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1.
Acta Med Okayama ; 70(6): 493-496, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28003675

RESUMO

Unexpected injuries can have a profound effect on a surgeon's performance and thus on patients and surgical departments. Here we describe a technique for performing surgery in the standing position, as done by a surgeon with an Achilles tendon rupture. During his prescribed 45-day non-weight-bearing period for the left ankle after surgery for an Achilles tendon rupture, the surgeon was able to participate in 15 surgeries as an operator or assistant, due to his use of a combination of injured-leg genuflection on a stool and a 'Surgical Body Support' device. Similarly injured surgeons may benefit from such support.


Assuntos
Tendão do Calcâneo/lesões , Equipamentos Ortopédicos , Ruptura/reabilitação , Cirurgiões , Procedimentos Cirúrgicos Operatórios/normas , Humanos , Masculino
2.
No Shinkei Geka ; 43(1): 51-6, 2015 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-25557099

RESUMO

Spinal dural arteriovenous fistulas(S-dAVFs)are rare vascular malformations of the spine. We experienced a case that presented with rapidly progressive brainstem dysfunction due to venous congestion of cervical dAVFs. A 56-year-old man diagnosed with cervical dAVF four years prior presented with gait disturbance and abnormal thermal nociception on his right side. In addition to the high-intensity lesion from the lower pons to the medulla oblongata on T2-weighted magnetic resonance imaging, diffusion-weighted imaging demonstrated cerebral infarction of the left ventrolateral medulla oblongata. Left vertebral angiography revealed that a feeding artery supplied by the radicular artery at the C4 level formed a fistula with the dilated ascending anterior perimedullary vein. We made a diagnosis of venous congestion due to cervical dAVFs. Numbness on the left upper limb occurred five days after the first symptom. Subsequently, hemiparesis on the left upper limb and swallowing disturbance occurred two weeks after the first symptom. The patient underwent surgical ligation of the dilated abnormal vein, with gradual improvement of his symptoms. Myelopathy due to venous congestion of S-dAVFs usually progresses slowly for several years. However, this case report warns about the possibility that some cases of S-dAVF with rapidly exacerbated symptoms may require prompt therapy.


Assuntos
Tronco Encefálico/patologia , Malformações Vasculares do Sistema Nervoso Central/terapia , Imageamento por Ressonância Magnética , Doenças da Medula Espinal/terapia , Medula Espinal/fisiopatologia , Medula Espinal/cirurgia , Tronco Encefálico/irrigação sanguínea , Malformações Vasculares do Sistema Nervoso Central/diagnóstico , Angiografia Cerebral/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Medula Espinal/diagnóstico
3.
J Neuroendovasc Ther ; 18(5): 142-148, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38808017

RESUMO

Objective: In recent years, the transradial artery approach has gained prominence and is increasingly employed in neurovascular angiography and therapy due to its safety, reduced complications, and minimal invasiveness. While various venous approaches, including the conventional transfemoral vein approach, exist for procedures such as transvenous embolization, recent reports have highlighted methods involving upper extremity cutaneous veins. However, the practicality and efficacy of these approaches remain unclear. Case Presentations: This study presents our experience with three cases of dural arteriovenous fistulas, where transvenous embolization was performed via upper limb cutaneous veins. In all instances, the arteriovenous approach was successfully executed using a single upper extremity, leading to the successful completion of treatment. Conclusion: This technique demonstrates significant advantages, not only in terms of its minimal invasiveness but also due to its simplicity and safety. Anticipating broader acceptance in the future, this approach offers a promising avenue for further exploration in neurovascular interventions.

4.
Acta Med Okayama ; 67(3): 197-202, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23804144

RESUMO

Some cases with lumbar degenerative diseases require multi-level fusion surgeries. At our institute, 27 and 4 procedures of 3- and 4-level fusion were performed out of a total 672 posterior lumbar interfusions (PLIFs) on patients with lumbar degenerative disease from 2005 to 2010. We present 2 osteoporotic patients who developed proximal vertebral body fracture after 4-level fusion. Both cases presented with gait disability for leg pain by degenerative lumbar scoliosis and canal stenosis at the levels of L1/2-4/5. After 4-level fusion using L1 as the upper instrumented vertebra, proximal vertebral body fractures were found along with the right pedicle fractures of L1 in both cases. One of these patients, aged 82 years, was treated as an outpatient using a hard corset for 24 months, but the fractures were exacerbated over time. In the other patient, posterolateral fusion was extended from Th10 to L5. Both patients can walk alone and have been thoroughly followed up. In both cases, the fracture of the right L1 pedicle might be related to the subsequent fractures and fusion failure. In consideration of multi-level fusion, L1 should be avoided as an upper instrumented vertebra to prevent junctional kyphosis, especially in cases with osteoporosis and flat back posture.


Assuntos
Vértebras Lombares/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Fraturas da Coluna Vertebral/etiologia , Fusão Vertebral/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Masculino , Osteoporose/diagnóstico por imagem , Osteoporose/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Radiografia , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos
5.
Int J Mol Sci ; 14(12): 23390-401, 2013 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-24287913

RESUMO

Epilepsy is a chronic neurological disorder, which presents with various forms of seizures. Traditional treatments, including medication using antiepileptic drugs, remain the treatment of choice for epilepsy. Recent development in surgical techniques and approaches has improved treatment outcomes. However, several epileptic patients still suffer from intractable seizures despite the advent of the multimodality of therapies. In this article, we initially provide an overview of clinical presentation of epilepsy then describe clinically relevant animal models of epilepsy. Subsequently, we discuss the concepts of regenerative medicine including cell therapy, neuroprotective agents, and electrical stimulation, which are reviewed within the context of our data.


Assuntos
Epilepsia/terapia , Medicina Regenerativa , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Terapia Baseada em Transplante de Células e Tecidos , Estimulação Elétrica , Epilepsia/metabolismo , Epilepsia/patologia , Humanos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/transplante , Fármacos Neuroprotetores/uso terapêutico
6.
Neurospine ; 20(3): 747-755, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37350168

RESUMO

OBJECTIVE: This study was aimed to report the clinical characteristics of intramedullary schwannomas and discuss imaging findings and treatment strategies. METHODS: The inclusion criterion was consecutive patients with intramedullary schwannomas who were surgically treated at 8 centers between 2009 and 2020. Clinical characteristics included age, sex, clinical presentation, disease duration, and follow-up period. The modified McCormick scale was used to compare the preoperative and postoperative conditions. Pre- and postoperative magnetic resonance images (MRI) of each case were analyzed. RESULTS: The mean age of the total 11 patients at the operation was 50.2 years. The mean duration of the symptoms was 23 months, with limb paresthesia being the most common clinical presentation. The cervical spine was the most common localization level of the tumor in 6 cases. The mean follow-up duration was 49.4 months. Gross total resection (GTR) and subtotal resection (STR) was achieved in 9 and 2 cases, respectively. According to the modified McCormick scale at 6 months postoperatively, 7 cases (63.6%) had improved and 4 cases (36.3%) had unchanged grades. Typical MRI findings of the intramedullary schwannoma included ring-like enhancement, syringomyelia, cystic formation, intramedullary edema, and hemosiderin deposition. Gadolinium enhancement was homogenous in 8 cases (72.7%). The tumor margins were well demarcated in all cases. CONCLUSION: Intramedullary schwannoma should be considered when sharp margins and well-enhanced tumors are present at the cervical spine level and the initial symptoms are relatively mild, such as dysesthesia. When GTR cannot be achieved, STR for tumor decompression is recommended.

7.
Chemistry ; 18(25): 7941-9, 2012 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-22556097

RESUMO

Further study of our aerobic intermolecular cyclization of acrylic acid with 1-octene to afford α-methylene-γ-butyrolactones, catalyzed by the Pd(OCOCF(3))(2)/Cu(OAc)(2)⋅H(2)O system, has clarified that the accumulation of water generated from oxygen during the reaction causes deactivation of the Cu cocatalyst. This prevents regeneration of the active Pd catalyst and, thus, has a harmful influence on the progress of the cyclization. As a result, both the substrate conversion and product yield are efficiently improved by continuous removal of water from the reaction mixture. Detailed analysis of the kinetic and spectroscopic measurements performed under the condition of continuous water removal demonstrates that the cyclization proceeds in four steps: 1) equilibrium coordination of 1-octene to the Pd acrylate species, 2) Markovnikov-type acryloxy palladation of 1-octene (1,2-addition), 3) intramolecular carbopalladation, and 4) ß-hydride elimination. Byproduct 2-acryloxy-1-octene is formed by ß-hydride elimination after step 2). These cyclization steps fit the Michaelis-Menten equation well and ß-hydride elimination is considered to be a rate-limiting step in the formation of the products. Spectroscopic data agree sufficiently with the existence of the intermediates bearing acrylate (Pd-O bond), η(3)-C(8)H(15) (Pd-C bond), or C(11)H(19)O(2) (Pd-C bond) moieties on the Pd center as the resting-state compounds. Furthermore, not only Cu(II), but also Cu(I), species are observed during the reaction time of 2-8 h when the reaction proceeds efficiently. This result suggests that the Cu(II) species is partially reduced to the Cu(I) species when the active Pd catalytic species are regenerated.

8.
J Cell Physiol ; 226(5): 1390-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20945350

RESUMO

Increased oxidative stress contributes to pathogenesis of Parkinson's disease (PD). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the oxidation product most frequently measured as an indicator of oxidative DNA damage. Several studies have shown increased 8-OHdG in PD patients. There are few basic laboratory data examining 8-OHdG levels in animal models of PD. In this study, we utilized hemiparkinsonian model of rats induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). The urinary 8-OHdG level was measured in relation to behavioral and pathological deficits arising from 6-OHDA-induced neurotoxic effects on the nigrostriatal dopaminergic pathway. All rats were subjected to a series of behavioral tests for 42 days after 6-OHDA injection. We collected urine samples with subsequent measurement of 8-OHdG level using ELISA kits. For immunohistochemical evaluation, tyrosine hydroxylase (TH) staining was performed. Significant increments in urinary 8-OHdG level were observed continuously from day 7 until day 35 compared to control group, which showed a trend of elevation as early as day 3. Such elevated urinary 8-OHdG level significantly correlated with all of the behavioral deficits measured here, suggesting that urinary 8-OHdG level provides a good index of severity of parkinsonism. Urinary 8-OHdG level also had a significant positive correlation with the survival rate of dopaminergic fibers or neurons, advancing the concept that oxidative stress during the early phase of 6-OHDA neurotoxicity may correspond to disease progression closely approximating neuronal degeneration in the nigrostriatal dopaminergic system. The present results demonstrate that alterations in urinary 8-OHdG level closely approximate onset and disease progression in PD.


Assuntos
Gânglios da Base/metabolismo , Comportamento Animal , Encéfalo/metabolismo , Desoxiguanosina/análogos & derivados , Dopamina/metabolismo , Degeneração Neural/metabolismo , Transtornos Parkinsonianos/metabolismo , Substância Negra/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Animais , Gânglios da Base/patologia , Biomarcadores/urina , Encéfalo/patologia , Desoxiguanosina/urina , Modelos Animais de Doenças , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Imuno-Histoquímica , Injeções , Atividade Motora , Degeneração Neural/induzido quimicamente , Degeneração Neural/patologia , Degeneração Neural/psicologia , Degeneração Neural/urina , Estresse Oxidativo , Oxidopamina/administração & dosagem , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/psicologia , Transtornos Parkinsonianos/urina , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Substância Negra/patologia , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/metabolismo
9.
Acta Med Okayama ; 65(1): 59-61, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21339798

RESUMO

A case of a Chiari malformation with an extraordinarily thick occipital bone is described. The thick occipital bone might make the posterior fossa narrow with consequent herniation of the cerebellar tonsils to the foramen magnum and formation of a syrinx. At dural plasty, well-developed marginal and occipital sinuses should be deliberately handled with the preservation of normal venous drainage. This case gives us the essence of the occurrence mechanisms of Chiari malformation and foramen magnum decompression.


Assuntos
Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/patologia , Osso Occipital/diagnóstico por imagem , Osso Occipital/patologia , Adulto , Malformação de Arnold-Chiari/cirurgia , Encefalocele/diagnóstico por imagem , Encefalocele/patologia , Encefalocele/cirurgia , Feminino , Forame Magno/diagnóstico por imagem , Forame Magno/patologia , Forame Magno/cirurgia , Humanos , Imageamento por Ressonância Magnética , Osso Occipital/cirurgia , Tomografia Computadorizada por Raios X
10.
Acta Med Okayama ; 65(2): 135-41, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21519372

RESUMO

An 18-year-old woman with a 2-year history of hypertension and headache was diagnosed with noradrenalin-secreting bilateral adrenal pheochromocytomas with paragangliomas in the background of von Hippel-Lindau disease with family histories and a missense mutation, 712C to T (Arg167Trp) in the VHL gene. She had optic disc hemangioma in the left eye which gradually enlarged and caused serous retinal detachment on the macula in one year. Low-dose external beam radiation (20 Gy) was administered to the left eye using a lens-sparing single lateral technique. She underwent craniotomy for cerebellar hemangioblastoma at the age of 22 years and total pancreatectomy for multiple neuroendocrine tumors at the age of 24 years. In the 6-year follow-up period after the radiotherapy, the optic disc hemangioma gradually reduced in size and its activity remained low, allowing good central vision to be maintained. External beam radiation is recommended as a treatment option for the initial therapy for optic disc hemangioma.


Assuntos
Hemangioma/radioterapia , Disco Óptico , Neoplasias do Nervo Óptico/radioterapia , Doença de von Hippel-Lindau/complicações , Adulto , Feminino , Hemangioma/complicações , Humanos , Neoplasias do Nervo Óptico/complicações , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
11.
J Neuroendovasc Ther ; 15(2): 120-123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-37502804

RESUMO

Objective: We report a case of a ruptured cerebral aneurysm in which a bifurcation pattern at the tip of the basilar artery was asymmetric fusion type and the superior cerebellar artery (SCA) branched from the posterior cerebral artery (PCA) on the caudal fusion type side. Case Presentation: A 45-year-old woman presented with a subarachnoid hemorrhage with a headache. Cerebral angiography revealed that the right SCA diverged from the PCA and a small cerebral aneurysm had developed at this site. This cerebral aneurysm was successfully treated by coil embolization. Conclusion: There have been no previous reports on cerebral aneurysms at the site of this normal variation.

12.
Neurol Med Chir (Tokyo) ; 61(10): 607-618, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34408107

RESUMO

Parkinson's disease (PD) patients often suffer from spinal diseases requiring surgeries, although the risk of complications is high. There are few reports on outcomes after spinal surgery for PD patients with deep brain stimulation (DBS). The objective of this study was to explore the data on spinal surgery for PD patients with precedent DBS. We evaluated 24 consecutive PD patients with 28 spinal surgeries from 2007 to 2017 who received at least a 2-year follow-up. The characteristics and outcomes of PD patients after spinal surgery were compared to those of 156 non-PD patients with degenerative spinal diseases treated in 2013-2017. Then, the characteristics, outcomes, and spinal alignment of PD patients receiving DBS were analyzed in degenerative spinal/lumbar diseases. The mean age at the time of spinal surgery was 68 years. The Hoehn and Yahr score regarding PD was stage 1 for 8 patients, stage 2 for 2 patients, stage 3 for 8 patients, stage 4 for 10 patients, and stage 5 for 0 patient. The median preoperative L-DOPA equivalent daily dose was 410 mg. Thirteen patients (46%) received precedent subthalamic nucleus (STN) DBS. Lumbar lesions with pain were common, and operation and anesthesia times were long in PD patients. Pain and functional improvement of PD patients persisted for 2 years after surgery with a higher complication rate than for non-PD patients. PD patients with STN DBS maintained better lumbar lordosis for 2 years after spinal surgery. STN DBS significantly maintained spinal alignment with subsequent pain and functional amelioration 2 years after surgery. The outcomes of spinal surgery for PD patients might be favorably affected by thorough treatment for PD including DBS.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Animais , Humanos , Dor , Doença de Parkinson/terapia , Estudos Retrospectivos , Resultado do Tratamento
13.
BMC Neurosci ; 11: 52, 2010 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-20420688

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1alpha (SDF-1alpha) is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1alpha were explored. 6-hydroxydopamine (6-OHDA, 20 microg) was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 x 107 cells, respectively) or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1alpha were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA) assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining. RESULTS: Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH)-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc) compared to that of control rats. In the in vitro study, SDF-1alpha treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. CONCLUSIONS: Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1alpha. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.


Assuntos
Quimiocina CXCL12/metabolismo , Citoproteção/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Transtornos Parkinsonianos/terapia , Anfetamina , Animais , Biomarcadores/metabolismo , Quimiocina CXCL12/farmacologia , Corpo Estriado/metabolismo , Corpo Estriado/fisiopatologia , Corpo Estriado/cirurgia , Modelos Animais de Doenças , Dopamina/biossíntese , Feminino , Sobrevivência de Enxerto/fisiologia , Infusões Intravenosas , Atividade Motora/fisiologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurotoxinas/toxicidade , Oxidopamina/toxicidade , Células PC12 , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/fisiopatologia , Ratos , Ratos Sprague-Dawley , Substância Negra/citologia , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
14.
No Shinkei Geka ; 38(12): 1103-7, 2010 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-21160102

RESUMO

The "mist irrigation system" (MIS) is a new and effective method at drilling in spinal surgery. In this report, MIS is introduced with subsequent demonstration that visibility at drilling is better with MIS because of the reduction of smoke, blood and irrigation water. Additionally using a 5 mm-thick acryl plate, the time for perforation by drilling and temperature after drilling with MIS, drip-irrigation (DI) or no irrigation, were measured respectivily. Using the acryl plate significantly reduced drilling time and high temperature after perforation in the group without irrigation were recognized, compared to cases in the groups with MIS or DI. The results might indicate that the high temperature of the drill might melt the acryl plate immediately. As a conclusion, MIS might help surgeons to drill in the deep and narrow operative field. Additionally it might help to reduce the risks of heat injury to neuronal tissue by cooling efficiently.


Assuntos
Procedimentos Neurocirúrgicos/instrumentação , Coluna Vertebral/cirurgia , Humanos , Procedimentos Neurocirúrgicos/métodos , Temperatura , Irrigação Terapêutica
15.
Stroke ; 40(11): e598-605, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19762690

RESUMO

BACKGROUND AND PURPOSE: Neuroprotective effects of electric stimulation have been recently shown in ischemic stroke, but the underlying mechanisms remain poorly understood. METHODS: Adult Wistar rats weighing 200 to 250 g received occlusion of the right middle cerebral artery for 90 minutes. At 1 hour after reperfusion, electrodes were implanted to rats on the right frontal epidural space. Electric stimulation, at preset current (0 to 200 microA) and frequency (0 to 50 Hz), was performed for 1 week. Stroke animals were subjected to behavioral tests at 3 days and 1 week postmiddle cerebral artery and then immediately euthanized for protein and immunohistochemical assays. After demonstration of behavioral and histological benefits, subsequent experiments pursued the mechanistic hypothesis that electric stimulation exerted antiapoptotic effects through the phosphoinositide 3-kinase-dependent pathway; thus, cortical stimulation was performed in the presence or absence of specific inhibitors of phosphoinositide 3-kinase (LY294002) in stroke rats. RESULTS: Cortical stimulation abrogated the ischemia-associated increase in apoptotic cells in the injured cortex by activating antiapoptotic cascades, which was reversed by the phosphoinositide 3-kinase inhibitor LY294002 as reflected behaviorally and immunohistochemically. Furthermore, brain levels of neurotrophic factors (glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, vascular endothelial growth factor) were upregulated, which coincided with enhanced angiogenesis and suppressed proliferation of inflammatory cells in the ischemic cortex. CONCLUSIONS: These results suggest that electric stimulation prevents apoptosis through the phosphoinositide 3-kinase pathway. Consequently, the ischemic brain might have been rendered as a nurturing microenvironment characterized by robust angiogenesis and diminished microglial/astrocytic proliferation, resulting in the reduction of infarct volumes and behavioral recovery. Electric stimulation is a novel and potent therapeutic tool for cerebral ischemia.


Assuntos
Apoptose , Isquemia Encefálica/terapia , Córtex Cerebral/patologia , Terapia por Estimulação Elétrica , Mediadores da Inflamação/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais/fisiologia , Acidente Vascular Cerebral/terapia , Animais , Apoptose/fisiologia , Isquemia Encefálica/enzimologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Córtex Cerebral/enzimologia , Córtex Cerebral/fisiopatologia , Terapia por Estimulação Elétrica/métodos , Masculino , Neovascularização Patológica/enzimologia , Neovascularização Patológica/patologia , Neovascularização Patológica/fisiopatologia , Neovascularização Patológica/terapia , Ratos , Ratos Wistar , Acidente Vascular Cerebral/enzimologia , Acidente Vascular Cerebral/fisiopatologia
16.
Neurol Res ; 31(4): 407-13, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18826756

RESUMO

The relationship between neurogenesis and epilepsy remains to be solved so far, although aberrant electric circuit recognized in epilepsy might be involved in neurogenesis. In this study, neurogenesis and the proliferation of astrocytes in the subgranular zone of the hippocampus were explored using unilateral amygdala-kindled rats with or without muscimol, a gamma-aminobutyric acid a (GABAa) agonist injection into the bilateral anterior thalamic nuclei (AN). Muscimol injection significantly ameliorated the behavioral scores of epilepsy without any significant alteration on the electroencephalography recorded at the stimulated basolateral amygdala, thus suggesting that muscimol injection might affect the secondary generalization, but not the initial discharge itself. The number of bromodeoxyuridine (BrdU), BrdU/doublecortin and BrdU/glial fibrillary acidic protein-positive cells in the subgranular zone of kindled animals increased markedly. Muscimol injection significantly suppressed neurogenesis, but not the proliferation of astrocyte, in the subgranular zone of the non-stimulated side, probably through the suppression of secondary generalization via AN. The results might indicate the underlying relationships between neurogenesis and epilepsy, that epileptic propagation in unilateral amygdala-kindled rats might go through AN into the contralateral side with subsequent neurogenesis, although further studies need to clarify the hypothesis.


Assuntos
Núcleos Anteriores do Tálamo/efeitos dos fármacos , Agonistas GABAérgicos/farmacologia , Hipocampo/fisiologia , Excitação Neurológica/efeitos dos fármacos , Muscimol/farmacologia , Neurogênese/efeitos dos fármacos , Tonsila do Cerebelo , Animais , Núcleos Anteriores do Tálamo/fisiologia , Bromodesoxiuridina/metabolismo , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Estimulação Elétrica/efeitos adversos , Eletroencefalografia/métodos , Epilepsia/tratamento farmacológico , Epilepsia/patologia , Epilepsia/fisiopatologia , Lateralidade Funcional , Proteína Glial Fibrilar Ácida/metabolismo , Indóis , Excitação Neurológica/fisiologia , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Neuropeptídeos/metabolismo , Ratos , Ratos Sprague-Dawley
17.
BMC Neurosci ; 9: 75, 2008 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-18671880

RESUMO

BACKGROUND: Parkinson's disease (PD) is a neurological disorder characterized by the degeneration of nigrostriatal dopaminergic systems. Free radicals induced by oxidative stress are involved in the mechanisms of cell death in PD. This study clarifies the neuroprotective effects of edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one), which has already been used for the treatment of cerebral ischemia in Japan, on TH-positive dopaminergic neurons using PD model both in vitro and in vivo. 6-hydroxydopamine (6-OHDA), a neurotoxin for dopaminergic neurons, was added to cultured dopaminergic neurons derived from murine embryonal ventral mesencephalon with subsequet administration of edaravone or saline. The number of surviving TH-positive neurons and the degree of cell damage induced by free radicals were analyzed. In parallel, edaravone or saline was intravenously administered for PD model of rats receiving intrastriatal 6-OHDA lesion with subsequent behavioral and histological analyses. RESULTS: In vitro study showed that edaravone significantly ameliorated the survival of TH-positive neurons in a dose-responsive manner. The number of apoptotic cells and HEt-positive cells significantly decreased, thus indicating that the neuroprotective effects of edaravone might be mediated by anti-apoptotic effects through the suppression of free radicals by edaravone. In vivo study demonstrated that edaravone-administration at 30 minutes after 6-OHDA lesion reduced the number of amphetamine-induced rotations significantly than edaravone-administration at 24 hours. Tyrosine hydroxylase (TH) staining of the striatum and substantia nigra pars compacta revealed that edaravone might exert neuroprotective effects on nigrostriatal dopaminergic systems. The neuroprotective effects were prominent when edaravone was administered early and in high concentration. TUNEL, HEt and Iba-1 staining in vivo might demonstrate the involvement of anti-apoptotic, anti-oxidative and anti-inflammatory effects of edaravone-administration. CONCLUSION: Edaravone exerts neuroprotective effects on PD model both in vitro and in vivo. The underlying mechanisms might be involved in the anti-apoptotic effects, anti-oxidative effects, and/or anti-inflammatory effects of edaravone. Edaravone might be a hopeful therapeutic option for PD, although the high therapeutic dosage remains to be solved for the clinical application.


Assuntos
Antipirina/análogos & derivados , Dopamina/fisiologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Animais , Antipirina/farmacologia , Antipirina/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Edaravone , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/patologia , Neurônios/fisiologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Ratos , Ratos Sprague-Dawley , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , Substância Negra/fisiologia
18.
Brain Res ; 1203: 189-96, 2008 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-18313647

RESUMO

Metabotropic glutamate receptors (mGluRs) have been recently implicated as robust therapeutic targets for Parkinson's disease (PD). Here, we explored how activation of mGluRs in globus pallidus (GP) affected the amphetamine-induced rotational behavior in the unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of PD. The amphetamine-induced rotations were completely suppressed by the ipsilateral intrapallidal injection of the non-selective mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) and the selective group I mGluR agonist, (R,S)-3,5-dihydroxyphenylglycine (DHPG), but not the selective group III mGluR agonist, l-2-amino-4-phosphonobutyric acid (l-AP4). The suppressive effects were detected at 2, 4, 6, 8, and 12 h after ACPD injection, but returned to the control level at 24 h. A remarkable c-fos expression was found in the lesioned side of GP, subthalamic nucleus (STN), and substantia nigra pars reticulata (SNr) of rats that received the ACPD or DHPG injection, compared to rats treated with L-AP-4 or phosphate buffer-injection. The results indicate that the blockade of amphetamine-induced rotations might be at least partially mediated by group I mGluR activation. This study advances the use of selective group I mGluRs directed toward the GP for PD treatment.


Assuntos
Comportamento Animal/fisiologia , Globo Pálido/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Receptores de Glutamato Metabotrópico/metabolismo , Adrenérgicos/toxicidade , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Dioxolanos/farmacologia , Modelos Animais de Doenças , Interações Medicamentosas , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/farmacologia , Atividade Motora/efeitos dos fármacos , Oxidopamina/toxicidade , Doença de Parkinson/etiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Purinas/farmacologia , Ratos , Ratos Sprague-Dawley , Substância Negra/efeitos dos fármacos , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/metabolismo
19.
Brain Res ; 1234: 172-82, 2008 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-18703033

RESUMO

Cell therapy using stem cells is awaited by stroke patients with impaired movement and cognitive functions, although intravenous alteplase-administration ameliorated outcomes of patients receiving the therapy within 3 h of onset. In this study, we explored the therapeutic effects of neural progenitor cells (NPC) upon middle cerebral artery occlusion (MCAO) model of rats with exploration of the differences between adult and embryonic NPCs in therapeutic effects. GFP-labeled adult or embryonic NPCs were transplanted for transient MCAO model of rats at 1h after reperfusion. Rats were examined behaviorally using limb placement test, rotarod test and cylinder test with neuroradiological assessment using magnetic resonance imaging (MRI). Consequently after euthanasia, rats were immunohistochemically investigated to explore graft survival and immune reaction. MRI of rats receiving NPCs revealed significant reduction of infarct volumes, compared to vehicle-treated rats with corresponding behavioral amelioration. The transplanted cells were surviving in rats receiving NPCs, although the number of embryonic NPCs was significantly higher than that of adult NPCs. Iba-1-positive inflammatory cells of rats receiving adult NPCs were prominent, compared to those receiving embryonic NPCs, which might be a rationale for the differences between rats receiving adult and embryonic NPCs in the number of surviving NPCs. On the contraries, adult NPCs surely demonstrated therapeutic effects with a few surviving cells, thus indicating that the therapeutic effects might be due to trophic/growth factor-secretion from transplanted NPCs, rather than replacement of damaged host neurons. Therapeutic effects of NPCs for MCAO model of rats were clarified in this study. Transplantation of NPCs will be a hopeful strategy for stroke patients, although further studies are required for the patient safety and underlying mechanisms.


Assuntos
Células-Tronco Adultas/transplante , Células-Tronco Embrionárias/transplante , Artéria Cerebral Média/fisiologia , Neurônios/transplante , Células-Tronco Adultas/metabolismo , Animais , Astrócitos/fisiologia , Comportamento Animal/fisiologia , Isquemia Encefálica/patologia , Diferenciação Celular/fisiologia , Proliferação de Células , Células-Tronco Embrionárias/metabolismo , Ensaio de Imunoadsorção Enzimática , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Proteínas de Fluorescência Verde , Imuno-Histoquímica , Infarto da Artéria Cerebral Média/patologia , Substâncias Luminescentes , Masculino , Microglia/fisiologia , Artéria Cerebral Média/citologia , Movimento/fisiologia , Equilíbrio Postural/fisiologia , Ratos , Ratos Wistar
20.
J Neurosurg ; 108(1): 149-59, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18173325

RESUMO

OBJECTIVES: The therapeutic effects of adult and embryonic neural precursor cells (NPCs) were evaluated and their therapeutic potential compared in a rat model of Parkinson disease. METHODS: Adult NPCs were obtained from the subventricular zone and embryonic NPCs were taken from the ganglionic eminence of 14-day-old embryos. Each NPC type was cultured with epidermal growth factor. The in vitro neuronal differentiation rate of adult NPCs was approximately equivalent to that of embryonic NPCs after two passages. Next, the NPCs were transfected with either green fluorescent protein or glial cell line-derived neurotrophic factor (GDNF) by adenoviral infection and transplanted into the striata in a rat model of Parkinson disease (PD) induced by unilateral intrastriatal injection of 6-hydroxydopamine. An amphetamine-induced rotation test was used to evaluate rat behavioral improvement, and immunohistochemical analysis was performed to compare grafted cell survival, differentiation, and host tissue changes. RESULTS: The rats with GDNF-transfected NPCs had significantly fewer amphetamine-induced rotations and less histological damage. Except for the proportion of surviving grafted cells, there were no significant differences between adult and embryonic NPCs. CONCLUSIONS: Adult and embryonic NPCs have a comparable therapeutic potential in a rat model of PD.


Assuntos
Células-Tronco Adultas/transplante , Células-Tronco Embrionárias/transplante , Doença de Parkinson/terapia , Transplante de Células-Tronco/métodos , Animais , Modelos Animais de Doenças , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Proteínas de Fluorescência Verde , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Ratos , Ratos Sprague-Dawley , Transfecção
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