNS regeneration, including: (i the response of neuronal cell bodies against the damage; (ii myelin-mediated inhibition by oligodendrocytes; (iii glial scarring, by astrocytes; (iv macrophage infiltration; and (v insufficient trophic factor support. The fundamental difference in the regenerative capacity between CNS and PNS neuronal cell bodies has been the subject of intensive research. In the CNS the target normally conveys a retrograde trophic signal to the cell body. CNS neurons die because of trophic deprivation. Damage to the optic nerve disconnects the neuronal cell body from its target-derived trophic peptides, leading to the death of retinal ganglion cells. Furthermore, the axontomized neurons become less responsive to the peptide trophic signals they do receive. On the other hand, adult PNS neurons are intrinsically responsive to neurotrophic factors and do not lose trophic responsiveness after axotomy. In this talk different strategies to promote optic-nerve regeneration in adult mammals are reviewed. Much work is still needed to resolve many issues. This is a very important area of neuroregeneration and neuroprotection, as currently there is no cure after traumatic optic nerve injury or retinal disease such as glaucoma, which

  18. Massive cerebellar infarction: a neurosurgical approach

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    Salazar Luis Rafael Moscote

    2015-12-01

    Full Text Available Cerebellar infarction is a challenge for the neurosurgeon. The rapid recognition will crucial to avoid devastating consequences. The massive cerebellar infarction has pseudotumoral behavior, should affect at least one third of the volume of the cerebellum. The irrigation of the cerebellum presents anatomical diversity, favoring the appearance of atypical infarcts. The neurosurgical management is critical for massive cerebellar infarction. We present a review of the literature.

  19. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit

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    Lisa eMapelli

    2015-05-01

    Full Text Available The way long-term potentiation (LTP and depression (LTD are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network , in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei and correspondingly regulate the function of their three main neurons: granule cells (GrCs, Purkinje cells (PCs and deep cerebellar nuclear (DCN cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  20. Cerebellar Shaping of Motor Cortical Firing Is Correlated with Timing of Motor Actions

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    Abdulraheem Nashef

    2018-05-01

    Full Text Available Summary: In higher mammals, motor timing is considered to be dictated by cerebellar control of motor cortical activity, relayed through the cerebellar-thalamo-cortical (CTC system. Nonetheless, the way cerebellar information is integrated with motor cortical commands and affects their temporal properties remains unclear. To address this issue, we activated the CTC system in primates and found that it efficiently recruits motor cortical cells; however, the cortical response was dominated by prolonged inhibition that imposed a directional activation across the motor cortex. During task performance, cortical cells that integrated CTC information fired synchronous bursts at movement onset. These cells expressed a stronger correlation with reaction time than non-CTC cells. Thus, the excitation-inhibition interplay triggered by the CTC system facilitates transient recruitment of a cortical subnetwork at movement onset. The CTC system may shape neural firing to produce the required profile to initiate movements and thus plays a pivotal role in timing motor actions. : Nashef et al. identified a motor cortical subnetwork recruited by cerebellar volley that was transiently synchronized at movement onset. Cerebellar control of cortical firing was dominated by inhibition that shaped task-related firing of neurons and may dictate motor timing. Keywords: motor control, primates, cerebellar-thalamo-cortical, synchrony, noise correlation, reaction time

  1. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit.

    Science.gov (United States)

    Mapelli, Lisa; Pagani, Martina; Garrido, Jesus A; D'Angelo, Egidio

    2015-01-01

    The way long-term potentiation (LTP) and depression (LTD) are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network, in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei) and correspondingly regulate the function of their three main neurons: granule cells (GrCs), Purkinje cells (PCs) and deep cerebellar nuclear (DCN) cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  2. Effect of the Nerve Growth Factor Mimetic GK-2 on Brain Structural and Functional State in the Early Postresuscitation Period

    Directory of Open Access Journals (Sweden)

    M. Sh. Avrushchenko

    2012-01-01

    Full Text Available Objective: to evaluate the efficacy of the nerve growth factor mimetic GK-2 used to improve the structural and functional state of the brain in the early postresuscitation period. Material and methods. Cardiac arrest was induced in mature male albino rats for 12 minutes, followed by resuscitation. The neurological state of the resuscitated animals was assessed by a scoring scale. On postresuscitation day 7, the density and composition of neuronal populations of Purkinje cells in the lateral cerebellar region and pyramidal neurons in the hippocampal CA1 sector were determined by a differential morphometric analysis. The results were statistically processed using the ANOVA method. Results. The use of GK-2 was found to accelerate neurological recovery in the resuscitated animals. On day 7 after 12-minute cardiac arrest, the resuscitated animals showed neuronal dystrophic changes and death in the neuronal populations highly susceptible to ischemia. It was shown that the systemic administration of the nerve growth factor mimetic GK-2 contributed to a reduction in the magnitude and depth of postresuscitation changes in the cerebellar Purkinje cells and prevented dystrophic changes in the pyramidal cells of the hippocampal CA1 sector. The findings suggest that GK-2 has a neuroprotective effect in the recovery period after total body ischemia. Conclusion. The results of this study indicate the efficiency of the systemic administration of the nerve growth factor mimetic GK-2 in improving the brain structural and functional state in the early postresuscitation period. This determines perspectives for the use of GK-2 to prevent and correct posthypoxic encephalopathies. Key words: the nerve growth factor mimetic GK-2, postresuscitation period, neuronal dystrophic changes and death, neurological status.

  3. Terminal nerve: cranial nerve zero

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    Jorge Eduardo Duque Parra

    2006-12-01

    Full Text Available It has been stated, in different types of texts, that there are only twelve pairs of cranial nerves. Such texts exclude the existence of another cranial pair, the terminal nerve or even cranial zero. This paper considers the mentioned nerve like a cranial pair, specifying both its connections and its functional role in the migration of liberating neurons of the gonadotropic hormone (Gn RH. In this paper is also stated the hypothesis of the phylogenetic existence of a cerebral sector and a common nerve that integrates the terminal nerve with the olfactory nerves and the vomeronasals nerves which seem to carry out the odors detection function as well as in the food search, pheromone detection and nasal vascular regulation.

  4. [Effect of electroacupuncture on differentiation and proliferation of hippocampal nerve stem cells in splenic asthenia pedo-rats].

    Science.gov (United States)

    Zhuo, Yuan-yuan; Yang, Zhuo-xin; Wu, Jia-man

    2011-10-01

    To observe the effect of electroacupuncture (EA) on the differentiation and proliferation of nerve stem cells in the hippocampal dentate gyrus (DG) in splenic asthenia pedo-rats so as to study its central mechanism. A total of 72 SD male rats were randomly assigned to normal control group (n=24), model group (n=24) and EA group (n=24) which were further divided into 7 d, 14 d, 28 d and 49 d time-points (n=6). Splenic asthenia model was established by intraperitoneal injection of reserpine and gavage of Dahuang (Radix et Rhizoma Rhei) fluid. EA was applied to bilateral "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 20 min, once daily for 7, 14, 28 and 49 days respectively. Brdu, Nestin, glial fibrillary acidic protein (GFAP), and neuron-specific enolase (NSE) expression in the DG of hippocampus were detected by immunohistochemistry double staining. Compared with the normal control group, the numbers of Brdu, Brdu/GFAP, Brdu/NSE Immunoreactive (IR) positive cells in the DG of hippocampus on day 7 and 14, and that of Brdu/Nestin IR-positive cells on day 7 were decreased considerably in the model group (P 0.05). EA of ST 36 and SP 6 can effectively suppress splenic asthenia syndrome-induced decrease of the numbers of Brdu, Brdu/GFAP, Brdu/Nestin and Brdu/NSE IR-positive cells in the DG of hippocampus at the early stage in the splenic asthenia rats, which may contribute to its effect in improving splenic asthenia symptoms in clinic by promoting the proliferation and differentiation of some nerve stem cells in the hippocampus.

  5. Synaptic glutamate spillover increases NMDA receptor reliability at the cerebellar glomerulus

    OpenAIRE

    Mitchell, Cassie S.; Lee, Robert H.

    2011-01-01

    Glutamate spillover in the mossy fiber to granule cell cerebellar glomeruli has been hypothesized to increase neurotransmission reliability. In this study, we evaluate this hypothesis using an experimentally-based quantitative model of glutamate spillover on the N-methyl-d-aspartate receptors (NMDA-Rs) at the cerebellar glomerulus. The transient and steady-state responses of NMDA-Rs were examined over a physiological range of firing rates. Examined cases included direct glutamate release acti...

  6. Effects of umbilical cord tissue mesenchymal stem cells (UCX® on rat sciatic nerve regeneration after neurotmesis injuries

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    Gärtner A

    2013-04-01

    Full Text Available Peripheral nerves have the intrinsic capacity of self-regeneration after traumatic injury but the extent of the regeneration is often very poor. Increasing evidence demonstrates that mesenchymal stem/stromal cells (MSCs may play an important role in tissue regeneration through the secretion of soluble trophic factors that enhance and assist in repair by paracrine activation of surrounding cells. In the present study, the therapeutic value of a population of umbilical cord tissue-derived MSCs, obtained by a proprietary method (UCX®, was evaluated on end-to-end rat sciatic nerve repair. Furthermore, in order to promote both, end-to-end nerve fiber contacts and MSC cell-cell interaction, as well as reduce the flush away effect of the cells after administration, a commercially available haemostatic sealant, Floseal®, was used as vehicle. Both, functional and morphologic recoveries were evaluated along the healing period using extensor postural thrust (EPT, withdrawal reflex latency (WRL, ankle kinematics analysis, and either histological analysis or stereology, in the hyper-acute, acute and chronic phases of healing. The histological analysis of the hyper-acute and acute phase studies revealed that in the group treated with UCX ® alone the Wallerian degeneration was improved for the subsequent process of regeneration, the fiber organization was higher, and the extent of fibrosis was lower. The chronic phase experimental groups revealed that treatment with UCX® induced an increased number of regenerated fibers and thickening of the myelin sheet. Kinematics analysis showed that the ankle joint angle determined for untreated animals was significantly different from any of the treated groups at the instant of initial contact (IC. At opposite toe off (OT and heel rise (HR, differences were found between untreated animals and the groups treated with either UCX® alone or UCX® administered with Floseal®. Overall, the UCX® application presented

  7. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis.

    Science.gov (United States)

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-03-30

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

  8. GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells.

    Science.gov (United States)

    Wang, Chang-Ying; Huang, An-Qi; Zhou, Meng-Hua; Mei, Yan-Ai

    2014-05-15

    GDF15 (growth/differentiation factor 15), a novel member of the TGFβ (transforming growth factor β) superfamily, plays critical roles in the central and peripheral nervous systems, but the signal transduction pathways and receptor subtypes involved are not well understood. In the present paper, we report that GDF15 specifically increases the IK (delayed-rectifier outward K+ current) in rat CGNs (cerebellar granule neurons) in time- and concentration-dependent manners. The GDF15-induced amplification of the IK is mediated by the increased expression and reduced lysosome-dependent degradation of the Kv2.1 protein, the main α-subunit of the IK channel. Exposure of CGNs to GDF15 markedly induced the phosphorylation of ERK (extracellular-signal-regulated kinase), Akt and mTOR (mammalian target of rapamycin), but the GDF15-induced IK densities and increased expression of Kv2.1 were attenuated only by Akt and mTOR, and not ERK, inhibitors. Pharmacological inhibition of the Src-mediated phosphorylation of TGFβR2 (TGFβ receptor 2), not TGFβR1, abrogated the effect of GDF15 on IK amplification and Kv2.1 induction. Immunoprecipitation assays showed that GDF15 increased the tyrosine phosphorylation of TGFβRII in the CGN lysate. The results of the present study reveal a novel regulation of Kv2.1 by GDF15 mediated through the TGFβRII-activated Akt/mTOR pathway, which is a previously uncharacterized Smad-independent mechanism of GDF15 signalling.

  9. β-Catenin is critical for cerebellar foliation and lamination.

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    Jing Wen

    Full Text Available The cerebellum has a conserved foliation pattern and a well-organized layered structure. The process of foliation and lamination begins around birth. β-catenin is a downstream molecule of Wnt signaling pathway, which plays a critical role in tissue organization. Lack of β-catenin at early embryonic stages leads to either prenatal or neonatal death, therefore it has been difficult to resolve its role in cerebellar foliation and lamination. Here we used GFAP-Cre to ablate β-catenin in neuronal cells of the cerebellum after embryonic day 12.5, and found an unexpected role of β-catenin in determination of the foliation pattern. In the mutant mice, the positions of fissure formation were changed, and the meninges were improperly incorporated into fissures. At later stages, some lobules were formed by Purkinje cells remaining in deep regions of the cerebellum and the laminar structure was dramatically altered. Our results suggest that β-catenin is critical for cerebellar foliation and lamination. We also found a non cell-autonomous role of β-catenin in some developmental properties of major cerebellar cell types during specific stages.

  10. Nasal-Type Extranodal Natural Killer/T-cell Neurolymphomatosis Confined to the Lumbar Nerve Roots: A Case Report

    International Nuclear Information System (INIS)

    Park, Jong Chun; Mun, Sung Hee; Lee, Young Hwan

    2009-01-01

    Neurolymphomatosis refers to lymphoma that has infiltrated the peripheral nervous system and this is the least common clinical presentation of nervous system lymphoma. Most neurolymphomatosis is due to B-cell non-Hodgkin lymphoma, and most patients show lymphomatous infiltration in the meninges and brain parenchyma, in addition to peripheral nervous system involvement. We diagnosed a case of neurolymphomatosis that was confined to the right 4th and 5th lumbar nerve roots without involvement of the meninges or brain parenchyma in a patient with the nasal-type extranodal natural killer/T-cell lymphoma. We made this diagnosis based on the MRI and 18F-FDG PET-CT findings and the clinical manifestations

  11. Nasal-Type Extranodal Natural Killer/T-cell Neurolymphomatosis Confined to the Lumbar Nerve Roots: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Chun; Mun, Sung Hee; Lee, Young Hwan [Catholic University, Daegu (Korea, Republic of)

    2009-11-15

    Neurolymphomatosis refers to lymphoma that has infiltrated the peripheral nervous system and this is the least common clinical presentation of nervous system lymphoma. Most neurolymphomatosis is due to B-cell non-Hodgkin lymphoma, and most patients show lymphomatous infiltration in the meninges and brain parenchyma, in addition to peripheral nervous system involvement. We diagnosed a case of neurolymphomatosis that was confined to the right 4th and 5th lumbar nerve roots without involvement of the meninges or brain parenchyma in a patient with the nasal-type extranodal natural killer/T-cell lymphoma. We made this diagnosis based on the MRI and 18F-FDG PET-CT findings and the clinical manifestations.

  12. Cerebellar atrophy in epileptic patients

    International Nuclear Information System (INIS)

    Taneva, N.

    1991-01-01

    52 patients with epileptic seizures of different form, frequency and duration who had received long term treatment with anticonvulsive drugs were examined on Siretom 2000, a brain scanner of II generation. 6 standard incisions were made in all patients in the area of cerebellum, side ventricules and high convexity. Additional scanning with an incision width of 5 mm was made when pathological changes were detected. There were found 3 cases of cerebellar atrophy, 3 - cerebral atrophy, 1 - combined atrophy and 4 - with other changes. It was difficult to establish any relation between the rerebellar atrophy and the type of anticonvulsant used because treatment had usually been complex. 1 fig., 1 tab., 4 refs

  13. The organization of plasticity in the cerebellar cortex: from synapses to control.

    Science.gov (United States)

    D'Angelo, Egidio

    2014-01-01

    The cerebellum is thought to play a critical role in procedural learning, but the relationship between this function and the underlying cellular and synaptic mechanisms remains largely speculative. At present, at least nine forms of long-term synaptic and nonsynaptic plasticity (some of which are bidirectional) have been reported in the cerebellar cortex and deep cerebellar nuclei. These include long-term potentiation (LTP) and long-term depression at the mossy fiber-granule cell synapse, at the synapses formed by parallel fibers, climbing fibers, and molecular layer interneurons on Purkinje cells, and at the synapses formed by mossy fibers and Purkinje cells on deep cerebellar nuclear cells, as well as LTP of intrinsic excitability in granule cells, Purkinje cells, and deep cerebellar nuclear cells. It is suggested that the complex properties of cerebellar learning would emerge from the distribution of plasticity in the network and from its dynamic remodeling during the different phases of learning. Intrinsic and extrinsic factors may hold the key to explain how the different forms of plasticity cooperate to select specific transmission channels and to regulate the signal-to-noise ratio through the cerebellar cortex. These factors include regulation of neuronal excitation by local inhibitory networks, engagement of specific molecular mechanisms by spike bursts and theta-frequency oscillations, and gating by external neuromodulators. Therefore, a new and more complex view of cerebellar plasticity is emerging with respect to that predicted by the original "Motor Learning Theory," opening issues that will require experimental and computational testing. © 2014 Elsevier B.V. All rights reserved.

  14. Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus

    Directory of Open Access Journals (Sweden)

    Miloslav eSedlacek

    2014-07-01

    Full Text Available Feedforward inhibition represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs, principal neurons of the dorsal cochlear nucleus (DCN that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and feed-forward inhibition in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven feed-forward inhibition (FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of feed-forward inhibition had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

  15. Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus.

    Science.gov (United States)

    Sedlacek, Miloslav; Brenowitz, Stephan D

    2014-01-01

    Feed-forward inhibition (FFI) represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs), principal neurons of the dorsal cochlear nucleus (DCN) that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs) on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and FFI in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of FFI had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition, we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs) in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

  16. Learning of Sensory Sequences in Cerebellar Patients

    Science.gov (United States)

    Frings, Markus; Boenisch, Raoul; Gerwig, Marcus; Diener, Hans-Christoph; Timmann, Dagmar

    2004-01-01

    A possible role of the cerebellum in detecting and recognizing event sequences has been proposed. The present study sought to determine whether patients with cerebellar lesions are impaired in the acquisition and discrimination of sequences of sensory stimuli of different modalities. A group of 26 cerebellar patients and 26 controls matched for…

  17. Scaffoldless tissue-engineered nerve conduit promotes peripheral nerve regeneration and functional recovery after tibial nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    Aaron M. Adams; Keith W. VanDusen; Tatiana Y. Kostrominova; Jacob P. Mertens; Lisa M. Larkin

    2017-01-01

    Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit (ENC), engineered fibroblast conduit (EFC), and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 (E15). EFCs were fabricated utilizing primary fi-broblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, re-spectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promot-ed nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the E15 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.

  18. Low-frequency pulsed electromagnetic field pretreated bone marrow-derived mesenchymal stem cells promote the regeneration of crush-injured rat mental nerve.

    Science.gov (United States)

    Seo, NaRi; Lee, Sung-Ho; Ju, Kyung Won; Woo, JaeMan; Kim, BongJu; Kim, SoungMin; Jahng, Jeong Won; Lee, Jong-Ho

    2018-01-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to promote the regeneration of injured peripheral nerves. Pulsed electromagnetic field (PEMF) reportedly promotes the proliferation and neuronal differentiation of BMSCs. Low-frequency PEMF can induce the neuronal differentiation of BMSCs in the absence of nerve growth factors. This study was designed to investigate the effects of low-frequency PEMF pretreatment on the proliferation and function of BMSCs and the effects of low-frequency PEMF pre-treated BMSCs on the regeneration of injured peripheral nerve using in vitro and in vivo experiments. In in vitro experiments, quantitative DNA analysis was performed to determine the proliferation of BMSCs, and reverse transcription-polymerase chain reaction was performed to detect S100 (Schwann cell marker), glial fibrillary acidic protein (astrocyte marker), and brain-derived neurotrophic factor and nerve growth factor (neurotrophic factors) mRNA expression. In the in vivo experiments, rat models of crush-injured mental nerve established using clamp method were randomly injected with low-frequency PEMF pretreated BMSCs, unpretreated BMSCs or PBS at the injury site (1 × 10 6 cells). DiI-labeled BMSCs injected at the injury site were counted under the fluorescence microscope to determine cell survival. One or two weeks after cell injection, functional recovery of the injured nerve was assessed using the sensory test with von Frey filaments. Two weeks after cell injection, axonal regeneration was evaluated using histomorphometric analysis and retrograde labeling of trigeminal ganglion neurons. In vitro experiment results revealed that low-frequency PEMF pretreated BMSCs proliferated faster and had greater mRNA expression of growth factors than unpretreated BMSCs. In vivo experiment results revealed that compared with injection of unpretreated BMSCs, injection of low-frequency PEMF pretreated BMSCs led to higher myelinated axon count and axon density and

  19. Cellular and Molecular Basis of Cerebellar Development

    Directory of Open Access Journals (Sweden)

    Salvador eMartinez

    2013-06-01

    Full Text Available Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function.

  20. The bihemispheric posterior inferior cerebellar artery

    International Nuclear Information System (INIS)

    Cullen, Sean P.; Ozanne, Augustin; Alvarez, Hortensia; Lasjaunias, Pierre

    2005-01-01

    Rarely, a solitary posterior inferior cerebellar artery (PICA) will supply both cerebellar hemispheres. We report four cases of this variant. We present a retrospective review of clinical information and imaging of patients undergoing angiography at our institution to identify patients with a bihemispheric PICA. There were four patients: three males and one female. One patient presented with a ruptured arteriovenous malformation, and one with a ruptured aneurysm. Two patients had normal angiograms. The bihemispheric PICA was an incidental finding in all cases. The bihemispheric vessel arose from the dominant left vertebral artery, and the contralateral posterior inferior cerebellar artery was absent or hypoplastic. In all cases, contralateral cerebellar supply arose from a continuation of the ipsilateral PICA distal to the choroidal point and which crossed the midline dorsal to the vermis. We conclude that the PICA may supply both cerebellar hemispheres. This rare anatomic variant should be considered when evaluating patients with posterior fossa neurovascular disease. (orig.)

  1. A Multiple-Plasticity Spiking Neural Network Embedded in a Closed-Loop Control System to Model Cerebellar Pathologies.

    Science.gov (United States)

    Geminiani, Alice; Casellato, Claudia; Antonietti, Alberto; D'Angelo, Egidio; Pedrocchi, Alessandra

    2018-06-01

    The cerebellum plays a crucial role in sensorimotor control and cerebellar disorders compromise adaptation and learning of motor responses. However, the link between alterations at network level and cerebellar dysfunction is still unclear. In principle, this understanding would benefit of the development of an artificial system embedding the salient neuronal and plastic properties of the cerebellum and operating in closed-loop. To this aim, we have exploited a realistic spiking computational model of the cerebellum to analyze the network correlates of cerebellar impairment. The model was modified to reproduce three different damages of the cerebellar cortex: (i) a loss of the main output neurons (Purkinje Cells), (ii) a lesion to the main cerebellar afferents (Mossy Fibers), and (iii) a damage to a major mechanism of synaptic plasticity (Long Term Depression). The modified network models were challenged with an Eye-Blink Classical Conditioning test, a standard learning paradigm used to evaluate cerebellar impairment, in which the outcome was compared to reference results obtained in human or animal experiments. In all cases, the model reproduced the partial and delayed conditioning typical of the pathologies, indicating that an intact cerebellar cortex functionality is required to accelerate learning by transferring acquired information to the cerebellar nuclei. Interestingly, depending on the type of lesion, the redistribution of synaptic plasticity and response timing varied greatly generating specific adaptation patterns. Thus, not only the present work extends the generalization capabilities of the cerebellar spiking model to pathological cases, but also predicts how changes at the neuronal level are distributed across the network, making it usable to infer cerebellar circuit alterations occurring in cerebellar pathologies.

  2. Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

    LENUS (Irish Health Repository)

    Costello, Richard W

    2012-02-01

    The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and\\/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.

  3. Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

    LENUS (Irish Health Repository)

    Costello, Richard W

    2011-05-01

    The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and\\/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.

  4. Nerve supply to the pelvis (image)

    Science.gov (United States)

    The nerves that branch off the central nervous system (CNS) provide messages to the muscles and organs for normal ... be compromised. In multiple sclerosis, the demyelinization of nerve cells may lead to bowel incontinence, bladder problems ...

  5. Post-embryonic nerve-associated precursors to adult pigment cells: genetic requirements and dynamics of morphogenesis and differentiation.

    Directory of Open Access Journals (Sweden)

    Erine H Budi

    2011-05-01

    Full Text Available The pigment cells of vertebrates serve a variety of functions and generate a stunning variety of patterns. These cells are also implicated in human pathologies including melanoma. Whereas the events of pigment cell development have been studied extensively in the embryo, much less is known about morphogenesis and differentiation of these cells during post-embryonic stages. Previous studies of zebrafish revealed genetically distinct populations of embryonic and adult melanophores, the ectotherm homologue of amniote melanocytes. Here, we use molecular markers, vital labeling, time-lapse imaging, mutational analyses, and transgenesis to identify peripheral nerves as a niche for precursors to adult melanophores that subsequently migrate to the skin to form the adult pigment pattern. We further identify genetic requirements for establishing, maintaining, and recruiting precursors to the adult melanophore lineage and demonstrate novel compensatory behaviors during pattern regulation in mutant backgrounds. Finally, we show that distinct populations of latent precursors having differential regenerative capabilities persist into the adult. These findings provide a foundation for future studies of post-embryonic pigment cell precursors in development, evolution, and neoplasia.

  6. Partially thrombosed giant aneurysm arising from a distal anterior inferior cerebellar artery–posterior inferior cerebellar artery variant: A case report

    Directory of Open Access Journals (Sweden)

    Hidetoshi Ooigawa

    2015-09-01

    Full Text Available Anterior inferior cerebellar artery (AICA–posterior inferior cerebellar artery (PICA is a well-known variant in cerebral arteries. However, aneurysms located on the variant are rare and a giant one has not been reported. We report a case of a partially thrombosed giant aneurysm arising from an AICA–PICA variant. The patient was a 42-year-old man who presented with right hearing loss and facial numbness associated with left hemidysesthesia. Magnetic resonance imaging revealed an approximately 3.0-cm mass lesion at the right cerebello-pontine angle (CPA. Angiography showed a partially thrombosed aneurysm arising from the right AICA–PICA. The aneurysm was treated with endovascular trapping and surgical thrombectomy. Although cerebral aneurysm is known to occur at this site, this case provides awareness, that manifestations of aneurysms in the CPA include progressive multiple cranial nerve palsies and sensory disturbance caused by brainstem compression.

  7. Genetics Home Reference: autosomal dominant cerebellar ataxia, deafness, and narcolepsy

    Science.gov (United States)

    ... may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of neurons to move (migrate) ... Ataxia Foundation National Sleep Foundation University of Kansas Medical Center Resource List: Deafness and Hard of Hearing ...

  8. Genetics Home Reference: autosomal recessive cerebellar ataxia type 1

    Science.gov (United States)

    ... Canada, but it has since been found in populations worldwide. Related Information What information about a genetic ... are involved in chemical signaling between nerve cells ( neurons ). SYNE1 gene mutations that cause ARCA1 result in ...

  9. STD-dependent and independent encoding of input irregularity as spike rate in a computational model of a cerebellar nucleus neuron

    NARCIS (Netherlands)

    J. Luthman (Johannes); F.E. Hoebeek (Freek); R. Maex (Reinoud); N. Davey (Neil); R. Adams (Rod); C.I. de Zeeuw (Chris); V. Steuber (Volker)

    2011-01-01

    textabstractNeurons in the cerebellar nuclei (CN) receive inhibitory inputs from Purkinje cells in the cerebellar cortex and provide the major output from the cerebellum, but their computational function is not well understood. It has recently been shown that the spike activity of Purkinje cells is

  10. Properties of bilateral spinocerebellar activation of cerebellar cortical neurons

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    Pontus eGeborek

    2014-10-01

    Full Text Available We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT and the dorsal spinocerebellar tract (DSCT, respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF and the ipsilateral LF (iLF at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e. that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.

  11. Ulnar nerve dysfunction

    Science.gov (United States)

    Neuropathy - ulnar nerve; Ulnar nerve palsy; Mononeuropathy; Cubital tunnel syndrome ... Damage to one nerve group, such as the ulnar nerve, is called mononeuropathy . Mononeuropathy means there is damage to a single nerve. Both ...

  12. Radial nerve dysfunction

    Science.gov (United States)

    Neuropathy - radial nerve; Radial nerve palsy; Mononeuropathy ... Damage to one nerve group, such as the radial nerve, is called mononeuropathy . Mononeuropathy means there is damage to a single nerve. Both ...

  13. Calcium Signaling in Mitral Cell Dendrites of Olfactory Bulbs of Neonatal Rats and Mice during Olfactory Nerve Stimulation and Beta-Adrenoceptor Activation

    Science.gov (United States)

    Yuan, Qi; Mutoh, Hiroki; Debarbieux, Franck; Knopfel, Thomas

    2004-01-01

    Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. Beta-adrenergic modulation of electrical…

  14. Regulation of Axolotl (Ambystoma mexicanum) Limb Blastema Cell Proliferation by Nerves and BMP2 in Organotypic Slice Culture.

    Science.gov (United States)

    Lehrberg, Jeffrey; Gardiner, David M

    2015-01-01

    We have modified and optimized the technique of organotypic slice culture in order to study the mechanisms regulating growth and pattern formation in regenerating axolotl limb blastemas. Blastema cells maintain many of the behaviors that are characteristic of blastemas in vivo when cultured as slices in vitro, including rates of proliferation that are comparable to what has been reported in vivo. Because the blastema slices can be cultured in basal medium without fetal bovine serum, it was possible to test the response of blastema cells to signaling molecules present in serum, as well as those produced by nerves. We also were able to investigate the response of blastema cells to experimentally regulated changes in BMP signaling. Blastema cells responded to all of these signals by increasing the rate of proliferation and the level of expression of the blastema marker gene, Prrx-1. The organotypic slice culture model provides the opportunity to identify and characterize the spatial and temporal co-regulation of pathways in order to induce and enhance a regenerative response.

  15. Regulation of Axolotl (Ambystoma mexicanum Limb Blastema Cell Proliferation by Nerves and BMP2 in Organotypic Slice Culture.

    Directory of Open Access Journals (Sweden)

    Jeffrey Lehrberg

    Full Text Available We have modified and optimized the technique of organotypic slice culture in order to study the mechanisms regulating growth and pattern formation in regenerating axolotl limb blastemas. Blastema cells maintain many of the behaviors that are characteristic of blastemas in vivo when cultured as slices in vitro, including rates of proliferation that are comparable to what has been reported in vivo. Because the blastema slices can be cultured in basal medium without fetal bovine serum, it was possible to test the response of blastema cells to signaling molecules present in serum, as well as those produced by nerves. We also were able to investigate the response of blastema cells to experimentally regulated changes in BMP signaling. Blastema cells responded to all of these signals by increasing the rate of proliferation and the level of expression of the blastema marker gene, Prrx-1. The organotypic slice culture model provides the opportunity to identify and characterize the spatial and temporal co-regulation of pathways in order to induce and enhance a regenerative response.

  16. Bridging the gap between postembryonic cell lineages and identified embryonic neuroblasts in the ventral nerve cord of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Oliver Birkholz

    2015-03-01

    Full Text Available The clarification of complete cell lineages, which are produced by specific stem cells, is fundamental for understanding mechanisms, controlling the generation of cell diversity and patterning in an emerging tissue. In the developing Central Nervous System (CNS of Drosophila, neural stem cells (neuroblasts exhibit two periods of proliferation: During embryogenesis they produce primary lineages, which form the larval CNS. After a phase of mitotic quiescence, a subpopulation of them resumes proliferation in the larva to give rise to secondary lineages that build up the CNS of the adult fly. Within the ventral nerve cord (VNC detailed descriptions exist for both primary and secondary lineages. However, while primary lineages have been linked to identified neuroblasts, the assignment of secondary lineages has so far been hampered by technical limitations. Therefore, primary and secondary neural lineages co-existed as isolated model systems. Here we provide the missing link between the two systems for all lineages in the thoracic and abdominal neuromeres. Using the Flybow technique, embryonic neuroblasts were identified by their characteristic and unique lineages in the living embryo and their further development was traced into the late larval stage. This comprehensive analysis provides the first complete view of which embryonic neuroblasts are postembryonically reactivated along the anterior/posterior-axis of the VNC, and reveals the relationship between projection patterns of primary and secondary sublineages.

  17. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor

    NARCIS (Netherlands)

    Buijink, A. W. G.; Broersma, M.; van der Stouwe, A. M. M.; van Wingen, G. A.; Groot, P. F. C.; Speelman, J. D.; Maurits, N. M.; van Rootselaar, A. F.

    2015-01-01

    Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar

  18. A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery.

    Science.gov (United States)

    Tamaki, Tetsuro; Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

    2016-01-01

    Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk

  19. A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs: An Achievement of Significant Morphological, Numerical and Functional Recovery.

    Directory of Open Access Journals (Sweden)

    Tetsuro Tamaki

    Full Text Available Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34 and CD34-/45-/29+ (Sk-DN/29+ cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells were also observed. A significant tetanic tension recovery (over 90% of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon and functional (80% vs. 60% in tetanus recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks of recovery was observed in both groups with the expression of key factors (mRNA and protein levels, suggesting the paracrine effects to angiogenesis. These results suggested that the

  20. Hepatocyte growth factor promotes long-term survival and axonal regeneration of retinal ganglion cells after optic nerve injury: comparison with CNTF and BDNF.

    Science.gov (United States)

    Wong, Wai-Kai; Cheung, Anny Wan-Suen; Yu, Sau-Wai; Sha, Ou; Cho, Eric Yu Pang

    2014-10-01

    Different trophic factors are known to promote retinal ganglion cell survival and regeneration, but each had their own limitations. We report that hepatocyte growth factor (HGF) confers distinct advantages in supporting ganglion cell survival and axonal regeneration, when compared to two well-established trophic factors ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). Ganglion cells in adult hamster were injured by cutting the optic nerve. HGF, CNTF, or BDNF was injected at different dosages intravitreally after injury. Ganglion cell survival was quantified at 7, 14, or 28 days postinjury. Peripheral nerve (PN) grafting to the cut optic nerve of the growth factor-injected eye was performed either immediately after injury or delayed until 7 days post-injury. Expression of heat-shock protein 27 and changes in microglia numbers were quantified in different growth factor groups. The cellular distribution of c-Met in the retina was examined by anti-c-Met immunostaining. Hepatocyte Growth Factor (HGF) was equally potent as BDNF in promoting short-term survival (up to 14 days post-injury) and also supported survival at 28 days post-injury when ganglion cells treated by CNTF or BDNF failed to be sustained. When grafting was performed without delay, HGF stimulated twice the number of axons to regenerate compared with control but was less potent than CNTF. However, in PN grafting delayed for 7 days after optic nerve injury, HGF maintained a better propensity of ganglion cells to regenerate than CNTF. Unlike CNTF, HGF application did not increase HSP27 expression in ganglion cells. Microglia proliferation was prolonged in HGF-treated retinas compared with CNTF or BDNF. C-Met was localized to both ganglion cells and Muller cells, suggesting HGF could be neuroprotective via interacting with both neurons and glia. Compared with CNTF or BDNF, HGF is advantageous in sustaining long-term ganglion cell survival and their propensity to respond to

  1. Etiology, Localization and Prognosis in Cerebellar Infarctions

    Directory of Open Access Journals (Sweden)

    Yavuz Yücel

    2006-01-01

    Full Text Available Cerebrovasculer disease are the most frequent disease of the brain. Cerebellar infarct remains % 1.5-4.2 of these diseases. Etiological factors, lesion localization, symptoms and findings and relationship with prognosis of our patients with cerebellar infarct were investigated in our study. For this purpose, 32 patients were evaluated who were admitted to the Dicle University Medical School Department of Neurology in 1995-2001 hospitalized with the diagnosis of clinically and radiological confirmed cerebellar infarction.All of patients in the study group, 21 (%65.6 were male and 11 (%34.3 female. Age of overall patients ranged between 40 and 75 years with a mean of 57.8±10.2 years. Atherothrombotic infarct was the most frequent reason at the etiologic clinical classification. The most frequently found localization was the posterior inferior cerebellar artery infarct (%50. The leading two risk factors were hypertension (%78.1 and cigarette smoking (%50. The most common sign and symptoms were vertigo (%93.7, vomiting (%75, headache (%68.7 and cerebellar dysfunction findings (%50. The mean duration of hospitalization was 16.3±7.6 days. Overall mortality rate was found to be % 6.2. Finally, the most remarkable risk factors at cerebellar infarct patients are hypertension and atherosclerosis at etiology. We are considering that, controlling of these factors will reduce the appearance frequency of cerebellar infarcts.

  2. [Memory transfer in cerebellar motor learning].

    Science.gov (United States)

    Nagao, Soichi

    2012-01-01

    Most of our motor skills are acquired through learning. Experiments of gain adaptation of ocular reflexes have consistently suggested that the memory of adaptation is initially formed in the cerebellar cortex, and is transferred to the cerebellar (vestibular) nuclei for consolidation to long-term memory after repetitions of training. We have recently developed a new system to evaluate the motor learning in human subjects using prism adaptation of hand reaching movement, by referring to the prism adaptation of dart throwing of Martin et al. (1996). In our system, the subject views the small target presented in the touch-panel screen, and touches it with his/her finger without direct visual feedback. After 15-30 trials of touching wearing prisms, an adaptation occurs in healthy subjects: they became able to touch the target correctly. Meanwhile, such an adaptation was impaired in patients of cerebellar disease. We have proposed a model of human prism adaptation that the memory of adaptation is initially encoded in the cerebellar cortex, and is later transferred to the cerebellar nuclei after repetitions of training. The memory in the cerebellar cortex may be formed and extinguished independently of the memory maintained in the cerebellar nuclei, and these two memories work cooperatively.

  3. An anatomical study of porcine peripheral nerve and its potential use in nerve tissue engineering

    Science.gov (United States)

    Zilic, Leyla; Garner, Philippa E; Yu, Tong; Roman, Sabiniano; Haycock, John W; Wilshaw, Stacy-Paul

    2015-01-01

    Current nerve tissue engineering applications are adopting xenogeneic nerve tissue as potential nerve grafts to help aid nerve regeneration. However, there is little literature that describes the exact location, anatomy and physiology of these nerves to highlight their potential as a donor graft. The aim of this study was to identify and characterise the structural and extracellular matrix (ECM) components of porcine peripheral nerves in the hind leg. Methods included the dissection of porcine nerves, localisation, characterisation and quantification of the ECM components and identification of nerve cells. Results showed a noticeable variance between porcine and rat nerve (a commonly studied species) in terms of fascicle number. The study also revealed that when porcine peripheral nerves branch, a decrease in fascicle number and size was evident. Porcine ECM and nerve fascicles were found to be predominately comprised of collagen together with glycosaminoglycans, laminin and fibronectin. Immunolabelling for nerve growth factor receptor p75 also revealed the localisation of Schwann cells around and inside the fascicles. In conclusion, it is shown that porcine peripheral nerves possess a microstructure similar to that found in rat, and is not dissimilar to human. This finding could extend to the suggestion that due to the similarities in anatomy to human nerve, porcine nerves may have utility as a nerve graft providing guidance and support to regenerating axons. PMID:26200940

  4. Cellular and Axonal Diversity in Molecular Layer Heterotopia of the Rat Cerebellar Vermis

    Directory of Open Access Journals (Sweden)

    Sarah E. Van Dine

    2013-01-01

    Full Text Available Molecular layer heterotopia of the cerebellar primary fissure are a characteristic of many rat strains and are hypothesized to result from defect of granule cells exiting the external granule cell layer during cerebellar development. However, the cellular and axonal constituents of these malformations remain poorly understood. In the present report, we use histochemistry and immunocytochemistry to identify neuronal, glial, and axonal classes in molecular layer heterotopia. In particular, we identify parvalbumin-expressing molecular layer interneurons in heterotopia as well as three glial cell types including Bergmann glia, Olig2-expressing oligodendrocytes, and Iba1-expressing microglia. In addition, we document the presence of myelinated, serotonergic, catecholaminergic, and cholinergic axons in heterotopia indicating possible spinal and brainstem afferent projections to heterotopic cells. These findings are relevant toward understanding the mechanisms of normal and abnormal cerebellar development.

  5. Computed tomography in alcoholic cerebellar atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Haubek, A; Lee, K [Hvidovre Hospital Copenhagen (Denmark). Dept. of Radiology; Municipal Hospital, Copenhagen (Denmark). Dept. of Neurology)

    1979-01-01

    This is a controlled CT evaluation of the infratentorial region in 41 male alcoholics under age 35. Criteria for the presence of atrophy are outlined. Twelve patients had cerebellar atrophy. Vermian atrophy was present in all. Atrophy of the cerebellar hemispheres was demonstrated in eight patients as well. The results are statistically significant when compared to an age-matched group of 40 non-alcoholic males among whom two cases of vermian atrophy were found. There were clinical signs of alcoholic cerebellar atrophy in one patient only. The disparity between the clinical and the radiological data are discussed with reference to previous pneumoencephalographic findings. (orig.) 891 AJ/orig. 892 MKO.

  6. Acute Cerebellar Ataxia Induced by Nivolumab

    Science.gov (United States)

    Kawamura, Reina; Nagata, Eiichiro; Mukai, Masako; Ohnuki, Yoichi; Matsuzaki, Tomohiko; Ohiwa, Kana; Nakagawa, Tomoki; Kohno, Mitsutomo; Masuda, Ryota; Iwazaki, Masayuki; Takizawa, Shunya

    2017-01-01

    A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment. PMID:29249765

  7. Cerebellar injury in preterm infants.

    Science.gov (United States)

    Tam, Emily W Y

    2018-01-01

    Although preterm birth is best known to result in adverse neurodevelopmental outcomes through injury of the supratentorial structures, including intraventricular hemorrhage and periventricular leukomalacia, the cerebellum has become increasingly recognized as an important target for injury and adverse motor and cognitive outcomes. Undergoing the most dramatic growth during the preterm period, the cerebellum is vulnerable to large and small hemorrhages, as well as hypoplasia resulting from a number of potentially modifiable risk factors. These factors include contact with intraventricular blood, crossed cerebrocerebellar diaschisis, postnatal glucocorticoid exposure, pain and opioid exposure, nutrition and somatic growth, cardiorespiratory factors, and socioeconomic status. Strategies targeting these factors may result in prevention of the motor and cognitive deficits seen after cerebellar hemorrhage or hypoplasia. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Structural and Functional Substitution of Deleted Primary Sensory Neurons by New Growth from Intrinsic Spinal Cord Nerve Cells: An Alternative Concept in Reconstruction of Spinal Cord Circuits

    Directory of Open Access Journals (Sweden)

    Nicholas D. James

    2017-07-01

    Full Text Available In a recent clinical report, return of the tendon stretch reflex was demonstrated after spinal cord surgery in a case of total traumatic brachial plexus avulsion injury. Peripheral nerve grafts had been implanted into the spinal cord to reconnect to the peripheral nerves for motor and sensory function. The dorsal root ganglia (DRG containing the primary sensory nerve cells had been surgically removed in order for secondary or spinal cord sensory neurons to extend into the periphery and replace the deleted DRG neurons. The present experimental study uses a rat injury model first to corroborate the clinical finding of a re-established spinal reflex arch, and second, to elucidate some of the potential mechanisms underlying these findings by means of morphological, immunohistochemical, and electrophysiological assessments. Our findings indicate that, after spinal cord surgery, the central nervous system sensory system could replace the traumatically detached original peripheral sensory connections through new neurite growth from dendrites.

  9. Stress Altered Stem Cells with Decellularized Allograft to Improve Rate of Nerve Regeneration

    Science.gov (United States)

    2015-12-01

    Analysis of the treated cells exhibited no evidence of expression of the generally accepted embryonic stem cell markers Oct4, nanog or sox-2 via either...detect the presence of any tissue containing cells representative of the three germ layers (endoderm, mesoderm, or ectoderm). Rationale for...gone awry. In a controlled environment, pluripotent cells should indeed be able to generate any of the three germ layers , but in a directed fashion

  10. Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.

    Science.gov (United States)

    Takito, Jiro; Kimura, Junko; Kajima, Koji; Uozumi, Nobuyuki; Watanabe, Makoto; Yokosuka, Akihito; Mimaki, Yoshihiro; Nakamura, Masanori; Ohizumi, Yasushi

    2016-07-01

    Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.

  11. Supramolecular assembly of biological molecules purified from bovine nerve cells: from microtubule bundles and necklaces to neurofilament networks

    International Nuclear Information System (INIS)

    Needleman, Daniel J; Jones, Jayna B; Raviv, Uri; Ojeda-Lopez, Miguel A; Miller, H P; Li, Y; Wilson, L; Safinya, C R

    2005-01-01

    With the completion of the human genome project, the biosciences community is beginning the daunting task of understanding the structures and functions of a large number of interacting biological macromolecules. Examples include the interacting molecules involved in the process of DNA condensation during the cell cycle, and in the formation of bundles and networks of filamentous actin proteins in cell attachment, motility and cytokinesis. In this proceedings paper we present examples of supramolecular assembly based on proteins derived from the vertebrate nerve cell cytoskeleton. The axonal cytoskeleton in vertebrate neurons provides a rich example of bundles and networks of neurofilaments, microtubules (MTs) and filamentous actin, where the nature of the interactions, structures, and structure-function correlations remains poorly understood. We describe synchrotron x-ray diffraction, electron microscopy, and optical imaging data, in reconstituted protein systems purified from bovine central nervous system, which reveal unexpected structures not predicted by current electrostatic theories of polyelectrolyte bundling, including three-dimensional MT bundles and two-dimensional MT necklaces

  12. The morpho/functional discrepancy in the cerebellar cortex: Looks alone are deceptive.

    Directory of Open Access Journals (Sweden)

    Dan Rokni

    2008-12-01

    Full Text Available In a recent report we demonstrated that stimulation of cerebellar mossy fibers synchronously activates Purkinje cells that are located directly above the site of stimulation. We found that the activated Purkinje cells are arranged in a radial patch on the cerebellar surface and that this organization is independent of the integrity of the inhibitory system. This arrangement of activity is counterintuitive. The anatomical structure with the extensive parallel fiber system implies that mossy fiber stimulation will activate Purkinje cells along a beam of parallel fibers. In this short review we highlight this discrepancy between anatomical structure and functional dynamics and suggest a plausible underlying mechanism.

  13. Diffusion tensor imaging for nerve fiber bundles in the brain stem and spinocerebellar degeneration

    International Nuclear Information System (INIS)

    Honma, Tsuguo

    2009-01-01

    Diffusion tensor imaging (DTI) can create an image of the anisotropic nature of diffusion and express it quantitatively. Nerve fibers have a large anisotropic diffusion, and it is possible to obtain images of the nerve fiber bundle. The purpose of this study is to observe the nerve fiber bundles in the brain stem using DTI and study its potential for diagnosing the type of spinocerebellar degeneration (SCD). Fractional anisotropy (FA) maps and 3D-tractography images were obtained for 41 subjects with no brain stem abnormalities. We created an apparent diffusion coefficient (ADC) map and an FA map using DTI for 16 subjects in the disease group (11 with hereditary SCD and 5 with non-hereditary SCD) and 25 in the control group. The diffusion value of the pons and middle cerebellar peduncle was measured using ADC, and the degree of anisotropic diffusion was measured using FA. The pyramidal tract, superior cerebellar peduncle, and inferior cerebellar peduncle were clearly demonstrated for all cases. ADC for the middle cerebellar peduncle in spinocerebellar ataxin (SCA)1 was significantly higher, similar to that for the pons in dentatorubro-pallidoluysian atrophy (DRPLA). In MSA-C, ADC for both the pons and middle cerebellar peduncle was significantly elevated and FA was significantly decreased. There were no significant changes in SCA3. We could observe the nerve fiber bundles in the brain stem using DTI. FA and ADC measurements with DTI can aid in diagnosing the type of SCD. (author)

  14. Insulin-like growth factors act synergistically with basic fibroblast growth factor and nerve growth factor to promote chromaffin cell proliferation

    DEFF Research Database (Denmark)

    Frödin, M; Gammeltoft, S

    1994-01-01

    We have investigated the effects of insulin-like growth factors (IGFs), basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) on DNA synthesis in cultured chromaffin cells from fetal, neonatal, and adult rats by using 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling for 24 or 48 h...... implications for improving the survival of chromaffin cell implants in diseased human brain....

  15. Sam68 promotes Schwann cell proliferation by enhancing the PI3K/Akt pathway and acts on regeneration after sciatic nerve crush

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Weijie, E-mail: 459586768@qq.com; Liu, Yuxi, E-mail: 924013616@qq.com; Wang, Youhua, E-mail: wyouhua1516@163.com

    2016-05-13

    Sam68 (Src-associated in mitosis of 68 kD), a KH domain RNA-binding protein, is not only important in signaling transduction cascades, but crucial in a variety of cellular processes. Sam68 is reported to be involved in the phospoinositide3-kinase (PI3K) and nuclear factor-kappa B (NF-κB) signaling pathways, and it is closely associated with cell proliferation, RNA metabolism, and tumor progression. However, we know little about the role of Sam68 during peripheral nervous system injury and regeneration. In this study, we investigated the expression of Sam68 and its biological significances in sciatic nerve crush. Interestingly, we found Sam68 had a co-localization with S100 (Schwann cell marker). Moreover, after crush, Sam68 had a spatiotemporal protein expression, which was in parallel with proliferation cell nuclear antigen (PCNA). In vitro, we also observed increased expression of Sam68 during the process of TNF-α-induced Schwann cell proliferation model. Besides, flow cytometry analyses, CCK-8, and EDU were all performed with the purpose of investigating the role of Sam68 in the regulation of Schwann cell proliferation. Even more importantly, we discovered that Sam68 could enhance the phosphorylation of Akt while LY294002 (a PI3K inhibitor) obviously reversed Sam68-induced cell proliferation. Finally, we detected the variance during regeneration progress through the rat walk footprint test. In summary, all these evidences demonstrated that Sam68 might participate in Schwann cell proliferation partially via PI3K/Akt pathway and also regulate regeneration after sciatic nerve crush. -- Highlights: •The dynamic changes and location of Sam68 after sciatic nerve crush. •Sam68 promoted Schwann cell proliferation via PI3K/Akt pathway. •Sam68 modulated functional recovery after sciatic nerve crush.

  16. Sam68 promotes Schwann cell proliferation by enhancing the PI3K/Akt pathway and acts on regeneration after sciatic nerve crush

    International Nuclear Information System (INIS)

    Wu, Weijie; Liu, Yuxi; Wang, Youhua

    2016-01-01

    Sam68 (Src-associated in mitosis of 68 kD), a KH domain RNA-binding protein, is not only important in signaling transduction cascades, but crucial in a variety of cellular processes. Sam68 is reported to be involved in the phospoinositide3-kinase (PI3K) and nuclear factor-kappa B (NF-κB) signaling pathways, and it is closely associated with cell proliferation, RNA metabolism, and tumor progression. However, we know little about the role of Sam68 during peripheral nervous system injury and regeneration. In this study, we investigated the expression of Sam68 and its biological significances in sciatic nerve crush. Interestingly, we found Sam68 had a co-localization with S100 (Schwann cell marker). Moreover, after crush, Sam68 had a spatiotemporal protein expression, which was in parallel with proliferation cell nuclear antigen (PCNA). In vitro, we also observed increased expression of Sam68 during the process of TNF-α-induced Schwann cell proliferation model. Besides, flow cytometry analyses, CCK-8, and EDU were all performed with the purpose of investigating the role of Sam68 in the regulation of Schwann cell proliferation. Even more importantly, we discovered that Sam68 could enhance the phosphorylation of Akt while LY294002 (a PI3K inhibitor) obviously reversed Sam68-induced cell proliferation. Finally, we detected the variance during regeneration progress through the rat walk footprint test. In summary, all these evidences demonstrated that Sam68 might participate in Schwann cell proliferation partially via PI3K/Akt pathway and also regulate regeneration after sciatic nerve crush. -- Highlights: •The dynamic changes and location of Sam68 after sciatic nerve crush. •Sam68 promoted Schwann cell proliferation via PI3K/Akt pathway. •Sam68 modulated functional recovery after sciatic nerve crush.

  17. Macular Ganglion Cell Inner Plexiform Layer Thickness in Glaucomatous Eyes with Localized Retinal Nerve Fiber Layer Defects.

    Directory of Open Access Journals (Sweden)

    Chunwei Zhang

    Full Text Available To investigate macular ganglion cell-inner plexiform layer (mGCIPL thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL defects on stereophotographs.112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS and the African Descent and Glaucoma Evaluation Study (ADAGES subjects had standard automated perimetry (SAP, optical coherence tomography (OCT imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs.47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P<0.001 and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 μm, P = 1.000. The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior mGCIPL was thinnest in the same hemiretina in 26 eyes (90%. Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001 and inferior mGCIPL (P = 0.030 compared to glaucomatous eyes without a visible RNFL defect.The current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect.

  18. Involvement of TRPM2 in peripheral nerve injury-induced infiltration of peripheral immune cells into the spinal cord in mouse neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Kouichi Isami

    Full Text Available Recent evidence suggests that transient receptor potential melastatin 2 (TRPM2 expressed in immune cells plays an important role in immune and inflammatory responses. We recently reported that TRPM2 expressed in macrophages and spinal microglia contributes to the pathogenesis of inflammatory and neuropathic pain aggravating peripheral and central pronociceptive inflammatory responses in mice. To further elucidate the contribution of TRPM2 expressed by peripheral immune cells to neuropathic pain, we examined the development of peripheral nerve injury-induced neuropathic pain and the infiltration of immune cells (particularly macrophages into the injured nerve and spinal cord by using bone marrow (BM chimeric mice by crossing wildtype (WT and TRPM2-knockout (TRPM2-KO mice. Four types of BM chimeric mice were prepared, in which irradiated WT or TRPM2-KO recipient mice were transplanted with either WT-or TRPM2-KO donor mouse-derived green fluorescence protein-positive (GFP(+ BM cells (TRPM2(BM+/Rec+, TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. Mechanical allodynia induced by partial sciatic nerve ligation observed in TRPM2(BM+/Rec+ mice was attenuated in TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. The numbers of GFP(+ BM-derived cells and Iba1/GFP double-positive macrophages in the injured sciatic nerve did not differ among chimeric mice 14 days after the nerve injury. In the spinal cord, the number of GFP(+ BM-derived cells, particularly GFP/Iba1 double-positive macrophages, was significantly decreased in the three TRPM2-KO chimeric mouse groups compared with TRPM2(BM+/Rec+ mice. However, the numbers of GFP(-/Iba1(+ resident microglia did not differ among chimeric mice. These results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than the infiltration of peripheral immune cells into the injured nerves and activation of spinal

  19. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

    Directory of Open Access Journals (Sweden)

    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  20. Cerebellar mutism: review of the literature

    DEFF Research Database (Denmark)

    Gudrunardottir, Thora; Sehested, Astrid; Juhler, Marianne

    2011-01-01

    Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention....

  1. Degenerative cerebellar diseases and differential diagnoses

    International Nuclear Information System (INIS)

    Reith, W.; Roumia, S.; Dietrich, P.

    2016-01-01

    Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions. (orig.) [de

  2. [Degenerative cerebellar diseases and differential diagnoses].

    Science.gov (United States)

    Reith, W; Roumia, S; Dietrich, P

    2016-11-01

    Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions.

  3. Non-neoplastic gliotic cerebellar cysts

    International Nuclear Information System (INIS)

    Weisberg, L.A.

    1982-01-01

    The clinical and CT findings in 3 patients with non-neoplastic gliotic cerebellar cyst are described. CT does not permit accurate preoperative differentiation of these lesions from neoplastic disorders. (orig.)

  4. Ataxias and Cerebellar or Spinocerebellar Degeneration

    Science.gov (United States)

    ... and conducts a broad range of basic and clinical research on cerebellar and spinocerebellar degeneration, including work aimed at finding the cause(s) of ataxias and ways to ... Publications Definition Ataxia ...

  5. Expression of DREAM A and DREAM B in primary cultured nerve cells of mice%DREAM A和B在原代培养的小鼠神经细胞中的表达

    Institute of Scientific and Technical Information of China (English)

    赵雪花; 孙峰波; 周艳玲

    2013-01-01

    目的:研究DREAM蛋白的2个主要亚型DREAM A和DREAM B在原代培养的小鼠大脑皮层星形胶质细胞、小鼠大脑皮层γ-氨基丁酸能神经元以及小鼠小脑谷氨酸能神经元中的表达水平的差异.方法:提取原代培养的小鼠大脑皮层星形胶质细胞、小鼠大脑皮层γ-氨基丁酸能神经元以及小鼠小脑谷氨酸能神经元的RNA,采用普通PCR及real time PCR的方法检测上述各种细胞中DREAM蛋白2个亚型A和B的mRNA的表达水平.结果:DREAM的两个亚型A和B在上述三种神经细胞都存在.在发育成熟的原代培养细胞中,DREAMA的mRNA水平要远高于DREAM B.在三种不同的细胞中,谷氨酸能神经元表达DREAM A的水平最高.结论:DREAM的两个亚型A和B在小鼠三种原代培养的神经细胞中的表达水平及其差异提示DREAM A是成年小鼠中DREAM的主要亚型,DREAM A和B在不同类型的神经细胞中发挥的作用及其机制有所不同.%Objective: To study the difference of the expression level between the two main isoforms of DREAM A and DREAM B in the primary cultured cerebral cortical astrocytes, GABAergic nerons and cerebellar glutamatergic neurons of the mice. Methods: RNA of the above three primary cultured cells from mice were extracted and then detected about the DREAM A and DREAM B's mRNA level by the polymerase chain reaction (PCR) and real time PCR. Results; Both DREAM A and DREAM B existed in the above three nerve cells. In the mature primary culture cells, the mRNA level of the DREAM A was higher than that of DREAM B, and the expression level of DREAM A of the glutamatergic neurons was the highest among the three cells. Conclusion: The expression levels and differences of the DREAM A and DREAM B show that DREAM A was the main type of DREAM in adult mice, DREAM A and DREAM B may play different roles throug diffenent action mechanisms in different types of nerve cells.

  6. Human iPSC-Derived Cerebellar Neurons from a Patient with Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Sam P. Nayler

    2017-10-01

    Full Text Available Ataxia-telangiectasia (A-T is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and GBX2, and later more mature cerebellar markers including PTF1α, MATH1, HOXB4, ZIC3, PAX6, and TUJ1. RNA sequencing was used to classify differentiated cerebellar neurons generated from integration-free A-T and control induced pluripotent stem cells. Comparison of RNA sequencing data with datasets from the Allen Brain Atlas reveals in vitro-derived cerebellar neurons are transcriptionally similar to discrete regions of the human cerebellum, and most closely resemble the cerebellum at 22 weeks post-conception. We show that patient-derived cerebellar neurons exhibit disrupted gene regulatory networks associated with synaptic vesicle dynamics and oxidative stress, offering the first molecular insights into early cerebellar pathogenesis of ataxia-telangiectasia.

  7. Cerebellar mutism: review of the literature

    DEFF Research Database (Denmark)

    Gudrunardottir, Thora; Sehested, Astrid; Juhler, Marianne

    2011-01-01

    Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention.......Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention....

  8. Acute Cerebellar Ataxia Induced by Nivolumab

    OpenAIRE

    Kawamura, Reina; Nagata, Eiichiro; Mukai, Masako; Ohnuki, Yoichi; Matsuzaki, Tomohiko; Ohiwa, Kana; Nakagawa, Tomoki; Kohno, Mitsutomo; Masuda, Ryota; Iwazaki, Masayuki; Takizawa, Shunya

    2017-01-01

    A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy follow...

  9. Magnetic resonance imaging of facial nerve schwannoma.

    Science.gov (United States)

    Thompson, Andrew L; Aviv, Richard I; Chen, Joseph M; Nedzelski, Julian M; Yuen, Heng-Wai; Fox, Allan J; Bharatha, Aditya; Bartlett, Eric S; Symons, Sean P

    2009-12-01

    This study characterizes the magnetic resonance (MR) appearances of facial nerve schwannoma (FNS). We hypothesize that the extent of FNS demonstrated on MR will be greater compared to prior computed tomography studies, that geniculate involvement will be most common, and that cerebellar pontine angle (CPA) and internal auditory canal (IAC) involvement will more frequently result in sensorineural hearing loss (SNHL). Retrospective study. Clinical, pathologic, and enhanced MR imaging records of 30 patients with FNS were analyzed. Morphologic characteristics and extent of segmental facial nerve involvement were documented. Median age at initial imaging was 51 years (range, 28-76 years). Pathologic confirmation was obtained in 14 patients (47%), and the diagnosis reached in the remainder by identification of a mass, thickening, and enhancement along the course of the facial nerve. All 30 lesions involved two or more contiguous segments of the facial nerve, with 28 (93%) involving three or more segments. The median segments involved per lesion was 4, mean of 3.83. Geniculate involvement was most common, in 29 patients (97%). CPA (P = .001) and IAC (P = .02) involvement was significantly related to SNHL. Seventeen patients (57%) presented with facial nerve dysfunction, manifesting in 12 patients as facial nerve weakness or paralysis, and/or in eight with involuntary movements of the facial musculature. This study highlights the morphologic heterogeneity and typical multisegment involvement of FNS. Enhanced MR is the imaging modality of choice for FNS. The neuroradiologist must accurately diagnose and characterize this lesion, and thus facilitate optimal preoperative planning and counseling.

  10. Mast cell-nerve interaction in the colon of Trypanosoma cruzi-infected individuals with chagasic megacolon.

    Science.gov (United States)

    Martins, Patrícia Rocha; Nascimento, Rodolfo Duarte; Dos Santos, Aline Tomaz; de Oliveira, Enio Chaves; Martinelli, Patricia Massara; d'Avila Reis, Débora

    2018-04-01

    Chagas disease is an infection caused by the parasite Trypanosoma cruzi that affects millions of people worldwide and is endemic in Latin America. Megacolon is the most frequent complication of the digestive chronic form and happens due to lesions of the enteric nervous system. The neuronal lesions seem to initiate in the acute phase and persist during the chronic phase, albeit the mechanisms involved in this process are still debated. Among the cells of the immune system possibly involved in this pathological process is the mast cell (MC) due to its well-known role in the bi-directional communication between the immune and nervous systems. Using ultrastructural analysis, we found an increased number of degranulated MCs in close proximity to nerve fibers in infected patients when compared with uninfected controls. We also immunostained MCs for the two pro-inflammatory molecules tryptase and chymase, the first being also important in neuronal death. The number of MCs immunostained for tryptase or chymase was increased in patients with megacolon, whereas increased tryptase staining was additionally observed in patients without megacolon. Moreover, we detected the expression of the tryptase receptor PAR2 in neurons of the enteric nervous system, which correlated to the tryptase staining results. Altogether, the data presented herein point to the participation of MCs on the denervation process that occurs in the development of T. cruzi-induced megacolon.

  11. Expression of the GABA(A) receptor alpha6 subunit in cultured cerebellar granule cells is developmentally regulated by activation of GABA(A) receptors

    DEFF Research Database (Denmark)

    Carlson, B X; Belhage, B; Hansen, Gert Helge

    1997-01-01

    Da (alpha6 subunit) radioactive peaks in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In contrast, THIP-treated granule cells at 8 DIV demonstrated a small but significant decrease from control cultures in the photoincorporation of [3H]Ro15-4513 in the 51-kDa peak; however...... that the major effect of THIP was to increase alpha6 subunit clustering on granule cell bodies as well as neurites, 15-fold and sixfold, respectively. Using in situ hybridization, a small THIP-induced increase in alpha6 mRNA was detected at 4 DIV; however, no effect was apparent at 8 DIV. These data suggest...

  12. Mitochondrial energy metabolism changes during aging-mouse cranial nerve cells treated with various doses and forms of Fructus schizandrae

    Institute of Scientific and Technical Information of China (English)

    Hongyan Guo; Jinhe Li

    2008-01-01

    BACKGROUND: During the cellular aging process, the number of mitochondria, generation of adenosine triphosphate (ATP), activity of respiratory chain enzyme complex 1 and 4, and oxidation decrease. OBJECTIVE: To observe the effects of aqueous and spirituous extract, as well as polysaccharides from Fructus schizandrae (Magnolia Vine) on energy metabolism and mitochondrial anti-oxidation in cranial nerve cells of a D-gal-induccd aging mouse model.DESIGN, TIME AND SETTING: A randomized, controlled, animal study. The experiment was conducted at the Department of Biochemistry, Qiqihar Medical College between March and July 2006.MATERIALS: Fifty healthy, Kunming mice of both sexes, aged 2 3 months old and weighing 18-22 g, were used for the present study. Fructus schizandrae was purchased from the Medical College of Jiamusi University. Aqueous extracts, spirituous extracts, and polysaccharides from Fructus schizandrae were prepared. D-galactose (D-gal) is a product of the Second Reagent Factory, Shanghai City, China. Mn-superoxide dismutase (Mn-SOD) kit, malonaldehyde (MDA) kit, protein quantification kit, and inorganic phosphorus testing kit were purchased from Jian Cheng Bioeng. Co., China.METHODS: Fifty mice were randomly divided into five groups, with 10 mice in each group: young control, aging model, aqueous Fructus schizandrae extract, spirituous Fructus schizandrae extract, and Fructus schizandrae polysaccharides. Over a course of 30 days, mice in aging model, aqueous Fructus schizandrae extract, spirituous Fructus schizandrae extract, and Fructus schizandrae polysaccharides groups were injected subcutaneously with D-gal (100 mg/kg) into the nape of the neck daily, and administered intragastrically with an equal volume of sterile, warm water (aging model), aqueous Fructus schizandrae extract (2 g/kg), spirituous Fructus schizandrae extract (2 g/kg), or Fructus schizandrae polysaccharides (0.2 g/kg), respectively. Mice in the young control group were injected into

  13. Effects of x-irradiation induced loss of cerebellar granule cells on the synaptosomal levels and the high affinity uptake of amino acids

    International Nuclear Information System (INIS)

    Rohde, B.H.; Rea, M.A.; Simon, J.R.; McBride, W.J.

    1979-01-01

    Crude synaptosomal (P 2 ) preparations were obtained from the cerebella of rats in which the granule cell population had been selectively reduced by X-irradiation treatment and from the cerebella of control animals. In the P 2 fraction form control cerebella, the level of glutamate was greater than any other of the 5 amino acids measured and was 2-fold higher than taurine. The content of taurine, GABA, glycine, and alanine were not changed by the X-irradiation treatment. The uptake of 1.0 micrometers-L-[ 3 H]glutamate and L-[ 3 H]aspartate was reduced approx 20% by X-irradiation treatment, whereas the uptake of 1.0 micrometers-[ 3 H]GABA and [ 3 H]taurine was unchanged. In a second study, the uptake of L-[ 3 H]glutamate, L-[ 3 H]aspartate and [ 3 H]GABA was measured using P 2 fractions obtained from the cerebella of rats in which the population of granule, stellate and basket cells had been reduced by X-irradiation treatment. The uptake of 1.0 micrometers-L-[ 3 H]glutamate, L-[ 3 H]aspartate and [ 3 H]GABA was significantly (P < 0.05) reduced to 57.68 and 59% respectively, of control values. The data are discussed in terms of glutamate being the excitatory neurotransmitter released from granule cells and GABA being the inhibitory neurotransmitter released from basket cells. (author)

  14. Gait rehabilitation in a patient affected with Charcot-Marie-Tooth disease associated with pyramidal and cerebellar features and blindness.

    Science.gov (United States)

    Vinci, Paolo

    2003-05-01

    Charcot-Marie-Tooth (CMT) disease, an inherited neuropathy characterized by length-dependent degeneration of the motor and sensory nerve fibers with consequent distal muscle atrophy and sensory reduction, can be associated with symptoms and signs of involvement of the central nervous system and/or cranial nerves. We present a patient with relatively severe CMT, cerebellar ataxia, pyramidal involvement, and blindness due to Leber's hereditary optic neuropathy. The patient presented with poor standing and gait, with consequent severe disability. Factors responsible for the patient's functional impairment (plantarflexor failure, footdrop, foot rotation, knee flexor contracture, poor proprioception, cerebellar dysfunction, spastic paraparesis, blindness) were identified and addressed by a rehabilitation management, which included, as a main intervention, ankle stabilization by drop-foot boots instead of ankle-foot orthoses. Improved balance and independent ambulation resulted from rehabilitation.

  15. Electrophysiological mapping of novel prefrontal - cerebellar pathways

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    Thomas C Watson

    2009-08-01

    Full Text Available Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre; they were not attenuated by local anesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency. Single-unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions.

  16. Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy

    DEFF Research Database (Denmark)

    Winkelmann, Juliane; Lin, Ling; Schormair, Barbara

    2012-01-01

    to HDAC2. It is also highly expressed in immune cells and required for the differentiation of CD4+ into T regulatory cells. Mutations in exon 20 of this gene were recently reported to cause hereditary sensory neuropathy with dementia and hearing loss (HSAN1). Our mutations are all located in exon 21......Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30-40 years old) cerebellar ataxia, sensory neuronal deafness, narcolepsy-cataplexy and dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds and identified DNMT...

  17. Effect of nerve growth factor on the synthesis of amino acids in PC12 cells

    International Nuclear Information System (INIS)

    Zielke, H.R.; Tildon, J.T.; Kauffman, F.C.; Baab, P.J.

    1989-01-01

    Radioactive short-chain fatty acids preferentially label glutamine relative to glutamate in brain due to compartmentation of glutamine and glutamate. To determine whether this phenomenon occurs in a single cell culture model, we examined the effect of fatty acid chain length on the synthesis as well as pool size of selected amino acids in rat pheochromocytoma PC12 cells, a cell culture model of the large glutamate compartment in neurons. Intracellular 14C-amino acids were quantitated by HPLC, and the incorporation of [U-14C]-glucose, [1-14C]-butyrate, [1-14C]-octanoate, and [1-14C]-palmitate into five amino acids was measured in native and NGF-treated PC12 cells. NGF pretreatment decreased the intracellular concentration of amino acids as did addition of fatty acids but these effects were not additive. Specific activities of amino acids in native cells labelled by 14C-octanoate were 1,300 DPM/nmol, 490 DPM/nmol, 200 DPM/nmol, and 110 DPM/nmol for glutamate, aspartate, glutamine, and serine, respectively. No radioactivity was detected in alanine. Similar specific activities were noted when 14C-butyrate was the precursor; however, there was at least 5-fold less if 14C-palmitate was the precursor. Pretreatment of cells with NGF decreased the specific activity of amino acids by 25-65%. Specific activities of amino acids synthesized from 14C-glucose decreased in the following order: glutamate, 1,640 DPM/nmol; aspartate, 1,210 DPM/nmol; alanine, 580 DPM/nmol; glutamine, 275 DPM/nmol; and serine, 80 DPM/nmol for native cells. NGF pretreatment decreased the specific activities of glutamate and glutamine, but not of the other 3 amino acids. The preferred precursor for glutamate synthesis in native PC12 cells was glucose followed by octanoate, butyrate and palmitate (16:6:3:1)

  18. The type II cGMP dependent protein kinase regulates GluA1 levels at the plasma membrane of developing cerebellar granule cells

    Science.gov (United States)

    Incontro, Salvatore; Ciruela, Francisco; Ziff, Edward; Hofmann, Franz; Sánchez-Prieto, José; Torres, Magdalena

    2014-01-01

    Trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is regulated by specific interactions with other proteins and by post-translational mechanisms, such as phosphorylation. We have found that the type II cGMP-dependent protein kinase (cGKII) phosphorylates GluA1 (formerly GluR1) at S845, augmenting the surface expression of AMPARs at both synaptic and extrasynaptic sites. Activation of cGKII by 8-Br-cGMP enhances the surface expression of GluA1, whereas its inhibition or suppression effectively diminished the expression of this protein at the cell surface. In granule cells, NMDA receptor activation (NMDAR) stimulates nitric oxide and cGMP production, which in turn activates cGKII and induces the phosphorylation of GluA1, promoting its accumulation in the plasma membrane. GluA1 is mainly incorporated into calcium permeable AMPARs as exposure to 8-Br-cGMP or NMDA activation enhanced AMPA-elicited calcium responses that are sensitive to NASPM inhibition. We summarize evidence for an increase of calcium permeable AMPA receptors downstream of NMDA receptor activation that might be relevant for granule cell development and plasticity. PMID:23545413

  19. Impaired Cerebellar Maturation, Growth Restriction, and Circulating Insulin-Like Growth Factor 1 in Preterm Rabbit Pups

    Science.gov (United States)

    Sveinsdóttir, Kristbjörg; Länsberg, John-Kalle; Sveinsdóttir, Snjólaug; Garwicz, Martin; Ohlsson, Lennart; Hellström, Ann; Smith, Lois; Gram, Magnus; Ley, David

    2018-01-01

    Cerebellar growth is impeded following very preterm birth in human infants and the observed reduction in cerebellar volume is associated with neurodevelopmental impairment. Decreased levels of circulating insulin-like growth factor 1 (IGF-1) are associated with decreased cerebellar volume. The relationship between preterm birth, circulating IGF-1, and key cell populations supporting cerebellar proliferation is unknown. The aim of this study was to evaluate the effect of preterm birth on postnatal growth, circulating IGF-1, and cerebellar maturation in a preterm rabbit pup model. Preterm rabbit pups (PT) were delivered by cesarean section at day 29 of gestation, cared for in closed incubators with humidified air, and gavage fed with formula. Control term pups (T) delivered by spontaneous vaginal delivery at day 32 of gestation were housed and fed by their lactating doe. In vivo perfusion-fixation for immunohistochemical evaluation of cerebellar proliferation, cell maturation, and apoptosis was performed at repeated time points in PT and T pups. Results show that the mean weight of the pups and circulating IGF-1 protein levels were lower in the PT group at all time points (p staining at P0 (p = 0.003), P2 (p = 0.004), and P5 (p = 0.04) in the PT group compared to in the T group. Staining for sonic hedgehog was positive in neuronal EGL progenitors and Purkinje cells at early time points but was restricted to a well-defined Purkinje cell monolayer at later time points. Preterm birth in rabbit pups is associated with lower circulating levels of IGF-1, decreased postnatal growth, and decreased cerebellar EGL proliferation and Purkinje cell maturation. The preterm rabbit pup model exhibits important characteristics of human preterm birth, and may thus be suitable for the evaluation of interventions aiming to modify growth and cerebellar development in the preterm population. PMID:28972955

  20. Characterization of depolarization-coupled release of glutamate from cultured mouse cerebellar granule cells using DL-threo-beta-benzyloxyaspartate (DL-TBOA) to distinguish between the vesicular and cytoplasmic pools

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

    2003-01-01

    Release of preloaded [3H]D-aspartate in response to depolarization induced by N-methyl-D-aspartate (NMDA) or the endogenous agonist glutamate was characterized using cultured glutamatergic cerebellar granule neurons. Release from the vesicular and the cytoplasmic glutamate pools, respectively, wa...

  1. Transgenic inhibition of astroglial NF-κB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis

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    Brambilla Roberta

    2012-09-01

    Full Text Available Abstract Background Optic neuritis is an acute, demyelinating neuropathy of the optic nerve often representing the first appreciable symptom of multiple sclerosis. Wallerian degeneration of irreversibly damaged optic nerve axons leads to death of retinal ganglion cells, which is the cause of permanent visual impairment. Although the specific mechanisms responsible for triggering these events are unknown, it has been suggested that a key pathological factor is the activation of immune-inflammatory processes secondary to leukocyte infiltration. However, to date, there is no conclusive evidence to support such a causal role for infiltrating peripheral immune cells in the etiopathology of optic neuritis. Methods To dissect the contribution of the peripheral immune-inflammatory response versus the CNS-specific inflammatory response in the development of optic neuritis, we analyzed optic nerve and retinal ganglion cells pathology in wild-type and GFAP-IκBα-dn transgenic mice, where NF-κB is selectively inactivated in astrocytes, following induction of EAE. Results We found that, in wild-type mice, axonal demyelination in the optic nerve occurred as early as 8 days post induction of EAE, prior to the earliest signs of leukocyte infiltration (20 days post induction. On the contrary, GFAP-IκBα-dn mice were significantly protected and showed a nearly complete prevention of axonal demyelination, as well as a drastic attenuation in retinal ganglion cell death. This correlated with a decrease in the expression of pro-inflammatory cytokines, chemokines, adhesion molecules, as well as a prevention of NAD(PH oxidase subunit upregulation. Conclusions Our results provide evidence that astrocytes, not infiltrating immune cells, play a key role in the development of optic neuritis and that astrocyte-mediated neurotoxicity is dependent on activation of a transcriptional program regulated by NF-κB. Hence, interventions targeting the NF-κB transcription

  2. Changes in the cerebellar and cerebro-cerebellar circuit in type 2 diabetes.

    Science.gov (United States)

    Fang, Peng; An, Jie; Tan, Xin; Zeng, Ling-Li; Shen, Hui; Qiu, Shijun; Hu, Dewen

    2017-04-01

    Currently, 422 million adults suffer from diabetes worldwide, leading to tremendous disabilities and a great burden to families and society. Functional and structural MRIs have demonstrated that patients with type 2 diabetes mellitus (T2DM) exhibit abnormalities in brain regions in the cerebral cortex. However, the changes of cerebellar anatomical connections in diabetic patients remains unclear. In the current study, diffusion tensor imaging deterministic tractography and statistical analysis were employed to investigate abnormal cerebellar anatomical connections in diabetic patients. This is the first study to investigate the altered cerebellar anatomical connectivity in T2DM patients. Decreased anatomical connections were found in the cerebellar and cerebro-cerebellar circuits of T2DM patients, providing valuable new insights into the potential neuro-pathophysiology of diabetes-related motor and cognitive deficits. Copyright © 2017. Published by Elsevier Inc.

  3. Bilateral Cerebellar Cortical Dysplasia without Other Malformations: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jung Seok; Ahn Kook Jin; Kim, Jee Young; Lee, Sun Jin; Park, Jeong Mi [Catholic University Yeouido St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of)

    2010-06-15

    Recent advances in MRI have revealed congenital brain malformations and subtle developmental abnormalities of the cerebral and cerebellar cortical architecture. Typical cerebellar cortical dysplasia as a newly categorized cerebellar malformation, has been seen in patients with Fukuyama congenital muscular dystrophy. Cerebellar cortical dysplasia occurs at the embryonic stage and is often observed in healthy newborns. It is also incidentally and initially detected in adults without symptoms. To the best of our knowledge, cerebellar dysplasia without any related disorders is very rare. We describe the MRI findings in one patient with disorganized foliation of both cerebellar hemispheres without a related disorder or syndrome

  4. Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia.

    Science.gov (United States)

    Main, Stacey L; Kulesza, Randy J

    2017-01-06

    Autism spectrum disorder (ASD) is a developmental brain disorder characterized by restricted and repetitive patterns of behavior, social and communication defects, and is commonly associated with difficulties with motor coordination. The etiology of ASD, while mostly idiopathic, has been linked to hereditary factors and teratogens, such as valproic acid (VPA). VPA is used clinically to treat epilepsy, mood disorders, and in the prevention of migraines. The use of VPA during pregnancy significantly increases the risk of ASD in the offspring. Neuropathological studies show decreased cerebellar function in patients with ASD, resulting in gait, balance and coordination impairments. Herein, we have exposed pregnant rats to a repeated oral dose of VPA on embryonic days 10 and 12 and performed a detailed investigation of the structure and function of the cerebellar vermis. We found that throughout all ten lobules of the cerebellar vermis, Purkinje cells were significantly smaller and expression of the calcium binding protein calbindin (CB) was significantly reduced. We also found that dendritic arbors of Purkinje cells were shorter and less complex. Additionally, animals exposed to a repeated dose of VPA performed significantly worse in a number of motor tasks, including beam walking and the rotarod. These results suggest that repeated embryonic exposure to VPA induces significant cerebellar dysfunction and is an effective animal model to study the cerebellar alterations in ASD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. First report of cerebellar abiotrophy in an Arabian foal from Argentina

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    S.A. Sadaba

    2016-12-01

    Full Text Available Evidence of cerebellar abiotrophy (CA was found in a six-month-old Arabian filly with signs of incoordination, head tremor, wobbling, loss of balance and falling over, consistent with a cerebellar lesion. Normal hematology profile blood test and cerebrospinal fluid analysis excluded infectious encephalitis, and serological testing for Sarcocystis neurona was negative. The filly was euthanized. Postmortem X-ray radiography of the cervical cephalic region identified not abnormalities, discounting spinal trauma. The histopathological analysis of serial transverse cerebellar sections by electron microscopy revealed morphological characteristics of apoptotic cells with pyknotic nuclei and degenerate mitochondria, cytoplasmic condensation and areas with absence of Purkinje cells, matching with CA histopathological characteristics. The indirect DNA test for CA was positive in the filly, and DNA test confirmed the CA carrier state in the parents and the recessive inheritance of the disease. To our knowledge this is the first report of a CA case in Argentina.

  6. Formation and function of synapses with respect to Schwann cells at the end of motor nerve terminal branches on mature amphibian (Bufo marinus) muscle.

    Science.gov (United States)

    Macleod, G T; Dickens, P A; Bennett, M R

    2001-04-01

    A study has been made of the formation and regression of synapses with respect to Schwann cells at the ends of motor nerve terminal branches in mature toad (Bufo marinus) muscle. Synapse formation and regression, as inferred from the appearance and loss of N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide (FM1-43)-stained vesicle clusters, occurred at the ends of terminal branches over a 16 hr period. Multiple microelectrodes placed in an array about FM1-43 blobs at the ends of terminal branches detected the electrical signs of neurotransmitter being released onto receptors. Injection of a calcium indicator (Oregon Green 488 BAPTA-1) into the motor nerve with subsequent imaging of the calcium transients, in response to stimulation, often showed a reduced calcium influx in the ends of terminal branches. Injection of a fluorescent dye into motor nerves revealed the full extent of their terminal branches and growing processes. Injection of the terminal Schwann cells (TSCs) often revealed pseudopodial TSC processes up to 10-microm-long. Imaging of these TSC processes over minutes or hours showed that they were highly labile and capable of extending several micrometers in a few minutes. Injection of motor nerve terminals with a different dye to that injected into their TSCs revealed that terminal processes sometimes followed the TSC processes over a few hours. It is suggested that the ends of motor nerve terminals in vivo are in a constant state of remodeling through the formation and regression of processes, that TSC processes guide the remodeling, and that it can occur over a relatively short period of time.

  7. [Effects of the maca extract on the ultrastructures of mitochondria in the spinal nerve cell and exercise endurance].

    Science.gov (United States)

    Yu, Fa-Rong; Yang, Bo; Li, Zuo-Ping; Lian, Xiu-Zhen; Xie, Ming-Ren; Li, Deng-Lou; Zhang, Shi-Shuang

    2017-06-08

    To investigate the effects of maca extract on the ultrastructures of mitochondria in the spinal nerve cell and exercise endurance. The Wistar rats were randomly divided into 5 groups, including the control group (no swimming), the swimming group (free swimming), and 3 treatment groups treated with the maca extract at the doses of 4.0, 5.3 and 8.0 g/kg body weight. The animals in swimming and treatment groups were then for free swimming in the circulating water flow daily for 15 days. On the 16 th day after swimming endurance, the spinal and muscular tissues were collected from all groups. The mitochondrial ultrastructures of the neurons of the spinal cells were observed with the projection electron microscope, and the levels of the glycogen, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and Ca 2+ in muscle tissues were determined by the RIA method. When rats were treated with maca extract (at 4.0, 5.3, 8.0 g/kg body weight), the total swimming time and the swimming duration before sinking were increased by 19.83%, 60.28%, 77.55%, and 55.34%, 73.91%, 94.47%, respectively, compared with the simple swimming group( P maca extract (4.0, 5.3, 8.0 g/kg body weight) were reduced by 7.79%, 18.18%, 31.17%, 16.95%, 27.34%, 43.31% and 13.51%, 23.19%, 43.15%, respectively. Our results demonstrated the protective effects of maca extract on the mitochondria of spinal cell and suggested that maca extract could improve the muscle antioxidant activity by increasing the levels of SOD, GSH-Px, and muscle glycogen.

  8. Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury.

    Science.gov (United States)

    Lin, Tao; Qiu, Shuai; Yan, Liwei; Zhu, Shuang; Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin

    2018-05-01

    Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018. © 2017 Wiley Periodicals, Inc.

  9. Talpid3-binding centrosomal protein Cep120 is required for centriole duplication and proliferation of cerebellar granule neuron progenitors.

    Directory of Open Access Journals (Sweden)

    Chuanqing Wu

    Full Text Available Granule neuron progenitors (GNPs are the most abundant neuronal type in the cerebellum. GNP proliferation and thus cerebellar development require Sonic hedgehog (Shh secreted from Purkinje cells. Shh signaling occurs in primary cilia originating from the mother centriole. Centrioles replicate only once during a typical cell cycle and are responsible for mitotic spindle assembly and organization. Recent studies have linked cilia function to cerebellar morphogenesis, but the role of centriole duplication in cerebellar development is not known. Here we show that centrosomal protein Cep120 is asymmetrically localized to the daughter centriole through its interaction with Talpid3 (Ta3, another centrosomal protein. Cep120 null mutant mice die in early gestation with abnormal heart looping. Inactivation of Cep120 in the central nervous system leads to both hydrocephalus, due to the loss of cilia on ependymal cells, and severe cerebellar hypoplasia, due to the failed proliferation of GNPs. The mutant GNPs lack Hedgehog pathway activity. Cell biological studies show that the loss of Cep120 results in failed centriole duplication and consequently ciliogenesis, which together underlie Cep120 mutant cerebellar hypoplasia. Thus, our study for the first time links a centrosomal protein necessary for centriole duplication to cerebellar morphogenesis.

  10. Short-term low-frequency electrical stimulation enhanced remyelination of injured peripheral nerves by inducing the promyelination effect of brain-derived neurotrophic factor on Schwann cell polarization.

    Science.gov (United States)

    Wan, Lidan; Xia, Rong; Ding, Wenlong

    2010-09-01

    Electrical stimulation (ES) has been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. However, the effect of ES on peripheral remyelination after nerve damage has been investigated less well, and the mechanism underlying its action remains unclear. In the present study, the crush-injured sciatic nerves in rats were subjected to 1 hr of continuous ES (20 Hz, 100 microsec, 3 V). Electron microscopy and nerve morphometry were performed to investigate the extent of regenerated nerve myelination. The expression profiles of P0, Par-3, and brain-derived neurotrophic factor (BDNF) in the injuried sciatic nerves and in the dorsal root ganglion neuron/Schwann cell cocultures were examined by Western blotting. Par-3 localization in the sciatic nerves was determined by immunohistochemistry to demonstrate Schwann cell polarization during myelination. We reported that 20-Hz ES increased the number of myelinated fibers and the thickness myelin sheath at 4 and 8 weeks postinjury. P0 level in the ES-treated groups, both in vitro and in vivo, was enhanced compared with the controls. The earlier peak of Par-3 in the ES-treated groups indicated an earlier initiation of Schwann cell myelination. Additionally, ES significantly elevated BDNF expression in nerve tissues and in cocultures. ES on the site of nerve injury potentiates axonal regrowth and myelin maturation during peripheral nerve regeneration. Furthermore, the therapeutic actions of ES on myelination are mediated via enhanced BDNF signals, which drive the promyelination effect on Schwann cells at the onset of myelination.

  11. Delayed peripheral nerve repair: methods, including surgical 'cross-bridging' to promote nerve regeneration.

    Science.gov (United States)

    Gordon, Tessa; Eva, Placheta; Borschel, Gregory H

    2015-10-01

    Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts (cross-bridges) into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to 'protect' chronically denervated Schwann cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries.

  12. Delayed peripheral nerve repair: methods, including surgical ′cross-bridging′ to promote nerve regeneration

    Directory of Open Access Journals (Sweden)

    Tessa Gordon

    2015-01-01

    Full Text Available Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts (cross-bridges into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to ′protect′ chronically denervated Schwann cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries.

  13. Atrial granular cells of the snail Achatina fulica release proteins into hemolymph after stimulation of the heart nerve.

    Science.gov (United States)

    Shabelnikov, Sergej V; Bystrova, Olga A; Ivanov, Vadim A; Margulis, Boris A; Martynova, Marina

    2009-10-01

    The atrium of the gastropod mollusc Achatina fulica receives rich innervation and contains numerous granular cells (GCs). We studied the atrial innervation and discovered that axon profiles typical in appearance of peptidergic neurons form close unspecialized membrane contacts with GCs. Then, we investigated, at both morphological and biochemical levels, the effect of electrical stimulation of the heart nerve on GCs of Achatina heart perfused in situ. The ultrastructural study demonstrated changes in granule morphology consistent with secretion. These events included alteration of granule content, intracellular granule fusion and formation of complex degranulation channels, within which the granule matrix solubilized. It was shown that electrical stimulation resulted in a significant increase of the total protein concentration in the perfusate. Furthermore, SDS-PAGE analysis of the perfusate revealed three new proteins with molecular masses of 16, 22, and 57 kDa. Affinity-purified polyclonal antibodies against the 16 kDa protein were obtained; the whole-mount immunofluorescence technique revealed the presence of this protein in the granules of atrial GCs. In GCs of the stimulated atrium, a progressive loss of their granular content was observed. The results suggest that the central nervous system can modulate the secretory activity of the atrial GCs through non-synaptic pathways.

  14. Expressed sequence tag analysis of adult human optic nerve for NEIBank: Identification of cell type and tissue markers

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    Peterson Katherine

    2009-09-01

    Full Text Available Abstract Background The optic nerve is a pure white matter central nervous system (CNS tract with an isolated blood supply, and is widely used in physiological studies of white matter response to various insults. We examined the gene expression profile of human optic nerve (ON and, through the NEIBANK online resource, to provide a resource of sequenced verified cDNA clones. An un-normalized cDNA library was constructed from pooled human ON tissues and was used in expressed sequence tag (EST analysis. Location of an abundant oligodendrocyte marker was examined by immunofluorescence. Quantitative real time polymerase chain reaction (qRT-PCR and Western analysis were used to compare levels of expression for key calcium channel protein genes and protein product in primate and rodent ON. Results Our analyses revealed a profile similar in many respects to other white matter related tissues, but significantly different from previously available ON cDNA libraries. The previous libraries were found to include specific markers for other eye tissues, suggesting contamination. Immune/inflammatory markers were abundant in the new ON library. The oligodendrocyte marker QKI was abundant at the EST level. Immunofluorescence revealed that this protein is a useful oligodendrocyte cell-type marker in rodent and primate ONs. L-type calcium channel EST abundance was found to be particularly low. A qRT-PCR-based comparative mammalian species analysis reveals that L-type calcium channel expression levels are significantly lower in primate than in rodent ON, which may help account for the class-specific difference in responsiveness to calcium channel blocking agents. Several known eye disease genes are abundantly expressed in ON. Many genes associated with normal axonal function, mRNAs associated with axonal transport, inflammation and neuroprotection are observed. Conclusion We conclude that the new cDNA library is a faithful representation of human ON and EST data

  15. Experimental study on lyophilized irradiation sterilized nerve allografts in rabbits

    International Nuclear Information System (INIS)

    Yang Zhiyuan; Sun Shiquan; Liu Hechen

    1991-01-01

    Lyophilized irradiation sterilized nerve grafts in rabbits were used in allogeneic nerve transplantation. The result show that about 76% of experimental rabbits had fairly well morphologic (microscopic and electron microscopic) and electrophysiological recovery 3 month after operation. Preservation of neurilemmal tubes in nerve grafts, repopulation of Schwann cells in this tube and suppression of immune rejection are the key points in allogeneic nerve transplantation

  16. Metabolic anatomy of paraneoplastic cerebellar degeneration

    International Nuclear Information System (INIS)

    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-01-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration [PCD]) were evaluated using neuropsychological tests and 18 F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and atax