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1.
Glia ; 66(7): 1267-1301, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29330870

RESUMO

The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating consequences of SCIs are due to the immediate and significant disruption of the ascending and descending spinal pathways, which result in varying degrees of motor and sensory impairment. Recent therapeutic studies for SCI have focused on cell transplantation in animal models, using cells capable of inducing axon regeneration like Schwann cells (SchCs), astrocytes, genetically modified fibroblasts and olfactory ensheathing glia cells (OECs). Nevertheless, and despite the improvements in such cell-based therapeutic strategies, there is still little information regarding the mechanisms underlying the success of transplantation and regarding any secondary effects. Therefore, further studies are needed to clarify these issues. In this review, we highlight the properties of OECs that make them suitable to achieve neuroplasticity/neuroregeneration in SCI. OECs can interact with the glial scar, stimulate angiogenesis, axon outgrowth and remyelination, improving functional outcomes following lesion. Furthermore, we present evidence of the utility of cell therapy with OECs to treat SCI, both from animal models and clinical studies performed on SCI patients, providing promising results for future treatments.


Assuntos
Transplante de Células , Neuroglia/transplante , Traumatismos da Medula Espinal/terapia , Animais , Humanos , Neuroglia/citologia , Bulbo Olfatório/citologia , Mucosa Olfatória/citologia
2.
Curr Pharm Des ; 24(1): 4-14, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28820078

RESUMO

Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation. Processes induced by NMDA antagonist drugs involve translocation of Bax protein to mitochondrial membranes, allowing extra-mitochondrial leakage of cytochrome C, followed by sequence of changes that ending in activation of CASP-3. The literature demonstrates that the use of these anesthetics in excitotoxic surgery increases neuroinflammation activity facilitating the effects of apoptosis and necrosis on nervous system cells, depending on the concentration and exposure duration of the anesthetic. High numbers of microglia and astrocytes and high levels of proinflammatory cytokines and caspase activation possibly mediate these inflammatory responses. However, it is necessary to continue studies in rodents to understand the effect of the use of inhaled anesthetics with excitotoxic lesions in different developmental stages, including newborns, juveniles and adults. Understanding the mechanisms of regulation of cell death during development can potentially provide tools to promote neuroprotection and eventually achieve the repair of the nervous system in pathological conditions.


Assuntos
Anestésicos Inalatórios/toxicidade , Sistema Nervoso/efeitos dos fármacos , Neurotoxinas/toxicidade , Anestésicos Inalatórios/administração & dosagem , Animais , Sistema Nervoso/patologia , Neurotoxinas/administração & dosagem , Roedores
3.
Cent Nerv Syst Agents Med Chem ; 18(1): 49-57, 2018 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-26285903

RESUMO

BACKGROUND: A complete neurological exam contributes in establishing spinal cord injury severity and its extent by identifying the damage to the sensory and motor pathways involved in order to address a more case-specific and precise pharmacological therapy. However, assessment of neurologic function in spinal cord injury models is usually reported by using sensory or motor tests independently. METHODS: A reliable integral method is needed to precisely evaluate location and severity of the injury at baseline and, in further assessments, to establish the degree of spontaneous recovery. A combination of sensation-based tests and motor-based tests was used to evaluate impaired neurologic function after spinal cord injury and the degree of spontaneous recovery, in different stages, on an in vivo model. RESULTS: Combined neurologic evaluation was useful to establish location and severity of the injury in all animals and also to detect degrees of spontaneous recovery at different stages after the injury. Comparisons of neurological function were assessed in time-days and groups between BBB motor score, latency maintenance of posture, locomotion and latency presentation of grooming before and after the injury. Our results suggest that a combined assessment strategy, including sensory and motor tests, can lead to better evaluation of spinal cord injury severity and location, and documentation of the extent of spontaneous recovery following SCI and identify specific motor and sensory pathway integrity. CONCLUSION: In conclusion, a combined assessment strategy provides a concise method for evaluating the impact of interventions in experimental models of SCI.


Assuntos
Modelos Animais de Doenças , Locomoção/fisiologia , Tempo de Reação/fisiologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Vértebras Torácicas
4.
Curr Pharm Des ; 23(28): 4154-4169, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28814235

RESUMO

The use of nanotechnology in neurosciences has been evolving since new treatments, diagnoses and biomolecule monitoring are needed to find safer treatments for central nervous system diseases (CNDs). Nanotechnology employs devices that interact with biological systems allowing molecular interactions with a high degree of specificity. This review considers concepts associated with nanotechnology and leading areas of neurosciences with nanotechnology research.


Assuntos
Fármacos do Sistema Nervoso Central/administração & dosagem , Doenças do Sistema Nervoso Central/tratamento farmacológico , Nanotecnologia/métodos , Animais , Fármacos do Sistema Nervoso Central/efeitos adversos , Doenças do Sistema Nervoso Central/diagnóstico , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Humanos
5.
Curr Pharm Des ; 23(28): 4145-4153, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28814236

RESUMO

An ability to store cells (if they cannot be used fresh) reduces cell wastage, thereby increasing the supply of transplantable material. Cell storage is also valuable in scientific research, allowing material to be archived and experiments to be repeated from the same tissue source and facilitating research collaboration by allowing stored samples to be distributed. Cryopreservation is currently considered the most promising and successful, long-term biological conservation method. Its use has led to optimizing survival, improving protocols and stem cell and neuroglia viability, thereby assuring its future use in neuroregeneration and restoration regarding cell therapy. The success of conservation processes in ensuring cell viability depends on aspects such as the characteristics, cells' cryobiological behavior, isolation methodologies, cell freezing, the use and choice of cryoprotectants and such aspects' influence on intra- and extra-cellular dynamics. This review deals with cells' cryobiological behavior, cryopreservation and cryoprotectants, emphasizing on stem cell and neuroglial populations as therapeutic target regarding nervous system diseases.


Assuntos
Criopreservação/métodos , Crioprotetores/farmacologia , Neuroglia/citologia , Animais , Sobrevivência Celular , Terapia Baseada em Transplante de Células e Tecidos/métodos , Humanos , Doenças do Sistema Nervoso/terapia , Células-Tronco/citologia
6.
Curr Top Med Chem ; 17(12): 1438-1447, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28049399

RESUMO

Gliomas are central nervous system tumors originated from glial cells, whose incidence and mortality is expected to rise in coming years, especially in developing countries. Diagnosis and classification of gliomas have largely relied on tumor histopathologic features that provide limited information regarding response to therapy or prognosis. Current treatment of gliomas is surgery combined with chemotherapy and/or radiotherapy. However, many tumors show a high resistance to these interventions, and recurrences are frequent since conventional therapies do not take into account the unique molecular features of different subtypes of glioma. Molecular genetics provide new insights in classifying gliomas and predicting response to therapy that can range from conventional treatments to new revolutionary therapeutic approaches. This article offers a review of the intracellular signaling pathways involved in carcinogenesis of gliomas, as well as a description of new tools for their diagnosis, prognosis, and treatment with a target-oriented approach.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central , Glioma , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/terapia , Glioma/diagnóstico , Glioma/genética , Glioma/terapia , Humanos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
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