RESUMEN
STUDY DESIGN: Adult human olfactory bulb neural stem cells (OBNSCs) were isolated from human patients undergoing craniotomy for tumor resection. They were genetically engineered to overexpresses green fluorescent protein (GFP) to help trace them following engraftment. Spinal cord injury (SCI) was induced in rats using standard laminectomy protocol, and GFP-OBNSC were engrafted into rat model of SCI at day 7 post injury. Three rat groups were used: (i) Control group, (ii) Sham group (injected with cerebrospinal fluid) and treated group (engrafted with OBNSCs). Tissues from different groups were collected weekly up to 2 months. The collected tissues were fixed in 4% paraformaldehyde, processed for paraffin sectioning, immunohistochemically stained for different neuronal and glial markers and examined with bright-field fluorescent microscopy. Restoration of sensory motor functions we assessed on a weekly bases using the BBB score. OBJECTIVES: To assess the therapeutic potential of OBNSCs-GFP and their ability to survive, proliferate, differentiate and to restore lost sensory motor functions following their engraftment in spinal cord injury (SCI). METHODS: GFP-OBNSC were engrafted into a rat model of SCI at day 7 post injury and were followed-up to 8 weeks using behavioral and histochemical methods. RESULTS: All transplanted animals exhibited successful engraftment. The survival rate was about 30% of initially transplanted cells. Twenty-seven percent of the engrafted cells differentiated along the NG2 and O4-positive oligodendrocyte lineage, 16% into MAP2 and ß-tubulin-positive neurons, and 56% into GFAP-positive astrocytes. CONCLUSION: GFP-OBNSCs had survived for >8 weeks after engraftment and were differentiated into neurons, astrocytes and oligodendrocytes, The engrafted cells were distributed throughout gray and white matter of the cord with no evidence of abnormal morphology or any mass formation indicative of tumorigenesis. However, the engrafted cells failed to restore lost sensory and motor functions as evident from behavioral analysis using the BBB score test.
Asunto(s)
Células-Madre Neurales/fisiología , Células-Madre Neurales/trasplante , Bulbo Olfatorio/citología , Traumatismos de la Médula Espinal/cirugía , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Humanos , Locomoción/fisiología , Proteínas del Tejido Nervioso/metabolismo , Desempeño Psicomotor , Ratas , Ratas Wistar , Factores de Tiempo , TransfecciónRESUMEN
Glioblastoma multiforme is a severe form of cancer most likely arising from the transformation of stem or progenitor cells resident in the brain. Although the tumorigenic population in glioblastoma is defined as composed by cancer stem cells (CSCs), the cellular target of the transformation hit remains to be identified. Glioma stem cells (SCs) are thought to have a differentiation potential restricted to the neural lineage. However, using orthotopic versus heterotopic xenograft models and in vitro differentiation assays, we found that a subset of glioblastomas contained CSCs with both neural and mesenchymal potential. Subcutaneous injection of CSCs or single CSC clones from two of seven patients produced tumor xenografts containing osteo-chondrogenic areas in the context of glioblastoma-like tumor lesions. Moreover, CSC clones from four of seven cases generated both neural and chondrogenic cells in vitro. Interestingly, mesenchymal differentiation of the tumor xenografts was associated with reduction of both growth rate and mitotic index. These findings suggest that in a subclass of glioblastomas the tumorigenic hit occurs on a multipotent stem cell, which may reveal its plasticity under specific environmental stimuli. The discovery of such biological properties might provide considerable information to the development of new therapeutic strategies aimed at forcing glioblastoma stem cell differentiation.
Asunto(s)
Neoplasias Encefálicas/patología , Glioblastoma/patología , Mesodermo/citología , Células Madre Neoplásicas/citología , Adulto , Anciano , Animales , Diferenciación Celular , Células Clonales , Femenino , Humanos , Masculino , Ratones , Ratones SCID , Persona de Mediana Edad , Células Madre Neoplásicas/química , Células Madre Neoplásicas/patología , Neuronas/citología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Glioblastoma is the most aggressive and most lethal primary brain tumor in the adulthood. Current standard therapies are not curative and novel therapeutic options are urgently required. Present knowledge suggests that the continued glioblastoma growth and recurrence is determined by glioblastoma stem-like cells (GSCs), which display self-renewal, tumorigenic potential, and increased radio- and chemo-resistance. The G-quadruplex ligand RHPS4 displays in vitro radiosensitizing effect in GBM radioresistant cells through the targeting and dysfunctionalization of telomeres but RHPS4 and Ionizing Radiation (IR) combined treatment efficacy in vivo has not been explored so far. METHODS: RHPS4 and IR combined effects were tested in vivo in a heterotopic mice xenograft model and in vitro in stem-like cells derived from U251MG and from four GBM patients. Cell growth assays, cytogenetic analysis, immunoblotting, gene expression and cytofluorimetric analysis were performed in order to characterize the response of differentiated and stem-like cells to RHPS4 and IR in single and combined treatments. RESULTS: RHPS4 administration and IR exposure is very effective in blocking tumor growth in vivo up to 65 days. The tumor volume reduction and the long-term tumor control suggested the targeting of the stem cell compartment. Interestingly, RHPS4 treatment was able to strongly reduce cell proliferation in GSCs but, unexpectedly, did not synergize with IR. Lack of radiosensitization was supported by the GSCs telomeric-resistance observed as the total absence of telomere-involving chromosomal aberrations. Remarkably, RHPS4 treatment determined a strong reduction of CHK1 and RAD51 proteins and transcript levels suggesting that the inhibition of GSCs growth is determined by the impairment of the replication stress (RS) response and DNA repair. CONCLUSIONS: We propose that the potent antiproliferative effect of RHPS4 in GSCs is not determined by telomeric dysfunction but is achieved by the induction of RS and by the concomitant depletion of CHK1 and RAD51, leading to DNA damage and cell death. These data open to novel therapeutic options for the targeting of GSCs, indicating that the combined inhibition of cell-cycle checkpoints and DNA repair proteins provides the most effective means to overcome resistance of GSC to genotoxic insults.
Asunto(s)
Acridinas/administración & dosificación , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Células Madre Neoplásicas/efectos de los fármacos , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Acridinas/farmacología , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/genética , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Ratones , Recombinasa Rad51/genética , Recombinasa Rad51/metabolismo , Fármacos Sensibilizantes a Radiaciones/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Targeted-therapies enhancing differentiation of glioma-initiating cells (GICs) are potential innovative approaches to the treatment of malignant gliomas. These cells support tumour growth and recurrence and are resistant to radiotherapy and chemotherapy. We have found that GICs express mGlu3 metabotropic glutamate receptors. Activation of these receptors sustained the undifferentiated state of GICs in culture by negatively modulating the action of bone morphogenetic proteins, which physiologically signal through the phosphorylation of the transcription factors, Smads. The cross-talk between mGlu3 receptors and BMP receptors was mediated by the activation of the mitogen-activated protein kinase pathway. Remarkably, pharmacological blockade of mGlu3 receptors stimulated the differentiation of cultured GICs into astrocytes, an effect that appeared to be long lasting, independent of the growth conditions, and irreversible. In in vivo experiments, a 3-month treatment with the brain-permeant mGlu receptor antagonist, LY341495 limited the growth of infiltrating brain tumours originating from GICs implanted into the brain parenchyma of nude mice. While clusters of tumour cells were consistently found in the brain of control mice, they were virtually absent in a large proportion of mice treated with LY341495. These findings pave the way to a new non-cytotoxic treatment of malignant gliomas based on the use of mGlu3 receptor antagonists.
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Receptores de Proteínas Morfogenéticas Óseas/metabolismo , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Receptores de Glutamato Metabotrópico/fisiología , Transducción de Señal/fisiología , Aminoácidos/farmacología , Animales , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/fisiopatología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Agonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Glioma/tratamiento farmacológico , Glioma/patología , Glioma/fisiopatología , Humanos , Imagen por Resonancia Magnética , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Fosforilación/efectos de los fármacos , Receptores de Glutamato Metabotrópico/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Xantenos/farmacologíaRESUMEN
Primary melanoma of the central nervous system (CNS) is rare and primary spinal melanoma (PSM) is even more unusual. Preoperative diagnosis of melanocytic lesion as a PSM is difficult, because of the heterogeneous magnetic resonance (MR) signal intensity, due to hemorrhagic foci and melanin deposits. We describe the case of a 68 year-old male with a MR showing at Th8-Th9 level a well-defined intramedullary lesion; for the characteristics of hemorrhagic signal on MR and its association with a presumptive brain cavernoma, a preoperative diagnosis of intramedullary cavernous angioma was suspected. Pathological examination revealed a melanoma, and for the absence of other localizations outside the spinal cord, a diagnosis of primary spinal melanoma was established. The growth of PSM is slower and survival is longer than in the most common spinal metastasis from skin melanoma. Patients who undergo surgical excision, alone or associated with additional treatments, often show a long survival. We report this case to underline the importance and difficulties concerning the preoperative diagnosis of a hemorrhagic intramedullary lesion.
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Melanoma/patología , Melanoma/cirugía , Médula Espinal/patología , Médula Espinal/cirugía , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/cirugía , Anciano , Neoplasias Encefálicas/patología , Diagnóstico Diferencial , Progresión de la Enfermedad , Lóbulo Frontal/patología , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Hemorragia/etiología , Hemorragia/patología , Hemorragia/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Melanoma/fisiopatología , Procedimientos Neuroquirúrgicos , Paraparesia/etiología , Paraparesia/patología , Paraparesia/fisiopatología , Cuidados Preoperatorios , Médula Espinal/fisiopatología , Neoplasias de la Columna Vertebral/fisiopatología , Vértebras Torácicas , Resultado del TratamientoRESUMEN
157Gd is a potential agent for neutron capture cancer therapy (GdNCT). We directly observed the microdistribution of Gd in cultured human glioblastoma cells exposed to Gd-diethylenetriaminepentaacetic acid (Gd-DTPA). We demonstrated, with three independent techniques, that Gd-DTPA penetrates the plasma membrane, and we observed no deleterious effect on cell survival. A systematic microchemical analysis revealed a higher Gd accumulation in cell nuclei compared with cytoplasm. This is significant for prospective GdNCT because the proximity of Gd to DNA increases the cell-killing potential of the short-range, high-energy electrons emitted during the neutron capture reaction. We also exposed Gd-containing cells to thermal neutrons and demonstrated the GdNC reaction effectiveness in inducing cell death. These results in vitro stimulated in vivo Gd-DTPA uptake studies, currently underway, in human glioblastoma patients.
Asunto(s)
Gadolinio/farmacocinética , Gadolinio/uso terapéutico , Glioblastoma/metabolismo , Glioblastoma/radioterapia , Terapia por Captura de Neutrón , Muerte Celular/efectos de la radiación , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Gadolinio DTPA/farmacocinética , Gadolinio DTPA/toxicidad , Humanos , Isótopos , Espectrometría de Masas , Espectrometría por Rayos X , Células Tumorales CultivadasRESUMEN
Glioblastoma (GBM) is one of the deadliest human cancers. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies based on biologically and clinically relevant subclassification systems. Analyzing a collection of seventeen patient-derived glioblastoma stem-like cells (GSCs) by gene expression profiling, NMR spectroscopy and signal transduction pathway activation, we identified two GSC clusters, one characterized by a pro-neural-like phenotype and the other showing a mesenchymal-like phenotype. Evaluating the levels of proteins differentially expressed by the two GSC clusters in the TCGA GBM sample collection, we found that SRC activation is associated with a GBM subgroup showing better prognosis whereas activation of RPS6, an effector of mTOR pathway, identifies a subgroup with a worse prognosis. The two clusters are also differentiated by NMR spectroscopy profiles suggesting a potential prognostic stratification based on metabolic evaluation. Our data show that the metabolic/proteomic profile of GSCs is informative of the genomic/proteomic GBM landscape, which differs among tumor subtypes and is associated with clinical outcome.
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Regulación Neoplásica de la Expresión Génica , Glioblastoma/metabolismo , Glioblastoma/mortalidad , Proteínas de Neoplasias/biosíntesis , Células Madre Neoplásicas/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Resonancia Magnética Nuclear Biomolecular , Proteómica , Tasa de SupervivenciaRESUMEN
Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour, with very poor prognosis. The high recurrence rate and failure of conventional treatments are expected to be related to the presence of radio-resistant cancer stem cells (CSCs) inside the tumour mass. CSCs can both self-renew and differentiate into the heterogeneous lineages of cancer cells. Recent evidence showed a higher effectiveness of C-ions and protons in inactivating CSCs, suggesting a potential advantage of Hadrontherapy compared with conventional radiotherapy for GBM treatment. To investigate the mechanisms involved in the molecular and cellular responses of CSCs to ionising radiations, two GBM stem cell (GSC) lines, named lines 1 and 83, which were derived from patients with different clinical outcomes and having different metabolic profiles (as shown by NMR spectroscopy), were irradiated with (137)Cs photons and with protons or C-ions of 62 MeV u(-1) in the dose range of 5-40 Gy. The biological effects investigated were: cell death, cell cycle progression, and DNA damage induction and repair. Preliminary results show a different response to ionising radiation between the two GSC lines for the different end points investigated. Further experiments are in progress to consolidate the data and to get more insights on the influence of radiation quality.
Asunto(s)
Neoplasias Encefálicas/radioterapia , Carbono/uso terapéutico , Radioisótopos de Cesio/uso terapéutico , Glioblastoma/radioterapia , Células Madre Neoplásicas/efectos de la radiación , Terapia de Protones , Radiación Ionizante , Apoptosis/efectos de la radiación , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Ciclo Celular/efectos de la radiación , Daño del ADN/efectos de la radiación , Glioblastoma/metabolismo , Glioblastoma/mortalidad , Glioblastoma/patología , Histonas/metabolismo , Humanos , Espectroscopía de Resonancia Magnética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Pronóstico , Radiobiología , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
The thiosulfate:cyanide sulfurtransferase (rhodanese) enzyme (EC 2.8.1.1.) was studied in human leukocytes from control subjects and from nine patients with Leber's hereditary optic atrophy. Enzyme activity was proportional to protein concentration in the tested range (0.09 to 0.39 mg) as well as to incubation time. The optimal pH for reaction was 8.7 and the apparent Km for thiosulfate was 7 X 10(-3) M. No significant difference of enzyme activity was present in Leber's disease.
Asunto(s)
Enfermedades Genéticas Congénitas/enzimología , Leucocitos/enzimología , Atrofia Óptica/enzimología , Sulfurtransferasas/metabolismo , Tiosulfato Azufretransferasa/metabolismo , Femenino , Humanos , MasculinoRESUMEN
AIM: To evaluate the diagnostic value of telomerase expression in intracranial tumours. METHODS: 98 surgical specimens from different neoplasms were analysed by the telomeric repeat amplification protocol (TRAP) and the presence of telomerase compared with the histological diagnosis and the proliferation index. RESULTS: A high degree of positivity for telomerase activity was found in glioblastomas and atypical/anaplastic meningiomas. Telomerase activity was poorly detected in anaplastic astrocytomas. CONCLUSIONS: The TRAP assay seems to be a valuable index for identifying meningeal tumours with aggressive behaviour.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/enzimología , Glioma/enzimología , Meningioma/enzimología , Telomerasa/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/patología , Niño , Diagnóstico Diferencial , Femenino , Técnicas Genéticas , Glioblastoma/enzimología , Glioblastoma/patología , Glioma/patología , Humanos , Masculino , Neoplasias Meníngeas/enzimología , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , PronósticoAsunto(s)
Axones/fisiología , Axones/ultraestructura , Regeneración Nerviosa , Neuroglía/trasplante , Traumatismos de la Médula Espinal/cirugía , Médula Espinal/fisiología , Animales , Trasplante de Tejido Encefálico , Trasplante de Células , Desnervación , Vaina de Mielina/fisiología , Neuroglía/fisiología , Bulbo Olfatorio/citología , Ratas , Células de Schwann/fisiología , Médula Espinal/citología , Traumatismos de la Médula Espinal/patologíaAsunto(s)
Colorantes Fluorescentes/metabolismo , Terapia Genética , Proteínas del Tejido Nervioso/genética , Fármacos Neuroprotectores , Enfermedad de Parkinson/terapia , Estilbamidinas , Sustancia Negra/patología , Animales , Dopamina/fisiología , Vectores Genéticos , Factor Neurotrófico Derivado de la Línea Celular Glial , Degeneración Nerviosa , Factores de Crecimiento Nervioso/genética , Neuronas/metabolismo , Neuronas/patología , Oxidopamina/farmacología , Enfermedad de Parkinson/patología , Ratas , Sustancia Negra/metabolismoRESUMEN
Because of the organization of visual and motor pathways, simple manual responses to a light stimulus in the right or left visual hemifields are performed faster with uncrossed hand-field combinations than with crossed hand-field combinations. Uncrossed responses can be integrated within a single hemisphere, whereas crossed responses require a time-consuming interhemispheric transfer via the corpus callosum which is reflected in the difference between crossed and uncrossed reaction times. We investigated crossed-uncrossed differences (CUDs) in speed of simple visuomotor responses to lateralized flashes in seven subjects with an anterior section of the corpus callosum sparing the splenium and in one subject with an agenetic absence of the splenium due to a cerebrovascular malformation. There was no evidence of an abnormal prolongation of the CUDs in any of these subjects, in sharp contrast with the very long CUDs exhibited by an epileptic subject with a complete callosal section and two subjects with total callosal agenesis tested in the same experimental situation [1]. The normality of the CUDs in the subjects with partial callosal defects was not due to a postoperatory reorganization of interhemispheric communication, since there was no indication of an increased CUD in a patient tested as early as 5 days after the anterior callosotomy. These results are compatible with the assumption that both anterior and posterior callosal routes may subserve the integration of speeded manual responses to a visual stimulus directed to the hemisphere ipsilateral to the responding hand.
Asunto(s)
Atención/fisiología , Cuerpo Calloso/fisiopatología , Dominancia Cerebral/fisiología , Lateralidad Funcional/fisiología , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología , Adulto , Agenesia del Cuerpo Calloso , Mapeo Encefálico , Cuerpo Calloso/cirugía , Epilepsia/fisiopatología , Epilepsia/cirugía , Femenino , Humanos , Malformaciones Arteriovenosas Intracraneales/fisiopatología , Malformaciones Arteriovenosas Intracraneales/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Valores de Referencia , Vías Visuales/fisiopatologíaRESUMEN
The effect of exogenous nerve growth factor (NGF) on axonal regeneration into autologous peripheral nerve (PN) grafts implanted to the spinal cord (SC) of rats was assessed by retrograde labeling of the parent soma of the regenerating axons with horseradish peroxidase. NGF was delivered at the graft site over periods of 15 and 30 days by using indwelling osmotic minipumps. In control rats, the minipumps were filled with saline. At 15 days after grafting in the NGF-treated rats, the mean number of SC as well as dorsal root ganglion (DRG) neurons that regenerated their axons into the peripheral nerve grafts was increased 55.3 and 26.4 times, respectively, as compared to the control group values. At 30 days, SC and DRG neurons in the NGF-treated group were 10.9 and 3.1 times greater than in the control group. In the NGF-treated group, the regenerating SC neurons were located within a range of 7 to 13 mm from the graft site as compared to 1 to 7 mm in the control group. Finally, the analysis of the soma diameters of the regenerating neurons showed that NGF enhanced and maintained with time the regenerative response from small-sized DRG neurons. Therefore, NGF is thought to promote directly the regenerative potential of SC as well as DRG neurons and to exert an indirect glial cell-mediated effect at the SC-graft interface.
Asunto(s)
Axones/efectos de los fármacos , Factores de Crecimiento Nervioso/farmacología , Regeneración Nerviosa/efectos de los fármacos , Nervio Ciático/trasplante , Médula Espinal/fisiología , Animales , Axones/fisiología , Axones/ultraestructura , Ganglios Espinales/fisiología , Ganglios Espinales/ultraestructura , Peroxidasa de Rábano Silvestre , Masculino , Factores de Crecimiento Nervioso/administración & dosificación , Ratas , Ratas Endogámicas , Nervio Ciático/efectos de los fármacos , Nervio Ciático/fisiología , Médula Espinal/ultraestructuraRESUMEN
The anatomic reorganization of the subnucleus that controls the stylohyoid muscle (the stylohyoid subnucleus) within the brain stem facial nucleus was studied after regeneration of the facial nerve in adult rats. Horseradish peroxidase was injected into the right stylohyoid muscle 3 to 21 months after transection and repair of the right facial nerve at the level of the stylomastoid foramen. Position, number, and soma diameter of retrogradely horseradish peroxidase-labeled motoneurons were established, as well as the rostro-caudal extension of the stylohyoid subnucleus. In experimental rats, the stylohyoid subnucleus showed either an ipsilateral (50% of the rats) or a bilateral representation. In all of the experimental rats, the motoneurons composing the stylohyoid subnucleus had a more dispersed horizontal distribution pattern when compared with controls. More than 80% of the motoneurons were located outside the borders of the normal stylohyoid subnucleus, either ventrally or, especially in the rostral sections, dorsally closer to the floor of the fourth ventricle. The mean rostro-caudal length of the stylohyoid subnucleus was 2028.6 +/- 152.7 microns. The mean motoneuron number was 481.4 +/- 109.5 (2.20-fold greater than control values), and the motoneuron diameter distribution ranged from 7 to 43 microns. This study demonstrates that after regeneration of the facial nerve in adult rats, major changes occur in both the location and number of motoneurons that make up the stylohyoid subnucleus.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Tronco Encefálico/fisiología , Músculos Faciales/inervación , Nervio Facial/fisiología , Neuronas Motoras/fisiología , Regeneración Nerviosa/fisiología , Factores de Edad , Animales , Mapeo Encefálico , Tronco Encefálico/anatomía & histología , Recuento de Células , División Celular/fisiología , Dominancia Cerebral/fisiología , Nervio Facial/anatomía & histología , Masculino , Microcirugia , Neuronas Motoras/ultraestructura , Plasticidad Neuronal/fisiología , Ratas , Ratas WistarRESUMEN
The spinal cord of adult female rats was completely transected at the T8 level. Nerve growth factor (NGF) was administered at the lesion site via indwelling, implanted, osmotic minipumps. Purified NGF was supplied at doses of 100, 200, and 500 micrograms during a 30-day period. Control rats were treated with saline. At the end of the treatment, the proximal stump of corticospinal tract axons in the spinal cord was labeled with anterograde transported horseradish peroxidase (HRP) injected into the sensorimotor cortex. In control rats, the corticospinal tract axons ended abruptly, proximal to the zone of maximal damage. Sterile swellings developed at the axon tips, and no labeled axonal sprouts were apparent. On the contrary, in NGF-treated animals, the leading front of the corticospinal tract axons showed a trend of approaching the zone of maximal damage following abnormal paths through the dorsal-injured white matter. Axonal sprouts were seen more proximally, traveling toward the transection site in aberrantly located dorsal paths, completely outside the normal position of the corticospinal tract. NGF seems to partly restore the pattern of the regenerative behavior of the severed corticospinal tract axons after spinal cord transection in newborn rats, i.e., the induction of axonal sprouting in aberrantly located dorsal paths. An automated image analysis of the HRP reaction field close to the transection site demonstrated that the density of HRP-labeled axons in the corticospinal tract was significantly higher in the NGF-treated rats than in the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Axones/efectos de los fármacos , Factores de Crecimiento Nervioso/farmacología , Regeneración Nerviosa/efectos de los fármacos , Tractos Piramidales/efectos de los fármacos , Traumatismos de la Médula Espinal/patología , Animales , Transporte Axonal/efectos de los fármacos , Transporte Axonal/fisiología , Axones/patología , Relación Dosis-Respuesta a Droga , Femenino , Peroxidasa de Rábano Silvestre , Bombas de Infusión Implantables , Inyecciones Epidurales , Regeneración Nerviosa/fisiología , Tractos Piramidales/patología , Ratas , Ratas Wistar , Corteza Somatosensorial/efectos de los fármacos , Corteza Somatosensorial/patologíaRESUMEN
It is well known that after reconstruction of sectioned peripheral nerves in adult mammals, denervated muscles are reinnervated by the axotomized motoneurons lying in the original motonucleus. It is less well known that these muscles can also be reinnervated by uninjured motoneurons lying in the homologous contralateral motonucleus. Therefore, after nerve reconstruction, bilateral motoneuron reinnervation of muscles can occur. Contralateral motoneurons sprout axons that cross the midline, grow in the reconstructed nerve, and reach muscle targets. This phenomenon was observed after reconstruction of several different peripheral nerves in adult mammals, including the oculomotor nerve in guinea pigs and the facial and sciatic nerves in rats. The retrograde axonal transport of horseradish peroxidase was used for the study of the organization of the brainstem and spinal cord motonuclei. Horseradish peroxidase was injected into the medial rectus muscle, the stylohyoid muscle, and the trunk of the sciatic nerve. The distance between the homologous motonuclei of both sides influenced the occurrence of this phenomenon. In fact, bilateral reinnervation of muscles after nerve reconstruction was found in 36% (sciatic nerve), 50% (facial nerve), and 100% (oculomotor nerve) of the operated animals. The total number of contralateral motoneurons found were 14% (oculomotor nerve), 8% (facial nerve), and 5% (sciatic nerve). Bilateral reinnervation of muscles was evoked by both immediate and delayed peripheral nerve repair and was a stable phenomenon, seen between 3 and 21 months after facial nerve reconstruction.
Asunto(s)
Nervio Facial/fisiología , Regeneración Nerviosa , Nervio Oculomotor/fisiología , Nervio Ciático/fisiología , Animales , Músculos Faciales/inervación , Traumatismos del Nervio Facial , Lateralidad Funcional , Cobayas , Masculino , Modelos Neurológicos , Músculos Oculomotores/inervación , Traumatismos del Nervio Oculomotor , Ratas , Ratas Endogámicas , Nervio Ciático/lesionesRESUMEN
A simple technique is described for protecting the cornea in patients with peripheral facial nerve palsy while waiting for recovery of nerve function. The application of an adhesive strip to the superior eyelid permits opening and closing of the eye, and provides good protection of the cornea.
Asunto(s)
Parálisis Facial/cirugía , Adhesivos , Enfermedades de la Córnea/prevención & control , Párpados , HumanosRESUMEN
The extent of the retrograde degeneration of corticospinal axons following transection of the spinal cord was studied in rats by labeling corticospinal axons with anterogradely transported horseradish peroxidase injected in the sensorimotor cortex. Axotomized corticospinal axons underwent progressive and continuing retrograde degeneration. In specimens examined 5, 14, 28, and 56 days after trauma, the tips of the transected corticospinal axons were seen to terminate at 181 +/- 80 microns, 977 +/- 203 microns, 1751 +/- 344 microns, and 2559 +/- 466 microns (mean +/- standard deviation), respectively, from the site of transection. The rate of retrograde degeneration varied according to the interval after spinal cord transection, as follows: 36.2 microns/day during the first 5 days; 88.4 microns/day between 5 and 14 days; 55.3 microns/day between 14 and 28 days; and 28.8 microns/day between 28 and 56 days. These findings may serve as useful parameters for the objective assessment of therapeutic modalities in spinal cord injury research.
Asunto(s)
Axones/patología , Degeneración Nerviosa , Tractos Piramidales/patología , Traumatismos de la Médula Espinal/patología , Animales , Axones/fisiología , Femenino , Peroxidasa de Rábano Silvestre , Ratas , Ratas Endogámicas , Traumatismos de la Médula Espinal/fisiopatología , Factores de TiempoRESUMEN
A patient with a long-recognized asymptomatic lipoma adjacent to the deep radial nerve developed paralysis of this nerve from a compression similar to the sleep palsy, or "Saturday-night palsy," mechanism.