Restorative Neurology and Neuroscience - Volume 30, issue 1

Authors: Moralí, Gabriela | Montes, Pedro | González-Burgos, Ignacio | Velázquez-Zamora, Dulce A. | Cervantes, Miguel

Article Type: Research Article

Abstract: Purpose: To analyze the cytoarchitectural characteristics of the remaining pyramidal neurons in the hippocampal CA1 subfield of rats, four months after global cerebral ischemia (GCI) and progesterone treatment. Methods: Dendritic arborization, and density and shape of the dendritic spines of CA1 pyramidal neurons in brains of intact rats, or rats submitted 120 days earlier to GCI and treatment with progesterone (8 mg/kg) or its vehicle, at 15 min, and 2, 6, 24, 48, and 72 h after the onset of reperfusion, were analyzed in samples processed by a modified Golgi method. Results: Few impregnated CA1 pyramidal neurons were identified in …the ischemic vehicle-treated rats, with a short apical dendrite devoid of bifurcations and dendritic spines. In contrast, the remaining CA1 pyramidal neurons sampled from ischemic progesterone-treated rats showed sinuously branched dendrites with similar number of bifurcations and whole density of spines, and higher proportional density of mushroom spines than those in the intact group. Conclusions: These cytoarchitectural characteristics may underlie the long-term preservation of place learning and memory functions seen after ischemia and progesterone neuroprotective treatment, possibly compensating for the severe reduction in neuronal population. Show more

Keywords: Progesterone neuroprotection, global cerebral ischemia, hippocampal pyramidal neurons cytoarchitecture, dendritic spines, rat

DOI: 10.3233/RNN-2011-0605

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 1, pp. 1-8, 2012

Authors: Wallenquist, U. | Holmqvist, K. | Hånell, A. | Marklund, N. | Hillered, L. | Forsberg-Nilsson, K.

Article Type: Research Article

Abstract: Purpose: There is hope for neural stem and progenitor cells (NSPC) to enhance regeneration when transplanted to the injured brain after traumatic brain injury (TBI). So far, the therapeutic effects of NSPC transplantation have been hampered mainly by the notable death of the transplanted cells. Neuroinflammation may lead to additional cell death after TBI and we hypothesized that survival of grafted NSPC could be enhanced by anti-inflammatory treatment. Methods: Mice that were subjected to controlled cortical impact TBI and grafted with NSPC, were treated with the non-steroidal anti-inflammatory drug ibuprofen. Results: Ibuprofen was found to down-regulate the TBI-induced inflammatory response. …In addition, migrating neuroblasts from transplanted cells were observed near the contusion and in the ipsilateral hippocampus in ibuprofen-treated animals only, suggesting that the anti-inflammatory treatment had beneficial effects on graft survival and/or differentiation. However, Morris Water Maze performance or TBI-induced tissue loss was not influenced by ibuprofen treatment. Conclusions: Our data suggests that anti-inflammatory strategies may be a complement to enhance the outcome for the cell transplants following TBI. Show more

Keywords: Neural stem cell, regeneration, transplantation, controlled cortical impact, eGFP

DOI: 10.3233/RNN-2011-0606

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 1, pp. 9-19, 2012

Authors: Wellejus, Anja | Elbrønd-Bek, Heidi | Kelly, Nicholas M. | Weidner, Morten S. | Jørgensen, Signe H.

Article Type: Research Article

Abstract: Purpose: Naturally occurring isothiocyanates (ITCs) are known to possess chemopreventive and neuroprotective properties. Our objective was to study the synthetic ITC 4-iodophenyl isothiocyanate (4-IPITC) in different models of neurodegeneration. Methods: In vitro, we exposed primary cortical neurons to various insults such as excessive glutamate exposure, oxygen-glucose deprivation, oxidative stress and 1-methyl-phenylpyridinium (MPP+ ). In vivo, experimental autoimmune encephalomyelitis (EAE) was induced in dark agouti rats treated with 4-IPITC in 3 different concentrations (10, 20 and 40 mg/kg), orally for 28 days. In a Parkinson's model, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected in mice pretreated with 4-IPITC (5 mg/kg, orally) for 1 week. …Nest building behavior at day 1, 3 and 6 after MPTP injection was assessed along with dopamine and metabolites, and tyrosine hydroxylase (TH) staining on termination day 6. Results: 4-IPITC successfully reduced cell death in all in vitro assays. Moreover, in two independent neurite outgrowth assays the compound showed neurotrophic properties. In the EAE study, 4-IPITC significantly delayed the day of onset and decreased the cumulative EAE score. Although the number of animals in this MPTP study was limited, 4-IPITC showed potential for dampening toxicity. Conclusions: Taken together, our in vitro findings suggest robust neuroprotective and neurotrophic properties of 4-IPITC, which was confirmed in two in vivo models of neurodegeneration. Show more

Keywords: 4-iodophenyl isothiocyanate, neuroprotection, EAE, excitotoxicity, reactive oxygen species, MPTP

DOI: 10.3233/RNN-2011-0617

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 1, pp. 21-38, 2012

Authors: Jungblut, Monika | Huber, Walter | Pustelniak, Monika | Schnitker, Ralph

Article Type: Research Article

Abstract: Purpose: Since rhythmical aspects of singing have been neglected up to now our objective was to investigate if it was possible to specify areas concerned with rhythm processing during simple singing. Methods: In an event-related fMRI experiment we tested 30 healthy non-musicians with rhythm sequences, which had to be repeated as monotonously sung vowel changes with (1) regular groupings, (2) regular groupings and rests, and (3) irregular groupings. Results: Common activations for all conditions were found in bilateral supplementary motor area, premotor cortex more distinct in the left hemisphere, left cingulate gyrus, and right basal ganglia. Only irregular groupings making …the highest demands on attention, working memory, and sequencing capabilities resulted in additional activation of pars orbitalis and insula more distinct in the left hemisphere, as well as bilateral cingulate gyrus, and parietal lobes. Our analyses demonstrated that bilateral pars orbitalis (BA 47), insula, and left cingulate gyrus are core areas whose activity correlates with rhythm complexity. Conclusions: Rhythm structure is a decisive factor concerning lateralization as well as activation of specific areas during simple singing. This finding suggests a directed use of the singing voice e.g., in order to support language rehabilitation in patients. Show more

Keywords: BA 47, fMRI, insula, cingulate gyrus, rhythm, singing

DOI: 10.3233/RNN-2011-0619

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 1, pp. 39-53, 2012

Authors: Bottai, Daniele | Cigognini, Daniela | Nicora, Emanuela | Moro, Monica | Grimoldi, Maria Grazia | Adami, Raffaella | Abrignani, Sergio | Marconi, Anna Maria | Di Giulio, Anna Maria | Gorio, Alfredo

Article Type: Research Article

Abstract: Purpose: Our aim was the search for new sources of cells potentially useful for central nervous system regenerative medicine. Extra-embryonic tissues are promising sources of pluripotent stem cells. Among these, human second-trimester amniotic fluid (AF) contains cell populations exhibiting self-renewal capacity, multipotency and the expression of embryonic cell markers. Methods: Here we report the properties of the easily available third-trimester AF cells (AFCs). Different cell types from 6 of 9 AF samples were separated, expanded, and characterized by assessing their morphological, proliferative, and differentiative properties. Results: All isolated cultures presented CD105, CD90 and CD73 mesenchymal markers, whereas they differed among …themselves in CD117, CD146, CD31, NG2 and CD133 expression. Their doubling time and telomere length were conserved throughout many passages. Importantly, immunofluorescence and Real-time PCR showed that, during their proliferative state and differentiation, several cultures expressed neuronal and glial markers such as nestin, GFAP, β-tubulin III and neurofilament H indicating their potential attitude towards a neural fate. Indeed, these cells showed a rather poor capacity to differentiate in adipogenic and osteogenic lineages. Conclusions: In this work we report that cells with neural differentiation capability can be isolated from third-trimester AF, such properties could be useful for neuro-regenerative purposes. Show more

Keywords: Amniotic fluid, third-trimester pregnancy, neuroregenerative medicine, neural markers

DOI: 10.3233/RNN-2011-0620

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 1, pp. 55-68, 2012

Authors: Moreno-Igoa, María | Calvo, Ana Cristina | Ciriza, Jesús | Muñoz, María Jesús | Zaragoza, Pilar | Osta, Rosario

Article Type: Research Article

Abstract: Purpose and background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease with no effective therapy. Glial-cell line derived neurotrophic factor (GDNF) has been translated to clinical trials for treatment of ALS and its selective delivery to the motoneurons could improve its therapeutic abilities. Methods: To test this idea, we genetically fused GDNF to the C-fragment of tetanus toxin (TTC), a peptide able to specifically deliver molecules to motoneurons. Results: Single intramuscular administration of naked-DNA encoding GDNF or GDNF-TTC significantly delayed the onset of symptoms and functional deficits into the SODG93A mouse model of ALS, prolonging their lifespan. Conclusions: …We have demonstrated a neuroprotective effect of GDNF-TTC as shown by the activation of survival pathways and inhibition of apoptotic proteins, such as Akt phosphorylation, or reduced caspase-3 activation respectively. However, the GDNF fusion with TTC did not improve the therapeutic effects when compared to GDNF alone. Show more

Keywords: Amyotrophic lateral sclerosis (ALS), Glial-cell line derived neurotrophic factor (GDNF), C-fragment tetanus toxin (TTC), neuronal apoptosis, SODG93A mouse model

DOI: 10.3233/RNN-2011-0621

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 1, pp. 69-80, 2012