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BACKGROUND: Chordoma is a rare congenital low-grade malignant tumor characterized by infiltrative growth. It often tends to compress important intracranial nerves and blood vessels, making its surgical treatment extremely difficult. Besides, the efficacy of radiotherapy and chemotherapy is limited. The photosensitizer hematoporphyrin derivative (HPD) can emit red fluorescence under 405 nm excitation and produce reactive oxygen species for tumor therapy under 630 nm excitation. Herein, we investigated the effects of the photosensitizer hematoporphyrin derivative (HPD) on different cell lines of chordoma and xenograft tumors under 405 nm and 630 nm excitation. METHODS: The photosensitizer hematoporphyrin derivative (HPD) and Two different chordoma cell lines (U-CH1, JHC7) were used for the test. The in vitro experiments were as follows: (1) the fluorescence intensity emitted by chordoma cells excited by different 405 nm light intensities was observed under a confocal microscope; (2) the Cell Counting Kit-8 (CCK-8) assay was performed to detect the effects of different photosensitizer concentrations and 630 nm light energy densities on the activity of chordoma cells. In the in vivo experiments, (3) Fluorescence visualization of chordoma xenograft tumors injected with photosensitizer via tail vein under 405 nm excitation; (4) Impact of 630 nm excitation of photosensitizer on the growth of chordoma xenograft tumors. RESULTS: (1) The photosensitizers in chordoma cells and chordoma xenografts of nude mice were excited by 405 nm to emit red fluorescence; (2) 630 nm excitation photosensitizer reduces chordoma cell activity and inhibits chordoma xenograft tumor growth in chordoma nude mice. CONCLUSION: Photodynamic techniques mediated by the photosensitizer hematoporphyrin derivatives can be used for the diagnosis and treatment of chordoma.
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Cordoma , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Cordoma/tratamento farmacológico , Animais , Camundongos , Linhagem Celular Tumoral , Humanos , Derivado da Hematoporfirina/farmacologia , Camundongos Nus , Hematoporfirinas/farmacologia , Hematoporfirinas/uso terapêuticoRESUMO
The available data on the localization of transforming growth factor beta1 (TGF-ß1), glial cell line-derived neurotrophic factor (GDNF), and platelet-derived growth factor-BB (PDGF-BB) in the adult primate and human central nervous system (CNS) are limited and lack comprehensive and systematic information. This study aimed to investigate the cellular localization and distribution of TGF-ß1, GDNF, and PDGF-BB in the CNS of adult rhesus macaque (Macaca mulatta). Seven adult rhesus macaques were included in the study. The protein levels of TGF-ß1, PDGF-BB, and GDNF in the cerebral cortex, cerebellum, hippocampus, and spinal cord were analyzed by western blotting. The expression and location of TGF-ß1, PDGF-BB, and GDNF in the brain and spinal cord was examined by immunohistochemistry and immunofluorescence staining, respectively. The mRNA expression of TGF-ß1, PDGF-BB, and GDNF was detected by in situ hybridization. The molecular weight of TGF-ß1, PDGF-BB, and GDNF in the homogenate of spinal cord was 25 KDa, 30 KDa, and 34 KDa, respectively. Immunolabeling revealed GDNF was ubiquitously distributed in the cerebral cortex, hippocampal formation, basal nuclei, thalamus, hypothalamus, brainstem, cerebellum, and spinal cord. TGF-ß1 was least distributed and found only in the medulla oblongata and spinal cord, and PDGF-BB expression was also limited and present only in the brainstem and spinal cord. Besides, TGF-ß1, PDGF-BB, and GDNF were localized in the astrocytes and microglia of spinal cord and hippocampus, and their expression was mainly found in the cytoplasm and primary dendrites. The mRNA of TGF-ß1, PDGF-BB, and GDNF was localized to neuronal subpopulations in the spinal cord and cerebellum. These findings suggest that TGF-ß1, GDNF and PDGF-BB may be associated with neuronal survival, neural regeneration and functional recovery in the CNS of adult rhesus macaques, providing the potential insights into the development or refinement of therapies based on these factors.
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Fator Neurotrófico Derivado de Linhagem de Célula Glial , Fator de Crescimento Transformador beta1 , Animais , Becaplermina , Macaca mulatta/metabolismo , RNA Mensageiro , Medula Espinal/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND: Functional preservation of cranial nerves remains an issue in surgical treatment of vestibular schwannoma. AIMS: To explore the functional outcomes of vestibular schwannoma removed by microsurgery via a retrosigmoid transmeatal approach with intraoperative monitoring techniques. STUDY DESIGN: A retrospective cross-sectional study was conducted on a group of patients with vestibular schwannoma operated by microsurgery. METHODS: The outcomes, including the extent of tumor removal, the anatomic positions of the facial nerve, and postoperative Karnofsky performance status score, facial nerve function, and hearing function were reviewed and were statistically compared among tumor sizes (small, medium, and giant) and intraoperative monitoring types [electrophysiological monitoring only (E), electrophysiological monitoring + intraoperative imaging examination (E+I), and electrophysiological monitoring + neuronavigation (E+N)]. RESULTS: A total of 436 patients with VS received microsurgery. The position of the facial nerve was anterior in 85.5% of cases with small vestibular schwannoma. Other position patterns, especially anterior- superior and anterior-inferior, increased in tumors > 2.0 cm. Total resections were performed in all patients with small vestibular schwannoma. A total of 98.1% and 84.8% of patients with medium and giant vestibular schwannoma, respectively, had total resections. More than 90% of patients in all of the 3 monitoring groups had total resections. More than 80% of patients had excellent Karnofsky performance status score regardless of tumor size and monitoring type. After surgery, 100%, 84.4%, and 59.8% of patients with small-, medium-, and giant-sized vestibular schwannoma, respectively, had good facial nerve function. More than 70% of patients in all of the 3 monitoring groups had good facial nerve function postoperatively. The hearing preservation rate was 26.7% and 7.7% in small- and medium-sized vestibular schwannoma, respectively, and was 21.6% and 27.3% in the E group and the E+N group, respectively. The statistical analyses showed that tumor size was significantly associated with the extent of tumor resection, facial nerve localization, complications, postoperative Karnofsky performance status score, facial nerve function, and hearing function (all P ≤ .001). Monitoring type was significantly associated with the extent of resection (P ≤ .001). Additionally, patients in the E+N group had higher total resection rates than those in the E group (P ≤ .001). No cerebrospinal fluid leakage and surgery-related death occurred. CONCLUSION: In vestibular schwannoma microsurgery, tumor size is an important parameter that affects the localization of the facial nerve, the extent of resection, postoperative outcomes and complications. Intraoperative electrophysiological techniques combined with neuronavigation may be helpful to improve the extent of resection.
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Microcirurgia/métodos , Monitorização Intraoperatória/métodos , Neuroma Acústico/cirurgia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Microcirurgia/estatística & dados numéricos , Pessoa de Meia-Idade , Monitorização Intraoperatória/estatística & dados numéricos , Estudos RetrospectivosRESUMO
Unraveling the pathology of stroke is a prerequisite for designing therapeutic strategies. It was reported that myelin injury exceeded axonal loss in the peri-infarct region of rodent white matter stroke. An in-depth investigation of the post-stroke white matter damage in higher-order species might innovate stroke intervention. In this study, adult male cynomolgus monkeys received surgical middle cerebral artery occlusion (MCAO), and serial magnetic resonance scans to non-invasively assess brain damage. Spontaneous movements were recorded to evaluate post-stroke behavior. The axon and myelin loss, as well as immune cell infiltration were examined using immunohistochemistry. Magnetic resonance imaging revealed cerebral infarcts and white matter injury after MCAO in monkeys, which were confirmed by neurological deficits. Immunostaining of white matter fibers showed substantial demyelination whilst retention of axons in the infarcts 8 days post MCAO, while a progressive loss of myelin and axons was observed after one month. Gliosis, microglia activation, and leukocyte infiltration were identified in the lesions. These results demonstrate that demyelination predates axonal injury in non-human primate ischemic stroke, which provides a time window for stroke intervention focusing on prevention of progressive axonal loss through myelin regeneration.
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Axônios/patologia , Isquemia Encefálica/patologia , Doenças Desmielinizantes/patologia , AVC Isquêmico/patologia , Substância Branca/patologia , Animais , Axônios/química , Axônios/imunologia , Isquemia Encefálica/imunologia , Doenças Desmielinizantes/imunologia , Gliose/imunologia , Gliose/patologia , AVC Isquêmico/imunologia , Macaca fascicularis , Masculino , Substância Branca/química , Substância Branca/imunologiaRESUMO
OBJECTIVE: This study aims to investigate the effect of minimal invasive microsurgery in treating primary hypertensive brainstem hemorrhage (PHBH). METHODS: 52 patients of PHBH (≥3.5 ml) who have taken the minimal invasive microsurgery with neuronavigation guidance were included between Jan. 2011 and Dec. 2018. The volume/location/type of hematoma, preoperative Glasgow Coma Scale (GCS), postoperative Glasgow Outcome Scale (GOS) and hemorrhagic dilatation of the fourth ventricle were analyzed during the follow-up period ranged from 3 to 57 months. RESULTS: Among all the patients, 18 achieved complete hematoma evacuation (≥95%), 31 achieved subtotal evacuation (≥90%), 3 achieved premodinantly evacuation (>75%). No rebleeding during or after surgery within 24 h were found. 45 patients survived after 3 months, the mean preoperative hematoma volume decreased from 7.1 ± 2.6 ml-0.9 ml (p < 0.05), 19 patients got GOS Grade V/â £. It is shown the volume less than 10 ml always led to better outcome while massive and bilateral hematoma were related with poor prognosis. CONCLUSION: The microsurgical hematoma evacuation under neuronavigation assistance is a rapid, effective, and safe technique for the removal of PHBH, especially for the volume less than 10 ml.
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Tronco Encefálico/cirurgia , Hemorragia Cerebral/cirurgia , Hipertensão/complicações , Microcirurgia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neuronavegação/métodos , Adulto , Idoso , Hemorragia Cerebral/etiologia , Feminino , Seguimentos , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Segurança , Resultado do TratamentoRESUMO
BACKGROUND This case series study evaluated the outcome and effect of portable 3D-head computed tomography (CT, MCT-I, 16 rows mobile CT made in China) navigation-guided key-hole microsurgery for supratentorial hypertensive hematomas. MATERIAL AND METHODS Thirty-five consecutive unconscious patients with a significant volume of hypertensive intracranial hemorrhages (HICH) were treated with 3D image-guided key-hole microsurgery, and the clinical features were summarized. Preoperative and postoperative hematoma volumes and reduction in midline shifts were calculated and recorded. The preoperative and postoperative (initial, discharge, and 180th day after stroke onset) neurological status was assessed by Glasgow Outcome Scale (GOS), Glasgow Coma Scale (GCS), and modified Rankin Scale (mRS) score, respectively. RESULTS The range of hematoma volumes of surgical patients was 24-99 ml (median, 50 ml). The median time of CT scan (from the time of the request to navigation finish) was 11 min. Total and near-total (>90%) hematoma evacuation was achieved in 96.9% cases. Compared with the initial state of neurological assessment, there was a significant improvement in MRS and GCS at discharge (P<0.001). After 6 months, 57.1% of patients had achieved functional recovery (GOS 4-5) and 2 patients had died. CONCLUSIONS As a minimally invasive technique, image-guided transcortical sulci or transsylvian approach is highly effective for immediate and complete hematoma evacuation.
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Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Hipertensão/diagnóstico por imagem , Hipertensão/cirurgia , Imageamento Tridimensional , Microcirurgia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/complicações , Feminino , Humanos , Hipertensão/complicações , Masculino , Microcirurgia/efeitos adversos , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cuidados Pré-OperatóriosRESUMO
OBJECTIVES: methyl-D-aspartate NMDA receptor (NMDAR) and aquaporin 4 (AQP4) are involved in the molecular cascade of edema after traumatic brain injury (TBI) and are potential targets of studies in pharmacology and medicine. However, their association and interactions are still unknown. MATERIALS AND METHODS: We established a rat TBI model in this study. The cellular distribution patterns of AQP4 after inhibition of NMDAR were determined by Western blotting and immunoreactive staining. Furthermore, the regulation of NMDA receptor 1 by AQP4 was studied by injection of a viral vector targeting AQP4 by RNAi into the rat brain before TBI. RESULTS: The results suggest that AQP4 protein expression increased significantly (P<0.05) after TBI and was down-regulated by the NMDAR inhibitor MK801. This decrease could be partly reversed using the NMDAR agonist NMDA. This indicated that AQP4 mRNA levels and protein expression are regulated by the NMDA signaling pathway. By injection of AQP4 RNAi viral vector into the brain of TBI rat models, we found that the mRNA and protein levels of NMDAR decreased significantly (P<0.05). This suggested that NMDAR is also regulated by AQP4. CONCLUSION: These data suggested that the inhibition of AQP4 down-regulates NMDAR expression, which might be one of the mechanisms involved in edema after TBI.
RESUMO
The efficacy and safety of surgery for patients with primary pontine hemorrhage (PPH) remain debatable. Twenty-eight consecutive patients with huge upper PPH were included in this study. They underwent surgical management through a subtemporal approach between January 2009 and October 2013. We analyzed clinical and radiological parameters to assess the patient outcomes. The near-complete (>90%) evacuation rate was 67.9%, and there was no surgery-related death. The overall survival rate at 3â¯months was 64.3% (17/28), including 28.6% (8/28) with good function, 10.7% (3/28) with disability and 25% (7/28) in a vegetative state. The mortality rate was 35.7% (10/28). Preoperative hemorrhage volume (Pâ¯=â¯0.019), preoperative (Pâ¯=â¯0.017) and postoperative (Pâ¯=â¯0.001) Glasgow coma scale (GCS) score, coma on admission (Pâ¯=â¯0.001), ventricular extension (Pâ¯=â¯0.001), preoperative mechanical ventilation (Pâ¯=â¯0.001) and hydrocephalus (Pâ¯=â¯0.007) were found to be statistically significant predictors for mortality on univariate analysis. On multivariate regression analysis, only GCS on admission and coma were found to be significant prognostic predictors. The subtemporal approach was found to be a safe method to treat upper PPH. Microsurgery may be beneficial for the treatment of PPH, but these results need further validation in a more comprehensive and comparative study. GCS on admission and coma were found to be the only significant prognostic predictors for mortality with multivariate regression analysis.
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Hemorragia Cerebral/cirurgia , Hematoma/cirurgia , Ponte/cirurgia , Adulto , Idoso , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidade , Feminino , Escala de Coma de Glasgow , Hematoma/diagnóstico , Hematoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de SobrevidaRESUMO
PURPOSE: To investigate the combination effect of methylprednisolone (MP) and mitochondrial division inhibitor-1 (Mdivi-1) on the neurological function recovery of rat spinal cord injury (SCI) model. METHODS: The weight-drop method was used to establish the rat SCI model; then, rats were randomized into sham group, SCI group, MP group, Mdivi-1 group and MP+Mdivi-1 group. Motor function scores were quantified to evaluate locomotor ability; HE staining was used to assess spinal cord histopathology; tissue water content, oxidative stress, tissue mitochondrial function, neurons apoptosis, and apoptosis-related protein expression were detected. RESULTS: From the third day after SCI, BBB score of the MP+Mdivi-1 group was obviously higher than the other experimental groups (p < 0.05). Compared with the SCI group, tissue water content of the Mdivi-1 group and MP+Mdivi-1 group reduced obviously (p < 0.05), mitochondrial membrane potential (MMP) level and ATP content in the Mdivi-1 group and MP+Mdivi-1 group were both higher (p < 0.05). Meanwhile, three kinds of treatment all reduced apoptosis significantly, while MP plus Mdivi-1 exhibited the best inhibition effect on apoptosis (p < 0.05). The expression levels of Drp1, cytochrome c, and caspase-3 were all upregulated obviously; Mdivi-1 could inhibit Drp1 upregulation induced by SCI; for the upregulation of cytochrome c and caspase-3, the inhibition effect of Mdivi-1 approached MP. When MP combined with Mdivi-1, there was the best inhibition effect. CONCLUSIONS: MP combined with Mdivi-1 may produce better neurological function recovery, through improving functional status of mitochondria and inhibiting lipid peroxidation in damaged tissue of SCI rats, and thus alleviating apoptosis.
Assuntos
Anti-Inflamatórios/administração & dosagem , Metilprednisolona/administração & dosagem , Quinazolinonas/administração & dosagem , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Quimioterapia Combinada , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologiaRESUMO
Most patients diagnosed with neurofibromatosis type 2 (NF2) have bilateral vestibular schwannomas (VS). Through reviewing surgical method and clinical outcomes, we tried to find out a strategy for treatments in NF2 patients with VS.We retrospectively reviewed patients diagnosed pathological NF2 and have had microsurgery (MS) for VS in the PLA Army General Hospital. Seventeen patients were included from January 2000 to December 2016. Fifteen patients had progressive hearing impairment, and 7 ears were totally deaf. Computed tomography and magnetic resonance imaging were used for preoperative and postoperative evaluation. House-Brackmann (H-B) classification was used to evaluate facial function, and the hearing outcome was classified according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification system. The outcomes included functional hearing, facial function, and complications.In the 17 patients, 9 were men, and the mean age was 27.2 years old. The mean duration of disease was 38.4 months. Twenty-six VS were excised. Nine patients with bilateral VS and unilateral surgery had repeated surgery for the contralateral tumor after 3 to 12 months. The hearing preservation rate was 41.6%. In the 26 excisions for VS, 24 had intact facial nerve. In the other 2 tumor excision, damaged facial nerves had head-to-head adhesion using biological fibrin glue. The rate of facial nerve function preservation was 60%. No mortality or major complication was reported. The follow-up time ranged from 11 to 78 months with a mean value of 39 months.MS is an effective treatment for NF2 patients with VS. The operation for bilateral VS should be staged according to tumor size and bilateral hearing function. However, methods on how to preserve functional hearing and facial function remain the issue. Further randomized controlled studies are needed to find out a better treatment for NF2 patients with VS according to the overall condition.
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Microcirurgia/métodos , Neurofibromatose 2/cirurgia , Neuroma Acústico/cirurgia , Procedimentos Cirúrgicos Otológicos/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Neurofibromatose 2/complicações , Neurofibromatose 2/diagnóstico por imagem , Neuroma Acústico/complicações , Neuroma Acústico/diagnóstico por imagem , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma. METHODS: Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis. RESULTS: Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1ß and TNF-α levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05). CONCLUSION: SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH.
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Antipirina/análogos & derivados , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/tratamento farmacológico , Colagenases/toxicidade , Sequestradores de Radicais Livres/administração & dosagem , Animais , Antipirina/administração & dosagem , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/fisiopatologia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Citocinas/metabolismo , Modelos Animais de Doenças , Edaravone , Imageamento por Ressonância Magnética , Masculino , Microglia/metabolismo , Microglia/patologia , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Sprague-Dawley , Técnicas Estereotáxicas , Fatores de Tempo , Resultado do TratamentoRESUMO
Here, we have investigated the synergistic effect of quercetin administration and transplantation of human umbilical cord mesenchymal stromal cells (HUMSCs) following middle cerebral artery occlusion in rat. Combining quercetin treatment with delayed transplantation of HUMSCs after local cerebral ischemia significantly (i) improved neurological functional recovery; (ii) reduced proinflammatory cytokines (interleukin(IL)-1ß and IL-6), increased anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor-ß1), and reduced ED-1 positive areas; (iii) inhibited cell apoptosis (caspase-3 expression); and (iv) improved the survival rate of HUMSCs in the injury site. Altogether, our results demonstrate that combined HUMSC transplantation and quercetin treatment is a potential strategy for reducing secondary damage and promoting functional recovery following cerebral ischemia.
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Isquemia Encefálica/terapia , Citocinas/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Quercetina/farmacologia , Cordão Umbilical/citologia , Animais , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/imunologia , Ratos Sprague-DawleyRESUMO
A 62-year-old male suffering from vomiting and mild preceding nausea for 15 days was examined in the present case report. Magnetic resonance imaging revealed a homogeneously enhancing cluster-like lesion involving the lateral, third and fourth ventricles. An endoscopic biopsy was performed, and histopathological examination led to the diagnosis of a high-grade diffuse large B-cell lymphoma. To the best of our knowledge, the present study reports the first case of a primary lymphoma involving the entire ventricular system. Therefore, primary lymphomas should be considered in the list of ventricular tumors. An endoscopic biopsy requires minimal invasion to obtain an adequate tissue sample, and frequently leads to the correct diagnosis and subsequent treatment protocols.
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There is much evidence to suggest that brain-derived neurotrophic factor (BDNF) is a prominent candidate in promoting neuroprotection, axonal regeneration, and synaptic plasticity following spinal cord injury (SCI). Although some evidence indicates that BDNF has potent anti-oxidative effects and may be involved in the regulation of the immune response, the effects of BDNF in the inflammatory response during the course of secondary damage after SCI is still unclear. The present study was designed to investigate the effects of BDNF with a special focus on their effect on macrophage polarization after SCI. Adult C57 mice underwent T10 spinal cord clip compression injury and received lenti-BDNF vector injections at the epicenter of the lesion site. Four days later, total BDNF levels were greatly increased in animals that received lenti-BDNF injections. Confocal imaging showed that more than 80 % of the lenti-virus infected cells were CD11b-positive macrophages. In addition, the expression of arginase-1 and CD206 (associated with M2 macrophage phenotype) significantly increased in the animals that received lenti-BDNF injections compared with those that received lenti-EGFP injections. On the contrary, the expression of CD16/32 and inducible nitric oxide synthase (M1 phenotype marker) was down-regulated as demonstrated using flow cytometry and immunohistochemistry. Furthermore, the production of interleukin 1ß and tumor necrosis factor alpha was significantly reduced whereas the levels of interleukin 10 and interleukin 13 were elevated in subjects that received lenti-BDNF vector injections. The time course of functional recovery revealed that gradual recovery was observed in the subacute phase in lenti-BDNF group, little improvement was observed in lenti-EGFP group. At the axonal level, significant retraction of the CST axons were observed in lenti-EGFP injected animals relative to lenti-BDNF group by biotinylated dextran amine tracing. In addition, compared to lenti-BDNF group markedly demyelination was observed in the lenti-EGFP group using luxol fast blue staining. In conclusion, we found that BDNF could promote the shift of M1 to M2 phenotype and ameliorate the inflammatory microenvironment. Furthermore, the roles of BDNF in immunity modulation may enhance neuroprotective effects and partially contribute to the locomotor functional recovery after SCI.
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Fator Neurotrófico Derivado do Encéfalo/administração & dosagem , Fator Neurotrófico Derivado do Encéfalo/genética , Terapia Genética/métodos , Macrófagos/fisiologia , Mielite/prevenção & controle , Traumatismos da Medula Espinal/terapia , Animais , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Polaridade Celular/efeitos dos fármacos , Feminino , Técnicas de Transferência de Genes , Vetores Genéticos , Injeções Intralesionais , Injeções Espinhais , Lentivirus/genética , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mielite/genética , Mielite/patologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologiaRESUMO
The immunoreactive responses are a two-edged sword after spinal cord injury (SCI). Macrophages are the predominant inflammatory cells responsible for this response. However, the mechanism underlying the effects of HBOT on the immunomodulation following SCI is unclear now. The present study was performed to examine the effects of hyperbaric oxygen therapy (HBOT) on macrophage polarization after the rat compressive injury of the spinal cord. HBOT was associated with significant increases in IL-4 and IL-13 levels, and reductions in TNF-α and IFN-É£ levels. This was associated simultaneously with the levels of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased levels of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional recovery in the HBOT-transplanted group, which correlated with preserved axons and increased myelin sparing. Our results suggested that HBOT after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, which may further promote the axonal extension and functional recovery.
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Polaridade Celular , Oxigenoterapia Hiperbárica , Macrófagos/fisiologia , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/terapia , Animais , Axônios/patologia , Citocinas/metabolismo , Inflamação/metabolismo , Locomoção , Macrófagos/metabolismo , Bainha de Mielina/patologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologiaRESUMO
Here, we aimed to evaluate the experience of transsylvian-transinsular microsurgical approach (TTH) to the huge lateral thalamic hemorrhages (THs). A total of 37 patients with huge lateral TH (hematoma volumes between 30 and 90 cm) who underwent surgical treatment through middle or distal TTH at the Bayi Brain Hospital from January 2007 to May 2012 were included in this series. By using TTH, near-complete (99%) evacuation was achieved in 29 patients (78.4%). Glasgow Coma Scale (GOS) scores were significantly improved at discharge compared with admission scores (P < 0.001). The overall survival rate at 3 months was 81.08% (30/37), including 51.35% (19/37) with good function (GOS, 4-5), 13.51% (5/37) with disability (GOS, 3), and 16.22% (6/37) in a vegetative state (GOS, 2). The mortality rate (GOS, 1) was 18.92% (7/37). Our series showed that, according to the extension direction of hematomas, to select middle or distal TTH is effective and safe for TH.
Assuntos
Hemorragia Cerebral/cirurgia , Hemostasia Cirúrgica/métodos , Microcirurgia/métodos , Procedimentos Neurocirúrgicos/métodos , Tálamo/irrigação sanguínea , Hemorragia Cerebral/diagnóstico , Humanos , Tálamo/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Adipocyte-derived stem cells have emerged as a novel source of stem cell therapy for their autologous and readily accessible and pluripotent potential to differentiate into different lineages such as neural stem cells (NSCs) and endothelial progenitor cells (EPCs). Transplantation of NSCs and EPCs has been promising for the repair of brain injury. We explored using co-transplanted hydrogel scaffold to improve the survival of the transplanted cells and recovery of neurological function. Adult Wistar rats were transplanted with EPC-hydrogel, NSC-hydrogel, NSC-EPC-hydrogel, EPC only, or NSC only 7 days after cortical contusion injury. Behavioral tests were performed to evaluate neurological function before, and 1, 2, 3, and 4 weeks after transplantation. Size of injury, extent of vascularization, as well as the survival and differentiation of the transplanted EPCs and NSCs, were evaluated at week 5. All transplantation groups displayed significantly better neurological function compared with the control groups. Improved neurological function correlated with significantly smaller injury volumes than that of the saline group. Using immunostaining, we have shown that while transplanted NSCs differentiated into both neurons and astrocytes, the EPCs were incorporated into vessel epithelia. The extent of reactive gliosis (based on glial fibrillary acidic protein immunostaining) was significantly reduced in all treatment groups (NSC-EPC-hydrogel, NSC-hydrogel, and EPC-hydrogel) when compared with the saline group, with the highest reduction in the NSC-EPC-hydrogel transplantation group. Thus, co-transplantation of hydrogel scaffold provides a more conducive environment for the survival and differentiation of NSCs and EPCs at the site of brain injury, leading to improved vascularization and better recovery of neurological function.
Assuntos
Adipócitos/transplante , Lesões Encefálicas/terapia , Recuperação de Função Fisiológica/fisiologia , Transplante de Células-Tronco/métodos , Animais , Comportamento Animal/fisiologia , Lesões Encefálicas/fisiopatologia , Modelos Animais de Doenças , Hidrogel de Polietilenoglicol-Dimetacrilato , Masculino , Atividade Motora/fisiologia , Ratos , Ratos Wistar , Alicerces Teciduais , Resultado do TratamentoRESUMO
OBJECTIVE: The purpose of this study is to provide a retrospective review of patients with brain stem cavernous malformation (BSCM) at single institution. METHODS: Clinical courses were retrospectively reviewed for 38 consecutive patients who underwent microsurgical resection of symptomatic BSCMs in the sub-acute phase between January 2000 and December 2009. Microsurgery was performed with the help of intraoperative neuronavigation and neurophysiological monitoring. The baseline information of patients, lesion characteristics, surgical approaches, and follow-up outcomes were analyzed. RESULTS: All 38 patients received microsurgical resections without surgery-related mortality, and 37 patients were completely extirpated. 21 patients who experienced neurological deficits had functional improvement after surgery, 15 patients had no change in the neurological status over time to their preoperative condition or better, and 2 patients deteriorated. During the follow-up, 28 patients had resumed activities of daily living (KPS=90-100), 8 patients were able to self-care with some efforts (KPS=70-80) and other 2 patients needed considerable assistance. None of the operated patient had recurrent hemorrhage. Postoperative complications included new cranial nerve deficits in 13 patients, motor deficits in 3 patients, and new sensory disturbances in 6 patients. CONCLUSION: Complete surgical resection could be achieved through careful preoperative planning, selection of the optimal operative approach, a meticulous microsurgical technique and intraoperative navigation. However, taking into account the relatively high postoperative morbidity, complete resection is not always the goal for BSCMs, especially for those deep-seated lesions.
Assuntos
Neoplasias do Tronco Encefálico/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Microcirurgia , Procedimentos Neurocirúrgicos , Adolescente , Adulto , Neoplasias do Tronco Encefálico/patologia , Nervos Cranianos/cirurgia , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Humanos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Up to now, no systemic studies about the surgical approaches and microsurgical techniques of distal transsylvian-transinsular approach to putaminal hypertensive intracranial hemorrhages (PHHs) were reported. METHODS: A retrospective analysis was performed on 68 consecutive patients with PHH who underwent surgical treatment at the Department of the affiliated Bayi Brain Hospital, the Military General Hospital of Beijing PLA, from May 2009 to December 2011. RESULTS: By using transsylvian-transinsular approach, near-complete (>90%) evacuation was achieved in 51 cases (75%). Glasgow Coma Scale scores were significantly improved at discharge compared with admission scores (P < 0.001). The overall survival rate at 6 months was 95.6% (65/68), including 60.3% (41/68) with good function (Glasgow Outcome Scale [GOS] score, 4-5), 19.1% (13/68) with disability (GOS score, 3), and 16.2% (11/68) in a vegetative state (GOS score, 2). The mortality rate (GOS score, 1) was 4.4% (3/68). CONCLUSIONS: Transsylvian-transinsular approach is effective and minimally invasive for PHH. The opening of sylvian fissure toward the pars opercularis behind the level of anterior ascending rami could provide a more suitable angle to hematoma and the ability to treat the responsible vessels.