Incidence of trocar site herniation following robotic gynecologic surgery.

PubMed

Clark, Leslie H; Soliman, Pamela T; Odetto, Diego; Munsell, Mark F; Schmeler, Kathleen M; Fleming, Nicole; Westin, Shannon N; Nick, Alpa M; Ramirez, Pedro T

2013-11-01

Trocar site herniation is a recognized complication of minimally invasive surgery, but published data on trocar site herniation after robotic surgery are scarce. We sought to determine the incidence of trocar site herniation in women undergoing robotic surgery for gynecologic disease. A retrospective review of robotic surgeries performed from January 1, 2006, through December 31, 2012, was conducted. Postoperative trocar site herniations were identified, along with time to presentation, location of herniation, and management. Patients were excluded if surgery was converted to laparotomy or traditional laparoscopy. The Wilcoxon rank-sum test was used to compare patients with and without herniation with respect to continuous variables, and Fisher's exact test was used to compare these 2 groups with respect to categorical variables. The study included 500 patients, 3 of whom experienced herniation at a single trocar site. The patients with and without herniation did not differ with respect to age, body mass index, smoking status, medical comorbidities, operating time, or estimated blood loss. All 3 herniations occurred at 12-mm trocar sites. Two herniations occurred at assistant port sites, and 1 occurred at the umbilical camera port site. The median time to herniation was 21 days (range, 8-38 days). One patient required immediate surgical intervention; the other 2 patients had conservative management. Trocar site herniation is a rare complication following robotic surgery. The most important risk factor for trocar site herniation appears to be larger trocar size, as all herniations occurred at 12-mm port sites. © 2013.

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation.

PubMed

Johnston, Robyn; Kaliaperumal, Chandrasekaran; Wyse, Gerald; Kaar, George

2013-01-08

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a 'false-negative' result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death.

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation

PubMed Central

Johnston, Robyn; Kaliaperumal, Chandrasekaran; Wyse, Gerald; Kaar, George

2013-01-01

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a ‘false-negative’ result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death. PMID:23302550

Breed-Specific Magnetic Resonance Imaging Characteristics of Necrotizing Encephalitis in Dogs

PubMed Central

Flegel, Thomas

2017-01-01

Diagnosing necrotizing encephalitis, with its subcategories of necrotizing leukoencephalitis and necrotizing meningoencephalitis, based on magnetic resonance imaging alone can be challenging. However, there are breed-specific imaging characteristics in both subcategories that allow establishing a clinical diagnosis with a relatively high degree of certainty. Typical breed specific imaging features, such as lesion distribution, signal intensity, contrast enhancement, and gross changes of brain structure (midline shift, ventriculomegaly, and brain herniation) are summarized here, using current literature, for the most commonly affected canine breeds: Yorkshire Terrier, French Bulldog, Pug, and Chihuahua. PMID:29255715

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

PubMed

Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

2005-01-01

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

Estimation of the brain stem volume by stereological method on magnetic resonance imaging.

PubMed

Erbagci, Hulya; Keser, Munevver; Kervancioglu, Selim; Kizilkan, Nese

2012-11-01

Neuron loss that occurs in some neurodegenerative diseases can lead to volume alterations by causing atrophy in the brain stem. The aim of this study was to determine the brain stem volume and the volume ratio of the brain stem to total brain volume related to gender and age using new Stereo Investigator system in normal subjects. For this purpose, MR images of 72 individuals who have no pathologic condition were evaluated. The total brain volumes of female and male were calculated as 966.81 ± 77.44 and 1,074.06 ± 111.75 cm3, respectively. Brain stem volumes of female and male were determined as 18.99 ± 2.36 and 22.05 ± 4.01 cm3, respectively. The ratios of brain stem volume to total brain volume were 1.96 ± 0.17 in female and 2.05 ± 0.29 in male. The total brain and brain stem volumes were observed smaller in female and it is statistically significant. Among the individuals whose ages are between 20 and 40, total brain and brain stem volume measurements with aging were not statistically significant. As a result, we believe that the measurement of brain stem volume with an objective and efficient calculation method will contribute to the early diagnosis of neurodegenerative diseases, as well as to determine the rate of disease progression, and the outcomes of treatment.

Hypertensive brain stem encephalopathy.

PubMed

Liao, Pen-Yuan; Lee, Chien-Chang; Chen, Cheng-Yu

2015-01-01

A 48-year-old man presented with headache and extreme hypertension. Computed tomography showed diffuse brain stem hypodensity. Magnetic resonance imaging revealed diffuse brain stem vasogenic edema. Hypertensive brain stem encephalopathy is an uncommon manifestation of hypertensive encephalopathy, which classically occurs at parietooccipital white matter. Because of its atypical location, the diagnosis can be challenging. Moreover, the coexistence of hypertension and brain stem edema could also direct clinicians toward a diagnosis of ischemic infarction, leading to a completely contradictory treatment goal.

Intrinsic epidermoid of the brain stem: case report and review of the literature.

PubMed

Singh, Saraj K; Jain, Kapil; Jain, Vijendra Kumar

2018-03-19

Purely cystic brain stem epidermoid is a rare diagnosis among all brainstem cystic lesions. Further, it is very rare in pediatric age group. Here, we are reporting a rare case of completely cystic brain stem epidermoid in a child. The patient presented with clinical features of brain stem involvement. MRI brain was suggestive of cystic brain stem lesion. Patient went through surgical procedure. Final diagnosis of epidermoid cyst was confirmed on histopathological report. With the help of various advanced sequences of MRI like diffusion and ADC, diagnosis of epidermoid cyst can be established at unusual intracranial site also. Surgical resection of epidermoid cyst at brain stem should be attempted judiciously utilizing all modern tools of neurosurgery.

Endogenous-lesioned cervical disc herniation: a retrospective review of 9 cases.

PubMed

Zhang, Zifeng; Bai, Yushu; Hou, Tiesheng

2011-01-01

The purpose of this study was to analyze the pathogenic mechanisms, clinical presentation, and surgical treatment of cervical disc herniation without external trauma. Between 2004 and 2008, 9 patients with cervical disc herniation and no antecedent history of trauma were diagnosed with cervical disc herniation and underwent surgical decompression. Pathogenic mechanisms, clinical presentation, surgical treatment, and prognosis were analyzed retrospectively. In 6 patients, herniation resulted from excessive neck motion rather than from external trauma. An injury from this source is termed an endogenous-lesioned injury. Patients exhibited neurologic symptoms of compression of the cervical spinal cord or nerve roots. In the other 3 patients, no clear cause for the herniation was recorded, but all patients had a desk job with long periods of head-down neck flexion posture. After surgery, all patients experienced a reduction in their symptoms and an uneventful recovery. Cervical disc herniation can occur in the absence of trauma. Surgical decompression is effective at reducing symptoms in these patients, similar to other patients with cervical disc herniation. Surgical treatment may be considered for this disorder when the herniation becomes symptomatic.

Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease.

PubMed

Lee, Ji Han; Jung, Won Sang; Choi, Woo Hee; Lim, Hyun Kook

2016-01-01

Among patients with Alzheimer's disease (AD), sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD. In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology. Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group. This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings.

Signals that regulate the oncogenic fate of neural stem cells and progenitors

PubMed Central

Swartling, Fredrik J.; Bolin, Sara; Phillips, Joanna J.; Persson, Anders I.

2013-01-01

Brain tumors have frequently been associated with a neural stem cell (NSC) origin and contain stem-like tumor cells, so-called brain tumor stem cells (BTSCs) that share many features with normal NSCs. A stem cell state of BTSCs confers resistance to radiotherapy and treatment with alkylating agents. It is also a hallmark of aggressive brain tumors and is maintained by transcriptional networks that are also active in embryonic stem cells. Advances in reprogramming of somatic cells into induced pluripotent stem (iPS) cells have further identified genes that drive stemness. In this review, we will highlight the possible drivers of stemness in medulloblastoma and glioma, the most frequent types of primary malignant brain cancer in children and adults, respectively. Signals that drive expansion of developmentally defined neural precursor cells are also active in corresponding brain tumors. Transcriptomal subgroups of human medulloblastoma and glioma match features of NSCs but also more restricted progenitors. Lessons from genetically-engineered mouse (GEM) models show that temporally and regionally defined NSCs can give rise to distinct subgroups of medulloblastoma and glioma. We will further discuss how acquisition of stem cell features may drive brain tumorigenesis from a non-NSC origin. Genetic alterations, signaling pathways, and therapy-induced changes in the tumor microenvironment can drive reprogramming networks and induce stemness in brain tumors. Finally, we propose a model where dysregulation of microRNAs (miRNAs) that normally provide barriers against reprogramming plays an integral role in promoting stemness in brain tumors. PMID:23376224

The Potential of Stem Cells in Treatment of Traumatic Brain Injury.

PubMed

Weston, Nicole M; Sun, Dong

2018-01-25

Traumatic brain injury (TBI) is a global public health concern, with limited treatment options available. Despite improving survival rate after TBI, treatment is lacking for brain functional recovery and structural repair in clinic. Recent studies have suggested that the mature brain harbors neural stem cells which have regenerative capacity following brain insults. Much progress has been made in preclinical TBI model studies in understanding the behaviors, functions, and regulatory mechanisms of neural stem cells in the injured brain. Different strategies targeting these cell population have been assessed in TBI models. In parallel, cell transplantation strategy using a wide range of stem cells has been explored for TBI treatment in pre-clinical studies and some in clinical trials. This review summarized strategies which have been explored to enhance endogenous neural stem cell-mediated regeneration and recent development in cell transplantation studies for post-TBI brain repair. Thus far, neural regeneration through neural stem cells either by modulating endogenous neural stem cells or by stem cell transplantation has attracted much attention. It is highly speculated that targeting neural stem cells could be a potential strategy to repair and regenerate the injured brain. Neuroprotection and neuroregeneration are major aspects for TBI therapeutic development. With technique advancement, it is hoped that stem cell-based therapy targeting neuroregeneration will be able to translate to clinic in not so far future.

Dorsal brain stem syndrome: MR imaging location of brain stem tegmental lesions in neonates with oral motor dysfunction.

PubMed

Quattrocchi, C C; Longo, D; Delfino, L N; Cilio, M R; Piersigilli, F; Capua, M D; Seganti, G; Danhaive, O; Fariello, G

2010-09-01

The anatomic extent of brain stem damage may provide information about clinical outcome and prognosis in children with hypoxic-ischemic encephalopathy and oral motor dysfunction. The aim of this study was to retrospectively characterize the location and extent of brain stem lesions in children with oral motor dysfunction. From January 2005 to August 2009, 43 infants hospitalized at our institution were included in the study because of a history of hypoxic-ischemic events. Of this group, 14 patients showed oral motor dysfunction and brain stem tegmental lesions detected at MR imaging. MR imaging showed hypoxic-ischemic lesions in supra- and infratentorial areas. Six of 14 patients revealed only infratentorial lesions. Focal symmetric lesions of the tegmental brain stem were always present. The lesions appeared hyperintense on T2-weighted images and hypointense on IR images. We found a strong association (P < .0001) between oral motor dysfunction and infratentorial lesions on MR imaging. Oral motor dysfunction was associated with brain stem tegmental lesions in posthypoxic-ischemic infants. The MR imaging examination should be directed to the brain stem, especially when a condition of prolonged gavage feeding is necessary in infants.

Automatic diagnosis of lumbar disc herniation with shape and appearance features from MRI

NASA Astrophysics Data System (ADS)

Alomari, Raja'S.; Corso, Jason J.; Chaudhary, Vipin; Dhillon, Gurmeet

2010-03-01

Intervertebral disc herniation is a major reason for lower back pain (LBP), which is the second most common neurological ailment in the United States. Automation of herniated disc diagnosis reduces the large burden on radiologists who have to diagnose hundreds of cases each day using clinical MRI. We present a method for automatic diagnosis of lumbar disc herniation using appearance and shape features. We jointly use the intensity signal for modeling the appearance of herniated disc and the active shape model for modeling the shape of herniated disc. We utilize a Gibbs distribution for classification of discs using appearance and shape features. We use 33 clinical MRI cases of the lumbar area for training and testing both appearance and shape models. We achieve over 91% accuracy in detection of herniation in a cross-validation experiment with specificity of 91% and sensitivity of 94%.

Posterior brain in fetuses with open spina bifida at 11 to 13 weeks.

PubMed

Lachmann, Robert; Chaoui, Rabih; Moratalla, Jose; Picciarelli, Gemma; Nicolaides, Kypros H

2011-01-01

To measure the changes in the posterior fossa in first-trimester fetuses with open spina bifida (OSB). The brain stem diameter and brain stem to occipital bone (BSOB) diameter were measured in stored images of the mid-sagittal view of the fetal face at 11(+0) to 13(+6) weeks from 30 fetuses with OSB and 1000 normal controls. In the control group, the brain stem and BSOB diameter increased significantly with crown-rump length (CRL) and the brain stem to BSOB ratio decreased. In the spina bifida group, the brain stem diameter was above the 95th percentile of the control group in 29 (96.7%) cases, the BSOB diameter was below the 5th percentile in 26 (86.7%) and the brain stem to BSOB ratio was above the 95th percentile in all cases. At 11 to 13 weeks the majority of fetuses with OSB have measurable abnormalities in the posterior brain.

Isolated brain stem edema in a pediatric patient with head trauma: a case report.

PubMed

Basarslan, K; Basarslan, F; Karakus, A; Yilmaz, C

2015-01-01

Brain stem is the most vital part of our body and is a transitional region of the brain that connects the cerebrum with the spinal cord. Though, being small in size, it is full of indispensible functions such as the breathing, heart beat. Injury to the brain stem has similar effects as a brain injury, but it is more fatal. Use of the Glasgow Coma Score as a prognostic indicator of outcome in patients with head injuries is widely accepted in clinical practice. Traumatic brain stem edema in children is rare, but is associated with poor outcome. The question is that whether it is being aware of computerized tomography appearance of the posterior fossa when initial evaluating pediatric patients with head trauma at emergency clinics. Normal and edematous brain stem without an additional pathology are slightly different and not distinguished easily. On the other hand, brain stem edema should be promptly identified and appropriately treated in a short time.

Cervical intradural disc herniation.

PubMed

Iwamura, Y; Onari, K; Kondo, S; Inasaka, R; Horii, H

2001-03-15

A case report of anterior en bloc resected cervical intradural disc herniation and a review of the literature. To discuss the pathogenesis of cervical intradural disc herniation. Including this study case, only 17 cases of cervical intradural disc herniation have been reported. There have been few detailed reports concerning the pathogenesis of cervical intradural disc herniation. A cervical intradural disc herniation at C6-C7, with localized hypertrophy and segmentally ossified posterior longitudinal ligament, is reported in a 45-year-old man who had Brown-Sequard syndrome diagnosed on neurologic examination. Neuroradiologic, operative, and histologic findings, particularly the pathology of the anterior en bloc resected posterior vertebral portion of C6 and C7, were evaluated for discussion of the pathogenesis. Adhesion of dura mater and hypertrophic posterior longitudinal ligament was observed around a perforated portion of the herniated disc, and histologic study showed irregularity in fiber alignment accompanied by scattered inflammatory cell infiltration and hypertrophy in the posterior longitudinal ligament. The cervical intradural disc herniation was removed successfully and followed by C5-Th1 anterior interbody fusion with fibular strut graft. Neurologic recovery was complete except for minor residual sensory disturbance in the leg 7 years after the surgery. Cervical intradural disc herniation is an extremely rare condition. The pathogenesis remains obscure. Only 16 cases have been reported in the literature, and there has been little discussion concerning the local pathology of the herniated portion. The pathogenesis of the disease in the patient reported here was considered to be the adhesion and fragility of dura mater and posterior longitudinal ligament. This was caused by hypertrophy, with chronic inflammation and ossification of the posterior longitudinal ligament sustaining chronic mechanical irritation to the dura mater, leading to perforation of the herniated disc by an accidental force.

Predictive value of abdominal CT in evaluating internal herniation after bariatric laparoscopic Roux-en-Y gastric bypass.

PubMed

Ederveen, J C; van Berckel, M M G; Nienhuijs, S W; Weber, R J P; Nederend, J

2018-06-04

Internal herniation, a serious complication after bariatric surgery, is challenging to diagnose. The aim of this study was to determine the accuracy of abdominal CT in diagnosing internal herniation. The study included consecutive patients who had undergone laparoscopic gastric bypass surgery between 1 January 2011 and 1 January 2015 at a bariatric centre of excellence. To select patients suspected of having internal herniation, reports of abdominal CT and reoperations up to 1 January 2017 were screened. CT was presumed negative for internal herniation if no follow-up CT or reoperation was performed within 90 days after the initial CT, or no internal herniation was found during reoperation. The accuracy of abdominal CT in diagnosing internal herniation was calculated using two-way contingency tables. A total of 1475 patients were included (84·7 per cent women, mean age 46·5 years, median initial BMI 41·8 kg/m 2 ). CT and/or reoperation was performed in 192 patients (13·0 per cent) in whom internal herniation was suspected. Internal herniation was proven laparoscopically in 37 of these patients. The incidence of internal herniation was 2·5 per cent. An analysis by complaint included a total of 265 episodes, for which 247 CT scans were undertaken. CT was not used to investigate 18 episodes, but internal herniation was encountered in one-third of these during reoperation. Combining the follow-up and intraoperative findings, the accuracy of CT for internal herniation had a sensitivity of 83·8 (95 per cent c.i. 67·3 to 93·2) per cent, a specificity of 87·1 (81·7 to 91·2) per cent, a positive predictive value of 53·4 (40·0 to 66·5) per cent and a negative predictive value of 96·8 (92·9 to 98·7) per cent. Abdominal CT is an important tool in diagnosing internal herniation, with a high specificity and a high negative predictive value. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

Electrical Guidance of Human Stem Cells in the Rat Brain.

PubMed

Feng, Jun-Feng; Liu, Jing; Zhang, Lei; Jiang, Ji-Yao; Russell, Michael; Lyeth, Bruce G; Nolta, Jan A; Zhao, Min

2017-07-11

Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

PubMed

Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

2015-05-01

Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

Degenerative myelopathy and vitamin A deficiency in a young black-maned lion (Panthera leo).

PubMed

Maratea, Kimberly A; Hooser, Stephen B; Ramos-Vara, José A

2006-11-01

Degenerative myelopathy and vitamin A deficiency were diagnosed in a 1-year-old, female, black-maned lion (Panthera leo). Diffuse white matter degeneration characterized by dilated myelin sheaths, Wallerian degeneration, and reactive astrocytosis was present at all levels of the spinal cord. With luxol fast blue-resyl echt violet stain, bilaterally symmetrical demyelination was observed in the fasciculus cuneatus of the cervical spinal cord and in peripheral white matter of cervical, thoracic, and lumbar segments. Additionally, the ventral gray columns and brain stem nuclei contained rare chromatolytic neurons with abnormal neurofilament accumulation. Leptomeninges of the cervical spinal cord were focally adhered to the dura and thickened by fibrosis and osseous metaplasia. Vitamin A deficiency was diagnosed based on hepatic vitamin A concentration of 1.71 microg/g dry weight. Adequate hepatic vitamin A concentration for yearling to adult domestic animals ranges between 150 and 1000 microg/g dry weight. Lesions were distinct from those previously described in young captive lions with vitamin A deficiency, which had thickened skull bones and cerebellar herniation. The pathogenesis of vitamin A-associated myelopathy in this lion may be similar to that described in adult cattle, which is believed to result from spinal cord compression secondary to elevated pressure of cerebrospinal fluid.

Magnetic resonance imaging of the kinked fetal brain stem: a sign of severe dysgenesis.

PubMed

Stroustrup Smith, Annemarie; Levine, Deborah; Barnes, Patrick D; Robertson, Richard L

2005-12-01

Magnetic resonance imaging (MRI) allows visualization of the fetal brain stem in a manner not previously possible. A "kinked" brain stem is a sign of severe neurodysgenesis. The purpose of this series was to describe cases of a kinked brain stem detected on prenatal MRI and to discuss the possible genetic and syndromic etiologies. Seven cases of a kinked brain stem on fetal MRI (gestational age range, 18-34 weeks) were reviewed and correlated with other clinical, genetic, imaging, and autopsy findings. In all cases, there was associated cerebellar hypogenesis. Additional findings were ventriculomegaly (4 cases), cerebral hypogenesis (3 cases), microcephaly (4 cases), schizencephaly (1 case), cephalocele (1 case), hypogenesis of the corpus callosum (1 case), and hydrocephalus (1 case). In 2 cases, prenatal sonography misidentified the kinked brain stem as the cerebellum. A kinked brain stem is an indicator of severe neurodysgenesis arising early in gestation. Magnetic resonance imaging provides the necessary resolution to detect this sign and delineate any associated anomalies in utero to assist with further genetic evaluation, management, and counseling.

Semiautomated volumetry of the cerebrum, cerebellum-brain stem, and temporal lobe on brain magnetic resonance images.

PubMed

Hayashi, Norio; Sanada, Shigeru; Suzuki, Masayuki; Matsuura, Yukihiro; Kawahara, Kazuhiro; Tsujii, Hideo; Yamamoto, Tomoyuki; Matsui, Osamu

2008-02-01

The aim of this study was to develop an automated method of segmenting the cerebrum, cerebellum-brain stem, and temporal lobe simultaneously on magnetic resonance (MR) images. We obtained T1-weighted MR images from 10 normal subjects and 19 patients with brain atrophy. To perform automated volumetry from MR images, we performed the following three steps: (1) segmentation of the brain region; (2) separation between the cerebrum and the cerebellum-brain stem; and (3) segmentation of the temporal lobe. Evaluation was based on the correctly recognized region (CRR) (i.e., the region recognized by both the automated and manual methods). The mean CRRs of the normal and atrophic brains were 98.2% and 97.9% for the cerebrum, 87.9% and 88.5% for the cerebellum-brain stem, and 76.9% and 85.8% for the temporal lobe, respectively. We introduce an automated volumetric method for the cerebrum, cerebellum-brain stem, and temporal lobe on brain MR images. Our method can be applied to not only the normal brain but also the atrophic brain.

MRI patterns in prolonged low response states following traumatic brain injury in children and adolescents.

PubMed

Patrick, Peter D; Mabry, Jennifer L; Gurka, Matthew J; Buck, Marcia L; Boatwright, Evelyn; Blackman, James A

2007-01-01

To explore the relationship between location and pattern of brain injury identified on MRI and prolonged low response state in children post-traumatic brain injury (TBI). This observational study compared 15 children who spontaneously recovered within 30 days post-TBI to 17 who remained in a prolonged low response state. 92.9% of children with brain stem injury were in the low response group. The predicted probability was 0.81 for brain stem injury alone, increasing to 0.95 with a regional pattern of injury to the brain stem, basal ganglia, and thalamus. Low response state in children post-TBI is strongly correlated with two distinctive regions of injury: the brain stem alone, and an injury pattern to the brain stem, basal ganglia, and thalamus. This study demonstrates the need for large-scale clinical studies using MRI as a tool for outcome assessment in children and adolescents following severe TBI.

Childhood Brain Stem Glioma Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood brain stem glioma treatment options can include surgery, radiation therapy, chemotherapy, cerebral spinal fluid diversion, observation, and targeted therapy. Learn more about newly diagnosed and recurrent childhood brain stem glioma in this expert-reviewed summary.

[Brainstem auditory evoked potentials in neurophysiological assessment of brain stem dysfunction in patients with atherostenosis of vertebral arteries].

PubMed

Maksimova, M Yu; Sermagambetova, Zh N; Skrylev, S I; Fedin, P A; Koshcheev, A Yu; Shchipakin, V L; Sinicyn, I A

To assess brain stem dysfunction in patients with hemodynamically significant stenosis of vertebral arteries (VA) using short latency brainstem auditory evoked potentials (BAEP). The study group included 50 patients (mean age 64±6 years) with hemodynamically significant extracranial VA stenosis. Patients with hemodynamically significant extracranial VA stenosis had BAEP abnormalities including the elongation of interpeak intervals I-V and peak V latency as well as the reduction of peak I amplitude. After transluminal balloon angioplasty with stenting of VA stenoses, there was a shortening of peak V latency compared to the preoperative period that reflected the improvement of brain stem conductive functions. Atherostenosis of vertebral arteries is characterized by the signs of brain stem dysfunction, predominantly in the pontomesencephal brain stem. After transluminal balloon angioplasty with stenting of VA, the improvement of brain stem conductive functions was observed.

Effect of ligamenta flava hypertrophy on lumbar disc herniation with contralateral symptoms and signs: a clinical and morphometric study

PubMed Central

Yildizhan, Ahmet; Atar, Elmas K.; Yaycioglu, Soner; Gocmen-Mas, Nuket; Yazici, Canan

2010-01-01

Introduction The purpose of this study was to determine whether ligamentum flavum hypertrophy among disc herniated patients causes contralateral pain symptoms. For this reason we measured the thickness of the ligament in disc herniated patients with ipsilateral or contralateral symptoms. Material and methods Two hundred disc herniated patients with ipsilateral symptoms as group I were compared with five disc herniated patients with only contralateral symptoms as group II. Ligamenta flava thicknesses and spinal canal diameters of both groups were measured on magnetic resonance imaging (MRI) with a micro-caliper. Results Both groups underwent surgery only on the disc herniated side. The total thicknesses of the ligamenta flava in group II was thicker than in group I. There was no spinal stenosis in either group and no significance difference between the groups. Statistically significant differences were found for both ipsilateral and contralateral thickness of the ligament flava in both groups. We also compared thickness of the ligamenta flava for each level of disc herniation in group I; ligamenta flava hypertrophy was more common at L3-L4 and L4-L5 levels of vertebrae in females. Conclusions Aetiology of contralateral sciatica among disc herniated patients may be related to hypertrophy of the ligamenta flava, especially on the opposite side. Surgical approaches of the disc herniated side alone may be sufficient for a good outcome. PMID:22371809

Gap Junction Proteins in the Blood-Brain Barrier Control Nutrient-Dependent Reactivation of Drosophila Neural Stem Cells

PubMed Central

Spéder, Pauline; Brand, Andrea H.

2014-01-01

Summary Neural stem cells in the adult brain exist primarily in a quiescent state but are reactivated in response to changing physiological conditions. How do stem cells sense and respond to metabolic changes? In the Drosophila CNS, quiescent neural stem cells are reactivated synchronously in response to a nutritional stimulus. Feeding triggers insulin production by blood-brain barrier glial cells, activating the insulin/insulin-like growth factor pathway in underlying neural stem cells and stimulating their growth and proliferation. Here we show that gap junctions in the blood-brain barrier glia mediate the influence of metabolic changes on stem cell behavior, enabling glia to respond to nutritional signals and reactivate quiescent stem cells. We propose that gap junctions in the blood-brain barrier are required to translate metabolic signals into synchronized calcium pulses and insulin secretion. PMID:25065772

Idiopathic thoracic transdural intravertebral spinal cord herniation

PubMed Central

Turel, Mazda K; Wewel, Joshua T; Kerolus, Mena G; O'Toole, John E

2017-01-01

Idiopathic spinal cord herniation is a rare and often missed cause of thoracic myelopathy. The clinical presentation and radiological appearance is inconsistent and commonly confused with a dorsal arachnoid cyst and often is a misdiagnosed entity. While ventral spinal cord herniation through a dural defect has been previously described, intravertebral herniation is a distinct entity and extremely rare. We present the case of a 70-year old man with idiopathic thoracic transdural intravertebral spinal cord herniation and discuss the clinico-radiological presentation, pathophysiology and operative management along with a review the literature of this unusual entity. PMID:29021685

MRI-Based Measurement of Brain Stem Cross-Sectional Area in Relapsing-Remitting Multiple Sclerosis.

PubMed

Chivers, Tomos R; Constantinescu, Cris S; Tench, Christopher R

2015-01-01

To determine if patients with relapsing-remitting multiple sclerosis (RRMS) have a reduced brain stem cross-sectional area (CSA) compared to age- and sex-matched controls. The brain stem is a common site of involvement in MS. However, relatively few imaging studies have investigated brain stem atrophy. Brain magnetic resonance imaging (MRI) was performed on patients and controls using a 1.5T MRI scanner with a quadrature head coil. Three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) images with 128 contiguous slices, covering the whole brain and brain stem and a T2-weighted image with 3 mm transverse contiguous images were acquired. We measured the brain stem CSA at three sites, the midbrain, the pons, and the medulla oblongata in 35 RRMS patients and 35 controls using a semiautomated algorithm. CSA readings were normalized using the total external cranial volume to reduce normal population variance and increase statistical power. A significant CSA reduction was found in the midbrain (P ≤ .001), pons (P ≤ .001), and the medulla oblongata (P = .047) postnormalization. A CSA reduction of 9.3% was found in the midbrain, 8.7% in the pons, and 6.5% in the medulla oblongata. A significantly reduced, normalized brain stem CSA was detected in all areas of the brain stem of the RRMS patients, when compared to age- and gender-matched controls. Lack of detectable upper cervical cord atrophy in the same patients suggests some independence of the MS pathology in these regions. Copyright © 2015 by the American Society of Neuroimaging.

Training stem cells for treatment of malignant brain tumors

PubMed Central

Li, Shengwen Calvin; Kabeer, Mustafa H; Vu, Long T; Keschrumrus, Vic; Yin, Hong Zhen; Dethlefs, Brent A; Zhong, Jiang F; Weiss, John H; Loudon, William G

2014-01-01

The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system. PMID:25258664

Magnetic Resonance Imaging Interpretation in Patients With Symptomatic Lumbar Spine Disc Herniations

PubMed Central

Lurie, Jon D.; Doman, David M.; Spratt, Kevin F.; Tosteson, Anna N. A.; Weinstein, James N.

2009-01-01

Study Design Retrospective review of imaging data from a clinical trial. Objective To compare the interpretation of lumbar spine magnetic resonance imaging (MRIs) by clinical spine specialists and radiologists in patients with lumbar disc herniation. Summary of Background Data MRI is the imaging modality of choice for evaluation of the lumbar spine in patients with suspected lumbar disc herniation. Guidelines provide standardization of terms to more consistently describe disc herniation. The extent to which these guidelines are being followed in clinical practice is unknown. Methods We abstracted data from radiology reports from patients with lumbar intervertebral disc herniation enrolled in the Spine Patient Outcomes Research Trial. We evaluated the frequency with which morphology (e.g., protrusions, extrusions, or sequestrations) was reported as per guidelines and when present we compared the morphology ratings to those of clinicians who completed a structured data form as part of the trial. We assessed agreement using percent agreement and the κ statistic. Results There were 396 patients with sufficient data to analyze. Excellent agreement was observed between clinician and radiologist on the presence and level of herniation (93.4%), with 3.3% showing disagreement regarding level, of which a third could be explained by the presence of a transitional vertebra. In 3.3% of the cases in which the clinician reported a herniation (protrusion, extrusion, or sequestration), the radiologist reported no herniation on the MRI. The radiology reports did not clearly describe morphology in 42.2% of cases. In the 214 cases with clear morphologic descriptions, agreement was fair (κ = 0.24) and the disagreement was asymmetric (Bowker’s test of symmetry P < 0.0001) with clinicians more often rating more abnormal morphologic categories. Agreement on axial location of the herniation was excellent (κ = 0.81). There was disagreement between left or right side in only 3.3% of cases (κ = 0.93). Conclusion Radiology reports frequently fail to provide sufficient detail to describe disc herniation morphology. Agreement between MRI readings by clinical spine specialists and radiologists was excellent when comparing herniation vertebral level and location within level, but only fair comparing herniation morphology. PMID:19333103

[Epidemiology investigation and biomechanics analyses for the correlation between sacroiliac joint disorder and lumbar intervertebral disc degeneration].

PubMed

Shi, Ning-Ning; Shen, Guo-Quan; He, Shui-Yong; Guo, Ru-Bao

2014-07-01

To study the correlation between lumber disc degeneration and sacroiliac joint disorder, in order to provides a new understanding concepts and therapeutic approach for the prevention and treatment of chronic intractable low back pain. From August 2009 to October 2010,129 cases with lumbar disc herniation were studied with epidemiological methods. Among them, 61 patients with L4, disc herniation included 37 males and 24 females, ranging in aged from 20 to 75 years old, duration of the disease ranged from 1 to 144 months; The other 68 patients with L5S1 disc herniation included 32 males and 36 females,ranging in aged froml8 to 76 years old,duration of the disease ranged from 0.5 to 240 months. The clinical data, symptoms and signs,X-ray characteristics of lumbar spine and pelvis of the patients were investigated by epidemiological. The risk of lumbar disc herniation was calculated with case-control study; independent variables were screened with single factor analysis; the risk factors for lumbar disc herniation were determined with logistic regression analysis, and biomechanics analyses were taken. Among 129 patients with lumbar disc herniation, 88 cases associated with sacroiliac joint disorders, sacroiliac joint disorder was a risk factor of lumbar disc herniation (OR = 4.61, P = 0.00); 47 cases associated with sacroiliac joint disorders in 61 patients with L4,5 disc herniation, iliac crest uneven caused by iliac rotational displacement was a high risk factor of L4,5 disc herniation (OR = 11.27, P = 0.00); 41 cases associated with sacroiliac joint disorders in 68 patients with L5S1 disc herniation, lumbar sacral angle abnormalities caused by sacral tilt shift was a high risk factor L5S1 disc herniation (OR = 2.31, P = 0.03). Lumbar disc herniation and sacroiliac joint disorder are two of fallot, the two factors affect each other and there is a causal relationship. They are common exists in low back pain.

Edema and elasticity of a fronto-temporal decompressive craniectomy

PubMed Central

Takada, Daikei; Nagai, Hidemasa; Moritake, Kouzo; Akiyama, Yasuhiko

2012-01-01

Background: Decompressive craniectomy is undertaken for relief of brain herniation caused by acute brain swelling. Brain stiffness can be estimated by palpating the decompressive cranial defect and can provide some relatively subjective information to the neurosurgeon to help guide care. The goal of the present study was to objectively evaluate transcutaneous stiffness of the cranial defect using a tactile resonance sensor and to describe the values in patients with a decompressive window in order to characterize the clinical association between brain edema and stiffness. Methods: Data were prospectively collected from 13 of 37 patients who underwent a decompressive craniectomy in our hospital during a 5-year period. Transcutaneous stiffness was measured as change in frequency and as elastic modulus. Results: Stiffness variables of the decompressive site were measured without any adverse effect and subsequent calculations revealed change in frequency = 101.71 ± 36.42 Hz, and shear elastic modulus = 1.99 ± 1.11 kPa. Conclusions: The elasticity of stiffness of a decompressive site correlated with brain edema, cisternal cerebrospinal fluid pressure, and brain shift, all of which are related to acute brain edema. PMID:22347679

Nuclear factor-kappa B decoy suppresses nerve injury and improves mechanical allodynia and thermal hyperalgesia in a rat lumbar disc herniation model.

PubMed

Suzuki, Munetaka; Inoue, Gen; Gemba, Takefumi; Watanabe, Tomoko; Ito, Toshinori; Koshi, Takana; Yamauchi, Kazuyo; Yamashita, Masaomi; Orita, Sumihisa; Eguchi, Yawara; Ochiai, Nobuyasu; Kishida, Shunji; Takaso, Masashi; Aoki, Yasuchika; Takahashi, Kazuhisa; Ohtori, Seiji

2009-07-01

Nuclear factor-kappa B (NF-kappaB) is a gene transcriptional regulator of inflammatory cytokines. We investigated the transduction efficiency of NF-kappaB decoy to dorsal root ganglion (DRG), as well as the decrease in nerve injury, mechanical allodynia, and thermal hyperalgesia in a rat lumbar disc herniation model. Forty rats were used in this study. NF-kappaB decoy-fluorescein isothiocyanate (FITC) was injected intrathecally at the L5 level in five rats, and its transduction efficiency into DRG measured. In another 30 rats, mechanical pressure was placed on the DRG at the L5 level and nucleus pulposus harvested from the rat coccygeal disc was transplanted on the DRG. Rats were classified into three groups of ten animals each: a herniation + decoy group, a herniation + oligo group, and a herniation only group. For behavioral testing, mechanical allodynia and thermal hyperalgesia were evaluated. In 15 of the herniation rats, their left L5 DRGs were resected, and the expression of activating transcription factor 3 (ATF-3) and calcitonin gene-related peptide (CGRP) was evaluated immunohistochemically compared to five controls. The total transduction efficiency of NF-kappaB decoy-FITC in DRG neurons was 10.8% in vivo. The expression of CGRP and ATF-3 was significantly lower in the herniation + decoy group than in the other herniation groups. Mechanical allodynia and thermal hyperalgesia were significantly suppressed in the herniation + decoy group. NF-kappaB decoy was transduced into DRGs in vivo. NF-kappaB decoy may be useful as a target for clarifying the mechanism of sciatica caused by lumbar disc herniation.

Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

PubMed

Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-06-01

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

IDH1 Mutation in Brain Stem Glioma: Case Report and Review of Literature.

PubMed

Javadi, Seyed Amirhossein; Hartmann, Christian; Walter, Gerhard Franz; Banan, Roozbeh; Samii, Amir

2018-01-01

The role of isocitrate dehydrogenase 1 (IDH1) mutation in brain stem glioma is not clear. To the best of our knowledge, six cases of brain stem gliomas carrying IDH1/2 mutations are currently reported in the literature. One case of diffuse brain stem glioma with IDH1 mutation, which was followed for 2 years, is presented and compared with IDH1 negative tumors. A 22-year-old lady was referred with diplopia and left arm palsy. Neuroimaging detected a nonenhancing, nonhomogeneous diffuse infiltrating brain stem tumor extending from pons to medulla. Microsurgical debulking was performed. Microscopic evaluation of the tissue specimen and immunohistochemistry revealed an astrocytoma WHO Grade II with proliferation rate of 3% and glial fibrillary acidic protein (GFAP)-positive tumor cells. Interestingly, the tumor cells expressed mutated IDH1 R132H protein. The patient underwent adjuvant radiation and chemotherapy. The primary and 2 years' clinical/radiological characteristics did not indicate any significant difference from other cases without IDH1 mutation. the prognostic value of IDH1/2 mutation in brain stem glioma is unclear. Brain stem biopsies may allow determination of a tissue-based tumor diagnosis for further investigations.

Volumetric evaluation of the relations among the cerebrum, cerebellum and brain stem in young subjects: a combination of stereology and magnetic resonance imaging.

PubMed

Ekinci, Nihat; Acer, Niyazi; Akkaya, Akcan; Sankur, Seref; Kabadayi, Taner; Sahin, Bünyamin

2008-08-01

The Cavalieri estimator using a point grid is used to estimate the volume of three-dimensional structures based on two-dimensional slices of the object. The size of the components of intracranial neural structures should have proportional relations among them. The volume fraction approach of stereological methods provides information about volumetric relations of the components of structures. The purpose of our study is to estimate the volume and volume fraction data related to the cerebrum, cerebellum and brain stem. In this study, volume of the total brain, cerebrum, cerebellum and brain stem were estimated in 24 young Turkish volunteers (12 males and 12 females) who are free of any neurological symptoms and signs. The volume and volume fraction of the total brain, cerebrum, cerebellum and brain stem were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods. The mean (+/-SD) total brain, cerebrum and cerebellum volumes were 1,202.05 +/- 103.51, 1,143.65 +/- 106.25 cm3 in males and females, 1,060.0 +/- 94.6, 1,008.9 +/- 104.3 cm3 in males and females, 117.75 +/- 10.7, 111.83 +/- 8.0 cm3 in males and females, respectively. The mean brain stem volumes were 24.3 +/- 2.89, 22.9 +/- 4.49 cm3 in males and females, respectively. Our results revealed that female subjects have less cerebral, cerebellar and brain stem volumes compared to males, although there was no statistically significant difference between genders (P > 0.05). The volume ratio of the cerebrum to total brain volume (TBV), cerebellum to TBV and brain stem to TBV were 88.16 and 88.13% in males and females, 9.8 and 9.8% in males and females, 2.03 and 2.03% in males and females, respectively. The volume ratio of the cerebellum to cerebrum, brain stem to cerebrum and brain stem to cerebellum were 11.12 and 11.16% in males and females, 2.30 and 2.31% in males and females, 20.7 and 20.6% in males and females, respectively. The difference between the genders was not statistically significant (P > 0.05). Our results revealed that the volumetric composition of the cerebrum, cerebellum and brain stem does not show sexual dimorphism.

Expansion of Multipotent Stem Cells from the Adult Human Brain

PubMed Central

Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

2013-01-01

The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse.

PubMed

Jean-Xavier, Céline; Perreault, Marie-Claude

2018-01-01

The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs) during drug-induced fictive locomotor-like activity (LLA) in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC) and hindlimb MNs in lateral motor column (LMC). The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor.

Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse

PubMed Central

Jean-Xavier, Céline; Perreault, Marie-Claude

2018-01-01

The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs) during drug-induced fictive locomotor-like activity (LLA) in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC) and hindlimb MNs in lateral motor column (LMC). The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor. PMID:29479302

Osthole Enhances the Therapeutic Efficiency of Stem Cell Transplantation in Neuroendoscopy Caused Traumatic Brain Injury.

PubMed

Tao, Zhen-Yu; Gao, Peng; Yan, Yu-Hui; Li, Hong-Yan; Song, Jie; Yang, Jing-Xian

2017-01-01

Neuroendoscopy processes can cause severe traumatic brain injury. Existing therapeutic methods, such as neural stem cell transplantation and osthole have not been proven effective. Therefore, there is an emerging need on the development of new techniques for the treatment of brain injuries. In this study we propose to combine the above stem cell based methods and then evaluate the efficiency and accuracy of the new method. Mice were randomly divided into four groups: group 1 (brain injury alone); group 2 (osthole); group 3 (stem cell transplantation); and group 4 (osthole combined with stem cell transplantation). We carried out water maze task to exam spatial memory. Immunocytochemistry was used to test the inflammatory condition of each group, and the differentiation of stem cells. To evaluate the condition of the damaged blood brain barrier restore, we detect the Evans blue (EB) extravasation across the blood brain barrier. The result shows that osthole and stem cell transplantation combined therapeutic method has a potent effect on improving the spatial memory. This combined method was more effective on inhibiting inflammation and preventing neuronal degeneration than the single treated ones. In addition, there was a distinct decline of EB extravasation in the combined treatment groups, which was not observed in single treatment groups. Most importantly, the combined usage of osthole and stem cell transplantation provide a better treatment for the traumatic brain injury caused by neuroendoscopy. The collective evidence indicates osthole combined with neural stem cell transplantation is superior than either method alone for the treatment of traumatic brain injury caused by neuroendoscopy.

Isolated brain stem lesion in children: is it acute disseminated encephalomyelitis or not?

PubMed

Alper, G; Sreedher, G; Zuccoli, G

2013-01-01

Isolated brain stem lesions presenting with acute neurologic findings create a major diagnostic dilemma in children. Although the brain stem is frequently involved in ADEM, solitary brain stem lesions are unusual. We performed a retrospective review in 6 children who presented with an inflammatory lesion confined to the brain stem. Two children were diagnosed with connective tissue disorder, CNS lupus, and localized scleroderma. The etiology could not be determined in 1, and clinical features suggested monophasic demyelination in 3. In these 3 children, initial lesions demonstrated vasogenic edema; all showed dramatic response to high-dose corticosteroids and made a full clinical recovery. Follow-up MRI showed complete resolution of lesions, and none had relapses at >2 years of follow-up. In retrospect, these cases are best regarded as a localized form of ADEM. We conclude that though ADEM is typically a disseminated disease with multifocal lesions, it rarely presents with monofocal demyelination confined to the brain stem.

Brainstem death: A comprehensive review in Indian perspective

PubMed Central

Dhanwate, Anant Dattatray

2014-01-01

With the advent of cardiopulmonary resuscitation techniques, the cardiopulmonary definition of death lost its significance in favor of brain death. Brain death is a permanent cessation of all functions of the brain in which though individual organs may function but lack of integrating function of the brain, lack of respiratory drive, consciousness, and cognition confirms to the definition that death is an irreversible cessation of functioning of the organism as a whole. In spite of medical and legal acceptance globally, the concept of brain death and brain-stem death is still unclear to many. Brain death is not promptly declared due to lack of awareness and doubts about the legal procedure of certification. Many brain dead patients are kept on life supporting systems needlessly. In this comprehensive review, an attempt has been made to highlight the history and concept of brain death and brain-stem death; the anatomical and physiological basis of brain-stem death, and criteria to diagnose brain-stem death in India. PMID:25249744

Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model.

PubMed

Jensen, Stine Skov; Meyer, Morten; Petterson, Stine Asferg; Halle, Bo; Rosager, Ann Mari; Aaberg-Jessen, Charlotte; Thomassen, Mads; Burton, Mark; Kruse, Torben A; Kristensen, Bjarne Winther

2016-01-01

Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking invasion and tumor stemness into account. Glioblastoma stem cell-like containing spheroid (GSS) cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models. We observed a pronounced invasion into brain slice cultures both by confocal time-lapse microscopy and immunohistochemistry. This invasion closely resembled the invasion in vivo. The Ki-67 proliferation indexes in spheroids implanted into brain slices were lower than in free-floating spheroids. The expression of stem cell markers varied between free-floating spheroids, spheroids implanted into brain slices and tumors in vivo. The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we suggest the model as an in vivo-like model with a great potential in glioma studies and drug discovery.

Intracerebral venous thrombosis and hematoma secondary to high-voltage brain injury.

PubMed

Sure, U; Kleihues, P

1997-06-01

We report the case of a 19-year-old male who sustained an electrodynamic (16.67 Hz) high-voltage (15,000 V) railway overhead cable injury. He lost consciousness 30 minutes after contact and died secondary to brainstem herniation as a result of intracerebral swelling within 8 days. Repeated cranial computed tomography revealed a huge hemispheric mass bleeding accompanied by subarachnoidal hemorrhage. Additionally, necropsy showed an extensive thrombosis of the adjacent cerebral veins. The pathophysiological mechanism of this unusual injury is discussed.

Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

PubMed

Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V

2013-01-01

Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

The Implications of the Cancer Stem Cell Hypothesis for Neuro-Oncology and Neurology.

PubMed

Rich, Jeremy N

2008-05-01

The cancer stem cell hypothesis posits that cancers contain a subset of neoplastic cells that propagate and maintain tumors through sustained self-renewal and potent tumorigenecity. Recent excitement has been generated by a number of reports that have demonstrated the existence of cancer stem cells in several types of brain tumors. Brain cancer stem cells - also called tumor initiating cells or tumor propagating cells - share features with normal neural stem cells but do not necessarily originate from stem cells. Although most cancers have only a small fraction of cancer stem cells, these tumor cells have been shown in laboratory studies to contribute to therapeutic resistance, formation of new blood vessels to supply the tumor, and tumor spread. As malignant brain tumors rank among the deadliest of all neurologic diseases, the identification of new cellular targets may have profound implications in neuro-oncology. Novel drugs that target stem cell pathways active in brain tumors have been efficacious against cancer stem cells suggesting that anti-cancer stem cell therapies may advance brain tumor therapy. The cancer stem cell hypothesis may have several implications for other neurologic diseases as caution must be exercised in activating stem cell maintenance pathways in cellular therapies for neurodegenerative diseases. The ability for a small fraction of cells to determine the overall course of a disease may also inform new paradigms of disease that may translate into improved patient outcomes.

Disc herniations in the national football league.

PubMed

Gray, Benjamin L; Buchowski, Jacob M; Bumpass, David B; Lehman, Ronald A; Mall, Nathan A; Matava, Matthew J

2013-10-15

Retrospective analysis of a prospectively collected database. To determine the overall incidence, location, and type of disc herniations in professional football players to target treatment issues and prevention. Disc herniations represent a common and debilitating injury to the professional athlete. The NFL's (National Football League's) Sports Injury Monitoring System is a surveillance database created to monitor the league for all injuries, including injuries to the cervical, thoracic, and lumbar spine. A retrospective analysis was performed on all disc herniations to the cervical, thoracic, and lumbar spine during a 12-season period (2000-2012) using the NFL's surveillance database. The primary data points included the location of the injury, player position, activity at time of injury, and playing time lost due to injury. During the 12 seasons, 275 disc herniations occurred in the spine. In regard to location, 76% occurred in the lumbar spine and most frequently affected the L5-S1 disc. The offensive linemen were most frequently injured. As expected, blocking was the activity that caused most injuries. Lumbar disc herniations rose in prevalence and had a mean loss of playing time of more than half the season (11 games). Thoracic disc herniations led to the largest mean number of days lost overall, whereas players with cervical disc herniations missed the most practices. Disc herniations represent a significant cause of morbidity in the NFL. Although much attention is placed on spinal cord injuries, preventive measures targeting the cervical, thoracic, and lumbar spine may help to reduce the overall incidence of these debilitating injuries.Level of Evidence: N/A.

Disc herniations in the National Football League.

PubMed

Gray, Benjamin L; Buchowski, Jacob M; Bumpass, David B; Lehman, Ronald A; Mall, Nathan A; Matava, Matthew J

2013-10-15

Retrospective analysis of a prospectively collected database. To determine the overall incidence, location, and type of disc herniations in professional football players to target treatment issues and prevention. Disc herniations represent a common and debilitating injury to the professional athlete. The NFL's (National Football League's) Sports Injury Monitoring System is a surveillance database created to monitor the league for all injuries, including injuries to the cervical, thoracic, and lumbar spine. A retrospective analysis was performed on all disc herniations to the cervical, thoracic, and lumbar spine during a 12-season period (2000–2012) using the NFL's surveillance database. The primary data points included the location of the injury, player position, activity at time of injury, and playing time lost due to injury. During the 12 seasons, 275 disc herniations occurred in the spine. In regard to location, 76% occurred in the lumbar spine and most frequently affected the L5–S1 disc. The offensive linemen were most frequently injured. As expected, blocking was the activity that caused most injuries. Lumbar disc herniations rose in prevalence and had a mean loss of playing time of more than half the season (11 games). Thoracic disc herniations led to the largest mean number of days lost overall, whereas players with cervical disc herniations missed the most practices. Disc herniations represent a significant cause of morbidity in the NFL. Although much attention is placed on spinal cord injuries, preventive measures targeting the cervical, thoracic, and lumbar spine may help to reduce the overall incidence of these debilitating injuries. N/A

Quantitative assessment of brain stem and cerebellar atrophy in spinocerebellar ataxia types 3 and 6: impact on clinical status.

PubMed

Eichler, L; Bellenberg, B; Hahn, H K; Köster, O; Schöls, L; Lukas, C

2011-05-01

Cerebellar and brain stem atrophy are important features in SCA3, whereas SCA6 has been regarded as a "pure" cerebellar disease. However, recent neuropathologic studies have described additional brain stem involvement in SCA6. We, therefore, aimed to investigate the occurrence and impact of regional infratentorial brain volume differences in patients with SCA3 and SCA6. Thirty-four patients with genetically proved SCA (SCA3, n = 17; SCA6, n = 17) and age-matched healthy control subjects (n = 51) were included. In all subjects, high-resolution T1-weighted images were acquired with a 1.5T MR imaging scanner. Individual brain stem and cerebellar volumes were calculated by using semiautomated volumetry approaches. For all patients with SCA, clinical dysfunction was scored according to the ICARS. Multiple regression analysis was used to identify the contribution of regional volumes to explain the variance in clinical dysfunction in each SCA genotype. Cerebellar volumes were lower in patients with SCA6 compared with controls and with those with SCA3. In contrast to controls, brain stem volume loss was observed in patients with SCA3 (P < .001) and, to a lesser extent, in those with SCA6 (P = .027). Significant linear dependencies were found between ICARS and cerebellum volume (SCA3: R(2) = 0.29, P = .02; SCA6: R(2) = 0.29, P = .03) and between ICARS and brain stem volume (SCA3: R(2) = 0.49, P = .002; SCA6: R(2) = 0.39, P < .01) in both subtypes. Both cerebellar and brain stem atrophy contributed independently to the variance in clinical dysfunction in SCA6, while in SCA3, only brain stem atrophy was of relevance. Our current findings in accordance with recent neuroradiologic and pathoanatomic studies suggest brain stem and cerebellar volume loss as attractive surrogate markers of disease severity in SCA3 and SCA6.

Effect of cell therapy on recovery of cognitive functions in rats during the delayed period after brain injury.

PubMed

Roshal, L M; Tzyb, A F; Pavlova, L N; Soushkevitch, G N; Semenova, J B; Javoronkov, L P; Kolganova, O I; Konoplyannikov, A G; Shevchuk, A S; Yujakov, V V; Karaseva, O V; Ivanova, T F; Chernyshova, T A; Konoplyannikova, O A; Bandurko, L N; Marey, M V; Sukhikh, G T

2009-07-01

We studied the effect of systemic transplantation of human stem cells from various tissues on cognitive functions of the brain in rats during the delayed period after experimental brain injury. Stem cells were shown to increase the efficacy of medical treatment with metabolic and symptomatic drugs for recovery of cognitive functions. They accelerated the formation of the conditioned defense response. Fetal neural stem cells had a stronger effect on some parameters of cognitive function 2 months after brain injury. The efficacy of bone marrow mesenchymal stem cells from adult humans or fetuses was higher 3 months after brain injury.

New Clinically Feasible 3T MRI Protocol to Discriminate Internal Brain Stem Anatomy.

PubMed

Hoch, M J; Chung, S; Ben-Eliezer, N; Bruno, M T; Fatterpekar, G M; Shepherd, T M

2016-06-01

Two new 3T MR imaging contrast methods, track density imaging and echo modulation curve T2 mapping, were combined with simultaneous multisection acquisition to reveal exquisite anatomic detail at 7 canonical levels of the brain stem. Compared with conventional MR imaging contrasts, many individual brain stem tracts and nuclear groups were directly visualized for the first time at 3T. This new approach is clinically practical and feasible (total scan time = 20 minutes), allowing better brain stem anatomic localization and characterization. © 2016 by American Journal of Neuroradiology.

Stem cells for brain repair in neonatal hypoxia-ischemia.

PubMed

Chicha, L; Smith, T; Guzman, R

2014-01-01

Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

Lumbar disc herniation in young children.

PubMed

Haidar, R; Ghanem, I; Saad, S; Uthman, I

2010-01-01

This article explores lumbar disc herniation in young children through focusing on matters relevant to patient presentation, physical examination, differential diagnosis, imaging and treatment. Major databases were searched for studies that addressed lumbar disc herniation in young children. Diagnosis of lumbar disc herniation in young children is usually delayed because of the rarity and lack of experience with this entity and the difficulty in extracting a reliable medical history. Nevertheless, lumbar disc herniation should be considered in the differential diagnosis of any young child presenting with a chief complaint of back pain and/or radiculopathy, especially in the setting of recent trauma. This should be coupled with a directed physical examination to elicit signs and narrow the differential diagnosis. Imaging studies, mainly magnetic resonance imaging, will help establish a diagnosis; yet radiographs are still required to exclude other spinal lesions. The initial management of lumbar disc herniation in children is the same as that in adults and consists of conservative treatment unless lumbar disc herniation affects the patient's motor and neurological functions in which case, early surgical treatment must be undertaken. Although the latter remains more difficult, current experience suggests a favourable outcome. Awareness of lumbar disc herniation will help the paediatrician extract a relevant medical history, perform a directed physical examination, and order appropriate imaging studies. This will aid in initiating early intervention, be it conservative or operative, and achieving a favourable outcome.

Brain Cancer Stem Cells Display Preferential Sensitivity to Akt Inhibition

PubMed Central

Eyler, Christine E.; Foo, Wen-Chi; LaFiura, Katherine M.; McLendon, Roger E.; Hjelmeland, Anita B.; Rich, Jeremy N.

2009-01-01

Malignant brain tumors are among the most lethal cancers, and conventional therapies are largely limited to palliation. Novel therapies targeted against specific molecular pathways may offer improved efficacy and reduced toxicity compared to conventional therapies, but initial clinical trials of molecular targeted agents in brain cancer therapy have been frequently disappointing. In brain tumors and other cancers, subpopulations of tumor cells have recently been characterized by their ability to self-renew and initiate tumors. Although these cancer stem cells, or tumor initiating cells, are often only present in small numbers in human tumors, mounting evidence suggests that cancer stem cells contribute to tumor maintenance and therapeutic resistance. Thus, the development of therapies that target cancer stem cell signal transduction and biologies may improve brain tumor patient survival. We now demonstrate that populations enriched for cancer stem cells are preferentially sensitive to an inhibitor of Akt, a prominent cell survival and invasion signaling node. Treatment with an Akt inhibitor more potently reduced the numbers of viable brain cancer stem cells relative to matched non-stem cancer cells associated with a preferential induction of apoptosis and a suppression of neurosphere formation. Akt inhibition also reduced the motility and invasiveness of all tumor cells but had a greater impact on cancer stem cell behaviors. Furthermore, inhibition of Akt activity in cancer stem cells increased survival of immunocompromised mice bearing human glioma xenografts in vivo. Together, these results suggest that Akt inhibitors may function as effective anti-cancer stem cell therapies. PMID:18802038

Lumbar spinal canal MRI diameter is smaller in herniated disc cauda equina syndrome patients

PubMed Central

Kruit, Mark C.; Peul, Wilco C.; Vleggeert-Lankamp, Carmen L. A.

2017-01-01

Introduction Correlation between magnetic resonance imaging (MRI) and clinical features in cauda equina syndrome (CES) is unknown; nor is known whether there are differences in MRI spinal canal size between lumbar herniated disc patients with CES versus lumbar herniated discs patients without CES, operated for sciatica. The aims of this study are 1) evaluating the association of MRI features with clinical presentation and outcome of CES and 2) comparing lumbar spinal canal diameters of lumbar herniated disc patients with CES versus lumbar herniated disc patients without CES, operated because of sciatica. Methods MRIs of CES patients were assessed for the following features: level of disc lesion, type (uni- or bilateral) and severity of caudal compression. Pre- and postoperative clinical features (micturition dysfunction, defecation dysfunction, altered sensation of the saddle area) were retrieved from the medical files. In addition, anteroposterior (AP) lumbar spinal canal diameters of CES patients were measured at MRI. AP diameters of lumbar herniated disc patients without CES, operated for sciatica, were measured for comparison. Results 48 CES patients were included. At MRI, bilateral compression was seen in 82%; complete caudal compression in 29%. MRI features were not associated with clinical presentation nor outcome. AP diameter was measured for 26 CES patients and for 31 lumbar herniated disc patients without CES, operated for sciatica. Comparison displayed a significant smaller AP diameter of the lumbar spinal canal in CES patients (largest p = 0.002). Compared to average diameters in literature, diameters of CES patients were significantly more often below average than that of the sciatica patients (largest p = 0.021). Conclusion This is the first study demonstrating differences in lumbar spinal canal size between lumbar herniated disc patients with CES and lumbar herniated disc patients without CES, operated for sciatica. This finding might imply that lumbar herniated disc patients with a relative small lumbar spinal canal might need to be approached differently in managing complaints of herniated disc. Since the number of studied patients is relatively small, further research should be conducted before clinical consequences are considered. PMID:29023556

A Novel Modality for Functional Imaging in Acute Intervertebral Disk Herniation via Tracking Leukocyte Infiltration.

PubMed

Xiao, Li; Ding, Mengmeng; Zhang, Yi; Chordia, Mahendra; Pan, Dongfeng; Shimer, Adam; Shen, Francis; Glover, David; Jin, Li; Li, Xudong

2017-10-01

Inflammation plays a key role in the progression of intervertebral disk (IVD) herniation and associated low back pain. However, real-time spatial diagnosis of inflammation associated with acute disk herniation has not been investigated. We sought to detect local neutrophil and macrophage infiltration near disk herniation via the formyl peptide receptor 1 (FPR1)-mediated molecular imaging in a disk puncture mouse model to elucidate pathophysiological process of disk herniation. Disk herniation was induced in mouse with an established needle puncture procedure. Degenerative change of disk and infiltration of neutrophils and macrophages were detected with Safranin-O, hematoxylin and eosin (H&E), and immunohistochemical staining after injury. FPR1-specific imaging probes cFLFLF-PEG-Cy7 and [ 99m Tc]HYNIC-PEG-cFLFLF were administered systemically to sham and disk injury mice. Leukocyte infiltration was tracked by in vivo near-infrared fluorescence (NIRF) and single-photon emission tomography (SPECT) imaging. The peptide-receptor binding specificity was further investigated with FPR1 -/- mice via ex vivo NIRF scan and in vitro binding assays. Safranin-O staining exhibited disorganized disk structure and loss of proteoglycan after puncture. Massive inflammatory cells were observed in the anterior region of punctured annulus in the injury group. The majority of neutrophils were detected at 1 through 3 days, while infiltration of macrophages appeared the most at 7 days after injury. NIRF and SPECT images revealed preferential accumulation of cFLFLF probes in herniation site in wild-type mice but not in FPR1 -/- mice. Binding of the cFLFLF peptide to FPR1 was also observed in RAW 267.4 cells and macrophages isolated from wild-type mice, whereas much less signal was observed in macrophages from FPR1 -/- mice. The presence of macrophage infiltration was also detected in human-herniated disk samples by immunohistochemistry. For the first time, leukocyte infiltration around acute disk herniation site was detected directly and non-invasively in a timely fashion using FPR1-targeted molecular imaging modalities. Such functional imaging of disk herniation via infiltrated leukocytes would advance the understanding of etiology and facilitate drug delivery and treatment monitoring of disk herniation.

Magnetic resonance imaging in follow-up assessment of sciatica.

PubMed

el Barzouhi, Abdelilah; Vleggeert-Lankamp, Carmen L A M; Lycklama à Nijeholt, Geert J; Van der Kallen, Bas F; van den Hout, Wilbert B; Jacobs, Wilco C H; Koes, Bart W; Peul, Wilco C

2013-03-14

Magnetic resonance imaging (MRI) is frequently performed during follow-up in patients with known lumbar-disk herniation and persistent symptoms of sciatica. The association between findings on MRI and clinical outcome is controversial. We studied 283 patients in a randomized trial comparing surgery and prolonged conservative care for sciatica and lumbar-disk herniation. Patients underwent MRI at baseline and after 1 year. We used a 4-point scale to assess disk herniation on MRI, ranging from 1 for "definitely present" to 4 for "definitely absent." A favorable clinical outcome was defined as complete or nearly complete disappearance of symptoms at 1 year. We compared proportions of patients with a favorable outcome among those with a definite absence of disk herniation and those with a definite, probable, or possible presence of disk herniation at 1 year. The area under the receiver-operating-characteristic (ROC) curve was used to assess the prognostic accuracy of the 4-point scores regarding a favorable or unfavorable outcome, with 1 indicating perfect discriminatory value and 0.5 or less indicating no discriminatory value. At 1 year, 84% of the patients reported having a favorable outcome. Disk herniation was visible in 35% with a favorable outcome and in 33% with an unfavorable outcome (P=0.70). A favorable outcome was reported in 85% of patients with disk herniation and 83% without disk herniation (P=0.70). MRI assessment of disk herniation did not distinguish between patients with a favorable outcome and those with an unfavorable outcome (area under ROC curve, 0.48). MRI performed at 1-year follow-up in patients who had been treated for sciatica and lumbar-disk herniation did not distinguish between those with a favorable outcome and those with an unfavorable outcome. (Funded by the Netherlands Organization for Health Research and Development and the Hoelen Foundation; Controlled Clinical Trials number, ISRCTN26872154.).

Brain-stem laceration and blunt rupture of thoracic aorta: is the intrapleural bleeding postmortem in origin?: an autopsy study.

PubMed

Zivković, Vladimir; Nikolić, Slobodan; Babić, Dragan; Juković, Fehim

2011-12-01

Some of the fatally injured car occupants could have had both blunt rupture of thoracic aorta with great amount of intrapleural blood, and pontomedullar laceration of brain-stem as well, with both injuries being fatal. The aim of this study was to answer if all intrapleural bleeding in these cases was antemortem, or the bleeding could also be partially postmortem. We observed the group of 66 cases of blunt aortic rupture: 21 case with brain-stem laceration, and 45 cases without it. The average amount of intrapleural bleeding in cases without brain-stem laceration (1993 ± 831 mL) was significantly higher than in those with this injury (1100 ± 708 mL) (t = 4.252, df = 64, P = 0.000). According to our results, in cases of the thoracic aorta rupture with concomitant brain-stem laceration, the amount of intrapleural bleeding less than 1500 mL, should be considered mostly as postmortem in origin, and in such cases, only the brain-stem injury should be considered as cause of death.

High-fat diet-induced downregulation of anorexic leukemia inhibitory factor in the brain stem.

PubMed

Licursi, Maria; Alberto, Christian O; Dias, Alex; Hirasawa, Kensuke; Hirasawa, Michiru

2016-11-01

High-fat diet (HFD) is known to induce low-grade hypothalamic inflammation. Whether inflammation occurs in other brain areas remains unknown. This study tested the effect of short-term HFD on cytokine gene expression and identified leukemia inhibitory factor (LIF) as a responsive cytokine in the brain stem. Thus, functional and cellular effects of LIF in the brain stem were investigated. Male rats were fed chow or HFD for 3 days, and then gene expression was analyzed in different brain regions for IL-1β, IL-6, TNF-α, and LIF. The effect of intracerebroventricular injection of LIF on chow intake and body weight was also tested. Patch clamp recording was performed in the nucleus tractus solitarius (NTS). HFD increased pontine TNF-α mRNA while downregulating LIF in all major parts of the brain stem, but not in the hypothalamus or hippocampus. LIF injection into the cerebral aqueduct suppressed food intake without conditioned taste aversion, suggesting that LIF can induce anorexia via lower brain regions without causing malaise. In the NTS, a key brain stem nucleus for food intake regulation, LIF induced acute changes in neuronal excitability. HFD-induced downregulation of anorexic LIF in the brain stem may provide a permissive condition for HFD overconsumption. This may be at least partially mediated by the NTS. © 2016 The Obesity Society.

Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review.

PubMed

Alvarim, Larissa T; Nucci, Leopoldo P; Mamani, Javier B; Marti, Luciana C; Aguiar, Marina F; Silva, Helio R; Silva, Gisele S; Nucci-da-Silva, Mariana P; DelBel, Elaine A; Gamarra, Lionel F

2014-01-01

The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle)-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain.

The cauda equina syndrome in pregnant woman with a massive disc herniation.

PubMed

Antón Capitán, B; Malillos Torán, M

Low back pain during pregnancy is a common cause of medical consultation. Although back pain is very common, the incidence of low back pain secondary to lumbar disk herniation in pregnancy is low (1: 10,000). Cauda equina syndrome from lumbar disk herniation is a serious complication. The delay in diagnosis and treatment can be a cause of chronic disability secondary to neurological sequelae. Numerous cases of disk herniation in pregnancy have been reported, however the association of a cauda equina syndrome as a result of disk herniation is rare. A case is presented of cauda equina syndrome in a pregnant woman at 12-week gestation. Copyright © 2015 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.

PubMed

Lu, Zhengqi; Zhang, Bingjun; Qiu, Wei; Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

Comparative Brain Stem Lesions on MRI of Acute Disseminated Encephalomyelitis, Neuromyelitis Optica, and Multiple Sclerosis

PubMed Central

Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

2011-01-01

Background Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). Objectives To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Methods Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Results Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Conclusions Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases. PMID:21853047

Transplantation of autologous bone marrow-derived mesenchymal stem cells for traumatic brain injury☆

PubMed Central

Jiang, Jindou; Bu, Xingyao; Liu, Meng; Cheng, Peixun

2012-01-01

Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury. PMID:25806058

Brain stem sites mediating specific and non-specific temperature effects on thermoregulation in the pekin duck.

PubMed Central

Martin, R; Simon, E; Simon-Oppermann, C

1981-01-01

1. Thermodes were chronically implanted into various levels of the brain stem of sixteen Pekin ducks. The effects of local thermal stimulation on metabolic heat production, core temperature, peripheral skin temperature and respiratory frequency were investigated. 2. Four areas of thermode positions were determined according to the responses observed and were histologically identified at the end of the investigation. 3. Thermal stimulation of the lower mid-brain/upper pontine brain stem (Pos. III) elicited an increase in metabolic heat production, cutaneous vasoconstriction and rises in core temperature in response to cooling at thermoneutral and cold ambient conditions and, further, inhibition of panting by cooling and activation of panting by heating at warm ambient conditions. The metabolic response to cooling this brain stem section amounted to -0.1 W/kg. degrees C as compared with -7 W/kg. degrees C in response to total body cooling. 4. Cooling of the anterior and middle hypothalamus (Pos. II) caused vasodilatation in the skin and did not elicit shivering. The resulting drop in core temperature at a given degree of cooling was greater than the rise in core temperature in response to equivalent cooling of the lower mid-brain/upper pontine brain stem. 5. Cooling of the preoptic forebrain (Pos. I) and of the myelencephalon (Pos. IV) did not elicit thermoregulatory reactions. 6. It is concluded that the duck's brain stem contains thermoreceptive structures in the lower mid-brain/upper pontine section. However, the brain stem as a whole appears to contribute little to cold defence during general hypothermia because of the inhibitory effects originating in the anterior and middle hypothalamus. Cold defence in the duck, which is comparable in strength to that in mammals, has to rely on extracerebral thermosensory structures. PMID:7310688

Similar outcome despite slight clinical differences between lumbar radiculopathy induced by lateral versus medial disc herniations in patients without previous foraminal stenosis: a prospective cohort study with 1-year follow-up.

PubMed

Mérot, Oriane A; Maugars, Yves M; Berthelot, Jean-Marie M

2014-08-01

It has been claimed that lumbar radiculopathy induced by foraminal disc herniations had poorer outcome and different clinical features, including: 1-more progressive onset, but shorter duration between the first sign and request of medical care; 2-more severe radiculopathy; 3-less frequent/severe back pain; 4-less limitation of straight leg raising (SLR); 5-more frequent neurologic deficiencies; 6-poorer outcome. To check whether this still holds true when including only patients without other reasons for foraminal stenosis, that is, whether patients with medial disc herniations had different features and outcome than those with more lateral disc herniations. All patients hospitalized to treat a lumbar radiculopathy within a 6-month period in two French rheumatology units in 2012 were included in this prospective study each time computed tomography scan or magnetic resonance imaging had already been performed and showed clear disc bulging/herniation but no features of medial or lateral spinal stenosis. Fifty-nine patients (31 males, 49 with sciatica only) were included: 31 (53%) had medial disc herniations and 28 (47%) had more lateral herniations (posterolateral in 3, foraminal in 20, and far lateral in 5). Outcome was assessed by a phone call 1 year after the baseline assessment using a standardized questionnaire. Patients were asked whether they experienced a relapse of their radiculopathy after discharge from the hospital; whether they had been operated or not; whether they felt it had improved or not; whether they felt cured or not; to assess their level of pain radiating in the leg when standing on a 0 to 10 verbal scale; and how long they could walk. Features of patients with medial disc herniations were compared with patients with more lateral herniations. No significant differences according to the location of herniations were noticed for the speed of radiculopathy onset, time elapsed since onset, back pain (both lying or standing), and leg pain (both lying or standing), but slight significant differences (t test<0.05) were observed for other items: the 28 patients with lateral herniations were 8 years older (53.4 ±15.8 vs. 45.2±12.6), their herniations involved discs from upper levels of the lumbar spine (above L4-L5: 7/28 vs. 3/31), motor weakness was more frequent (25% vs. 3%), SLR was less restricted (65.0°±24.5° vs. 51.1°±25.7°), DN4 score of neuropathic pain was higher (4.4±2.1 vs. 3.2±1.8), anxiety level was higher (10.3±4.1 vs. 7.9±3.2), length of hospital stay was longer (5.7±2.4 days vs. 4.5±1.4 days), and physician's prognosis of a good outcome was poorer (6.6±2.2 vs. 8.0±1.6). However, at the end of follow-up (12.2±3.3 months), outcome was similar: 37% (vs. 41% for medial herniations) had transiently relapsed, 66% felt finally improved (vs. 63%), and walking capacity was nearly identical despite the fact that only 18% had to be operated (vs. 32% of those with medial herniations). Despite differences in clinical presentation, the outcome of radiculopathy induced by the more lateral lumbar disc herniations was not worse than the outcome of patients with only medial disc herniations. Previous claims of poorer outcome in foraminal herniations might be explained by the inclusion of patients with associated foraminal stenosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Good outcome of brain stem progressive multifocal leukoencephalopathy in an immunosuppressed renal transplant patient: Importance of early detection and rapid immune reconstitution.

PubMed

Sauer, Roland; Gölitz, Philipp; Jacobi, Johannes; Schwab, Stefan; Linker, Ralf A; Lee, De-Hyung

2017-04-15

Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remission of symptoms with improvement of the brain stem lesion over a follow-up over 20months. In summary, early detection of PML and consequent treatment may improve neurological outcomes even in brain stem disease with a notorious bad prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Is there any relationship between proinflammatory mediator levels in disc material and myelopathy with cervical disc herniation and spondylosis? A non-randomized, prospective clinical study

PubMed Central

Asir, Alparslan; Cetinkal, Ahmet; Gedik, Nursal; Kutlay, Ahmet Murat; Çolak, Ahmet; Kurtar, Sedat; Simsek, Hakan

2007-01-01

The proinflammatory mediator (PIM) levels were assessed in surgically removed samples of herniated cervical intervertebral discs. The objective of this study was to investigate if there is a correlation between the levels of PIMs in disc material and myelopathy associated with cervical intervertebral disc herniation and spondylosis. The role of proinflammatory mediators in the degeneration of intervertebral disc and the inflammatory effects of disc herniations on radicular pain has been previously published. However, the possible relationship between PIMs and myelopathy related to cervical disc herniation and spondylosis has not been investigated before. Thirty-two patients undergoing surgery for cervical disc herniation and spondylosis were investigated. Surgically obtained disc materials, stored at 70°C, were classified into two groups: cervical disc herniation alone or with myelopathy. Biochemical preparation and solid phase enzyme amplified sensitivity immunoassay (ELISIA) analysis of the samples were performed to assess the concentration of mediators in the samples. Very similar values of interleukin-6 were found in both groups whereas the concentrations of mediators were significantly higher in myelopathy group. This study has demonstrated that PIMs are involved in cervical intervertebral disc degeneration with higher concentrations in the samples associated with myelopathy. PMID:17476536

Brain vascular pericytes following ischemia have multipotential stem cell activity to differentiate into neural and vascular lineage cells.

PubMed

Nakagomi, Takayuki; Kubo, Shuji; Nakano-Doi, Akiko; Sakuma, Rika; Lu, Shan; Narita, Aya; Kawahara, Maiko; Taguchi, Akihiko; Matsuyama, Tomohiro

2015-06-01

Brain vascular pericytes (PCs) are a key component of the blood-brain barrier (BBB)/neurovascular unit, along with neural and endothelial cells. Besides their crucial role in maintaining the BBB, increasing evidence shows that PCs have multipotential stem cell activity. However, their multipotency has not been considered in the pathological brain, such as after an ischemic stroke. Here, we examined whether brain vascular PCs following ischemia (iPCs) have multipotential stem cell activity and differentiate into neural and vascular lineage cells to reconstruct the BBB/neurovascular unit. Using PCs extracted from ischemic regions (iPCs) from mouse brains and human brain PCs cultured under oxygen/glucose deprivation, we show that PCs developed stemness presumably through reprogramming. The iPCs revealed a complex phenotype of angioblasts, in addition to their original mesenchymal properties, and multidifferentiated into cells from both a neural and vascular lineage. These data indicate that under ischemic/hypoxic conditions, PCs can acquire multipotential stem cell activity and can differentiate into major components of the BBB/neurovascular unit. Thus, these findings support the novel concept that iPCs can contribute to both neurogenesis and vasculogenesis at the site of brain injuries. © 2015 AlphaMed Press.

Roles of mTOR Signaling in Brain Development.

PubMed

Lee, Da Yong

2015-09-01

mTOR is a serine/threonine kinase composed of multiple protein components. Intracellular signaling of mTOR complexes is involved in many of physiological functions including cell survival, proliferation and differentiation through the regulation of protein synthesis in multiple cell types. During brain development, mTOR-mediated signaling pathway plays a crucial role in the process of neuronal and glial differentiation and the maintenance of the stemness of neural stem cells. The abnormalities in the activity of mTOR and its downstream signaling molecules in neural stem cells result in severe defects of brain developmental processes causing a significant number of brain disorders, such as pediatric brain tumors, autism, seizure, learning disability and mental retardation. Understanding the implication of mTOR activity in neural stem cells would be able to provide an important clue in the development of future brain developmental disorder therapies.

A case of a brain stem abscess with a favorable outcome

PubMed Central

Bulthuis, Vincent J.; Gubler, Felix S.; Teernstra, Onno P. M.; Temel, Yasin

2015-01-01

Background: A brain stem abscess is a rare and severe medical condition. Here, we present a rare case of a brain stem abscess in a young pregnant woman, requiring acute stereotactic intervention. Case Description: A 36-year-old woman presented with a headache, nausea, and vomiting, and computed tomography showed a space-occupying lesion in the brain stem. She became shortly after comatose, and we decided to perform an acute stereotactic aspiration of the abscess. Soon after surgery, her neurological condition improved dramatically. Conclusion: A brainstem abscess is a life-threatening condition with a potentially good outcome if treated adequately. PMID:26543670

Diagnosing Internal Herniation After Roux-en-Y Gastric Bypass Surgery: Literature Overview, Cadaver Study and the Added Value of 3D CT Angiography.

PubMed

Klop, Cornelis; Deden, Laura N; Aarts, Edo O; Janssen, Ignace M C; Pijl, Milan E J; van den Ende, Anneline; Witteman, Bart P L; de Jong, Gabie M; Aufenacker, Theo J; Slump, Cornelis H; Berends, Frits J

2018-02-05

The purposes of the study are to outline the complexity of diagnosing internal herniation after Roux-en-Y gastric bypass (RYGB) surgery and to investigate the added value of computed tomography angiography (CTA) for diagnosing internal herniation. A cadaver study was performed to investigate the manifestations of internal hernias and mesenteric vascularization. Furthermore, a prospective, ethics approved study with retrospective interpretation was conducted. Ten patients, clinically suspected for internal herniation, were prospectively included. After informed consent was obtained, these subjects underwent abdominal CT examination, including additional arterial phase CTA. All subjects underwent diagnostic laparoscopy for suspected internal herniation. The CTA was used to create a 3D reconstruction of the mesenteric arteries and surgical staples (3D CTA). The 3D CTA was interpreted, taking into account the presence and type of internal hernia that was found upon laparoscopy. Cadaveric analysis demonstrated the complexity of internal herniation. It also confirmed the expected changes in vascular structure and surgical staple arrangement in the presence of internal herniation. 3D CTA studies of the subjects with active internal hernias demonstrated remarkable differences when compared to control 3D CTA studies. The blood supply of herniated intestinal limbs in particular showed abnormal trajectories. Additionally, enteroenterostomy staple lines had migrated or altered orientation. 3D CTA is a promising technique for diagnosing active internal hernias. Our findings suggest that for diagnosing internal hernias, focus should probably shift from routine abdominal CT examination towards the 3D assessment of the mesenteric vasculature and surgical staples.

Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.

PubMed

Cheng, Zhuo; Wang, Liping; Qu, Meijie; Liang, Huaibin; Li, Wanlu; Li, Yongfang; Deng, Lidong; Zhang, Zhijun; Yang, Guo-Yuan

2018-05-03

Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 10 5 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p < 0.05). IgG leakage, tight junction protein loss, and inflammatory cytokines IL-1β, IL-6, and TNF-α reduced in mesenchymal stem cell-treated mice compared to the control group following ischemia (p < 0.05). After transplantation, MMP-9 was decreased in protein and activity levels as compared with controls (p < 0.05). Furthermore, myeloperoxidase-positive cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p < 0.05). The results showed that mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.

Stem cell-based therapies for tumors in the brain: are we there yet?

PubMed Central

Shah, Khalid

2016-01-01

Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation. PMID:27282399

Brain stem NOS and ROS in neural mechanisms of hypertension.

PubMed

Chan, Samuel H H; Chan, Julie Y H

2014-01-01

There is now compelling evidence to substantiate the notion that by depressing baroreflex regulation of blood pressure and augmenting central sympathetic outflow through their actions on the nucleus tractus solitarii (NTS) and rostral ventrolateral medulla (RVLM), brain stem nitric oxide synthase (NOS) and reactive oxygen species (ROS) are important contributing factors to neural mechanisms of hypertension. This review summarizes our contemporary views on the impact of NOS and ROS in the NTS and RVLM on neurogenic hypertension, and presents potential antihypertensive strategies that target brain stem NOS/ROS signaling. NO signaling in the brain stem may be pro- or antihypertensive depending on the NOS isoform that generates this gaseous moiety and the site of action. Elevation of the ROS level when its production overbalances its degradation in the NTS and RVLM underlies neurogenic hypertension. Interventional strategies with emphases on alleviating the adverse actions of these molecules on blood pressure regulation have been investigated. The pathological roles of NOS in the RVLM and NTS in neural mechanisms of hypertension are highly complex. Likewise, multiple signaling pathways underlie the deleterious roles of brain-stem ROS in neurogenic hypertension. There are recent indications that interactions between brain stem ROS and NOS may play a contributory role. Given the complicity of action mechanisms of brain-stem NOS and ROS in neural mechanisms of hypertension, additional studies are needed to identify the most crucial therapeutic target that is applicable not only in animal models but also in patients suffering from neurogenic hypertension.

Diffusion-weighted imaging score of the brain stem: A predictor of outcome in acute basilar artery occlusion treated with the Solitaire FR device.

PubMed

Mourand, I; Machi, P; Nogué, E; Arquizan, C; Costalat, V; Picot, M-C; Bonafé, A; Milhaud, D

2014-06-01

The prognosis for ischemic stroke due to acute basilar artery occlusion is very poor: Early recanalization remains the main factor that can improve outcomes. The baseline extent of brain stem ischemic damage can also influence outcomes. We evaluated the validity of an easy-to-use DWI score to predict clinical outcome in patients with acute basilar artery occlusion treated by mechanical thrombectomy. We analyzed the baseline clinical and DWI parameters of 31 patients with acute basilar artery occlusion, treated within 24 hours of symptom onset by using a Solitaire FR device. The DWI score of the brain stem was assessed with a 12-point semiquantitative score that separately considered each side of the medulla, pons, and midbrain. Clinical outcome was assessed at 180 days by using the mRS. According to receiver operating characteristic analyses, the cutoff score determined the optimal positive predictive value for outcome. The Spearman rank correlation coefficient assessed the correlation between the DWI brain stem score and baseline characteristics. Successful recanalization (Thrombolysis in Cerebral Infarction 3-2b) was achieved in 23 patients (74%). A favorable outcome (mRS ≤ 2) was observed in 11 patients (35%). An optimal DWI brain stem score of <3 predicted a favorable outcome. The probability of a very poor outcome (mRS ≥ 5) if the DWI brain stem score was ≥5 reached 80% (positive predictive value) and 100% if this score was ≥6. Interobserver reliability of the DWI brain stem score was excellent, with an intraclass correlation coefficient of 0.97 (95% CI, 0.96-0.99). The DWI brain stem score was significantly associated with baseline tetraplegia (P = .001) and coma (P = .005). In patients with acute basilar artery occlusion treated by mechanical thrombectomy, the baseline DWI brain lesion score seems to predict clinical outcome. © 2014 by American Journal of Neuroradiology.

Spinal cord herniation following cervical meningioma excision: a rare clinical entity and review of literature.

PubMed

Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi; Maheswaran, Anupama; Rajasekaran, S

2016-05-01

Spinal cord herniation following surgery is an extremely uncommon clinical condition with very few reports in published literature. This condition usually occurs as a spontaneous idiopathic phenomenon often in the thoracic spine or following a scenario of post traumatic spinal cord/nerve root injury. Rarely has it been reported following spinal cord tumor surgery. To document a case of cervical spinal cord herniation as a late onset complication following spinal cord tumor surgery with an atypical presentation of monoparesis. Case report. We describe the clinical presentation, operative procedure, post operative outcome and review of literature of this rare clinical condition. A 57-year-old man presented with right upper limb monoparesis due to a spinal cord herniation 6 years after a cervical intradural meningioma excision. The patients underwent surgery to reduce the herniation and duroplasty with subsequent complete resolution of symptoms. Spinal cord herniation must be considered as differential diagnosis in scenarios of spinal cord tumor excision presenting with late onset neurological deficit. These cases may present as paraparesis, Brown-sequard syndrome and rarely as in our case as monoparesis.

Does T2 mapping of the posterior annulus fibrosus indicate the presence of lumbar intervertebral disc herniation? A 3.0 Tesla magnetic resonance study.

PubMed

Messner, Alina; Stelzeneder, David; Trattnig, Stefan; Welsch, Götz H; Schinhan, Martina; Apprich, Sebastian; Brix, Martin; Windhager, Reinhard; Trattnig, Siegfried

2017-03-01

Indicating lumbar disc herniation via magnetic resonance imaging (MRI) T2 mapping in the posterior annulus fibrosus (AF). Sagittal T2 maps of 313 lumbar discs of 64 patients with low back pain were acquired at 3.0 Tesla (3T). The discs were rated according to disc herniation and bulging. Region of interest (ROI) analysis was performed on median, sagittal T2 maps. T2 values of the AF, in the most posterior 10% (PAF-10) and 20% of the disc (PAF-20), were compared. A significant increase in the T2 values of discs with herniations affecting the imaged area, compared to bulging discs and discs with lateral herniation, was shown in the PAF-10, where no association to the NP was apparent. The PAF-20 exhibited a moderate correlation to the nucleus pulposus (NP). High T2 values in the PAF-10 suggest the presence of disc herniation (DH). The results indicate that T2 values in the PAF-20 correspond more to changes in the NP.

Gynecomastia associated with herniated nipples: an optimal surgical approach.

PubMed

Jaiswal, Rohit; Pu, Lee L Q

2012-04-01

Gynecomastia is a common disorder observed in male plastic surgery patients. Treatment options may include observation, surgical excision, or liposuction techniques. Congenital herniated nipple is a more rare condition, especially in male patients. We present the case of a 12-year-old boy with bilateral gynecomastia and herniated nipple-areolar complexes. A staged repair was undertaken in this patient with grade 2 gynecomastia. The first operation was ultrasonic liposuction bilaterally, yielding 200 mL of aspirate from the left and 400 mL on the right, to correct the gynecomastia. The second procedure, performed 6 months later, was a bilateral periareolar mastopexy to repair the herniated nipple-areolar complexes. The result of the first procedure was flattened and symmetrical breast tissue bilaterally, essentially a correction of the gynecomastia. The herniated nipples were still present, however. Bilateral periareolar mastopexies were then performed with resulting reduction of the herniations. There were no complications with either procedure, and a good cosmetic result was achieved. A staged surgical approach was successful in correcting both conditions with an excellent aesthetic result and the advantage of decreased risk for nipple complications.

Cost savings associated with prevention of recurrent lumbar disc herniation with a novel annular closure device: a multicenter prospective cohort study.

PubMed

Parker, Scott L; Grahovac, Gordan; Vukas, Duje; Ledic, Darko; Vilendecic, Milorad; McGirt, Matthew J

2013-09-01

Same-level recurrent disc herniation is a well-defined complication following lumbar discectomy. Reherniation results in increased morbidity and health care costs. Techniques to reduce these consequences may improve outcomes and reduce cost after lumbar discectomy. In a prospective cohort study, we set out to evaluate the cost associated with surgical management of recurrent, same-level lumbar disc herniation following primary discectomy. Forty-six consecutive European patients undergoing lumbar discectomy for a single-level herniated disc at two institutions were prospectively followed with clinical and radiographic evaluations. A second consecutive cohort of 30 patients undergoing 31 lumbar discectomies with implantation of an annular closure device was followed at the same hospitals and same follow-up intervals. Cost estimates for reherniation were modeled on Medicare national allowable payment amounts (direct cost) and patient work-day losses (indirect cost). Annular closure and control cohorts were matched at baseline. By 2 years follow-up, symptomatic recurrent same-level disc herniation occurred in three (6.5%) patients in the control cohort versus zero (0%) patients in the annular closure cohort. For patients experiencing recurrent disc herniation, mean estimated direct and indirect cost of management of recurrent disc herniation was $34,242 and $3,778, respectively. Use of an annular closure device potentially results in a cost savings of $222,573 per 100 primary discectomy procedures performed (or $2,226 per discectomy), based solely on the reduction of reoperated reherniations when modeled on U.S. Medicare costs. Recurrent disc herniation did not occur in any patients after annular closure within the 12-month follow-up. The reduction in the incidence of reherniation was associated with potentially significant cost savings. Development of novel techniques to prevent recurrent lumbar disc herniation is warranted to decrease the associated morbidity and health care costs associated with this complication. Georg Thieme Verlag KG Stuttgart · New York.

Primary brain tumors, neural stem cell, and brain tumor cancer cells: where is the link?

PubMed Central

Germano, Isabelle; Swiss, Victoria; Casaccia, Patrizia

2010-01-01

The discovery of brain tumor-derived cells (BTSC) with the properties of stem cells has led to the formulation of the hypothesis that neural stem cells could be the cell of origin of primary brain tumors (PBT). In this review we present the most common molecular changes in PBT, define the criteria of identification of BTSC and discuss the similarities between the characteristics of these cells and those of the endogenous population of neural stem cells (NPCs) residing in germinal areas of the adult brain. Finally, we propose possible mechanisms of cancer initiation and progression and suggest a model of tumor initiation that includes intrinsic changes of resident NSC and potential changes in the microenvironment defining the niche where the NSC reside. PMID:20045420

Confounding Brain Stem Function During Pediatric Brain Death Determination: Two Case Reports.

PubMed

Hansen, Gregory; Joffe, Ari R

2017-06-01

A patient who has been declared brain dead is considered to be both legally and clinically dead. However, we report 2 pediatric cases in which the patients demonstrated clinical signs of brain stem function that are not recognized or tested in current Canadian or US guidelines.

Childhood Brain Stem Glioma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Childhood brain stem glioma presents as a diffuse intrinsic pontine glioma (DIPG; a fast-growing tumor that is difficult to treat and has a poor prognosis) or a focal glioma (grows more slowly, is easier to treat, and has a better prognosis). Learn about the diagnosis, cellular classification, staging, treatment, and clinical trials for pediatric brain stem glioma in this expert-reviewed summary.

The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course.

PubMed

Schaefer, Jennifer E

2016-01-01

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis on student competencies such as scientific process, scientific communication, and societal relevance while teaching foundational neurobiological content such as brain anatomy, cellular neurophysiology, and activity modulation. Student feedback indicates that the BRAIN Initiative is an engaging and instructional context for this course. Course module organization, suitable BRAIN Initiative commentary literature, sample primary literature, and important assignments are presented.

Sensibility testing in patients with a lumbosacral radicular syndrome.

PubMed

Peeters, G G; Aufdemkampe, G; Oostendorp, R A

1998-02-01

To examine whether there is a significant difference in gnostic sensibility between affected and unaffected legs of patients suffering from lumbosacral radicular syndrome (LRS) resulting from a disc herniation and to determine the validity of the sensibility test for detecting a disc herniation. Observer blind study of sensibility testing. Four general hospitals (neurology department) and one practice of physical and manual therapy. Fifty-one patients with radicular pain in the lumbosacral nerve roots for at least 4 wk and/or neurological deficits. The gnostic sensibility of 51 patients with a unilateral LRS was tested using Semmes-Weinstein monofilaments for the L4, L5 and S1 dermatomes. Gnostic hypoesthetic impairments in the L4, L5 and S1 dermatomes were found in 84.6% of the 43 patients in which the presence of disc herniation was confirmed by CT. There was significant difference in gnostic sensibility between the affected and unaffected legs in the L4, L5, and S1 dermatomes for disc herniation at the L4-L5 level and for the L5 and S1 dermatomes for a disc herniation at the L5-S1 level. There was no significant difference in gnostic sensibility in the L4 dermatome for a disc herniation at the L5-S1 level. The gnostic sensibility of the affected leg is hypoesthetic compared with the unaffected leg. The specificity of the sensibility test using monofilaments is acceptable, but the sensitivity is not. The monofilament test is a useful and practical tool for excluding the presence of a disc herniation at dermatomes L4, L5 and S1 and disc herniations at the L4-L5, L5-S1 level.

ILEAL HERNIATION THROUGH THE FORAMEN OF WINSLOW: OVEREATING AS A RISK FACTOR FOR INTERNAL HERNIATION.

PubMed

Kirigin, Lora Stanka; Nikolić, Marko; Kruljac, Ivan; Marjan, Domagoj; Penavić, Ivan; Ljubicić, Neven; Budimir, Ivan; Vrkljan, Milan

2016-03-01

Internal hernias have an overall incidence of less than 1% and are difficult to diagnose clinically due to their nonspecific presentation. Most internal hernias present as strangulating closed-loop obstruction and delay in surgical intervention is responsible for a high mortality rate (49%). We present a case of ileal herniation through the foramen of Winslow. A 29-year-old previously healthy female presented with acute onset right upper quadrant pain, abdominal fullness, and nausea. The pain was sudden in onset and began shortly after a dinner party where she consumed larger portions of food. Laboratory investigations revealed mild leukocytosis with left shift. Dual-phase multi-detector computed tomography disclosed herniation of the small bowel into the lesser sac. The patient underwent an emergency median laparotomy that revealed ileal herniation through the foramen of Winslow. Adhesiolysis and manual reduction of the bowel was performed, and the reduced bowel showed only congestive changes. The postoperative recovery was uneventful and the patient was discharged on the third postoperative day. Risk factors for internal herniation still remain unclear, although excessively mobile bowel loops and an enlarged foramen of Winslow have been described. Our case demonstrated that overeating could be an additional risk factor for internal herniation. We describe our clinical and radiology findings, as well as surgical management. Due to the high rates of morbidity and mortality, it is imperative that clinicians be aware of the possible risks factors for internal herniation. Internal hernias should be included in the differential diagnosis of small bowel obstruction so that appropriate steps can be made in the work-up of these patients, followed by timely surgical intervention.

Paraneoplastic brain stem encephalitis.

PubMed

Blaes, Franz

2013-04-01

Paraneoplastic brain stem encephalitis can occur as an isolated clinical syndrome or, more often, may be part of a more widespread encephalitis. Different antineuronal autoantibodies, such as anti-Hu, anti-Ri, and anti-Ma2 can be associated with the syndrome, and the most frequent tumors are lung and testicular cancer. Anti-Hu-associated brain stem encephalitis does not normally respond to immunotherapy; the syndrome may stabilize under tumor treatment. Brain stem encephalitis with anti-Ma2 often improves after immunotherapy and/or tumor therapy, whereas only a minority of anti-Ri positive patients respond to immunosuppressants or tumor treatment. The Opsoclonus-myoclonus syndrome (OMS) in children, almost exclusively associated with neuroblastoma, shows a good response to steroids, ACTH, and rituximab, some patients do respond to intravenous immunoglobulins or cyclophosphamide. In adults, OMS is mainly associated with small cell lung cancer or gynecological tumors and only a small part of the patients show improvement after immunotherapy. Earlier diagnosis and treatment seem to be one major problem to improve the prognosis of both, paraneoplastic brain stem encephalitis, and OMS.

Spontaneous complete regression of a brain stem glioma pathologically diagnosed as a high-grade glioma.

PubMed

Ishihara, Masahiro; Yamamoto, Kazumi; Miwa, Hideaki; Nishi, Masaya

2017-12-01

Spontaneous regressions of brain stem gliomas are extremely rare. Only six cases have been reported in the literature. We describe the case of a patient who was diagnosed with a pontomedullary dorsal brain stem glioma at the age of 15 years. An open biopsy showed the presence of an anaplastic glioma. Because the patient and her parents refused conventional therapies, including radiation and chemotherapy, we followed up the patient by performing magnetic resonance imaging scans on her every 3 months. At 3 months after biopsy, we observed the radiological disappearance of her tumor. One year after biopsy, the tumor retained the spontaneous complete regression observed earlier. In this case report, we present the first report of the spontaneous complete regression of a brain stem glioma that was histologically proven to be a high-grade glioma and we believe that this regression was the natural progression of this case, as may be the scenario in a few other cases of brain stem gliomas.

[Therapeutic strategies targeting brain tumor stem cells].

PubMed

Toda, Masahiro

2009-07-01

Progress in stem cell research reveals cancer stem cells to be present in a variety of malignant tumors. Since they exhibit resistance to anticancer drugs and radiotherapy, analysis of their properties has been rapidly carried forward as an important target for the treatment of intractable malignancies, including brain tumors. In fact, brain cancer stem cells (BCSCs) have been isolated from brain tumor tissue and brain tumor cell lines by using neural stem cell culture methods and isolation methods for side population (SP) cells, which have high drug-efflux capacity. Although the analysis of the properties of BCSCs is the most important to developing methods in treating BCSCs, the absence of BCSC purification methods should be remedied by taking it up as an important research task in the immediate future. Thus far, there are no effective treatment methods for BCSCs, and several treatment methods have been proposed based on the cell biology characteristics of BCSCs. In this article, I outline potential treatment methods damaging treatment-resistant BCSCs, including immunotherapy which is currently a topic of our research.

Reversible uncal herniation in a neonate with a large MCA infarct.

PubMed

Thibert, Ronald L; Burns, Joseph D; Bhadelia, Rafeeque; Takeoka, Masanori

2009-11-01

Uncal herniation due to a large cerebral infarct is well-described in adults, with high rates of morbidity and mortality. This phenomenon, however, has not been previously reported in neonates. We present a newborn male delivered via cesarean section with difficult extraction who presented with frequent seizures. He was found to have an acute left MCA territory infarct secondary to an M1 occlusion detected on MRI/MRA. He became lethargic and developed a left uncal herniation on CT at 72h of life. He was treated medically with osmolar agents and hemodynamic support, and had resolution of the herniation on CT at 120h of life. At 19 months he had residual moderate right hemiparesis with only mild gait disturbance and mild speech delay. As seen in this case, uncal herniation, though rare, may occur in neonates. Also, the outcome for this neonate was much better than for typical adults with a similar disease course.

Percutaneous endoscopic intra-annular subligamentous herniotomy for large central disc herniation: a technical case report.

PubMed

Lee, Sang-Ho; Choi, Kyung-Chul; Baek, Oon Ki; Kim, Ho Jin; Yoo, Seung-Hwa

2014-04-01

Technical case report. To describe the novel technique of percutaneous endoscopic herniotomy using a unilateral intra-annular subligamentous approach for the treatment of large centrally herniated discs. Open discectomy for large central disc herniations may have poor long-term prognosis due to heavy loss of intervertebral disc tissue, segmental instability, and recurrence of pain. Six consecutive patients who presented with back and leg pain, and/or weakness due to a large central disc herniation were treated using percutaneous endoscopic herniotomy with a unilateral intra-annular subligamentous approach. The patients experienced relief of symptoms and intervertebral disc spaces were well maintained. The annular defects were noted to be in the process of healing and recovery. Percutaneous endoscopic unilateral intra-annular subligamentous herniotomy was an effective and affordable minimally invasive procedure for patients with large central disc herniations, allowing preservation of nonpathological intradiscal tissue through a concentric outer-layer annular approach.

Lumbar disc herniation with contralateral radiculopathy: do we neglect the epidural fat?

PubMed

Yang, Jun-Song; Zhang, Dong-Jie; Hao, Ding-Jun

2015-01-01

Lumbar disc herniation (LDH) is the most common cause of radiculopathy, whose pathological entity underlying nerve root compression is usually on the same side as the symptoms. However, LDH causing contralateral radiculopathy are sometimes encountered by pain physicians. There have been tremendous developments in the treatment options for LDH; the situation of LDH causing contralateral radiculopathy is indeed a dilemma for some pain physicians. We will report a case of a patient with a L4-5 disc herniation whose left herniated disc caused radiculopathy on the right side. After a percutaneous lumbar endoscopic discectomy via the side ipsilateral to the symptomatic side, this case obtained a significant symptom remission. The migrated epidural fat is discussed as a cause of associated contralateral neurological deficit. Only via a surgical approach ipsilateral to the herniated side, could there be a clinical improvement postoperatively.

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

PubMed

Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

2015-10-01

Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation potential in vitro and in vivo after in utero transplantation. This study showed the lack of an innate neuronal but high mesodermal differentiation potential. Because of their relationship to mesenchymal stem cells, these adult brain perivascular mesodermal cells are of great interest for possible autologous therapeutic use. ©AlphaMed Press.

The functional curcumin liposomes induce apoptosis in C6 glioblastoma cells and C6 glioblastoma stem cells in vitro and in animals.

PubMed

Wang, Yahua; Ying, Xue; Xu, Haolun; Yan, Helu; Li, Xia; Tang, Hui

2017-01-01

Glioblastoma is a kind of malignant gliomas that is almost impossible to cure due to the poor drug transportation across the blood-brain barrier and the existence of glioma stem cells. We prepared a new kind of targeted liposomes in order to improve the drug delivery system onto the glioma cells and induce the apoptosis of glioma stem cells afterward. In this experiment, curcumin was chosen to kill gliomas, while quinacrine was used to induce apoptosis of the glioma stem cells. Also, p -aminophenyl-α-D-mannopyranoside could facilitate the transport of liposomes across the blood-brain barrier and finally target the brain glioma cells. The cell experiments in vitro indicated that the targeted liposomes could significantly improve the anti-tumor effects of the drugs, while enhancing the uptake effects, apoptosis effects, and endocytic effects of C6 glioma cells and C6 glioma stem cells. Given the animal experiments in vivo, we discovered that the targeted liposomes could obviously increase the survival period of brain glioma-bearing mice and inhibit the growth of gliomas. In summary, curcumin and quinacrine liposomes modified with p -aminophenyl-α-D-mannopyranoside is a potential preparation to treat brain glioma cells and brain glioma stem cells.

The functional curcumin liposomes induce apoptosis in C6 glioblastoma cells and C6 glioblastoma stem cells in vitro and in animals

PubMed Central

Wang, Yahua; Ying, Xue; Xu, Haolun; Yan, Helu; Li, Xia; Tang, Hui

2017-01-01

Glioblastoma is a kind of malignant gliomas that is almost impossible to cure due to the poor drug transportation across the blood–brain barrier and the existence of glioma stem cells. We prepared a new kind of targeted liposomes in order to improve the drug delivery system onto the glioma cells and induce the apoptosis of glioma stem cells afterward. In this experiment, curcumin was chosen to kill gliomas, while quinacrine was used to induce apoptosis of the glioma stem cells. Also, p-aminophenyl-α-D-mannopyranoside could facilitate the transport of liposomes across the blood–brain barrier and finally target the brain glioma cells. The cell experiments in vitro indicated that the targeted liposomes could significantly improve the anti-tumor effects of the drugs, while enhancing the uptake effects, apoptosis effects, and endocytic effects of C6 glioma cells and C6 glioma stem cells. Given the animal experiments in vivo, we discovered that the targeted liposomes could obviously increase the survival period of brain glioma-bearing mice and inhibit the growth of gliomas. In summary, curcumin and quinacrine liposomes modified with p-aminophenyl-α-D-mannopyranoside is a potential preparation to treat brain glioma cells and brain glioma stem cells. PMID:28260885

Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain.

PubMed

Tajiri, Naoki; Lee, Jea Young; Acosta, Sandra; Sanberg, Paul R; Borlongan, Cesar V

2016-01-01

Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.

Activation of neurons in cardiovascular areas of cat brain stem affects spinal reflexes.

PubMed

Wu, W C; Wang, S D; Liu, J C; Horng, H T; Wayner, M J; Ma, J C; Chai, C Y

1994-01-01

In 65 cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg), the effects of electrical stimulation and microinjection of sodium glutamate (0.25 M, 100-200 nl) in the pressor areas in the rostral brain stem on the evoked L5 ventral root response (EVRR) due to intermittent stimulation of sciatic afferents were compared to stimulating the dorsomedial (DM) and ventrolateral (VLM) medulla. In general, stimulating these rostral brain stem pressor areas including the diencephalon (DIC) and rostral pons (RP) produced increases in systemic arterial pressure (SAP). In most of the cases (85%) there were associated changes in the EVRR, predominantly a decrease in EVRR (72%). Stimulation of the midbrain (MB, principally in the periaqueductal grey) produced decreases in SAP and EVRR. Decreases in EVRR was observed in 91% of the DM and VLM stimulations in which an increase in SAP was produced. This EVRR inhibition was essentially unaltered after acute midcollicular decerebration. Increases in EVRR were also observed and occurred more often in the rostral brain stem than in the medulla. Since changes of both EVRR and SAP could be reproduced by microinjection of Glu into the cardiovascular-reactive areas of the brain stem, this suggests that neuronal perikarya in these areas are responsible for both actions. On some occasions, Glu induced changes in EVRR but not in SAP. This effect occurred more frequently in the rostral brain stem than in the medulla. The present data suggest that separate neuron population exist in the brain stem for the integration of SAP and spinal reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain stem hypoplasia associated with Cri-du-Chat syndrome.

PubMed

Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

2013-01-01

Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

Regulation of body temperature in the blue-tongued lizard.

PubMed

Hammel, H T; Caldwell, F T; Abrams, R M

1967-06-02

Lizards (Tiliqua scincoides) regulated their internal body temperature by moving back and forth between 15 degrees and 45 degrees C environments to maintain colonic and brain temperatures between 30 degrees and 37 degrees C. A pair of thermodes were implanted across the preoptic region of the brain stem, and a reentrant tube for a thermocouple was implanted in the brain stem. Heating the brain stem to 41 degrees C activated the exit response from the hot environment at a colonic temperature 1 degrees to 2 degrees C lower than normal, whereas cooling the brain stem to 25 degrees C delayed the exit from the hot environment until the colonic temperature was 1 degrees to 2 degrees C higher than normal. The behavioral thermoregulatory responses of this ectotherm appear to be activated by a combination of hypothalamic and other body temperatures.

Brain mesenchymal stem cells: The other stem cells of the brain?

PubMed

Appaix, Florence; Nissou, Marie-France; van der Sanden, Boudewijn; Dreyfus, Matthieu; Berger, François; Issartel, Jean-Paul; Wion, Didier

2014-04-26

Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression.

Brain mesenchymal stem cells: The other stem cells of the brain?

PubMed Central

Appaix, Florence; Nissou, Marie-France; van der Sanden, Boudewijn; Dreyfus, Matthieu; Berger, François; Issartel, Jean-Paul; Wion, Didier

2014-01-01

Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression. PMID:24772240

Lumbar disc herniation presenting with contralateral symptoms: a case report

PubMed Central

Koh, Zhi Sheng Darren; Lin, Shuxun

2017-01-01

Lumbar disc herniation is common and may be symptomatic. The magnetic resonance imaging (MRI) scan is an appropriate tool to confirm the diagnosis and affected level of the spine. While a disc herniation is usually associated with ipsilateral symptoms, a few cases have been reported to present with contralateral symptoms. We report a unique case of left lumbar disc herniation at L5/S1 who presented with contralateral symptoms and was successfully treated with a right L5/S1 foraminal block. However, the patient developed concordant ipsilateral symptoms 6 weeks later and was treated with left L5/S1 microdiscectomy. PMID:28435926

Lumbar disc herniation presenting with contralateral symptoms: a case report.

PubMed

Koh, Zhi Sheng Darren; Lin, Shuxun; Hey, Hwee Weng Dennis

2017-03-01

Lumbar disc herniation is common and may be symptomatic. The magnetic resonance imaging (MRI) scan is an appropriate tool to confirm the diagnosis and affected level of the spine. While a disc herniation is usually associated with ipsilateral symptoms, a few cases have been reported to present with contralateral symptoms. We report a unique case of left lumbar disc herniation at L5/S1 who presented with contralateral symptoms and was successfully treated with a right L5/S1 foraminal block. However, the patient developed concordant ipsilateral symptoms 6 weeks later and was treated with left L5/S1 microdiscectomy.

Local skull trephination before transfer is associated with favorable outcomes in cerebral herniation from epidural hematoma.

PubMed

Nelson, James A

2011-01-01

The patient with epidural hematoma and cerebral herniation has a good prognosis with immediate drainage, but a poor prognosis with delay to decompression. Such patients who present to nonneurosurgical hospitals are commonly transferred without drainage to the nearest neurosurgical center. This practice has never been demonstrated to be the safest approach to treating these patients. A significant minority of emergency physicians (EPs) have advised and taught bedside burr hole drainage or skull trephination before transfer for herniating patients. The objective of this study was to assess the effect of nonneurosurgeon drainage on neurologic outcome in patients with cerebral herniation from epidural hematoma. A structured literature review was performed using EMBASE, the Cochrane Library, and the Emergency Medicine Abstracts database. No evidence meeting methodologic criteria was found describing outcomes in patients transferred without decompressive procedures. For patients receiving local drainage before transfer, 100% had favorable outcomes. Although the total number of patients is small and the population highly selected, the natural history of cerebral herniation from epidural hematoma and the best available evidence suggests that herniating patients have improved outcomes with drainage procedures before transport. © 2010 by the Society for Academic Emergency Medicine.

Sinking skin flap syndrome and paradoxical herniation secondary to lumbar drainage.

PubMed

Zhao, Jinchuan; Li, Guichen; Zhang, Yang; Zhu, Xiaobo; Hou, Kun

2015-06-01

Decompressive craniectomy (DC) has been regaining popularity in the field of neurosurgery because it can alleviate intracranial hypertension and brain swelling. Lumbar drainage (LD) is affective in managing numerous neurosurgical circumstances such as aneurysmal subarachnoid hemorrhage, refractory intracranial hypertension, cerebrospinal fluid (CSF) leakage and intraoperative brain relaxation. Sinking skin flap syndrome (SSFS) or paradoxical herniation (PH) is a rare complication and sporadically occurs in patients after DC. Hereby, we report for the first time that DC patients with LD can progress to SSFS or PH. We also evaluated the risk factors for the incidence of SSFS in DC patients with LD. We retrospectively assessed 37 patients who underwent DC and LD for cerebrovascular diseases from the First Hospital of Jilin University between January, 2007 and December, 2012. Nine (4 male and 5 female) of 37 patients experienced SSFS or PH following LD. At the last follow-up (mean 9 months, range 6-12 months), eight patients recovered completely due to timely conservative management and one patient died from PH. The mortality rate was 11% (1/9) from the complications of PH or SSFS. Further statistical analysis revealed that mean daily CSF volume was a risk factor for the incidence of SSFS in DC patients with LD. SSFS or PH can be identified in DC patients following LD. Patients that undergo DC and LD should be monitored more intensively. Most patients can completely recover with timely conservative management, bed rest, Trendelenburg position, sufficient intravenous fluid, and temporary clipping of the catheter. Copyright © 2015 Elsevier B.V. All rights reserved.

The sensitivity and specificity of the Slump and the Straight Leg Raising tests in patients with lumbar disc herniation.

PubMed

Majlesi, Javid; Togay, Halit; Unalan, Halil; Toprak, Sadk

2008-04-01

An accurate and specific diagnosis prevents the recurrences of low back pain and chronic spinal pain. The physical examination is the most useful tool to diagnosis. The examiner must aim to determine the exact tissue that pain arises from to make the specific diagnosis. Lumbar disc herniation is 1 disease that physical examination, symptoms, and findings on imaging technique do not always correlate with each other. The Straight Leg Raising (SLR) test has been used as the primary test to diagnosis lumbar disc herniations and found to have high correlation with findings on operation since its sensitivity is high in only disc herniations leading to root compression that may eventually need operation. More sensitive test, like the Slump, might be used in herniations in which the SLR is negative. The Slump test is really a variant of the SLR and the Lasègue's tests performed in the seated position and is a progressive series of maneuvers designed to place the sciatic nerve roots under increasing tension. At each step in the procedure, the patient informs the examiner what is being felt and whether radicular pain is produced. As a result, the Slump test applies traction to the nerve roots by incorporating spinal and hip joint flexion into the leg raising and would warn the examiner of the presence of nerve root compression when there is a negative SLR test. This study measured the sensitivity and specificity of the Slump test and compare it with the SLR test in patients with and without lumbar disc herniations. A prospective case control study of 75 patients with complaints suggestive of lumbar disc herniation was carried out in the outpatient clinics of the neurosurgery department of a state teaching hospital. Seventy-five referred or self-admitted patients with low back, leg, or low back and leg pain who had results of magnetic resonance imaging (MRI) of the lumbar spine were included in the study. Thirty-eight patients had signs of herniation demonstrated by MRI. Control patients (n = 37) had no disc bulges or herniations on MRI. Both the Slump and SLR tests were performed during the assessment of all the patients by the second author. The MRI results were assessed and recorded by the first author. The Slump test was found to be more sensitive (0.84) than the SLR (0.52) in the patients with lumbar disc herniations. However, the SLR was found to be a slightly more specific test (0.89) than the Slump test (0.83). The Slump test might be used more frequently as a sensitive physical examination tool in patients with symptoms of lumbar disc herniations. In contrast, owing to its higher specificity, the SLR test may especially help identify patients who have herniations with root compression requiring surgery.

Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain.

PubMed

Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan

2016-04-01

Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mannitol-Enhanced Delivery of Stem Cells and Their Growth Factors Across the Blood–Brain Barrier

PubMed Central

Gonzales-Portillo, Gabriel S.; Sanberg, Paul R.; Franzblau, Max; Gonzales-Portillo, Chiara; Diamandis, Theo; Staples, Meaghan; Sanberg, Cyndy D.; Borlongan, Cesar V.

2014-01-01

Ischemic brain injury in adults and neonates is a significant clinical problem with limited therapeutic interventions. Currently, clinicians have only tPA available for stroke treatment and hypothermia for cerebral palsy. Owing to the lack of treatment options, there is a need for novel treatments such as stem cell therapy. Various stem cells including cells from embryo, fetus, perinatal, and adult tissues have proved effective in preclinical and small clinical trials. However, a limiting factor in the success of these treatments is the delivery of the cells and their by-products (neurotrophic factors) into the injured brain. We have demonstrated that mannitol, a drug with the potential to transiently open the blood–brain barrier and facilitate the entry of stem cells and trophic factors, as a solution to the delivery problem. The combination of stem cell therapy and mannitol may improve therapeutic outcomes in adult stroke and neonatal cerebral palsy. PMID:24480552

Characteristics of taurine release in slices from adult and developing mouse brain stem.

PubMed

Saransaari, P; Oja, S S

2006-07-01

Taurine has been thought to function as a regulator of neuronal activity, neuromodulator and osmoregulator. Moreover, it is essential for the development and survival of neural cells and protects them under cell-damaging conditions. Taurine is also involved in many vital functions regulated by the brain stem, including cardiovascular control and arterial blood pressure. The release of taurine has been studied both in vivo and in vitro in higher brain areas, whereas the mechanisms of release have not been systematically characterized in the brain stem. The properties of release of preloaded [(3)H]taurine were now characterized in slices prepared from the mouse brain stem from developing (7-day-old) and young adult (3-month-old) mice, using a superfusion system. In general, taurine release was found to be similar to that in other brain areas, consisting of both Ca(2+)-dependent and Ca(2+)-independent components. Moreover, the release was mediated by Na(+)-, Cl(-)-dependent transporters operating outwards, as both Na(+)-free and Cl(-) -free conditions greatly enhanced it. Cl(-) channel antagonists and a Cl(-) transport inhibitor reduced the release at both ages, indicating that a part of the release occurs through ion channels. Protein kinases appeared not to be involved in taurine release in the brain stem, since substances affecting the activity of protein kinase C or tyrosine kinase had no significant effects. The release was modulated by cAMP second messenger systems and phospholipases at both ages. Furthermore, the metabotropic glutamate receptor agonists likewise suppressed the K(+)-stimulated release at both ages. In the immature brain stem, the ionotropic glutamate receptor agonists N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) potentiated taurine release in a receptor-mediated manner. This could constitute an important mechanism against excitotoxicity, protecting the brain stem under cell-damaging conditions.

[Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects].

PubMed

Aleksandrova, M A; Marey, M V

2015-01-01

Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs.

The effect of electromagnetic radiation on the rat brain: an experimental study.

PubMed

Eser, Olcay; Songur, Ahmet; Aktas, Cevat; Karavelioglu, Ergun; Caglar, Veli; Aylak, Firdevs; Ozguner, Fehmi; Kanter, Mehmet

2013-01-01

The aim of this study is to determine the structural changes of electromagnetic waves in the frontal cortex, brain stem and cerebellum. 24 Wistar Albino adult male rats were randomly divided into four groups: group I consisted of control rats, and groups II-IV comprised electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per day for 2 months. While the histopathological changes in the frontal cortex and brain stem were normal in the control group, there were severe degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative Capacity level was significantly decreased in the EMR groups and also Total Oxidative Capacity and Oxidative Stress Index levels were significantly increased in the frontal cortex, brain stem and cerebellum. IL-1β level was significantly increased in the EMR groups in the brain stem. EMR causes to structural changes in the frontal cortex, brain stem and cerebellum and impair the oxidative stress and inflammatory cytokine system. This deterioration can cause to disease including loss of these areas function and cancer development.

Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

PubMed

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

Nuclear Receptor TLX Regulates Cell Cycle Progression in Neural Stem Cells of the Developing Brain

PubMed Central

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain. PMID:17901127

Pathophysiological changes of the cerebellum and brain stem in a rabbit model after superior petrosal vein sacrifice.

PubMed

Cheng, Lei; Guo, Pin; Liao, Yi-Wei; Zhang, Hong-Liang; Li, Huan-Ting; Yuan, Xianrui

2017-11-13

In certain surgical procedures sacrifice of the superior petrosal vein (SPV) is required. Previous studies have reported transient cerebellar edema, venous infarction or hemorrhage might occur after sectioning of the SPV. This study investigated the pathophysiological changes of cerebellum and brain stem after SPV sacrifice. Rabbits were divided into the operation group where the SPV was sacrificed and the control group where the SPV remained intact. Each group was further subdivided into 4, 8, 12, 24, 48 and 72 hours groups which represented the time period from sacrifice of the SPV to sacrifice of the rabbits. The water content (WC), Na + content, K + content and pathophysiological changes of cerebellum and brain stem tissue were measured. In comparison to the control, the WC and Na + content of cerebellar tissue were increased in the 4h, 8h, 12h and 24h operation subgroups (p<0.05), but only increased in the 4h subgroup of the brain stem tissue (p<0.05). The K + content of the cerebellar tissue decreased in the 4h, 8h, 12h and 24h operation subgroups (p<0.05) but only decreased in the 4h subgroup of brain stem tissue (p<0.05). Nissl staining and transmission electron microscopy demonstrated that cerebellar edema occurred in the 4h, 8h, 12h and 24h operation subgroups but not in the 48h and 72h subgroups. Brain stem edema occurred in the 4h operation subgroup. In summary, cerebellum and brain stem edema can be observed at different time points after sacrifice of the SPV in the rabbit model. ©2017 The Author(s).

Islam, brain death, and transplantation: culture, faith, and jurisprudence.

PubMed

Arbour, Richard; AlGhamdi, Hanan Mesfer Saad; Peters, Linda

2012-01-01

A significant gap exists between availability of organs for transplant and patients with end-stage organ failure for whom organ transplantation is the last treatment option. Reasons for this mismatch include inadequate approach to potential donor families and donor loss as a result of refractory cardiopulmonary instability during and after brainstem herniation. Other reasons include inadequate cultural competence and sensitivity when communicating with potential donor families. Clinicians may not have an understanding of the cultural and religious perspectives of Muslim families of critically ill patients who may be approached about brain death and organ donation. This review analyzes Islamic cultural and religious perspectives on organ donation, transplantation, and brain death, including faith-based directives from Islamic religious authorities, definitions of death in Islam, and communication strategies when discussing brain death and organ donation with Muslim families. Optimal family care and communication are highlighted using case studies and backgrounds illustrating barriers and approaches with Muslim families in the United States and in the Kingdom of Saudi Arabia that can improve cultural competence and family care as well as increase organ availability within the Muslim population and beyond.

Multiple small hemorrhagic infarcts in cerebral air embolism: a case report.

PubMed

Togo, Masaya; Hoshi, Taku; Matsuoka, Ryosuke; Imai, Yukihiro; Kohara, Nobuo

2017-11-16

Cerebral air embolism is a rare cause of cerebral infarction. In cerebral air embolism, T2 star-weighted imaging shows numerous spotty hypointense signals. Previous reports have suggested that these signals represent air in the brain and are gradually diminished and absorbed. We experienced two cases of cerebral air embolism, and in one of them, we conducted an autopsy. Case 1 was a 76-year-old Japanese man with lung cancer and emphysema. A spasmodic cough induced massive cerebral and cardiac air embolisms and the patient died because of cerebral herniation. T2 star-weighted imaging of brain magnetic resonance imaging showed multiple spotty low signals. Brain autopsy showed numerous spotty hemorrhagic infarcts in the area of T2 star-weighted imaging signals. Case 2 was an 85-year-old Japanese man with emphysema who suffered from acute stroke. Similar spotty T2 star-weighted imaging signals were observed and remained unchanged 2 months after the onset. These findings indicate that T2 star-weighted imaging in cerebral air embolism partially represents micro-hemorrhagic infarction caused by air bubbles that have migrated into the brain.

Possible role of brain stem respiratory neurons in mediating vomiting during space motion sickness

NASA Technical Reports Server (NTRS)

Miller, A. D.; Tan, L. K.

1987-01-01

The object of this study was to determine if brain stem expiratory neurons control abdominal muscle activity during vomiting. The activity of 27 ventral respiratory group expiratory neurons, which are known to be of primary importance for control of abdominal muscle activity during respiration, was recorded. It is concluded that abdominal muscle activity during vomiting must be controlled not only by some brain stem expiratory neurons but also by other input(s).

Hoyeraal-Hreidarsson syndrome: magnetic resonance imaging findings.

PubMed

Kuwashima, Shigeko

2009-10-01

Hoyeraal-Hreidarsson syndrome (HH) has been defined as a severe variant of dyskeratosis congenita (DKC). We report here a case of a 6-year-old girl with HH who presented with bone marrow hypoplasia, skin pigmentation, nail dystrophy, growth retardation, and bilateral retinal hemorrhage. Brain MRI revealed cerebellar hypoplasia, hypoplasia of the corpus callosum, a small pituitary gland, a small brain stem, and focal long T2 lesions in the thalamus and brain stem. A brain computed tomography scan revealed intracranial calcification as well. To the best of our knowledge, a small pituitary gland and focal long T2 lesions in the thalamus and brain stem have never been reported as a feature of HH.

A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?: Brain tumors and microcephaly arise from opposing derangements regulating progenitor growth. Drivers of microcephaly could be attractive brain tumor targets.

PubMed

Lang, Patrick Y; Gershon, Timothy R

2018-05-01

New targets for brain tumor therapies may be identified by mutations that cause hereditary microcephaly. Brain growth depends on the repeated proliferation of stem and progenitor cells. Microcephaly syndromes result from mutations that specifically impair the ability of brain progenitor or stem cells to proliferate, by inducing either premature differentiation or apoptosis. Brain tumors that derive from brain progenitor or stem cells may share many of the specific requirements of their cells of origin. These tumors may therefore be susceptible to disruptions of the protein products of genes that are mutated in microcephaly. The potential for the products of microcephaly genes to be therapeutic targets in brain tumors are highlighted hereby reviewing research on EG5, KIF14, ASPM, CDK6, and ATR. Treatments that disrupt these proteins may open new avenues for brain tumor therapy that have increased efficacy and decreased toxicity. © 2018 WILEY Periodicals, Inc.

Sudden quadriplegia after acute cervical disc herniation.

PubMed

Sadanand, Venkatraman; Kelly, Michael; Varughese, George; Fourney, Daryl R

2005-08-01

Acute neurological deterioration secondary to cervical disc herniation not related to external trauma is very rare, with only six published reports to date. In most cases, acute symptoms were due to progression of disc herniation in the presence of pre-existing spinal canal stenosis. A 42-year-old man developed weakness and numbness in his arms and legs immediately following a sneeze. On physical examination he had upper motor neuron signs that progressed over a few hours to a complete C5 quadriplegia. An emergent magnetic resonance imaging study revealed a massive C4/5 disc herniation. He underwent emergency anterior cervical discectomy and fusion. Postoperatively, the patient remained quadriplegic. Eighteen days later, while receiving rehabilitation therapy, he expired secondary to a pulmonary embolus. Autopsy confirmed complete surgical decompression of the spinal cord. Our case demonstrates that acute quadriplegia secondary to cervical disc herniation may occur without a history of myelopathy or spinal canal stenosis after an event as benign as a sneeze.

Herniated disk

MedlinePlus

... help support the spine. A brace may prevent injuries in people who lift heavy objects at work. But ... Cervical radiculopathy; Herniated intervertebral disk; Prolapsed intervertebral disk; Slipped ...

Eyelid Edema: A Rare Cause of a Common Sign

PubMed Central

Almeida, Cristina; Freitas, Cristina; Sales-Sanz, Marco; Ribeiro, Sara

2017-01-01

We report a 48-year-old female patient who presented to the emergency room with right eyelid edema, with 3 days of evolution. She had suffered minor trauma to this eye one week before. She reported episodes of right eyelid swelling of spontaneous resolution since the occurrence of a traumatic brain injury 5 years ago. Ophthalmological examination showed a soft and painless eyelid edema of the right eye. Brain computed tomography showed an area of bone discontinuity of the orbital roof with brain herniation and a CSF leak into the eyelid (blepharocele). Magnetic resonance confirmed the result of TC and revealed an area of frontal encephalomalacia. Ibuprofen (800 mg/day) was prescribed, with complete resolution within 20 days. She was evaluated by Neurosurgery with no indication of surgery due to the resolution of the edema and absence of symptoms. Blepharocele is a rare entity that should be considered in the differential diagnosis of unilateral eyelid edema. It can be secondary to an orbital fracture or congenital lesion. PMID:28848682

Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication.

PubMed

Li, Faith C H; Yen, J C; Chan, Samuel H H; Chang, Alice Y W

2012-02-07

Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time. Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism. We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse.

Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication

PubMed Central

2012-01-01

Background Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. Methods The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time. Results Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism. Conclusions We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse. PMID:22313577

Mechanical Restoration and Failure Analyses of a Hydrogel and Scaffold Composite Strategy for Annulus Fibrosus Repair

PubMed Central

Long, Rose G; Bürki, Alexander; Zysset, Philippe; Eglin, David; Grijpma, Dirk W.; Blanquer, Sebastien BG; Hecht, Andrew C; Iatridis, James C

2015-01-01

Unrepaired defects in the annulus fibrosus of intervertebral discs are associated with degeneration and persistent back pain. A clinical need exists for a disc repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disc height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disc biomechanics with low herniation risk, suggesting further evaluation for disc repair may be warranted. PMID:26577987

Lumbar Disc Screening Using Back Pain Questionnaires: Oswestry Low Back Pain Score, Aberdeen Low Back Pain Scale, and Acute Low Back Pain Screening Questionnaire

PubMed Central

Kim, Do Yeon; Oh, Chang Hyun; Park, Hyung Chun; Park, Chong Oon

2012-01-01

Objective To evaluate the usefulness of back pain questionnaires for lumbar disc screening among Korean young males. Methods We carried out a survey for lumbar disc screening through back pain questionnaires among the volunteers with or without back pain. Three types of back pain questionnaire (Oswestry Low Back Pain Score, Aberdeen Low Back Pain Scale, and Acute Low Back Pain Screeing Questionnaire) were randomly assigned to the examinees. The authors reviewed lumbar imaging studies (simple lumbar radiographs, lumbar computed tomography, and magnetic resolutional images), and the severity of lumbar disc herniation was categorized according to the guidelines issued by the Korean military directorate. We calculated the relationship between the back pain questionnaire scores and the severity of lumbar disc herniation. Results The scores of back pain questionnaires increased according to the severity of lumbar disc herniation. But, the range of scores was very vague, so it is less predictable to detect lumbar disc herniation using only back pain questionnaires. The sensitivity between the back pain questionnaires and the presence of lumbar disc herniation was low (16-64%). Conclusion Screening of lumbar disc herniation using only back pain questionnaires has limited value. PMID:25983807

Comparison between cranial thoracic intervertebral disc herniations in German Shepherd dogs and other large breed dogs.

PubMed

Gaitero, Luis; Nykamp, Stephanie; Daniel, Rob; Monteith, Gabrielle

2013-01-01

Cranial thoracic intervertebral disc herniations have been reported to be rare in dogs due to the presence of the intercapital ligament, however some studies have proposed they may not be uncommon in German Shepherd dogs. The purpose of this retrospective study was to compare cranial thoracic intervertebral disc herniations in German Shepherd dogs and other large breed dogs (control group). Medical records at the Ontario Veterinary College were searched for German Shepherd dogs and other large breed dogs that had magnetic resonance imaging studies including the T1-T9 region. For each dog and each disc space from T1-T9, three variables (compression, disc degeneration, and herniation) were recorded and graded based on review of sagittal T2-weighted images. Twenty-three German Shepherd dogs and 47 other large breed dogs met inclusion criteria. The German Shepherd dog group had higher scores than the control group for compression (P = 0.0099) and herniation (P < 0.001), but not disc degeneration (P = 0.97). In the German Shepherd dog group, intervertebral discs T2-T3 and T4-T5 had an increased risk for compression and T3-T4 had an increased risk for compression and herniation. Findings from this study indicated that German Shepherd dogs may be more likely than other large breed dogs to have spinal cord compression due to cranial thoracic disc herniations. Imaging of the cranial thoracic spine, including T2-T3, is recommended for German Shepherd dogs with T3-L3 neurological signs. © 2012 Veterinary Radiology & Ultrasound.

Quantification of the association between intervertebral disk calcification and disk herniation in Dachshunds.

PubMed

Jensen, Vibeke F; Beck, Sarah; Christensen, Knud A; Arnbjerg, Jens

2008-10-01

To quantify the association between intervertebral disk calcification and disk herniation in Dachshunds. Longitudinal study. 61 Dachshunds that had been radiographically screened for calcification of intervertebral disks at 2 years of age in other studies. Thirty-seven of the dogs had survived to the time of the present study and were > or = 8 years of age; 24 others had not survived. Radiographic examination of 36 surviving dogs was performed, and information on occurrence of disk calcification at 2 years of age were obtained from records of all 61 Dachshunds. Information on occurrence of disk herniation between 2 and 8 years of age was obtained from owners via questionnaire. Associations between numbers of calcified disks and disk herniation were analyzed via maximum likelihood logistic regression. Disk calcification at 2 years of age was a significant predictor of clinical disk herniation (odds ratio per calcified disk, 1.42; 95% confidence interval, 1.19 to 1.81). Number of calcified disks in the full vertebral column was a better predictor than number of calcified disks between vertebrae T10 and L3. Numbers of calcified disks at > or = 8 years of age and at 2 years of age were significantly correlated. Number of calcified disks at 2 years of age was a good predictor of clinical disk herniation in Dachshunds. Because of the high heritability of disk calcification, it is possible that an effective reduction in occurrence of severe disk herniation in Dachshunds could be obtained by selective breeding against high numbers of calcified disks at 2 years of age.

Prevention of parastomal herniation with biologic/composite prosthetic mesh: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Wijeyekoon, Sanjaya Prabhath; Gurusamy, Kurinchi; El-Gendy, Khalid; Chan, Christopher L

2010-11-01

Parastomal herniation is a frequent complication of stoma formation and can be difficult to repair satisfactorily, making it a recognized cause of significant morbidity. A systematic review with meta-analysis of randomized clinical trials was performed to determine the benefits and risks of mesh reinforcement versus conventional stoma formation in preventing parastomal herniation. Trials were identified from The Cochrane Library trials register, Medline, Embase, Science Citation Index Expanded, and reference lists. The primary outcome was the incidence of parastomal herniation. The secondary outcomes were the incidence of parastomal herniation requiring surgical repair, postoperative morbidity, and mortality. Meta-analysis was performed using a random-effects model. The risk ratio (RR) was estimated with 95% confidence intervals (CI) based on an intention-to-treat analysis. Three trials with 129 patients were included. Composite or biologic mesh was used in either the preperitoneal or sublay position. Mesh reinforcement was associated with a reduction in parastomal herniation versus conventional stoma formation (RR 0.23, 95%CI 0.06 to 0.81; p = 0.02), and a reduction in the percentage of parastomal hernias requiring surgical treatment (RR 0.13, 95%CI 0.02 to 1.02; p = 0.05). There was no difference between groups in stoma-related morbidity (2 of 58, 3.4% in the mesh group versus 2 of 57, 3.5% in the conventional group; p = 0.97), nor was there any mortality related to the placement of mesh. Composite or biologic mesh reinforcement of stomas in the preperitoneal/sublay position is associated with a reduced incidence of parastomal herniation with no excess morbidity. Mesh reinforcement also demonstrates a trend toward a decreased incidence of parastomal herniation requiring surgical repair. Copyright © 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Physical examination, magnetic resonance image, and electrodiagnostic study in patients with lumbosacral disc herniation or spinal stenosis.

PubMed

Lee, Jung Hwan; Lee, Sang-Ho

2012-10-01

To compare the clinical implications of electro-diagnostic study with those of magnetic resonance imaging in patients with lumbosacral intervertebral herniated disc or spinal stenosis. Retrospective study of clinical data. Patients with lumbosacral intervertebral herniated disc or spinal stenosis, diagnosed by clinical assessment and magnetic resonance imaging (MRI), were selected. A total of 753 patients (437 with lumbosacral intervertebral herniated disc and 316 with spinal stenosis) were included in the study. Clinical data for electrodiagnostic study (EDX)and MRI were compared and the sensitivity and specificity of these studies were evaluated. Among all subjects, 267 had radiculopathy on EDX (EDX (+)) and 486 no radiculopathy (EDX(-)). Furthermore, 391 had root compression on MRI (MRI (+)) and 362 no root compression on MRI (MRI (-)). Patients with radioculopathy on EDX (+) showed a significantly higher visual analogue scale score for radiating pain and a higher Oswestry Disability Index than those with negative findings by EDX (-) in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, and there was a trend toward higher Oswestry Disability Index in the spinal stenosis subgroup. Although patients with radioculopathy on root compression on MRI (+) also had a higher visual analogue scale for radiating pain than patients with negative findings by MRI (-) in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, no significant difference was seen in the Oswestry Disability Index. EDX revealed a significant correlation with muscle weakness in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, and trends toward muscle weakness in the spinal stenosis subgroup, whereas there was no such significant correlation for MRI findings in any group. Electrodiagnostic study had a higher specificity in terms of physical examination data than MRI, in spite of its lower sensitivity. Electrodiagnostic study was significantly more correlated with clinical data, especially leg muscle weakness and functional status, and showed a higher specificity than MRI in patients with lumbosacral intervertebral herniated disc or spinal stenosis.

Aggravation and subsequent disappearance of cervical disc herniation after cervical open-door laminoplasty: A case report.

PubMed

Meng, Yang; Wang, Xiaofei; Wang, Beiyu; Wu, Tingkui; Liu, Hao

2018-03-01

Cervical open-door laminoplasty can enlarge the volume of the cervical vertebral canal and thus has become an effective and safe treatment for multilevel cervical disc herniation and cervical stenosis. Some post-surgery complications exist, such as reduction of cervical alignment and local kyphosis. However, aggravation of cervical disc herniation at the surgical level during short-term follow-up has not been discussed. Additionally, spontaneous disappearance of herniated disc pulposus is a common phenomenon in the lumbar region but is relatively rare in the cervical region. A 42-year-old female presented with a 7-year history of neck pain and a 2-year history of paresthesia and weakness in the upper and lower limbs. The sensations and muscle strength of both upper and lower limbs were decreased. The radiological findings showed that the Pavlov ratios from C3-7 were decreased obviously. Osteophytes as well as spinal cord compression were observed at C4/5, C5/6, and C6/7. Considering the symptoms and clinical examinations, the patient was diagnosed with cervical stenosis. We performed cervical open-door laminoplasty at C3-7 to enlarge the space of the cervical vertebral canal. At the 6-month post-surgery follow-up, the patient showed obvious improvement in paresthesia and weakness in the upper limbs. The cervical disc herniation at C3/4 was aggravated. However, at the 18-month follow-up, the symptoms were relieved, and the herniated cervical disc at C3/4 spontaneously disappeared without any special treatment. We suggest that the attachment points of deep muscles in the neck region should be carefully protected during this surgery. Patients who undergo cervical open-door laminoplasty should pay attention to their cervical position and perform neck exercises to train their neck muscles. MRI is an important imaging method to observe dynamic changes in herniated discs for patients with cervical disc herniation.

Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells

PubMed Central

Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi

2015-01-01

Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. PMID:25910782

YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Dasol; Byun, Sung-Hyun; Park, Soojeong

Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and sizemore » of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics.« less

Severe traumatic head injury: prognostic value of brain stem injuries detected at MRI.

PubMed

Hilario, A; Ramos, A; Millan, J M; Salvador, E; Gomez, P A; Cicuendez, M; Diez-Lobato, R; Lagares, A

2012-11-01

Traumatic brain injuries represent an important cause of death for young people. The main objectives of this work are to correlate brain stem injuries detected at MR imaging with outcome at 6 months in patients with severe TBI, and to determine which MR imaging findings could be related to a worse prognosis. One hundred and eight patients with severe TBI were studied by MR imaging in the first 30 days after trauma. Brain stem injury was categorized as anterior or posterior, hemorrhagic or nonhemorrhagic, and unilateral or bilateral. Outcome measures were GOSE and Barthel Index 6 months postinjury. The relationship between MR imaging findings of brain stem injuries, outcome, and disability was explored by univariate analysis. Prognostic capability of MR imaging findings was also explored by calculation of sensitivity, specificity, and area under the ROC curve for poor and good outcome. Brain stem lesions were detected in 51 patients, of whom 66% showed a poor outcome, as expressed by the GOSE scale. Bilateral involvement was strongly associated with poor outcome (P < .05). Posterior location showed the best discriminatory capability in terms of outcome (OR 6.8, P < .05) and disability (OR 4.8, P < .01). The addition of nonhemorrhagic and anterior lesions or unilateral injuries showed the highest odds and best discriminatory capacity for good outcome. The prognosis worsens in direct relationship to the extent of traumatic injury. Posterior and bilateral brain stem injuries detected at MR imaging are poor prognostic signs. Nonhemorrhagic injuries showed the highest positive predictive value for good outcome.

Where and When to Cut? Fluorescein Guidance for Brain Stem and Spinal Cord Tumor Surgery-Technical Note.

PubMed

Molina, Eric Suero; Stummer, Walter

2017-12-29

Spinal cord and brain stem lesions require a judicious approach with an optimized trajectory due to a clustering of functions on their surfaces. Intraoperative mapping helps locate function. To confidently locate such lesions, neuronavigation alone lacks the desired accuracy and is of limited use in the spinal cord. To evaluate the clinical value of fluoresceins for initial delineation of such critically located lesions. We evaluated fluorescein guidance in the surgical resection of lesions with blood-brain barrier disruption demonstrating contrast enhancement in magnet resonance imaging in the spinal cord and in the brain stem in 3 different patients. Two patients harbored a diffuse cervical and thoracic spinal cord lesion, respectively. Another patient suffered metastatic lesions in the brain stem and at the floor of the fourth ventricle. Low-dose fluorescein (4 mg/kg body weight) was applied after anesthesia induction and visualized using the Zeiss Pentero 900 Yellow560 filter (Carl Zeiss, Oberkochen, Germany). Fluorescein was helpful for locating lesions and for defining the best possible trajectory. During resection, however, we found unspecific propagation of fluorescein within the brain stem up to 6 mm within 3 h after application. As these lesions were otherwise distinguishable from surrounding tissue, monitoring resection was not an issue. Fluorescein guidance is a feasible tool for defining surgical entry zones when aiming for surgical removal of spinal cord and brain stem lesions. Unselective fluorescein extravasation cautions against using such methodology for monitoring completeness of resection. Providing the right timing, a window of pseudoselectivity could increase fluoresceins' clinical value in these cases. © Congress of Neurological Surgeons 2017.

Malformations of the craniocervical junction (chiari type I and syringomyelia: classification, diagnosis and treatment)

PubMed Central

2009-01-01

Chiari disease (or malformation) is in general a congenital condition characterized by an anatomic defect of the base of the skull, in which the cerebellum and brain stem herniate through the foramen magnum into the cervical spinal canal. The onset of Chiari syndrome symptoms usually occurs in the second or third decade (age 25 to 45 years). Symptoms may vary between periods of exacerbation and remission. The diagnosis of Chiari type I malformation in patients with or without symptoms is established with neuroimaging techniques. The most effective therapy for patients with Chiari type I malformation/syringomyelia is surgical decompression of the foramen magnum, however there are non-surgical therapy to relieve neurophatic pain: either pharmacological and non-pharmacological. Pharmacological therapy use drugs that act on different components of pain. Non-pharmacological therapies are primarly based on spinal or peripheral electrical stimulation. It is important to determine the needs of the patients in terms of health-care, social, educational, occupational, and relationship issues, in addition to those derived from information aspects, particularly at onset of symptoms. Currently, there is no consensus among the specialists regarding the etiology of the disease or how to approach, monitor, follow-up, and treat the condition. It is necessary that the physicians involved in the care of people with this condition comprehensively approach the management and follow-up of the patients, and that they organize interdisciplinary teams including all the professionals that can help to increase the quality of life of patients. PMID:20018097

Inguinal herniation with hydrometra/mucometra in a poodle bitch

PubMed Central

Sontas, B. Hasan; Toydemir, F.T. Seval; Erdogan, Özge; Şennazli, Gülbin; Ekici, Hayri

2013-01-01

A 5-year-old, sexually intact poodle bitch was presented with a 2-year history of inguinal mass. A tentative diagnosis of hydrometra/mucometra with inguinal herniation was made and ovariohysterectomy with hernia repair was performed. Both fluid-filled uterine horns, both broad ligaments, and the uterine body were observed to be herniated through the inguinal ring. On histopathology, marked edema and diffuse hemorrhage were diagnosed in the uterus. PMID:24155486

Release and repair of a ventral thoracic spinal cord herniation.

PubMed

McCormick, Paul C

2014-09-01

Ventral thoracic spinal cord herniation is a rare but increasingly recognized cause of progressive myelopathy. This video demonstrates the imaging characteristics and surgical techniques for release and reduction of the spinal cord herniation as well as primary repair and reinforcement of the ventral dural hernia defect through an extended posterior approach. An instrumented fusion was concomitantly performed. The video can be found here: http://youtu.be/6Pcokep6Tug.

Lung herniation: an uncommon presentation of Poland's syndrome in a neonate at birth

PubMed Central

Chandran, Suresh; Revanna, Krishna Gopagondanahalli; Ari, Dinesh; Rana, Aftab Ahmed

2013-01-01

A term male infant was admitted to the neonatal intensive care unit with an asymmetric chest wall and a herniating mass through the left fourth intercostal space. While crying, the left fourth intercostal space revealed a mass which herniated on expiration and receded on inspiration. On auscultation, the heart sounds were audible on the right side of the chest. Systemic examination was otherwise unremarkable. A roentgenogram of the chest revealed dextrocardia and hyperlucent left lung fields. Echocardiogram showed dextrocardia with a structurally normal heart. A clinical diagnosis of Poland's syndrome was made based on the hypoplasia of the left pectoral muscles, ribs and nipple, dextrocardia and lung herniation. He was thriving well when reviewed at 2 years of age. PMID:23921692

Blood-brain barrier and foetal-onset hydrocephalus, with a view on potential novel treatments beyond managing CSF flow.

PubMed

Guerra, M; Blázquez, J L; Rodríguez, E M

2017-07-13

Despite decades of research, no compelling non-surgical therapies have been developed for foetal hydrocephalus. So far, most efforts have pointed to repairing disturbances in the cerebrospinal fluid (CSF) flow and to avoid further brain damage. There are no reports trying to prevent or diminish abnormalities in brain development which are inseparably associated with hydrocephalus. A key problem in the treatment of hydrocephalus is the blood-brain barrier that restricts the access to the brain for therapeutic compounds or systemically grafted cells. Recent investigations have started to open an avenue for the development of a cell therapy for foetal-onset hydrocephalus. Potential cells to be used for brain grafting include: (1) pluripotential neural stem cells; (2) mesenchymal stem cells; (3) genetically-engineered stem cells; (4) choroid plexus cells and (5) subcommissural organ cells. Expected outcomes are a proper microenvironment for the embryonic neurogenic niche and, consequent normal brain development.

Stem Cell Therapy: Repurposing Cell-Based Regenerative Medicine Beyond Cell Replacement.

PubMed

Napoli, Eleonora; Lippert, Trenton; Borlongan, Cesar V

2018-02-27

Stem cells exhibit simple and naive cellular features, yet their exact purpose for regenerative medicine continues to elude even the most elegantly designed research paradigms from developmental biology to clinical therapeutics. Based on their capacity to divide indefinitely and their dynamic differentiation into any type of tissue, the advent of transplantable stem cells has offered a potential treatment for aging-related and injury-mediated diseases. Recent laboratory evidence has demonstrated that transplanted human neural stem cells facilitate endogenous reparative mechanisms by initiating multiple regenerative processes in the brain neurogenic areas. Within these highly proliferative niches reside a myriad of potent regenerative molecules, including anti-inflammatory cytokines, proteomes, and neurotrophic factors, altogether representing a biochemical cocktail vital for restoring brain function in the aging and diseased brain. Here, we advance the concept of therapeutically repurposing stem cells not towards cell replacement per se, but rather exploiting the cells' intrinsic properties to serve as the host brain regenerative catalysts.

Stem cell-based therapies for tumors in the brain: are we there yet?

PubMed

Shah, Khalid

2016-08-01

Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case without elevated white matter lactate.

PubMed

Sharma, Suvasini; Sankhyan, Naveen; Kumar, Atin; Scheper, Gert C; van der Knaap, Marjo S; Gulati, Sheffali

2011-06-01

A 17-year-old Indian boy with gradually progressive ataxia with onset at 12 years of age is described. Magnetic resonance imaging (MRI) of the brain revealed extensive, inhomogeneous signal abnormalities in the cerebral white matter, with involvement of selected tracts in the brain stem and spinal cord. The imaging findings were characteristic of leukoencephalopathy with brain stem and spinal cord involvement and high lactate, a recently described leukodystrophy. Interestingly, magnetic resonance spectroscopy of the abnormal white matter did not reveal elevated lactate. The patient was compound heterozygous for 2 new mutations in DARS2, genetically confirming the diagnosis.

Breath-holding spells may be associated with maturational delay in myelination of brain stem.

PubMed

Vurucu, Sebahattin; Karaoglu, Abdulbaki; Paksu, Sukru M; Oz, Oguzhan; Yaman, Halil; Gulgun, Mustafa; Babacan, Oguzhan; Unay, Bulent; Akin, Ridvan

2014-02-01

To evaluate possible contribution of maturational delay of brain stem in the etiology of breath-holding spells in children using brain stem auditory evoked potentials. The study group included children who experienced breath-holding spells. The control group consisted of healthy age- and sex-matched children. Age, gender, type and frequency of spell, hemoglobin, and ferritin levels in study group and brain stem auditory evoked potentials results in both groups were recorded. Study group was statistically compared with control group for brain stem auditory evoked potentials. The mean age of study and control groups was 26.3 ± 14.6 and 28.9 ± 13.9 months, respectively. The III-V and I-V interpeak latencies were significantly prolonged in the study group compared with the control group (2.07 ± 0.2 milliseconds; 1.92 ± 0.13 milliseconds and 4.00 ± 0.27 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.009 and P = 0.03, respectively). At the same time, III-V and I-V interpeak latencies of patients without anemia in the study group compared with those of control group were significantly prolonged (2.09 ± 0.24 milliseconds; 1.92 ± 0.13 milliseconds and 4.04 ± 0.28 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.007 and P = 0.01, respectively). Our results consider that maturational delay in myelination of brain stem may have a role in the etiology of breath-holding spells in children.

Concise review: Patient-derived olfactory stem cells: new models for brain diseases.

PubMed

Mackay-Sim, Alan

2012-11-01

Traditional models of brain diseases have had limited success in driving candidate drugs into successful clinical translation. This has resulted in large international pharmaceutical companies moving out of neuroscience research. Cells are not brains, obviously, but new patient-derived stem models have the potential to elucidate cell biological aspects of brain diseases that are not present in worm, fly, or rodent models, the work horses of disease investigations and drug discovery. Neural stem cells are present in the olfactory mucosa, the organ of smell in the nose. Patient-derived olfactory mucosa has demonstrated disease-associated differences in a variety of brain diseases and recently olfactory mucosa stem cells have been generated from patients with schizophrenia, Parkinson's disease, and familial dysautonomia. By comparison with cells from healthy controls, patient-derived olfactory mucosa stem cells show disease-specific alterations in gene expression and cell functions including: a shorter cell cycle and faster proliferation in schizophrenia, oxidative stress in Parkinson's disease, and altered cell migration in familial dysautonomia. Olfactory stem cell cultures thus reveal patient-control differences, even in complex genetic diseases such as schizophrenia and Parkinson's disease, indicating that multiple genes of small effect can converge on shared cell signaling pathways to present as a disease-specific cellular phenotype. Olfactory mucosa stem cells can be maintained in homogeneous cultures that allow robust and repeatable multiwell assays suitable for screening libraries of drug candidate molecules. Copyright © 2012 AlphaMed Press.

The course and prognostic factors of symptomatic cervical disc herniation with radiculopathy: a systematic review of the literature.

PubMed

Wong, Jessica J; Côté, Pierre; Quesnele, Jairus J; Stern, Paula J; Mior, Silvano A

2014-08-01

Cervical spine disc herniation is a disabling source of cervical radiculopathy. However, little is known about its course and prognosis. Understanding the course and prognosis of symptomatic cervical disc herniation is necessary to guide patients' expectations and assist clinicians in managing patients. To describe the natural history, clinical course, and prognostic factors of symptomatic cervical disc herniations with radiculopathy. Systematic review of the literature and best evidence synthesis. A systematic search of MEDLINE, EMBASE, CINAHL, SportsDiscus, and the Cochrane Central Register of Controlled Trials from inception to 2013 was conducted to retrieve eligible articles. Eligible articles were critically appraised using the Scottish Intercollegiate Guidelines Network criteria. The results from articles with low risk of bias were analyzed using best evidence synthesis principles. We identified 1,221 articles. Of those, eight articles were eligible and three were accepted as having a low risk of bias. Two studies pertained to course and one study pertained to prognosis. Most patients with symptomatic cervical disc herniations with radiculopathy initially present with intense pain and moderate levels of disability. However, substantial improvements tend to occur within the first 4 to 6 months post-onset. Time to complete recovery ranged from 24 to 36 months in, approximately, 83% of patients. Patients with a workers' compensation claim appeared to have a poorer prognosis. Our best evidence synthesis describes the best available evidence on the course and prognosis of cervical disc herniations with radiculopathy. Most patients with symptomatic cervical spine disc herniation with radiculopathy recover. Possible recurrences and time to complete recovery need to be further studied. More studies are also needed to understand the prognostic factors for this condition. Copyright © 2014 Elsevier Inc. All rights reserved.

Imaging of Herniated Discs of the Cervical Spine: Inter-Modality Differences between 64-Slice Multidetector CT and 1.5-T MRI

PubMed Central

Yi, Ji Sook; Han, Jong Kyu; Kim, Hyun-Joo

2015-01-01

Objective To assess inter-modality variability when evaluating cervical intervertebral disc herniation using 64-slice multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI). Materials and Methods Three musculoskeletal radiologists independently reviewed cervical spine 1.5-T MRI and 64-slice MDCT data on C2-3 though C6-7 of 51 patients in the context of intervertebral disc herniation. Interobserver and inter-modality agreements were expressed as unweighted kappa values. Weighted kappa statistics were used to assess the extents of agreement in terms of the number of involved segments (NIS) in disc herniation and epicenter measurements collected using MDCT and MRI. Results The interobserver agreement rates upon evaluation of disc morphology by the three radiologists were in fair to moderate agreement (k = 0.39-0.53 for MDCT images; k = 0.45-0.56 for MRIs). When the disc morphology was categorized into two and four grades, the inter-modality agreement rates were moderate (k-value, 0.59) and substantial (k-value, 0.66), respectively. The inter-modality agreements for evaluations of the NIS (k-value, 0.78) and the epicenter (k-value, 0.79) were substantial. Also, the interobserver agreements for the NIS (CT; k-value, 0.85 and MRI; k-value, 0.88) and epicenter (CT; k-value, 0.74 and MRI; k-value, 0.70) evaluations by two readers were substantial. MDCT tended to underestimate the extent of herniated disc lesions compared with MRI. Conclusion Multidetector-row computed tomography and MRI showed a moderate-to-substantial degree of inter-modality agreement for the assessment of herniated cervical discs. MDCT images have a tendency to underestimate the anterior/posterior extent of the herniated disc compared with MRI. PMID:26175589

Chronic cerebral herniation in shunted Dandy-Walker malformation.

PubMed

Naidich, T P; Radkowski, M A; McLone, D G; Leestma, J

1986-02-01

A review of serial computed tomography (CT) scans of 25 patients with the Dandy-Walker malformation revealed six patients with chronic downward transincisural herniation of the cerebrum after shunt decompression of the posterior fossa cyst or malfunction of a lateral ventricular drainage catheter, or both. Chronic cerebral herniation was detected postmortem in a seventh patient with the Dandy-Walker malformation. The CT findings and autopsy appearance of this previously undescribed feature of shunted Dandy-Walker malformation are illustrated.

Radial glia - from boring cables to stem cell stars.

PubMed

Malatesta, Paolo; Götz, Magdalena

2013-02-01

The discovery in the year 2000 that radial glial cells act as neural stem and progenitor cells in development has led to a change in the concept of neural stem cells in the adult brain. Not only are adult stem cells in the neurogenic niches glial in nature, but also glial cells outside these niches display greater potential when reacting to brain injury. Thus, a concept that emerged from developmental studies may hold the clue for neural repair.

The developmental origin of brain tumours: a cellular and molecular framework.

PubMed

Azzarelli, Roberta; Simons, Benjamin D; Philpott, Anna

2018-05-14

The development of the nervous system relies on the coordinated regulation of stem cell self-renewal and differentiation. The discovery that brain tumours contain a subpopulation of cells with stem/progenitor characteristics that are capable of sustaining tumour growth has emphasized the importance of understanding the cellular dynamics and the molecular pathways regulating neural stem cell behaviour. By focusing on recent work on glioma and medulloblastoma, we review how lineage tracing contributed to dissecting the embryonic origin of brain tumours and how lineage-specific mechanisms that regulate stem cell behaviour in the embryo may be subverted in cancer to achieve uncontrolled proliferation and suppression of differentiation. © 2018. Published by The Company of Biologists Ltd.

Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

PubMed

Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito; Ye, Peng; Shi, Yanhong

2012-01-01

TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.

Characterization of TLX Expression in Neural Stem Cells and Progenitor Cells in Adult Brains

PubMed Central

Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito; Ye, Peng; Shi, Yanhong

2012-01-01

TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression.Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells. PMID:22952666

Intermittent midline suprasternal neck mass caused by superior herniation of the thymus.

PubMed

Su, Siew Choo; Hess, Thomas; Whybourne, Annie; Chang, Anne B

2015-03-01

Neck masses in infants and children have a wide differential diagnosis. However, neck masses apparent only during raised intrathoracic pressure are rare with a limited number of causes, including superior herniation of the normal thymus, apical lung herniation, jugular phlebectasia and laryngocoele. These conditions can easily be differentiated from one another by imaging. We present an infant with intermittent suprasternal neck mass visible only during increased intrathoracic pressure, produced either by crying or straining. Diagnosis of superior herniation of the thymus into the neck was confirmed by ultrasonography with the characteristic sonographic appearances of the normal thymus as well as its shape, size and location. Ultrasonography should be the first imaging modality of choice. Management of superior herniation of the thymus into the neck should be conservative as the thymus naturally involutes with increasing age. Awareness of the differential diagnosis of neck swelling present only on Vasalva manoeuvre or increased intrathoracic pressure is important to prevent unnecessary tests, avoid radiation, biopsy and surgery. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Management of parturients in active labor with Arnold Chiari malformation, tonsillar herniation, and syringomyelia

PubMed Central

Ghaly, Ramsis F.; Tverdohleb, Tatiana; Candido, Kenneth D.; Knezevic, Nebojsa Nick

2017-01-01

Background: Arnold-Chiari malformation Type 1 (ACM-1) in parturients is a topic of ongoing discussion between obstetricians and anesthesiologists. The primary unanswered question remains; How should the anesthesia provider proceed with labor analgesia and anesthesia for cesarean section when confronted with an advanced, asymptomatic, or minimally symptomatic case of ACM-1 during labor? Case Description: A 24-year-old, ASA II, G1P0 full-term parturient presented to Labor and Delivery for vaginal delivery. A diagnosis of ACM-1 was made 12 years ago when a brain magnetic resonance imaging (MRI) was performed for right-sided numbness following a rear-end motor vehicle collision. The patient had been asymptomatic since then and had been seen by an outside neurologist frequently for the past 10 years. During the anesthesia evaluation, it was noted that she had an exaggerated patellar reflex, and a questionable left-sided Babinski; subsequently, an MRI study was requested. Review of a brain MRI demonstrated an advanced form of ACM with a 1.7 cm transtonsillar herniation and a large syrinx extending from C1 down to C5. Following a discussion with the patient, family, and primary OB team, a plan for elective cesarean section was made per neurosurgical recommendations. This was conducted uneventfully under general anesthesia. The patient had no complaints in the post-anesthesia care unit. Conclusion: Unfamiliarity of health care providers with regards to ACM-1 parturients can be countered by increasing awareness of this condition throughout medical specialties involved in their care. The Ghaly Obstetric Guide to Arnold-Chiari malformation Type 1, along with proper training of anesthesia care providers regarding the specificities of ACM-1 parturients aids in better management and understanding of this complex condition. PMID:28217389

Management of parturients in active labor with Arnold Chiari malformation, tonsillar herniation, and syringomyelia.

PubMed

Ghaly, Ramsis F; Tverdohleb, Tatiana; Candido, Kenneth D; Knezevic, Nebojsa Nick

2017-01-01

Arnold-Chiari malformation Type 1 (ACM-1) in parturients is a topic of ongoing discussion between obstetricians and anesthesiologists. The primary unanswered question remains; How should the anesthesia provider proceed with labor analgesia and anesthesia for cesarean section when confronted with an advanced, asymptomatic, or minimally symptomatic case of ACM-1 during labor? A 24-year-old, ASA II, G1P0 full-term parturient presented to Labor and Delivery for vaginal delivery. A diagnosis of ACM-1 was made 12 years ago when a brain magnetic resonance imaging (MRI) was performed for right-sided numbness following a rear-end motor vehicle collision. The patient had been asymptomatic since then and had been seen by an outside neurologist frequently for the past 10 years. During the anesthesia evaluation, it was noted that she had an exaggerated patellar reflex, and a questionable left-sided Babinski; subsequently, an MRI study was requested. Review of a brain MRI demonstrated an advanced form of ACM with a 1.7 cm transtonsillar herniation and a large syrinx extending from C1 down to C5. Following a discussion with the patient, family, and primary OB team, a plan for elective cesarean section was made per neurosurgical recommendations. This was conducted uneventfully under general anesthesia. The patient had no complaints in the post-anesthesia care unit. Unfamiliarity of health care providers with regards to ACM-1 parturients can be countered by increasing awareness of this condition throughout medical specialties involved in their care. The Ghaly Obstetric Guide to Arnold-Chiari malformation Type 1, along with proper training of anesthesia care providers regarding the specificities of ACM-1 parturients aids in better management and understanding of this complex condition.

Morphofunctional study of the therapeutic efficacy of human mesenchymal and neural stem cells in rats with diffuse brain injury.

PubMed

Tsyb, A F; Yuzhakov, V V; Roshal', L M; Sukhikh, G T; Konoplyannikov, A G; Sushkevich, G N; Yakovleva, N D; Ingel', I E; Bandurko, L N; Sevan'kaeva, L E; Mikhina, L N; Fomina, N K; Marei, M V; Semenova, Zh B; Konoplyannikova, O A; Kal'sina, S Sh; Lepekhina, L A; Semenkova, I V; Agaeva, E V; Shevchuk, A S; Pavlova, L N; Tokarev, O Yu; Karaseva, O V; Chernyshova, T A

2009-01-01

We studied the effect of transplantation of human stem cells from various tissues on reparative processes in the brain of rats with closed craniocerebral injury. Combined treatment with standard drugs and systemic administration of xenogeneic stem cells had a neuroprotective effect. The morphology of neurons rapidly returned to normal after administration of fetal neural stem cells. Fetal mesenchymal stem cells produced a prolonged effect on proliferative activity of progenitor cells in the subventricular zone of neurogenesis. Adult mesenchymal stem cells had a strong effect on recovery of the vascular bed in ischemic regions.

Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease.

PubMed

Kanoto, Masafumi; Hosoya, Takaaki; Toyoguchi, Yuuki; Oda, Atsuko

2013-01-01

Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. The subjects consist of a CPNBD group (n=4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n=19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n=23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p<0.05), and between the CPNBD group and the normal control group (p<0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p<0.001, p<0.01 respectively), and between the CPNBD group and the normal control group (p<0.001). Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Viability and neuronal differentiation of neural stem cells encapsulated in silk fibroin hydrogel functionalized with an IKVAV peptide.

PubMed

Sun, Wei; Incitti, Tania; Migliaresi, Claudio; Quattrone, Alessandro; Casarosa, Simona; Motta, Antonella

2017-05-01

Three-dimensional (3D) porous scaffolds combined with therapeutic stem cells play vital roles in tissue engineering. The adult brain has very limited regeneration ability after injuries such as trauma and stroke. In this study, injectable 3D silk fibroin-based hydrogel scaffolds with encapsulated neural stem cells were developed, aiming at supporting brain regeneration. To improve the function of the hydrogel towards neural stem cells, silk fibroin was modified by an IKVAV peptide through covalent binding. Both unmodified and modified silk fibroin hydrogels were obtained, through sonication, with mechanical stiffness comparable to that of brain tissue. Human neural stem cells were encapsulated in both hydrogels and the effects of IKVAV peptide conjugation on cell viability and neural differentiation were assessed. The silk fibroin hydrogel modified by IKVAV peptide showed increased cell viability and an enhanced neuronal differentiation capability, which contributed to understanding the effects of IKVAV peptide on the behaviour of neural stem cells. For these reasons, IKVAV-modified silk fibroin is a promising material for brain tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Sex differences in the expression of estrogen receptor alpha within noradrenergic neurons in the sheep brain stem.

PubMed

Rose, J L; Hamlin, A S; Scott, C J

2014-10-01

In female sheep, high levels of estrogen exert a positive feedback action on gonadotropin releasing hormone (GnRH) secretion to stimulate a surge in luteinizing hormone (LH) secretion. Part of this action appears to be via brain stem noradrenergic neurons. By contrast, estrogen action in male sheep has a negative feedback action to inhibit GnRH and LH secretion. To investigate whether part of this sex difference is due to differences in estrogen action in the brain stem, we tested the hypothesis that the distribution of estrogen receptor α (ERα) within noradrenergic neurons in the brain stem differs between rams and ewes. To determine the distribution of ERα, we used double-label fluorescence immunohistochemistry for dopamine β-Hydroxylase, as a marker for noradrenergic and adrenergic cells, and ERα. In the ventrolateral medulla (A1 region), most ERα-immunoreactive (-ir) cells were located in the caudal part of the nucleus. Overall, there were more ERα-ir cells in rams than ewes, but the proportion of double-labeled cells was did not differ between sexes. Much greater numbers of ERα-ir cells were found in the nucleus of the solitary tract (A2 region), but <10% were double labeled and there were no sex differences. The majority of ERα-labeled cells in this nucleus was located in the more rostral areas. ERα-labeled cells were found in several rostral brain stem regions but none of these were double labeled and so were not quantified. Because there was no sex difference in the number of ERα-ir cells in the brain stem that were noradrenergic, the sex difference in the action of estrogen on gonadotropin secretion in sheep is unlikely to involve actions on brain stem noradrenergic cells. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice.

PubMed

Kim, Ju Hwan; Yu, Da-Hyeon; Kim, Hyo-Jeong; Huh, Yang Hoon; Cho, Seong-Wan; Lee, Jin-Koo; Kim, Hyung-Gun; Kim, Hak Rim

2018-01-01

The exploding popularity of mobile phones and their close proximity to the brain when in use has raised public concern regarding possible adverse effects from exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Numerous studies have suggested that RF-EMF emitted by mobile phones can influence neuronal functions in the brain. Currently, there is still very limited information on what biological mechanisms influence neuronal cells of the brain. In the present study, we explored whether autophagy is triggered in the hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835 MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks; afterward, the hippocampus and brain stem of mice were dissected and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that several autophagic genes, which play key roles in autophagy regulation, were significantly upregulated only in the hippocampus and not in the brain stem. Expression levels of LC3B-II protein and p62, crucial autophagic regulatory proteins, were significantly changed only in the hippocampus. In parallel, transmission electron microscopy (TEM) revealed an increase in the number of autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed mice. The present study revealed that autophagy was induced in the hippocampus, not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks. These results could suggest that among the various adaptation processes to the RF-EMF exposure environment, autophagic degradation is one possible mechanism in specific brain regions.

Moebius Syndrome

MedlinePlus

... by small or absent brain stem nuclei that control the cranial nerves; Group II, characterized by loss and degeneration of neurons ... by small or absent brain stem nuclei that control the cranial nerves; Group II, characterized by loss and degeneration of neurons ...

Distinct Neural Stem Cell Populations Give Rise to Disparate Brain Tumors in Response to N-MYC

PubMed Central

Swartling, Fredrik J.; Savov, Vasil; Persson, Anders I.; Chen, Justin; Hackett, Christopher S.; Northcott, Paul A.; Grimmer, Matthew R.; Lau, Jasmine; Chesler, Louis; Perry, Arie; Phillips, Joanna J.; Taylor, Michael D.; Weiss, William A.

2012-01-01

SUMMARY The proto-oncogene MYCN is mis-expressed in various types of human brain tumors. To clarify how developmental and regional differences influence transformation, we transduced wild-type or mutationally-stabilized murine N-mycT58A into neural stem cells (NSCs) from perinatal murine cerebellum, brain stem and forebrain. Transplantation of N-mycWT NSCs was insufficient for tumor formation. N-mycT58A cerebellar and brain stem NSCs generated medulloblastoma/primitive neuroectodermal tumors, whereas forebrain NSCs developed diffuse glioma. Expression analyses distinguished tumors generated from these different regions, with tumors from embryonic versus postnatal cerebellar NSCs demonstrating SHH-dependence and SHH-independence, respectively. These differences were regulated in-part by the transcription factor SOX9, activated in the SHH subclass of human medulloblastoma. Our results demonstrate context-dependent transformation of NSCs in response to a common oncogenic signal. PMID:22624711

Control of abdominal muscles by brain stem respiratory neurons in the cat

NASA Technical Reports Server (NTRS)

Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

1985-01-01

The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells.

PubMed

Koyama-Nasu, R; Haruta, R; Nasu-Nishimura, Y; Taniue, K; Katou, Y; Shirahige, K; Todo, T; Ino, Y; Mukasa, A; Saito, N; Matsui, M; Takahashi, R; Hoshino-Okubo, A; Sugano, H; Manabe, E; Funato, K; Akiyama, T

2014-04-24

Increasing evidence suggests that brain tumors arise from the transformation of neural stem/precursor/progenitor cells. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma. Here we show that anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for the self-renewal and tumorigenicity of glioblastoma stem cells (GSCs). Furthermore, we demonstrate that pleiotrophin is transactivated directly by SOX2, a transcription factor essential for the maintenance of both neural stem cells and GSCs. We speculate that the pleiotrophin-ALK axis may be a promising target for the therapy of glioblastoma.

Behavior of Xeno-Transplanted Undifferentiated Human Induced Pluripotent Stem Cells Is Impacted by Microenvironment Without Evidence of Tumors.

PubMed

Martínez-Cerdeño, Veronica; Barrilleaux, Bonnie L; McDonough, Ashley; Ariza, Jeanelle; Yuen, Benjamin T K; Somanath, Priyanka; Le, Catherine T; Steward, Craig; Horton-Sparks, Kayla; Knoepfler, Paul S

2017-10-01

Human pluripotent stem cells (hPSC) have great clinical potential through the use of their differentiated progeny, a population in which there is some concern over risks of tumorigenicity or other unwanted cellular behavior due to residual hPSC. Preclinical studies using human stem cells are most often performed within a xenotransplant context. In this study, we sought to measure how undifferentiated hPSC behave following xenotransplant. We directly transplanted undifferentiated human induced pluripotent stem cells (hIPSC) and human embryonic stem cells (hESC) into the adult mouse brain ventricle and analyzed their fates. No tumors or precancerous lesions were present at more than one year after transplantation. This result differed with the tumorigenic capacity we observed after allotransplantation of mouse ESC into the mouse brain. A substantial population of cellular derivatives of undifferentiated hESC and hIPSC engrafted, survived, and migrated within the mouse brain parenchyma. Within brain structures, transplanted cell distribution followed a very specific pattern, suggesting the existence of distinct microenvironments that offer different degrees of permissibility for engraftment. Most of the transplanted hESC and hIPSC that developed into brain cells were NeuN+ neuronal cells, and no astrocytes were detected. Substantial cell and nuclear fusion occurred between host and transplanted cells, a phenomenon influenced by microenvironment. Overall, hIPSC appear to be largely functionally equivalent to hESC in vivo. Altogether, these data bring new insights into the behavior of stem cells without prior differentiation following xenotransplantation into the adult brain.

Central Cord Syndrome

MedlinePlus

... and vertebral instability. Vertebral instability due to acute traumatic injury or cervical disc herniation is often treated by ... and vertebral instability. Vertebral instability due to acute traumatic injury or cervical disc herniation is often treated by ...

Learning Disability Assessed through Audiologic and Physiologic Measures: A Case Study.

ERIC Educational Resources Information Center

Greenblatt, Edward R.; And Others

1983-01-01

The report describes a child with central auditory dysfunction, the first reported case where brain-stem dysfunction on audiologic tests were associated with specific electrophysiologic changes in the brain-stem auditory-evoked responses. (Author/CL)

Cell Therapy in Parkinson's Disease: Host Brain Repair Machinery Gets a Boost From Stem Cell Grafts.

PubMed

Napoli, Eleonora; Borlongan, Cesar V

2017-06-01

This commentary highlights the major findings and future research directions arising from the recent publication by Zuo and colleagues in Stem Cells 2017 (in press). Here, we discuss the novel observations that transplanted human neural stem cells can induce endogenous brain repair by specifically stimulating a host of regenerative processes in the neurogenic niche (i.e., subventricular zone [SVZ]) in an animal model of Parkinson's disease. That the identified therapeutic proteomes, neurotrophic factors, and anti-inflammatory cytokines in the SVZ may facilitate brain regeneration and behavioral recovery open a new venue of research for our understanding of the pathology and treatment of Parkinson's disease. Stem Cells 2017;35:1443-1445. © 2017 AlphaMed Press.

SU-E-T-493: Analysis of the Impact of Range and Setup Uncertainties On the Dose to Brain Stem and Whole Brain in the Passively Scattered Proton Therapy Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahoo, N; Zhu, X; Zhang, X

Purpose: To quantify the impact of range and setup uncertainties on various dosimetric indices that are used to assess normal tissue toxicities of patients receiving passive scattering proton beam therapy (PSPBT). Methods: Robust analysis of sample treatment plans of six brain cancer patients treated with PSPBT at our facility for whom the maximum brain stem dose exceeded 5800 CcGE were performed. The DVH of each plan was calculated in an Eclipse treatment planning system (TPS) version 11 applying ±3.5% range uncertainty and ±3 mm shift of the isocenter in x, y and z directions to account for setup uncertainties. Worst-casemore » dose indices for brain stem and whole brain were compared to their values in the nominal plan to determine the average change in their values. For the brain stem, maximum dose to 1 cc of volume, dose to 10%, 50%, 90% of volume (D10, D50, D90) and volume receiving 6000, 5400, 5000, 4500, 4000 CcGE (V60, V54, V50, V45, V40) were evaluated. For the whole brain, maximum dose to 1 cc of volume, and volume receiving 5400, 5000, 4500, 4000, 3000 CcGE (V54, V50, V45, V40 and V30) were assessed. Results: The average change in the values of these indices in the worst scenario cases from the nominal plan were as follows. Brain stem; Maximum dose to 1 cc of volume: 1.1%, D10: 1.4%, D50: 8.0%, D90:73.3%, V60:116.9%, V54:27.7%, V50: 21.2%, V45:16.2%, V40:13.6%,Whole brain; Maximum dose to 1 cc of volume: 0.3%, V54:11.4%, V50: 13.0%, V45:13.6%, V40:14.1%, V30:13.5%. Conclusion: Large to modest changes in the dosiemtric indices for brain stem and whole brain compared to nominal plan due to range and set up uncertainties were observed. Such potential changes should be taken into account while using any dosimetric parameters for outcome evaluation of patients receiving proton therapy.« less

Systemic Injection of Neural Stem/Progenitor Cells in Mice with Chronic EAE

PubMed Central

Donegà, Matteo; Giusto, Elena; Cossetti, Chiara; Schaeffer, Julia; Pluchino, Stefano

2014-01-01

Neural stem/precursor cells (NPCs) are a promising stem cell source for transplantation approaches aiming at brain repair or restoration in regenerative neurology. This directive has arisen from the extensive evidence that brain repair is achieved after focal or systemic NPC transplantation in several preclinical models of neurological diseases. These experimental data have identified the cell delivery route as one of the main hurdles of restorative stem cell therapies for brain diseases that requires urgent assessment. Intraparenchymal stem cell grafting represents a logical approach to those pathologies characterized by isolated and accessible brain lesions such as spinal cord injuries and Parkinson's disease. Unfortunately, this principle is poorly applicable to conditions characterized by a multifocal, inflammatory and disseminated (both in time and space) nature, including multiple sclerosis (MS). As such, brain targeting by systemic NPC delivery has become a low invasive and therapeutically efficacious protocol to deliver cells to the brain and spinal cord of rodents and nonhuman primates affected by experimental chronic inflammatory damage of the central nervous system (CNS). This alternative method of cell delivery relies on the NPC pathotropism, specifically their innate capacity to (i) sense the environment via functional cell adhesion molecules and inflammatory cytokine and chemokine receptors; (ii) cross the leaking anatomical barriers after intravenous (i.v.) or intracerebroventricular (i.c.v.) injection; (iii) accumulate at the level of multiple perivascular site(s) of inflammatory brain and spinal cord damage; and (i.v.) exert remarkable tissue trophic and immune regulatory effects onto different host target cells in vivo. Here we describe the methods that we have developed for the i.v. and i.c.v. delivery of syngeneic NPCs in mice with experimental autoimmune encephalomyelitis (EAE), as model of chronic CNS inflammatory demyelination, and envisage the systemic stem cell delivery as a valuable technique for the selective targeting of the inflamed brain in regenerative neurology. PMID:24798882

The endogenous regenerative capacity of the damaged newborn brain: boosting neurogenesis with mesenchymal stem cell treatment.

PubMed

Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; Kavelaars, Annemieke; Heijnen, Cobi J

2013-05-01

Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxia-ischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortality rates and long-term neurologic deficits in babies worldwide. Therefore, there is an urgent need to develop more efficient therapeutic strategies. The latest findings indicate that stem cells represent a novel therapeutic possibility to improve outcome in models of neonatal encephalopathy. Transplanted stem cells secrete factors that stimulate and maintain neurogenesis, thereby increasing cell proliferation, neuronal differentiation, and functional integration. Understanding the molecular and cellular mechanisms underlying neurogenesis after an insult is crucial for developing tools to enhance the neurogenic capacity of the brain. The aim of this review is to discuss the endogenous capacity of the neonatal brain to regenerate after a cerebral ischemic insult. We present an overview of the molecular and cellular mechanisms underlying endogenous regenerative processes during development as well as after a cerebral ischemic insult. Furthermore, we will consider the potential to use stem cell transplantation as a means to boost endogenous neurogenesis and restore brain function.

Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody.

PubMed

Barnett, M; Prosser, J; Sutton, I; Halmagyi, G M; Davies, L; Harper, C; Dalmau, J

2001-02-01

A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patient's clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.

Expression and function of orphan nuclear receptor TLX in adult neural stem cells.

PubMed

Shi, Yanhong; Chichung Lie, D; Taupin, Philippe; Nakashima, Kinichi; Ray, Jasodhara; Yu, Ruth T; Gage, Fred H; Evans, Ronald M

2004-01-01

The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody

PubMed Central

Barnett, M; Prosser, J; Sutton, I; Halmagyi, G; Davies, L; Harper, C; Dalmau, J

2001-01-01

A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patient's clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.

 PMID:11160472

Percutaneous endoscopic lumbar discectomy via contralateral approach: a technical case report.

PubMed

Kim, Jin-Sung; Choi, Gun; Lee, Sang-Ho

2011-08-01

Technical case report. The authors report a new percutaneous endoscopic lumbar discectomy (PELD) technique for the treatment of lumbar disc herniation via a contralateral approach. When there are highly down-migrated lumbar disc herniation along just medial to pedicle and narrow ipsilateral intervertebral foramen, the conventional PELD is not easily accessible via ipsilateral transforaminal route. Five patients manifested gluteal and leg pain because of a soft disc herniation at the L4-L5 level. Transforaminal PELD via a contralateral approach was performed to remove the herniated fragment, achieving complete decompression of the nerve root. The symptom was relieved and the patient was discharged the next day. When a conventional transforaminal PELD is difficult because of some anatomical reasons, PELD via a contralateral route could be a good alternative option in selected cases.

Interference of Detection Rate of Lumbar Disc Herniation by Socioeconomic Status

PubMed Central

Ji, Gyu Yeul; Jung, Nak-Yong; An, Seong Dae; Choi, Won-Seok; Kim, Jung Hoon

2013-01-01

Study Design Retrospective study. Purpose The objective of the study is to evaluate the relationship between the detection rate of lumbar disc herniation and socioeconomic status. Overview of Literature Income is one important determinant of public health. Yet, there are no reports about the relationship between socioeconomic status and the detective rate of disc herniation. Methods In this study, 443 cases were checked for lumbar computed tomography for lumbar disc herniation, and they reviewed questionnaires about their socioeconomic status, the presence of back pain or radiating pain and the presence of a medical certificate (to check the medical or surgical treatment for the pain) during the Korean conscription. Results Without the consideration for the presence of a medical certificate, there was no difference in spinal physical grade according to socioeconomic status (p=0.290). But, with the consideration of the presence of a medical certificate, the significant statistical differences were observed according to socioeconomic status in 249 cases in the presence of a medical certificate (p=0.028). There was a lower detection rate in low economic status individuals than those in the high economic class. The common reason for not submitting a medical certificate is that it is neither necessary for the people of lower socioeconomic status nor is it financially affordable. Conclusions The prevalence of lumbar disc herniation is not different according to socioeconomic status, but the detective rate was affected by socioeconomic status. Socioeconomic status is an important factor for detecting lumbar disc herniation. PMID:23508288

Interference of detection rate of lumbar disc herniation by socioeconomic status.

PubMed

Ji, Gyu Yeul; Oh, Chang Hyun; Jung, Nak-Yong; An, Seong Dae; Choi, Won-Seok; Kim, Jung Hoon

2013-03-01

Retrospective study. The objective of the study is to evaluate the relationship between the detection rate of lumbar disc herniation and socioeconomic status. Income is one important determinant of public health. Yet, there are no reports about the relationship between socioeconomic status and the detective rate of disc herniation. In this study, 443 cases were checked for lumbar computed tomography for lumbar disc herniation, and they reviewed questionnaires about their socioeconomic status, the presence of back pain or radiating pain and the presence of a medical certificate (to check the medical or surgical treatment for the pain) during the Korean conscription. Without the consideration for the presence of a medical certificate, there was no difference in spinal physical grade according to socioeconomic status (p=0.290). But, with the consideration of the presence of a medical certificate, the significant statistical differences were observed according to socioeconomic status in 249 cases in the presence of a medical certificate (p=0.028). There was a lower detection rate in low economic status individuals than those in the high economic class. The common reason for not submitting a medical certificate is that it is neither necessary for the people of lower socioeconomic status nor is it financially affordable. The prevalence of lumbar disc herniation is not different according to socioeconomic status, but the detective rate was affected by socioeconomic status. Socioeconomic status is an important factor for detecting lumbar disc herniation.

Adult neural stem cells: The promise of the future

PubMed Central

Taupin, Philippe

2007-01-01

Stem cells are self-renewing undifferentiated cells that give rise to multiple types of specialized cells of the body. In the adult, stem cells are multipotents and contribute to homeostasis of the tissues and regeneration after injury. Until recently, it was believed that the adult brain was devoid of stem cells, hence unable to make new neurons and regenerate. With the recent evidences that neurogenesis occurs in the adult brain and neural stem cells (NSCs) reside in the adult central nervous system (CNS), the adult brain has the potential to regenerate and may be amenable to repair. The function(s) of NSCs in the adult CNS remains the source of intense research and debates. The promise of the future of adult NSCs is to redefine the functioning and physiopathology of the CNS, as well as to treat a broad range of CNS diseases and injuries. PMID:19300610

[Biomechanical analysis on the correlation between iliac rotation displacement and L(4,5) disc degeneration].

PubMed

Shi, Ning-ning; Shen, Guo-quan; He, Shui-yong; Guo, Ru-bao

2016-05-01

To study the biomechanical relationship between iliac rotation displacement and L(4,5) disc degeneration, and to provide clinical evidences for the prevention and treatment of L(4,5) disc degeneration and herniation. From March 2012 to February 2014,68 patients with lumbar disc herniation combined with sacroiliac joint disorders were selected. Among them, 42 patients with L(4,5) disc herniation combined with sacroiliac joint disorders included 22 males and 20 females, ranging in age from 19 to 63 years old, with an average of (51.78 +/- 20.18) years old, and the duration of the disease ranged from 1 to 126 months with an average of (11.18 +/- 9.23) months. Twenty-six patients with L5S1 disc herniation combined with sacroiliac joint disorders included 11 males and 15 females, ranging in age from18 to 65 years old with an average of (45.53 +/- 27.23) years old, and the duration of the disease ranged from 0.5 to 103 months with an average of (11.99 +/- 12.56) months. Sixty-eight anteroposterior lumbar radiographs, 68 lateral lumbar radiographs,and 68 pelvic plain films were taken. The degree of lumbar scoliosis, pelvic tilt,and disc thickness were measured. The correlation between pelvic tilt and lumbar scoliosis ,lumbar scoliosis and disc thickness were studied by using linear and regression methods. The hiomechanical analysis was performed. There was a positive correlation between pelvic tilt and lumbar scoliosis in patients with L(4,5) disk herniation (R=0.49, P=0.00). There was a causal relationship and good linear proportional relationship (Y=3.05+1.07X, P=0.00) in the two variables. There was a negative correlation between lumbar scoliosis and intervertebral space in male patients with L (4,5) disk herniation (R = -0.50, P=0.01). There was a causal relationship and good linear proportional relationship in the two variables (Y=13.09-0.27X, P=0.02). But there was a positive correlation between lumbar scoliosis and intervertebral space in male patients with L5S1 disk herniation (R=0.46, P=0.04). Iliac rotational displacement are closely related with L(4,5) disc degeneration and herniation in biomechanics. A new concepts and therapeutic approach is provided for clinical treatment of chronic and refractory herniation of L(4,5) disc in patients

Bioreactivity: Studies on a Simple Brain Stem Reflex in Behaving Animals

DTIC Science & Technology

1988-07-22

neuromodulation , or complex behavioral processes, such as arousal, is finding a simple system that will permit such analyses. The brain stem...systems important in neuromodulation and arousal. Initial pharmacologic studies showed that locally applied norepinephrine facilitated the reflex

Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma

ClinicalTrials.gov

2017-10-11

Brain Stem Glioma; Cerebral Astrocytoma; Childhood Cerebellar Anaplastic Astrocytoma; Childhood Cerebral Anaplastic Astrocytoma; Childhood Spinal Cord Neoplasm; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebral Astrocytoma

Effects of neuroinflammation on the regenerative capacity of brain stem cells.

PubMed

Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

2011-03-01

In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system associated with neuroinflammation, inflammatory mediators such as cytokines and chemokines can affect the capacity of brain stem cells and alter neurogenesis. In this review, we summarize the state of the art on the effects of neuroinflammation on adult neurogenesis and discuss the use of the lipopolysaccharide-model to study the effects of inflammation and reactive-microglia on brain stem cells and neurogenesis. Furthermore, we discuss the possible causes underlying reduced neurogenesis with normal aging and potential anti-inflammatory, pro-neurogenic interventions aimed at improving memory deficits in normal and pathological aging and in neurodegenerative diseases. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Canine pancreatic lipase immunoreactivity concentrations associated with intervertebral disc disease in 84 dogs.

PubMed

Schueler, R O; White, G; Schueler, R L; Steiner, J M; Wassef, A

2018-05-01

To determine the differences in serum canine pancreatic lipase immunoreactivity between dogs with intervertebral disc herniation and healthy control dogs. Eighty-four client-owned dogs with intervertebral disc herniation, diagnosed by neurologic examination and imaging, and 18 healthy control dogs. Samples of whole blood were collected within 90 minutes of admission. Serum canine pancreatic lipase immunoreactivity concentrations were measured by a commercial immunoassay and evaluated for association with intervertebral disc herniation, signalment, neurolocalisation and the preadmission administration of glucocorticosteriods or non-steroidal anti-inflammatory drugs. Serum canine pancreatic lipase immunoreactivity concentrations were statistically increased in dogs with intervertebral disc herniation (P<0·01, n=38). A subgroup of dogs (19/38) with elevated canine pancreatic lipase immunoreactivity concentrations was re-evaluated between 2 and 4 weeks later, and 15 had resolution of clinical signs and values less than 200 μg/L. Serum canine pancreatic lipase immunoreactivity concentrations were not significantly correlated with clinical gastrointestinal disease, neurolocalisation or the preadmission administration of corticosteroids or non-steroidal anti-inflammatory drugs. These results suggest that serum canine pancreatic lipase immunoreactivity concentrations are significantly elevated in dogs with intervertebral disc herniation. © 2018 British Small Animal Veterinary Association.

Neural stem cell quiescence and stemness are molecularly distinct outputs of the Notch3 signalling cascade in the vertebrate adult brain.

PubMed

Than-Trong, Emmanuel; Ortica-Gatti, Sara; Mella, Sébastien; Nepal, Chirag; Alunni, Alessandro; Bally-Cuif, Laure

2018-05-15

Neural stem cells (NSCs) in the adult vertebrate brain are found in a quiescent state and can preserve long-lasting progenitor potential (stemness). Whether and how these two properties are linked, and to what extent they can be independently controlled by NSC maintenance pathways, is unresolved. We have previously identified Notch3 signalling as a major quiescence-promoting pathway in adult NSCs of the zebrafish pallium. We now show that Notch3 also controls NSC stemness. Using parallel transcriptomic characterizations of notch3 mutant NSCs and adult NSC physiological states, we demonstrate that a set of potentially direct Notch3 target genes distinguishes quiescence and stemness control. As a proof of principle, we focus on one 'stemness' target, encoding the bHLH transcription factor Hey1, that has not yet been analysed in adult NSCs. We show that abrogation of Hey1 function in adult pallial NSCs in vivo , including quiescent NSCs, leads to their differentiation without affecting their proliferation state. These results demonstrate that quiescence and stemness are molecularly distinct outputs of Notch3 signalling, and identify Hey1 as a major Notch3 effector controlling NSC stemness in the vertebrate adult brain. © 2018. Published by The Company of Biologists Ltd.

High Incidence of Progressive Postnatal Cerebellar Enlargement in Costello Syndrome: Brain Overgrowth Associated with HRAS Mutations as the Likely Cause of Structural Brain and Spinal Cord Abnormalities

PubMed Central

Gripp, Karen W.; Hopkins, Elisabeth; Doyle, Daniel; Dobyns, William B.

2010-01-01

Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS. Its presentation includes failure-to-thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. In a systematic review we found absolute or relative macrocephaly (100%), ventriculomegaly (50%), and other abnormalities on brain and spinal cord imaging studies in 27/28 individuals. Posterior fossa crowding with cerebellar tonsillar herniation (CBTH) was noted in 27/28 (96%), and in 10/17 (59%) with serial studies posterior fossa crowding progressed. Sequelae of posterior fossa crowding and CBTH included hydrocephalus requiring shunt or ventriculostomy (25%), Chiari 1 malformation (32%) and syrinx formation (25%). Our data reveal macrocephaly with progressive frontal bossing and CBTH, documenting an ongoing process rather than a static congenital anomaly. Comparison of images obtained in young infants to subsequent studies demonstrated postnatal development of posterior fossa crowding. This process of evolving megalencephaly and cerebellar enlargement is in keeping with mouse model data, delineating abnormal genesis of neurons and glia, resulting in an increased number of astrocytes and enlarged brain volume. In Costello syndrome and macrocephaly-capillary malformation syndrome disproportionate brain growth is the main factor resulting in postnatal CBTH and Chiari 1 malformation. PMID:20425820

A patient with thoracic intradural disc herniation.

PubMed

Whitmore, Robert G; Williams, Brian J; Lega, Bradley C; Sanborn, Matthew R; Marcotte, Paul

2011-12-01

Intradural disc herniation is a rare disease that occurs most commonly in the lumbar region, while fewer than 5% occur in the thoracic and cervical regions. We report a patient with thoracic intradural disc herniation at T12-L1 who presented with radiculopathy and motor weakness. The preoperative MRI did not demonstrate an intradural lesion, and it was identified intraoperatively by inspection and palpation of the thecal sac. The disc was removed, and the patient experienced good neurological recovery and remains pain free 1 year after surgery. Copyright © 2011 Elsevier Ltd. All rights reserved.

Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro.

PubMed

Aleksandrova, M A; Poltavtseva, R A; Marei, M V; Sukhikh, G T

2016-05-01

Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed.

Neural conduction abnormality in the brain stem and prevalence of the abnormality in late preterm infants with perinatal problems.

PubMed

Jiang, Ze Dong

2013-08-01

Neurodevelopment in late preterm infants has recently attracted considerable interest. The prevalence of brain stem conduction abnormality remains unknown. We examined maximum length sequence brain stem auditory evoked response in 163 infants, born at 33-36 weeks gestation, who had various perinatal problems. Compared with 49 normal term infants without problems, the late preterm infants showed a significant increase in III-V and I-V interpeak intervals at all 91-910/s clicks, particularly at 455 and 910/s (p < 0.01-0.001). The I-III interval was slightly increased, without statistically significant difference from the controls at any click rates. These results suggest that neural conduction along the, mainly more central or rostral part of, auditory brain stem is abnormal in late preterm infants with perinatal problems. Of the 163 late preterm infant, the number (and percentage rate) of infants with abnormal I-V interval at 91, 227, 455, and 910/s clicks was, respectively, 11 (6.5%), 17 (10.2%), 37 (22.3%), and 31 (18.7%). The number (and percentage rate) of infants with abnormal III-V interval at these rates was, respectively, 10 (6.0%), 17 (10.2%), 28 (16.9), and 36 (21.2%). Apparently, the abnormal rates were much higher at 455 and 910/s clicks than at lower rates 91 and 227/s. In total, 42 (25.8%) infants showed abnormal I-V and/or III-V intervals. Conduction in, mainly in the more central part, the brain stem is abnormal in late preterm infants with perinatal problems. The abnormality is more detectable at high- than at low-rate sensory stimulation. A quarter of late preterm infants with perinatal problems have brain stem conduction abnormality.

Concomitance of cervical intramedullary traumatic neuroma and cervical cord herniation in a tetraplegic woman.

PubMed

Su, Hui-Yi; Wu, Yung-Tsan; Liu, Ming-Ying; Lin, Yu-Chun; Chu, Heng-Yi; Chang, Shin-Tsu

2013-01-01

We present the first case of concomitant intramedullary traumatic neuroma and spinal cord herniation. A 57-year-old woman injured her cervical spine with subluxation and cord compression at the C5-C6 level. After the operation, the patient received intensive rehabilitation for one year with well response. Unfortunately, she experienced weakness and progressive numbness extending to all the limbs later. Cervical magnetic resonance imaging revealed spinal cord herniation at the C5-C6 level and pathology proved intramedullary traumatic neuroma. After the second operation, the paresthesia over the trunk and limbs persisted, and the patient was nearly totally assisted in her activities of daily living. The intramedullary traumatic neuroma and spinal cord herniation are rare causes in patients with spinal cord dysfunction. The case presented here indicates the possibility of the coexisting conditions leading to progressive neurologic deficits in patients with old spinal cord injury.

The effects of flexion-distraction and drop techniques on disorders and Ferguson’s angle in female patients with lumbar intervertebral disc herniation

PubMed Central

Oh, Hyunju; Lee, Sangyong; Lee, Kwansub; Jeong, Mugeun

2018-01-01

[Purpose] This study examines the effects of the flexion-distraction technique and the drop technique on disorders and on Ferguson’s angle in female patients with lumbar intervertebral disc herniation. [Subjects and Methods] Thirty female patients with lumbar intervertebral disc herniation were divided into an experimental group (n=15) treated with flexion-distraction and drop techniques and a control group (n=15) treated with spinal decompression therapy. Both groups were treated three times a week over an eight-week period. [Results] In the comparison of changes within each group after treatment, both groups showed statistically significant decreases in disorders and in Ferguson’s angle. [Conclusion] Flexion-distraction and drop techniques may be an effective intervention to improve disorders and Ferguson’s angle in female patients with lumbar intervertebral disc herniation. PMID:29706701

An Unexpected Adverse Event during Colonoscopy Screening: Bochdalek Hernia.

PubMed

Lee, Joon Seop; Kim, Eun Soo; Jung, Min Kyu; Kim, Sung Kook; Jin, Sun; Lee, Deok Heon; Seo, Jun Won

2018-05-25

Bochdalek hernia (BH) is defined as herniated abdominal contents appearing throughout the posterolateral segment of the diaphragm. It is usually observed during the prenatal or newborn period. Here, we report a case of an adult patient with herniated omentum and colon due to BH that was discovered during a colonoscopy. A 41-year-old woman was referred to our hospital with severe left chest and abdominal pain that began during a colonoscopy. Her chest radiography showed colonic shadow filling in the lower half of the left thoracic cavity. A computed tomography scan revealed an approximately 6-cm-sized left posterolateral diaphragmatic defect and a herniated omentum in the colon. The patient underwent thoracoscopic surgery, during which, the diaphragmatic defect was closed and herniated omentum was repaired. The patient was discharged without further complications. To the best of our knowledge, this case is the first report of BH in an adult found during a routine colonoscopy screening.

Increased toll-like receptor 4 in cerebral endothelial cells contributes to the astrocyte swelling and brain edema in acute hepatic encephalopathy.

PubMed

Jayakumar, Arumugam R; Tong, Xiao Y; Curtis, Kevin M; Ruiz-Cordero, Roberto; Abreu, Maria T; Norenberg, Michael D

2014-03-01

Astrocyte swelling and the subsequent increase in intracranial pressure and brain herniation are major clinical consequences in patients with acute hepatic encephalopathy. We recently reported that conditioned media from brain endothelial cells (ECs) exposed to ammonia, a mixture of cytokines (CKs) or lipopolysaccharide (LPS), when added to astrocytes caused cell swelling. In this study, we investigated the possibility that ammonia and inflammatory agents activate the toll-like receptor 4 (TLR4) in ECs, resulting in the release of factors that ultimately cause astrocyte swelling. We found a significant increase in TLR4 protein expression when ECs were exposed to ammonia, CKs or LPS alone, while exposure of ECs to a combination of these agents potentiate such effects. In addition, astrocytes exposed to conditioned media from TLR4-silenced ECs that were treated with ammonia, CKs or LPS, resulted in a significant reduction in astrocyte swelling. TLR4 protein up-regulation was also detected in rat brain ECs after treatment with the liver toxin thioacetamide, and that thioacetamide-treated TLR4 knock-out mice exhibited a reduction in brain edema. These studies strongly suggest that ECs significantly contribute to the astrocyte swelling/brain edema in acute hepatic encephalopathy, likely as a consequence of increased TLR4 protein expression by blood-borne noxious agents. © 2013 International Society for Neurochemistry.

Stereotaxic gamma knife surgery in treatment of critically located pilocytic astrocytoma: preliminary result

PubMed Central

Hafez, Raef FA

2007-01-01

Background Low-grade gliomas are uncommon primary brain tumors, located more often in the posterior fossa, optic pathway, and brain stem and less commonly in the cerebral hemispheres. Case presentations Two patients with diagnosed recurrent cystic pilocytic astrocytoma critically located within the brain (thalamic and brain stem) were treated with gamma knife surgery. Gamma knife surgery (GKS) did improve the patient's clinical condition very much which remained stable later on. Progressive reduction on the magnetic resonance imaging (MRI) studies of the solid part of the tumor and almost disappearance of the cystic component was achieved within the follow-up period of 36 months in the first case with the (thalamic located lesion) and 22 months in the second case with the (brain stem located lesion). Conclusion Gamma knife surgery represents an alternate tool in the treatment of recurrent and/or small postoperative residual pilocytic astrocytoma especially if they are critically located PMID:17394660

Magnetic Resonance Imaging of Malformations of Midbrain-Hindbrain.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Castillo, Mauricio

2016-01-01

We aim to review the magnetic resonance imaging appearance of malformations of midbrain and hindbrain. These can be classified as predominantly cerebellar malformations, combined cerebellar and brain stem malformations, and predominantly brain stem malformations. The diagnostic criteria for the majority of these morphological malformations are based on neuroimaging findings. The predominantly cerebellar malformations include predominantly vermian hypoplasia seen in Dandy-Walker malformation and rhombencephalosynapsis, global cerebellar hypoplasia reported in lissencephaly and microlissencephaly, and unilateral cerebellar hypoplasia seen in PHACES, vanishing cerebellum, and cerebellar cleft. Cerebellar dysplasias are seen in Chudley-McCullough syndrome, associated with LAMA1 mutations and GPR56 mutations; Lhermitte-Duclos disease; and focal cerebellar dysplasias. Cerebellar hyperplasias are seen in megalencephaly-related syndromes and hemimegalencephaly with ipsilateral cerebellomegaly. Cerebellar and brain stem malformations include tubulinopathies, Joubert syndrome, cobblestone malformations, pontocerebellar hypoplasias, and congenital disorders of glycosylation type Ia. Predominantly brain stem malformations include congenital innervation dysgenesis syndrome, pontine tegmental cap dysplasia, diencephalic-mesencephalic junction dysplasia, disconnection syndrome, and pontine clefts.

Continuous myocloni and tonic spasms in a 2-month-old infant with enterovirus 71 brain stem encephalitis.

PubMed

Lee, Kyung Yeon; Yeh, Hye-Ryun

2015-02-01

Brain stem encephalitis is a cardinal presentation of central nervous system involvement in enterovirus 71 infection, and manifests as myoclonus, ataxia, tremor, and autonomic dysfunction. A 2-month-old infant with enterovirus 71 brain stem encephalitis demonstrated continuous myocloni and tonic spasms. On admission, the patient's myoclonus, which mainly involved the shoulders and the arms, was considerably worse during wakefulness and occurred once or twice a minute. Several hours after admission, the myoclonic jerks steadily worsened, appeared ceaselessly every 1 to 2 seconds, and were intermixed with tonic spasms of all four extremities accompanied by crying. Video electroencephalography revealed a normal background without epileptiform discharges and no ictal electroencephalographic changes during the myoclonic jerks and tonic spasms. Complete remission was achieved without complications after completion of a 3-day immunoglobulin therapy. This case suggests that the brain stem may be a major origin site for not only myoclonus but also tonic spasm. Georg Thieme Verlag KG Stuttgart · New York.

Prevalence of Lumbar Disc Herniation in Adolescent Males in Seoul, Korea: Prevalence of Adolescent LDH in Seoul, Korea

PubMed Central

Kim, Do-Keun; Oh, Chang Hyun; Lee, Myoung Seok; Park, Hyung-chun; Park, Chong Oon

2011-01-01

Objective The authors surveyed the prevalence and the clinical character of lumbar disc herniation (LDH) in Korean male adolescents, and the usefulness of current conscription criteria. Methods The data of 39,673 nineteen-year-old males that underwent a conscription examination at the Seoul Regional Korean Military Manpower Administration (MMA) from October 2010 to May 2011 were investigated. For those diagnosed as having lumbar disc herniation, prevalences, subject characteristics, herniation severities, levels of herniation, and modified Korean Oswestry low back pain disability scores by MMA physical grade were evaluated. The analysis was performed using medical certificates, medical records, medical images, and electromyographic and radiologic findings. Results The prevalence of adolescent LDH was 0.60%(237 of the 39,673 study subjects), and the prevalence of serious adolescent LDH with thecal sac compression or significant discogenic spinal stenosis was 0.28%(110 of the 39,673 study subjects). Of the 237 adolescent LDH cases, 105 (44.3%) were of single level LDH and 132 (55.7%) were of multiple level LDH, and the L4-5 level was the most severely and frequently affected. Oswestry back pain disability scores increased with herniation severity (p<0.01), and were well correlated with MMA grade. Conclusions In this large cohort of 19-year-old Korean males, the prevalence of adolescent LDH was 0.60% and the prevalence of serious adolescent LDH, which requires management, was relatively high at 0.28%. MMA physical grade was confirmed to be a useful measure of the disability caused by LDH. PMID:26064143

Regional and stage-specific effects of prospectively purified vascular cells on the adult V-SVZ neural stem cell lineage.

PubMed

Crouch, Elizabeth E; Liu, Chang; Silva-Vargas, Violeta; Doetsch, Fiona

2015-03-18

Adult neural stem cells reside in specialized niches. In the ventricular-subventricular zone (V-SVZ), quiescent neural stem cells (qNSCs) become activated (aNSCs), and generate transit amplifying cells (TACs), which give rise to neuroblasts that migrate to the olfactory bulb. The vasculature is an important component of the adult neural stem cell niche, but whether vascular cells in neurogenic areas are intrinsically different from those elsewhere in the brain is unknown. Moreover, the contribution of pericytes to the neural stem cell niche has not been defined. Here, we describe a rapid FACS purification strategy to simultaneously isolate primary endothelial cells and pericytes from brain microregions of nontransgenic mice using CD31 and CD13 as surface markers. We compared the effect of purified vascular cells from a neurogenic (V-SVZ) and non-neurogenic brain region (cortex) on the V-SVZ stem cell lineage in vitro. Endothelial and pericyte diffusible signals from both regions differentially promote the proliferation and neuronal differentiation of qNSCs, aNSCs, and TACs. Unexpectedly, diffusible cortical signals had the most potent effects on V-SVZ proliferation and neurogenesis, highlighting the intrinsic capacity of non-neurogenic vasculature to support stem cell behavior. Finally, we identify PlGF-2 as an endothelial-derived mitogen that promotes V-SVZ cell proliferation. This purification strategy provides a platform to define the functional and molecular contribution of vascular cells to stem cell niches and other brain regions under different physiological and pathological states. Copyright © 2015 the authors 0270-6474/15/354528-12$15.00/0.

Side population in human glioblastoma is non-tumorigenic and characterizes brain endothelial cells

PubMed Central

Golebiewska, Anna; Bougnaud, Sébastien; Stieber, Daniel; Brons, Nicolaas H. C.; Vallar, Laurent; Hertel, Frank; Klink, Barbara; Schröck, Evelin; Bjerkvig, Rolf

2013-01-01

The identification and significance of cancer stem-like cells in malignant gliomas remains controversial. It has been proposed that cancer stem-like cells display increased drug resistance, through the expression of ATP-binding cassette transporters that detoxify cells by effluxing exogenous compounds. Here, we investigated the ‘side population’ phenotype based on efflux properties of ATP-binding cassette transporters in freshly isolated human glioblastoma samples and intracranial xenografts derived thereof. Using fluorescence in situ hybridization analysis on sorted cells obtained from glioblastoma biopsies, as well as human tumour xenografts developed in immunodeficient enhanced green fluorescence protein-expressing mice that allow an unequivocal tumour-stroma discrimination, we show that side population cells in human glioblastoma are non-neoplastic and exclusively stroma-derived. Tumour cells were consistently devoid of efflux properties regardless of their genetic background, tumour ploidy or stem cell associated marker expression. Using multi-parameter flow cytometry we identified the stromal side population in human glioblastoma to be brain-derived endothelial cells with a minor contribution of astrocytes. In contrast with their foetal counterpart, neural stem/progenitor cells in the adult brain did not display the side population phenotype. Of note, we show that CD133-positive cells often associated with cancer stem-like cells in glioblastoma biopsies, do not represent a homogenous cell population and include CD31-positive endothelial cells. Interestingly, treatment of brain tumours with the anti-angiogenic agent bevacizumab reduced total vessel density, but did not affect the efflux properties of endothelial cells. In conclusion our findings contribute to an unbiased identification of cancer stem-like cells and stromal cells in brain neoplasms, and provide novel insight into the complex issue of drug delivery to the brain. Since efflux properties of endothelial cells are likely to compromise drug availability, transiently targeting ATP-binding cassette transporters may be a valuable therapeutic strategy to improve treatment effects in brain tumours. PMID:23460667

[Immunohistochemical studies on neuronal changes in brain stem nucleus of forensic autopsied cases. I. Various cases of asphyxia and respiratory disorder].

PubMed

Kubo, S; Orihara, Y; Gotohda, T; Tokunaga, I; Tsuda, R; Ikematsu, K; Kitamura, O; Yamamoto, A; Nakasono, I

1998-12-01

Several nuclei in brain stem are well known to play an important role in supporting human life. However, the connection between neural changes of brain stem and the cause of death is not yet fully understood. To investigate the correlation of brain stem damage with various cause of respiratory disorders, neural changes of the arcuate nucleus (ARC), the hypoglossal nucleus (HN) and the inferior olivary nucleus (IO) were examined using immunohistochemical technique. Based on the cause of death, the forensic autopsy cases were divided into 5 groups as follows. Group I: hanging, ligature strangulation and manual strangulation, Group II: smothering and choking, Group III: drowning, Group IV: respiratory failure, control group: heat stroke and sun stroke. Brain was fixed with phosphate-buffer formalin, and the brain stem was horizontally dissected at the level of apex, then embedded in paraffin. The sections were stained with the antibodies against microtubule-associated protein 2 (MAP2), muscalinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos) and 72 kD heat-shock protein (HSP70). Three nuclei showed no obvious morphological changes in all examined groups. However, in case of asphyxia (Group I to III), neurons in HN were positively stained with both HSP70 and c-Fos antibodies. This may indicate that the occlusion of upper airway results in the neuronal damage of HN without their morphological changes. Positive staining of HSP70 and c-Fos in IO was more frequently observed in Group III than other 4 groups. Since IO is involved in maintaining body balance which is often disturbed by drowning, it seems possible that neuronal damage in IO observed in drowning may be related to the disturbance of body balance. These observations indicate that immunohistochemical study on the damage to neurons in brain stem nuclei can provide useful information for determining the cause of death.

Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.

PubMed

Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji

2016-05-01

Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

Brain stem auditory evoked responses in human infants and adults

NASA Technical Reports Server (NTRS)

Hecox, K.; Galambos, R.

1974-01-01

Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

Tracking stem cell migration and survival in brain injury: current approaches and future prospects.

PubMed

Darkazalli, Ali; Levenson, Cathy W

2012-10-01

In recent years, stem cell-mediated therapies have gained considerable ground as potential treatments for a wide variety of brain pathologies including traumatic brain injury, stroke and neurodegenerative diseases. Despite extensive preclinical studies, many of these therapies have not been fully translated into viable clinical approaches. This is partly due to our inability to reliably track and monitor transplanted stem cells longitudinally over long periods of time in vivo. In this review, we discuss the predominant histological cell tracing methodologies, such as immunohistochemistry, and fluorescent cellular dyes and proteins, and compare them to emerging cellular imaging technologies. We show that advances in magnetic resonance imaging (MRI) have resulted in opportunities to use this technology to further our understanding of stem cell characteristics and behaviors in vivo. While MRI may not completely replace conventional cell tracking methods in pre-clinical, mechanistic work, it is clear that it has the potential to function as a powerful diagnostic tool for tracking stem cell migration and survival as well as for evaluating the efficacy of stem cell-mediated therapies.

Increased circulating stem cells and better cognitive performance in traumatic brain injury subjects following hyperbaric oxygen therapy.

PubMed

Shandley, Sabrina; Wolf, E George; Schubert-Kappan, Christine M; Baugh, Laura M; Richards, Michael F; Prye, Jennifer; Arizpe, Helen M; Kalns, John

2017-01-01

Traumatic brain injury (TBI) may cause persistent cognitive dysfunction. A pilot clinical study was performed to determine if hyperbaric oxygen (HBO₂) treatment improves cognitive performance. It was hypothesized that stem cells, mobilized by HBO₂ treatment, are recruited to repair damaged neuronal tissue. This hypothesis was tested by measuring the relative abundance of stem cells in peripheral blood and cognitive performance during this clinical trial. The subject population consisted of 28 subjects with persistent cognitive impairment caused by mild to moderate TBI suffered during military deployment to Iraq or Afghanistan. Fluorescence-activated cell sorting (FACS) analysis was performed for stem cell markers in peripheral blood and correlated with variables resulting from standard tests of cognitive performance and post-traumatic stress disorder: ImPACT, BrainCheckers and PCL-M test results. HBO₂ treatment correlated with stem cell mobilization as well as increased cognitive performance. Together these results support the hypothesis that stem cell mobilization may be required for cognitive improvement in this population. Copyright© Undersea and Hyperbaric Medical Society.

The stem cell secretome and its role in brain repair

PubMed Central

Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

2014-01-01

Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. PMID:23827856

Neural stem cell quiescence and stemness are molecularly distinct outputs of the Notch3 signalling cascade in the vertebrate adult brain

PubMed Central

Than-Trong, Emmanuel; Ortica-Gatti, Sara; Mella, Sébastien; Nepal, Chirag; Alunni, Alessandro

2018-01-01

ABSTRACT Neural stem cells (NSCs) in the adult vertebrate brain are found in a quiescent state and can preserve long-lasting progenitor potential (stemness). Whether and how these two properties are linked, and to what extent they can be independently controlled by NSC maintenance pathways, is unresolved. We have previously identified Notch3 signalling as a major quiescence-promoting pathway in adult NSCs of the zebrafish pallium. We now show that Notch3 also controls NSC stemness. Using parallel transcriptomic characterizations of notch3 mutant NSCs and adult NSC physiological states, we demonstrate that a set of potentially direct Notch3 target genes distinguishes quiescence and stemness control. As a proof of principle, we focus on one ‘stemness’ target, encoding the bHLH transcription factor Hey1, that has not yet been analysed in adult NSCs. We show that abrogation of Hey1 function in adult pallial NSCs in vivo, including quiescent NSCs, leads to their differentiation without affecting their proliferation state. These results demonstrate that quiescence and stemness are molecularly distinct outputs of Notch3 signalling, and identify Hey1 as a major Notch3 effector controlling NSC stemness in the vertebrate adult brain. PMID:29695612

Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

ClinicalTrials.gov

2018-06-19

Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Brain Stem Glioma; Childhood Glioblastoma; Giant Cell Glioblastoma; Gliosarcoma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Gliosarcoma

Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas

ClinicalTrials.gov

2018-03-30

Anaplastic Astrocytoma; Brain Stem Glioma; Childhood Mixed Glioma; Fibrillary Astrocytoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma

Aquaporin-4 in brain and spinal cord oedema.

PubMed

Saadoun, S; Papadopoulos, M C

2010-07-28

Brain oedema is a major clinical problem produced by CNS diseases (e.g. stroke, brain tumour, brain abscess) and systemic diseases that secondarily affect the CNS (e.g. hyponatraemia, liver failure). The swollen brain is compressed against the surrounding dura and skull, which causes the intracranial pressure to rise, leading to brain ischaemia, herniation, and ultimately death. A water channel protein, aquaporin-4 (AQP4), is found in astrocyte foot processes (blood-brain border), the glia limitans (subarachnoid cerebrospinal fluid-brain border) and ependyma (ventricular cerebrospinal fluid-brain border). Experiments using mice lacking AQP4 or alpha syntrophin (which secondarily downregulate AQP4) showed that AQP4 facilitates oedema formation in diseases causing cytotoxic (cell swelling) oedema such as cerebral ischaemia, hyponatraemia and meningitis. In contrast, AQP4 facilitates oedema elimination in diseases causing vasogenic (vessel leak) oedema and therefore AQP4 deletion aggravates brain oedema produced by brain tumour and brain abscess. AQP4 is also important in spinal cord oedema. AQP4 deletion was associated with less cord oedema and improved outcome after compression spinal cord injury in mice. Here we consider the possible routes of oedema formation and elimination in the injured cord and speculate about the role of AQP4. Finally we discuss the role of AQP4 in neuromyelitis optica (NMO), an inflammatory demyelinating disease that produces oedema in the spinal cord and optic nerves. NMO patients have circulating AQP4 IgG autoantibody, which is now used for diagnosing NMO. We speculate how NMO-IgG might produce CNS inflammation, demyelination and oedema. Since AQP4 plays a key role in the pathogenesis of CNS oedema, we conclude that AQP4 inhibitors and activators may reduce CNS oedema in many diseases. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Music modulation of pain perception and pain-related activity in the brain, brain stem, and spinal cord: a functional magnetic resonance imaging study.

PubMed

Dobek, Christine E; Beynon, Michaela E; Bosma, Rachael L; Stroman, Patrick W

2014-10-01

The oldest known method for relieving pain is music, and yet, to date, the underlying neural mechanisms have not been studied. Here, we investigate these neural mechanisms by applying a well-defined painful stimulus while participants listened to their favorite music or to no music. Neural responses in the brain, brain stem, and spinal cord were mapped with functional magnetic resonance imaging spanning the cortex, brain stem, and spinal cord. Subjective pain ratings were observed to be significantly lower when pain was administered with music than without music. The pain stimulus without music elicited neural activity in brain regions that are consistent with previous studies. Brain regions associated with pleasurable music listening included limbic, frontal, and auditory regions, when comparing music to non-music pain conditions. In addition, regions demonstrated activity indicative of descending pain modulation when contrasting the 2 conditions. These regions include the dorsolateral prefrontal cortex, periaqueductal gray matter, rostral ventromedial medulla, and dorsal gray matter of the spinal cord. This is the first imaging study to characterize the neural response of pain and how pain is mitigated by music, and it provides new insights into the neural mechanism of music-induced analgesia within the central nervous system. This article presents the first investigation of neural processes underlying music analgesia in human participants. Music modulates pain responses in the brain, brain stem, and spinal cord, and neural activity changes are consistent with engagement of the descending analgesia system. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Surgical management of brain-stem cavernous malformations: report of 137 cases.

PubMed

Wang, Chung-cheng; Liu, Ali; Zhang, Jun-ting; Sun, Bo; Zhao, Yuan-li

2003-06-01

With the improvement in neuroimaging and microsurgical techniques, brain stem cavernous malformations are no longer considered inoperable. Surgical indications for brainstem cavernoma are evolving, with better understanding of its natural history and decreasing surgical complications. During 1986 through 1998, a series of 137 patients (4 patients each with two brain stem lesions, total number of lesions, 141) with brain stem cavernous malformations were treated microsurgically at Beijing Neurosurgery Institute. The age distribution, lesion location, and clinical presentations were analyzed. The bleeding rate, surgical indications and microsurgical techniques were also discussed. In our series, 92 of 137 cases (67.2%) suffered more than one hemorrhage. Female patients had a higher risk of recurrent hemorrhage than that of male patients. Unlike cavernomas malformations from other locations, repeated hemorrhages from brain stem malformations are much more common and usually lead to new neurologic deficits. Among all 137 surgically treated patients, there was no operative mortality. Ninety-nine patients (72.3%) either improved or remained clinically stable postoperatively. The size of the cavernoma/hematoma does not necessarily correlate with the surgical result. While the acute hematoma can facilitate the surgical dissection, longer clinical history with multiple hemorrhages often makes total surgical resection difficult, partially because of the firmer capsule that may not shrink or collapse after hematoma is released. Pathologically those capsules were associated with more hyaline degeneration, fibrous proliferation and even calcifications. During the follow-up period between 0.5 to 11 years in 129 cases, 115 patients (89.2%) have been working, studying, or doing house work. Three patients (2.3%) suffered recurrent hemorrhages. Surgical indications of brain stem cavernoma include (1) progressive neurologic deficits; (2) overt acute or subacute hemorrhage on MRI either inside or outside cavernous malformations with mass effect; (3) cavernoma/hematoma reaching brainstem surface (<2 mm brain tissue between cavernoma /hematoma and pial surface). Grave clinical presentations like coma, respiratory, or cardiac instability are not surgical contraindications. Emergent surgical evacuation may lead to satisfactory outcome. Repeated hemorrhages will worsen the pre-existing neurologic deficits and possibly make the surgical dissections more difficult. Patients with minimum, stable neurologic deficits and lesion/hematoma that has not reached the brain stem surface should be followed conservatively.

The construction of the multifunctional targeting ursolic acids liposomes and its apoptosis effects to C6 glioma stem cells

PubMed Central

Ying, Xue; Wang, Yahua; Xu, Haolun; Li, Xia; Yan, Helu; Tang, Hui; Wen, Chen; Li, Yingchun

2017-01-01

Brain gliomas, one of the most fatal tumors to human, severely threat the health and life of human. They are capable of extremely strong invasion ability. And invasive glioma cells could rapidly penetrate into normal brain tissues and break them. We prepared a kind of functional liposomes, which could be transported acrossing the blood-brain barrier (BBB) and afterwards induce the apoptosis of glioma stem cells. In this research, we chose ursolic acids (UA) as an anti-cancer drug to inhibit the growth of C6 glioma cells, while epigallocatechin 3-gallate(EGCG) as the agent that could induce the apoptosis of C6 glioma stem cells. With the targeting ability of MAN, the liposomes could be delivered through the BBB and finally were concentrated on the brain gliomas. Cell experiments in vitro demonstrated that the functional liposomes were able to significantly enhance the anti-cancer effects of the drugs due to promoting the apoptosis and endocytosis effects of C6 glioma cells and C6 glioma stem cells at the same time. Furthermore, the evaluations through animal models showed that the drugs could obviously prolong the survival period of brain glioma-bearing mice and inhibit the tumor growth. Consequently, multifunctional targeting ursolic acids liposomes could potentially improve the therapeutic effects on C6 glioma cells and C6 glioma stem cells. PMID:28969057

High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

PubMed

Gizewski, Elke R; Maderwald, Stefan; Linn, Jennifer; Dassinger, Benjamin; Bochmann, Katja; Forsting, Michael; Ladd, Mark E

2014-03-01

The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures.

Cauda Equina Syndrome Due to Vigorous Back Massage With Spinal Manipulation in a Patient With Pre-Existing Lumbar Disc Herniation: A Case Report and Literature Review.

PubMed

Yang, Si-Dong; Chen, Qian; Ding, Wen-Yuan

2018-04-01

Cauda equina syndrome (CES) resulting from acute lumbar disc herniation due to spinal massage is extremely rare. We present a case of CES caused by the acute worsening of a lumbar disc herniation after a vigorous back massage that included spinal manipulation. After vigorous back massage with spinal manipulation performed by a massage therapist, a 38-yr-old male patient experienced CES with severe numbness in both lower limbs, inability to walk due to weakness of bilateral lower limbs, and incontinence of urine and feces. The magnetic resonance imaging and computer tomography scan results showed that the L4-5 disc herniated down into the spinal canal, extensively compressing the ventral dural sac. The patient was successfully treated with an emergency operation including laminectomy, spinal canal decompression, discectomy, interbody fusion, and pedicle screw fixation. The muscle power in both lower limbs of the patient recovered rapidly to support standing only 1 wk later. Moreover, he regained continence of urine and feces. In conclusion, this case brings us novel knowledge that spinal massage or manipulation may worsen pre-existing disc herniation causing CES, and a timely emergency surgery is necessary and effective for treatment of CES-related symptoms.

Surgical management of giant lumbar disc herniation: analysis of 154 patients over a decade.

PubMed

Akhaddar, A; Belfquih, H; Salami, M; Boucetta, M

2014-10-01

We describe a decade of our experience in the surgical management of patients with giant lumbar intervertebral disc herniation (GILID). This is a case series of patients operated for a GILID between 2000 and 2009. Among 1334 patients eligible for the present study: 154 patients presented with GILID (study group) and 1180 patients without GILID (control group). Clinical symptoms and preoperative imaging results were obtained from medical records. Complications and long-term results were assessed. This retrospective study documents the characteristic features between patients with and without GILID. The difference in the incidence of female patients was statistically significant between the study group and the control group as was the mean duration of symptoms, hyperalgic radicular pain, bilaterality of symptoms, preoperative motor deficit, central location of lumbar disc herniation (LDH), contained herniation and recurrence of LDH. GILIDs are a distinct entity: they are distinctly uncommon compared with smaller herniations, patients were statistically more likely to be hyperalgic with bilateral radicular pain and often associated with neurological deficits. The majority of patients do not display a cauda equina syndrome (CES). Low lumbar disc sites are mostly affected and disc fragments are more likely to be central-uncontained. The recurrence rate is lower for GILIDs. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Long-term 10-year outcome after chemonucleolysis for lumbar disc herniation].

PubMed

Aribit, F; Charissoux, J L; Arnaud, J P

2002-05-01

We studied the efficacy of papaine for treatment of herniated discs at a mean 10-year follow-up and compared results with other series and other treatments. From an initial group of 160 patients, 96 patients, 53 men and 43 women, mean age 39 years, were selected for evaluation. These patients had 46 L4L5 herniations and 50 L5S1 herniations. All 96 patients were operated in the same department and received the same dose of papaine under the same anesthesia conditions. All patients were followed regularly to 3 months postoperatively then were reviewed 3 to 17 years after surgery. Inquiries were made about return to work, pain, and activity. Physical examination and x-rays were obtained for all patients. There were no neurological complications in our series. Seventeen patients required a second procedure for sciatic pain. Most of the patients continued their normal occupational and social activities after papaine treatment, but many of them had chronic lumbar pain. Our results were comparable with series reporting a similar long follow-up. Surgery is more efficient than papaine but long-term results are equivalent. Chemopapaine treatment provided good long-term results in our patients, similar to surgery. Chemonucleolysis may be employed as first line treatment for young patients with non-excluded disc herniation with sciatic pain.

Prenatal diagnosis of herniated Dandy-Walker cysts.

PubMed

Lee, Wesley; Vettraino, Ivana M; Comstock, Christine H; Lal, Nirish; Kazmierczak, Chris; Shetty, Anil; Raff, Gil; Zakalik, Karol; Romero, Roberto

2005-06-01

The purpose of this series is to describe the prenatal diagnosis and pregnancy outcome of fetuses affected with Dandy-Walker malformation in which a posterior cyst herniated through a bony defect of the occipital skull, foramen magnum, or both. Two- and 3-dimensional sonography were used to examine 2 fetuses with poorly delineated cerebellar structures and a large posterior cystic neck mass. Fetal magnetic resonance imaging (MRI) was added to this evaluation as a complementary diagnostic modality. Three-dimensional sonography helped characterize the precise site of cyst herniation through the occipital skull or foramen magnum. Fetal MRI confirmed the sonographic findings. Neonatal MRI studies identified heterotopic gray matter as evidence of a neuronal migration disorder in both fetuses. The second fetus also had agenesis of the corpus callosum. Retrospective review of the fetal MRI (25.9 weeks' menstrual age) and 3-dimensional sonographic (18.7 weeks' menstrual age) studies confirmed ventricular wall nodularity involving the occipital horns of the second fetus. The antenatal detection of a large posterior cystic neck mass and a poorly defined or nonvisualized cerebellar vermis suggest Dandy-Walker malformation with a herniated cyst. Three-dimensional sonography and fetal MRI are important adjunctive methods that can be used to evaluate the herniation site and a possible neuronal migrational disorder.

Percutaneous bipolar radiofrequency thermocoagulation for the treatment of lumbar disc herniation.

PubMed

Zeng, Zhenhua; Yan, Min; Dai, Yi; Qiu, Weidong; Deng, Shuo; Gu, Xinzhu

2016-08-01

Lumbar disc herniation is usually managed with conservative treatment or surgery. However, conservative therapy seldom yields good results, and surgery is associated with multiple complications. This study aimed to assess bipolar radiofrequency thermocoagulation for the treatment of lumbar disc herniation. A total of 168 patients with lumbar disc herniation suitable for radiofrequency thermocoagulation were enrolled and randomized to monopolar radiofrequency thermocoagulation (control group, n=84) or bipolar radiofrequency thermocoagulation (experimental group, n=84) treatment groups. Ablation sites were targeted under CT scan guidance, and consecutive radiofrequency therapy was used. One and two probes were used for monopolar and bipolar thermocoagulation, respectively. Thermocoagulation was achieved at 50°C, 60°C, and 70°C for 60s each, 80°C for 90s, and 92°C for 100s. Symptoms and complications were evaluated using the modified Macnab criteria and Visual Analog Scale at 7, 30, and 180days postoperatively. At 180days, a significantly higher efficacy rate was obtained in the experimental group compared with control patients (91.6% versus 79.7%, P<0.05). No severe complications were occurred in either group. Targeted ablation via bipolar radiofrequency thermocoagulation is efficient for lumbar disc herniation treatment, and should be further explored for broad clinical application. Copyright © 2016 Elsevier Ltd. All rights reserved.

Percutaneous treatment of intervertebral disc herniation.

PubMed

Buy, Xavier; Gangi, Afshin

2010-06-01

Interventional radiology plays a major role in the management of symptomatic intervertebral disc herniations. In the absence of significant pain relief with conservative treatment including oral pain killers and anti-inflammatory drugs, selective image-guided periradicular infiltrations are generally indicated. The precise control of needle positioning allows optimal distribution of steroids along the painful nerve root. After 6 weeks of failure of conservative treatment including periradicular infiltration, treatment aiming to decompress or remove the herniation is considered. Conventional open surgery offers suboptimal results and is associated with significant morbidity. To achieve minimally invasive discal decompression, different percutaneous techniques have been developed. Their principle is to remove a small volume of nucleus, which results in an important reduction of intradiscal pressure and subsequently reduction of pressure inside the disc herniation. However, only contained disc herniations determined by computed tomography or magnetic resonance are indicated for these techniques. Thermal techniques such as radiofrequency or laser nucleotomy seem to be more effective than purely mechanical nucleotomy; indeed, they achieve discal decompression but also thermal destruction of intradiscal nociceptors, which may play a major role in the physiopathology of discal pain. The techniques of image-guided spinal periradicular infiltration and percutaneous nucleotomy with laser and radiofrequency are presented with emphasis on their best indications.

Organotypic distribution of stem cell markers in formalin-fixed brain harboring glioblastoma multiforme.

PubMed

Schrot, Rudolph J; Ma, Joyce H; Greco, Claudia M; Arias, Angelo D; Angelastro, James M

2007-11-01

The role of stem cells in the origin, growth patterns, and infiltration of glioblastoma multiforme is a subject of intense investigation. One possibility is that glioblastoma may arise from transformed stem cells in the ventricular zone. To explore this hypothesis, we examined the distribution of two stem cell markers, activating transcription factor 5 (ATF5) and CD133, in an autopsy brain specimen from an individual with glioblastoma multiforme. A 41-year-old male with a right posterior temporal glioblastoma had undergone surgery, radiation, and chemotherapy. The brain was harvested within several hours after death. After formalin fixation, sectioning, and mapping of tumor location in the gross specimen, histologic specimens were prepared from tumor-bearing and grossly normal hemispheres. Fluorescence immunohistochemistry and colorimetric staining were performed for ATF5 and CD133. Both markers co-localized to the ependymal and subependymal zones on the side of the tumor, but not in the normal hemisphere or more rostrally in the affected hemisphere. ATF5 staining was especially robust within the diseased hemisphere in histologically normal ependyma. To our knowledge, this is the first in situ demonstration of stem cell markers in whole human brain. These preliminary results support the hypothesis that some glioblastomas may arise from the neurogenic zone of the lateral ventricle. The robust staining for ATF5 and CD133 in histologically normal ventricular zone suggests that an increase in periventricular stem cell activity occurred in this patient on the side of the tumor, either as a localized response to brain injury or as an integral component of oncogenesis and tumor recurrence.

Brain tumor specifies intermediate progenitor cell identity by attenuating β-catenin/Armadillo activity

PubMed Central

Komori, Hideyuki; Xiao, Qi; McCartney, Brooke M.; Lee, Cheng-Yu

2014-01-01

During asymmetric stem cell division, both the daughter stem cell and the presumptive intermediate progenitor cell inherit cytoplasm from their parental stem cell. Thus, proper specification of intermediate progenitor cell identity requires an efficient mechanism to rapidly extinguish the activity of self-renewal factors, but the mechanisms remain unknown in most stem cell lineages. During asymmetric division of a type II neural stem cell (neuroblast) in the Drosophila larval brain, the Brain tumor (Brat) protein segregates unequally into the immature intermediate neural progenitor (INP), where it specifies INP identity by attenuating the function of the self-renewal factor Klumpfuss (Klu), but the mechanisms are not understood. Here, we report that Brat specifies INP identity through its N-terminal B-boxes via a novel mechanism that is independent of asymmetric protein segregation. Brat-mediated specification of INP identity is critically dependent on the function of the Wnt destruction complex, which attenuates the activity of β-catenin/Armadillo (Arm) in immature INPs. Aberrantly increasing Arm activity in immature INPs further exacerbates the defects in the specification of INP identity and enhances the supernumerary neuroblast mutant phenotype in brat mutant brains. By contrast, reducing Arm activity in immature INPs suppresses supernumerary neuroblast formation in brat mutant brains. Finally, reducing Arm activity also strongly suppresses supernumerary neuroblasts induced by overexpression of klu. Thus, the Brat-dependent mechanism extinguishes the function of the self-renewal factor Klu in the presumptive intermediate progenitor cell by attenuating Arm activity, balancing stem cell maintenance and progenitor cell specification. PMID:24257623

Taking a Toll on Self-Renewal: TLR-Mediated Innate Immune Signaling in Stem Cells.

PubMed

Alvarado, Alvaro G; Lathia, Justin D

2016-07-01

Innate immunity has evolved as the front-line cellular defense mechanism to acutely sense and decisively respond to microenvironmental alterations. The Toll-like receptor (TLR) family activates signaling pathways in response to stimuli and is well-characterized in both resident and infiltrating immune cells during neural inflammation, injury, and degeneration. Innate immune signaling has also been observed in neural cells during development and disease, including in the stem and progenitor cells that build the brain and are responsible for its homeostasis. Recently, the activation of developmental programs in malignant brain tumors has emerged as a driver for growth via cancer stem cells. In this review we discuss how innate immune signaling interfaces with stem cell maintenance in the normal and neoplastic brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

ClinicalTrials.gov

2013-10-07

Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Traumatic Buccal Fat Pad Herniation in Young Children: A Systematic Review and Case Report.

PubMed

Kim, Seon-Yeong; Alfafara, Angenine; Kim, Jin-Woo; Kim, Sun-Jong

2017-09-01

Traumatic herniation of a buccal fat pad, predominantly seen in young children, is a rare condition. Because of its rarity and clinical features that resemble tumors, clinicians are faced with challenges at the initial diagnosis. This report describes a case of buccal fat pad herniation with excellent long-term prognosis after surgical relocation and conservative treatment and presents a systematic review of the literature on its management. Through a PubMed search, 811 articles were initially identified. Case series, case reports, technical notes, case and review reports, and retrospective case series were included. After screening and manual review, the sample was narrowed to 35 reports (41 patients) based on eligibility criteria. Articles were included if the standard criteria for traumatic intraoral herniation of buccal fat pad were met. Patients' ages ranged from 4 months to 12 years, with no specific gender predilection. Management consisted of excision (82.9%), relocation (14.6%), and observation (2.4%). Follow-up ranged from 1 week to 4 months. No reports presented a follow-up longer than 4 months; hence, data on long-term prognosis were not reported. For the present case report, a 19-month-old boy diagnosed with traumatic buccal fat pad herniation was successfully treated with surgical relocation and antibiotic support. Twelve-month follow-up showed no esthetic or functional disturbance or recurrence. Traumatic herniation of the buccal fat pad requires special attention at the initial diagnosis. Considering its clinical importance in young children and few studies have reported long-term postresection follow-up, surgical relocation can be regarded as an excellent and more conservative treatment option. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Cervical stability training with and without core stability training for patients with cervical disc herniation: A randomized, single-blind study.

PubMed

Buyukturan, B; Guclu-Gunduz, A; Buyukturan, O; Dadali, Y; Bilgin, S; Kurt, E E

2017-11-01

This study aims at evaluating and comparing the effects of cervical stability training to combined cervical and core stability training in patients with neck pain and cervical disc herniation. Fifty patients with neck pain and cervical disc herniation were included in the study, randomly divided into two groups as cervical stability and cervical-core stability. Training was applied three times a week in three phases, and lasted for a total duration of 8 weeks. Pain, activation and static endurance of deep cervical flexor muscles, static endurance of neck muscles, cross-sectional diameter of M. Longus Colli, static endurance of trunk muscles, disability and kinesiophobia were assessed. Pain, activation and static endurance of deep cervical flexors, static endurance of neck muscles, cross-sectional diameter of M. Longus Colli, static endurance of trunk muscles, disability and kinesiophobia improved in both groups following the training sessions (p < 0.05). Comparison of the effectiveness of these two training methods revealed that the cervical stability group produced a greater increase in the right transverse diameter of M. Longus Colli (p < 0.05). However, static endurance of trunk muscles and kinesiophobia displayed better improvement in the cervical-core stability group (p < 0.05). Cervical stability training provided benefit to patients with cervical disc herniation. The addition of core stability training did not provide any additional significant benefit. Further research is required to investigate the efficacy of combining other techniques with cervical stability training in patients with cervical disc herniation. Both cervical stability training and its combination with core stability training were significantly and similarly effective on neck pain and neck muscle endurance in patients with cervical disc herniation. © 2017 European Pain Federation - EFIC®.

Do Turkish patients with lumbar disc herniation know body mechanics?

PubMed

Topcu, Sacide Yildizeli

2017-01-01

Most common and important cause of the low back pain is lumbar disc herniation. Patients with lumbar disc herniation face with difficulties during daily activities due to the reduction of physical functions. In order to maintain daily activities without pain and discomfort, the patients should be informed about proper positions and body mechanics. The aim of the study was to determine the knowledge and the applications of the patients with lumbar disc herniation about body mechanics. This descriptive study was conducted with 75 patients with lumbar disc herniation in Edirne, Turkey. The population consisted of 75 patients who accepted to participate in the study. In the collection of data the questionnaire, which was developed according to literature by the researcher, was used. Descriptive statistics, student t-test, variance and correlation analysis were used for assessment of the data. The significance level was accepted at 0.05. It was found that 53.3% of the patients experienced awful/very severe pain. and there were some points that the patients have enough information about; mobilisation, standing, carrying the goods, leaning back while sitting, leaning somewhere while standing, getting support from the chair when standing up, avoiding sudden position changes, changing feet frequently while standing. It was detected that a statistical relation between educational level and knowledge about body mechanics exists. This study shows that individuals with lumbar disc herniation have not enough information about body mechanics and they experienced long-term severe pain. Nurses and other health care workers have important role in explaining the importance of body mechanics to the patients and should encourage them to use that in daily life.

Brain components

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The brain is composed of more than a thousand billion neurons. Specific groups of them, working in concert, provide ... of information. The 3 major components of the brain are the cerebrum, cerebellum, and brain stem. The ...

Traumatic Pulmonary Herniation at the Diaphragmatic Junction in a Pediatric Patient: A Rare Complication of Blunt Chest Trauma.

PubMed

Orlik, Kseniya; Simon, Erin Leslie; Hemmer, Carrie; Ramundo, Maria

2016-07-01

We present a case of traumatic intercostal pulmonary herniation in an 11-year-old boy after blunt trauma to the chest, without associated chest wall disruption or pneumothorax. This condition is especially uncommon in children, with only 5 previously reported cases and most occurring after penetrating chest trauma. To date, there are no reports in literature describing traumatic intercostal lung herniation at the diaphragmatic junction with a closed chest cavity in a child. The number of traumatic lung herniation diagnoses may be expanded by a more liberal use of computed tomography when serious injury is suspected. Computed tomography and advanced imaging should be considered in pediatric trauma patients presenting with concern for intrathoracic injury that may not be seen on plain film. Traumatic blunt intrathoracic and intra-abdominal injuries in the pediatric population that are within proximity of diaphragmatic insertion should be thoroughly evaluated to rule out diaphragmatic injury. As in our case, invasive surgical intervention such as thoracoscopy may be necessary.

Unexpected findings at diagnostic laparoscopy: caecal incarceration with concurrent appendicitis in a patient with bilateral broad ligament defects

PubMed Central

Onida, S; Lynes, K; Whitehouse, PA

2010-01-01

Internal herniations through broad ligament defects are very rare. We present the first report of the triad of broad ligament defect, internal herniation of the caecum and appendicitis. A 36-year-old woman with phocomelia presented with right iliac fossa pain and vomiting. The patient had no previous history of trauma or surgery. Abdominal ultrasound showed a small amount of free fluid. At laparoscopy, bilateral broad ligament defects were found, with herniation of the caecum and an inflamed appendix through the right-sided defect. A laparoscopic salpingo-oophorectomy was required for reduction of the herniated bowel, and an appendicectomy was performed. Broad ligament defects may be congenital or acquired. In this case, in light of the limb abnormality and absence of previous surgery, a congenital aetiology is more likely. Ultrasound scan is not reliable and, although computed tomography may be of help, a diagnostic laparoscopy is the best investigation. PMID:20566032

Traumatic Transient Herniation Concomitant with Tonsillar Hemorrhagic Contusion in a Child

PubMed Central

Öğrenci, Ahmet; Koban, Orkun; Ekşi, Murat; Yaman, Onur; Dalbayrak, Sedat

2017-01-01

Downward displacement of cerebellar tonsils more than 5 mm below the foramen magnum is named as Chiari type I malformation and named benign tonsillar ectopia if herniation is less than 3 mm. It does not just depend on congenital causes. There are also some reasons for acquired Chiari Type 1 and benign tonsillar ectopia/herniation. Trauma is one of them. Trauma may increase tonsillar ectopia or may be the cause of new-onset Chiari type 1. The relationship between the tonsil contusion and its position is unclear. We present a case of pediatric age group with tonsillar herniation with a hemorrhagic contusion. Only 1 case has been presented so far in the literature. A case with unilateral tonsil contusion has not been presented to date. We will discuss the possible reasons for taking the place of the tonsils to the above level of the foramen magnum in the follow-up period, by looking at the literature. PMID:29104687

Sonographic prevalence of groin hernias and adductor tendinopathy in patients with femoroacetabular impingement.

PubMed

Naal, Florian D; Dalla Riva, Francesco; Wuerz, Thomas H; Dubs, Beat; Leunig, Michael

2015-09-01

Femoroacetabular impingement (FAI) is a common debilitating condition that is associated with groin pain and limitation in young and active patients. Besides FAI, various disorders such as hernias, adductor tendinopathy, athletic pubalgia, lumbar spine affections, and others can cause similar symptoms. To determine the prevalence of inguinal and/or femoral herniation and adductor insertion tendinopathy using dynamic ultrasound in a cohort of patients with radiographic evidence of FAI. Case series; Level of evidence, 4. This retrospective study consisted of 74 patients (36 female and 38 male; mean age, 29 years; 83 symptomatic hips) with groin pain and radiographic evidence of FAI. In addition to the usual diagnostic algorithm, all patients underwent a dynamic ultrasound examination for signs of groin herniation and tendinopathy of the proximal insertion of the adductors. Evidence of groin herniation was found in 34 hips (41%). There were 27 inguinal (6 female, 21 male) and 10 femoral (9 female, 1 male) hernias. In 3 cases, inguinal and femoral herniation was coexistent. Overall, 5 patients underwent subsequent hernia repair. Patients with groin herniation were significantly older than those without (33 vs 27 years, respectively; P = .01). There were no significant differences for any of the radiographic or clinical parameters. Tendinopathy of the proximal adductor insertion was detected in 19 cases (23%; 11 female, 8 male). Tendinopathy was coexistent with groin herniation in 8 of the 19 cases. There were no significant differences for any of the radiographic or clinical parameters between patients with or without tendinopathy. Patients with a negative diagnostic hip injection result were more likely to have a concomitant groin hernia than those with a positive injection result (80% vs 27%, respectively). Overall, 38 hips underwent FAI surgery with satisfactory outcomes in terms of score values and subjective improvement. The results demonstrate that groin herniation and adductor insertion tendinopathy coexist frequently in patients with FAI. Although the clinical effect is yet unclear, 5 patients underwent hernia repair. Dynamic ultrasound is a useful tool to detect such pathological abnormalities. Diagnostic hip injections can be helpful to differentiate between the sources of pain. © 2015 The Author(s).

Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1β and TNFα expression profile

PubMed Central

Le Maitre, Christine Lyn; Hoyland, Judith Alison; Freemont, Anthony J

2007-01-01

Low back pain is a common and debilitating disorder. Current evidence implicates intervertebral disc (IVD) degeneration and herniation as major causes, although the pathogenesis is poorly understood. While several cytokines have been implicated in the process of IVD degeneration and herniation, investigations have predominately focused on Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNFα). However, to date no studies have investigated the expression of these cytokines simultaneously in IVD degeneration or herniation, or determined which may be the predominant cytokine associated with these disease states. Using quantitative real time PCR and immunohistochemistry we investigated gene and protein expression for IL-1β, TNFα and their receptors in non-degenerate, degenerate and herniated human IVDs. IL-1β gene expression was observed in a greater proportion of IVDs than TNFα (79% versus 59%). Degenerate and herniated IVDs displayed higher levels of both cytokines than non-degenerate IVDs, although in degenerate IVDs higher levels of IL-1β gene expression (1,300 copies/100 ng cDNA) were observed compared to those of TNFα (250 copies of TNFα/100 ng cDNA). Degenerate IVDs showed ten-fold higher IL-1 receptor gene expression compared to non-degenerate IVDs. In addition, 80% of degenerate IVD cells displayed IL-1 receptor immunopositivity compared to only 30% of cells in non-degenerate IVDs. However, no increase in TNF receptor I gene or protein expression was observed in degenerate or herniated IVDs compared to non-degenerate IVDs. We have demonstrated that although both cytokines are produced by human IVD cells, IL-1β is expressed at higher levels and in more IVDs, particularly in more degenerate IVDs (grades 4 to 12). Importantly, this study has highlighted an increase in gene and protein production for the IL-1 receptor type I but not the TNF receptor type I in degenerate IVDs. The data thus suggest that although both cytokines may be involved in the pathogenesis of IVD degeneration, IL-1 may have a more significant role than TNFα, and thus may be a better target for therapeutic intervention. PMID:17688691

Brain tumour stem cells: implications for cancer therapy and regenerative medicine.

PubMed

Sanchez-Martin, Manuel

2008-09-01

The cancer relapse and mortality rate suggest that current therapies do not eradicate all malignant cells. Currently, it is accepted that tumorigenesis and organogenesis are similar in many respects, as for example, homeostasis is governed by a distinct sub-population of stem cells in both situations. There is increasing evidence that many types of cancer contain their own stem cells: cancer stem cells (CSC), which are characterized by their self-renewing capacity and differentiation ability. The investigation of solid tumour stem cells has gained momentum particularly in the area of brain tumours. Gliomas are the most common type of primary brain tumours. Nearly two-thirds of gliomas are highly malignant lesions with fast progression and unfortunate prognosis. Despite recent advances, two-year survival for glioblastoma (GBM) with optimal therapy is less than 30%. Even among patients with low-grade gliomas that confer a relatively good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells endowed with features of primitive neural progenitor cells and a tumour-initiating function. In general, this fraction is characterized for forming neurospheres, being endowed with drug resistance properties and often, we can isolate some of them using sorting methods with specific antibodies. The molecular characterization of these stem populations will be critical to developing an effective therapy for these tumours with very dismal prognosis. To achieve this aim, the development of a mouse model which recapitulates the nature of these tumours is essential. This review will focus on glioma stem cell knowledge and discuss future implications in brain cancer therapy and regenerative medicine.

Innate (inherent) control of brain infection, brain inflammation and brain repair: the role of microglia, astrocytes, "protective" glial stem cells and stromal ependymal cells.

PubMed

Hauwel, Mathieu; Furon, Emeline; Canova, Cecile; Griffiths, Mark; Neal, Jim; Gasque, Philippe

2005-04-01

In invertebrates and primitive vertebrates, the brain contains large numbers of "professional" macrophages associated with neurones, ependymal tanycytes and radial glia to promote robust regenerative capacity. In higher vertebrates, hematogenous cells are largely excluded from the brain, and innate immune molecules and receptors produced by the resident "amateur" macrophages (microglia, astrocytes and ependymal cells) control pathogen infiltration and clearance of toxic cell debris. However, there is minimal capacity for regeneration. The transfer of function from hematogenous cells to macroglia and microglia is associated with the sophistication of a yet poorly-characterized neurone-glia network. This evolutionary pattern may have been necessary to reduce the risk of autoimmune attack while preserving the neuronal web but the ability to repair central nervous system damage may have been sacrificed in the process. We herein argue that it may be possible to re-educate and stimulate the resident phagocytes to promote clearance of pathogens (e.g., Prion), toxic cell debris (e.g., amyloid fibrils and myelin) and apoptotic cells. Moreover, as part of this greater division of labour between cell types in vertebrate brains, it may be possible to harness the newly described properties of glial stem cells in neuronal protection (revitalization) rather than replacement, and to control brain inflammation. We will also highlight the emerging roles of stromal ependymal cells in controlling stem cell production and migration into areas of brain damage. Understanding the mechanisms involved in the nurturing of damaged neurons by protective glial stem cells with the safe clearance of cell debris could lead to remedial strategies for chronic brain diseases.

The stem cell secretome and its role in brain repair.

PubMed

Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

2013-12-01

Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. Copyright © 2013 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates.

PubMed

Keeney, J G; Davis, J M; Siegenthaler, J; Post, M D; Nielsen, B S; Hopkins, W D; Sikela, J M

2015-09-01

Genome sequences encoding DUF1220 protein domains show a burst in copy number among anthropoid species and especially humans, where they have undergone the greatest human lineage-specific copy number expansion of any protein coding sequence in the genome. While DUF1220 copy number shows a dosage-related association with brain size in both normal populations and in 1q21.1-associated microcephaly and macrocephaly, a function for these domains has not yet been described. Here we provide multiple lines of evidence supporting the view that DUF1220 domains function as drivers of neural stem cell proliferation among anthropoid species including humans. First, we show that brain MRI data from 131 individuals across 7 anthropoid species shows a strong correlation between DUF1220 copy number and multiple brain size-related measures. Using in situ hybridization analyses of human fetal brain, we also show that DUF1220 domains are expressed in the ventricular zone and primarily during human cortical neurogenesis, and are therefore expressed at the right time and place to be affecting cortical brain development. Finally, we demonstrate that in vitro expression of DUF1220 sequences in neural stem cells strongly promotes proliferation. Taken together, these data provide the strongest evidence so far reported implicating DUF1220 dosage in anthropoid and human brain expansion through mechanisms involving increasing neural stem cell proliferation.

Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke.

PubMed

Wei, Ling; Wei, Zheng Z; Jiang, Michael Qize; Mohamad, Osama; Yu, Shan Ping

2017-10-01

One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures. Meanwhile, stem cells and neural progenitor cells are well-known for their potential for trophic support after transplantation into the ischemic brain. Thus, stem cell-based therapies provide an attractive future for protecting and repairing damaged brain tissues after injury and in various disease states. Moreover, basic research on naïve and differentiated stem cells including iPS cells has markedly improved our understanding of cellular and molecular mechanisms of neurological disorders, and provides a platform for the discovery of novel drug targets. The latest advances indicate that combinatorial approaches using cell based therapy with additional treatments such as protective reagents, preconditioning strategies and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the characteristics of cell therapy in different ischemic models and the application of stem cells and progenitor cells as regenerative medicine for the treatment of stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

The "pseudo-CT myelogram sign": an aid to the diagnosis of underlying brain stem and spinal cord trauma in the presence of major craniocervical region injury on post-mortem CT.

PubMed

Bolster, F; Ali, Z; Daly, B

2017-12-01

To document the detection of underlying low-attenuation spinal cord or brain stem injuries in the presence of the "pseudo-CT myelogram sign" (PCMS) on post-mortem computed tomography (PMCT). The PCMS was identified on PMCT in 20 decedents (11 male, nine female; age 3-83 years, mean age 35.3 years) following fatal blunt trauma at a single forensic centre. Osseous and ligamentous craniocervical region injuries and brain stem or spinal cord trauma detectable on PMCT were recorded. PMCT findings were compared to conventional autopsy in all cases. PMCT-detected transection of the brain stem or high cervical cord in nine of 10 cases compared to autopsy (90% sensitivity). PMCT was 92.86% sensitive in detection of atlanto-occipital joint injuries (n=14), and 100% sensitive for atlanto-axial joint (n=8) injuries. PMCT detected more cervical spine and skull base fractures (n=22, and n=10, respectively) compared to autopsy (n=13, and n=5, respectively). The PCMS is a novel description of a diagnostic finding, which if present in fatal craniocervical region trauma, is very sensitive for underlying spinal cord and brain stem injuries not ordinarily visible on PMCT. Its presence may also predict major osseous and/or ligamentous injuries in this region when anatomical displacement is not evident on PMCT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Effects of atelocollagen on neural stem cell function and its migrating capacity into brain in psychiatric disease model.

PubMed

Yoshinaga, Toshihiro; Hashimoto, Eri; Ukai, Wataru; Ishii, Takao; Shirasaka, Tomohiro; Kigawa, Yoshiyasu; Tateno, Masaru; Kaneta, Hiroo; Watanabe, Kimihiko; Igarashi, Takeshi; Kobayashi, Seiju; Sohma, Hitoshi; Kato, Tadafumi; Saito, Toshikazu

2013-10-01

Stem cell therapy is well proposed as a potential method for the improvement of neurodegenerative damage in the brain. Among several different procedures to reach the cells into the injured lesion, the intravenous (IV) injection has benefit as a minimally invasive approach. However, for the brain disease, prompt development of the effective treatment way of cellular biodistribution of stem cells into the brain after IV injection is needed. Atelocollagen has been used as an adjunctive material in a gene, drug and cell delivery system because of its extremely low antigenicity and bioabsorbability to protect these transplants from intrabody environment. However, there is little work about the direct effect of atelocollagen on stem cells, we examined the functional change of survival, proliferation, migration and differentiation of cultured neural stem cells (NSCs) induced by atelocollagen in vitro. By 72-h treatment 0.01-0.05% atelocollagen showed no significant effects on survival, proliferation and migration of NSCs, while 0.03-0.05% atelocollagen induced significant reduction of neuronal differentiation and increase of astrocytic differentiation. Furthermore, IV treated NSCs complexed with atelocollagen (0.02%) could effectively migrate into the brain rather than NSC treated alone using chronic alcohol binge model rat. These experiments suggested that high dose of atelocollagen exerts direct influence on NSC function but under 0.03% of atelocollagen induces beneficial effect on regenerative approach of IV administration of NSCs for CNS disease.

Brain injury expands the numbers of neural stem cells and progenitors in the SVZ by enhancing their responsiveness to EGF

PubMed Central

Alagappan, Dhivyaa; Lazzarino, Deborah A; Felling, Ryan J; Balan, Murugabaskar; Kotenko, Sergei V; Levison, Steven W

2009-01-01

There is an increase in the numbers of neural precursors in the SVZ (subventricular zone) after moderate ischaemic injuries, but the extent of stem cell expansion and the resultant cell regeneration is modest. Therefore our studies have focused on understanding the signals that regulate these processes towards achieving a more robust amplification of the stem/progenitor cell pool. The goal of the present study was to evaluate the role of the EGFR [EGF (epidermal growth factor) receptor] in the regenerative response of the neonatal SVZ to hypoxic/ischaemic injury. We show that injury recruits quiescent cells in the SVZ to proliferate, that they divide more rapidly and that there is increased EGFR expression on both putative stem cells and progenitors. With the amplification of the precursors in the SVZ after injury there is enhanced sensitivity to EGF, but not to FGF (fibroblast growth factor)-2. EGF-dependent SVZ precursor expansion, as measured using the neurosphere assay, is lost when the EGFR is pharmacologically inhibited, and forced expression of a constitutively active EGFR is sufficient to recapitulate the exaggerated proliferation of the neural stem/progenitors that is induced by hypoxic/ischaemic brain injury. Cumulatively, our results reveal that increased EGFR signalling precedes that increase in the abundance of the putative neural stem cells and our studies implicate the EGFR as a key regulator of the expansion of SVZ precursors in response to brain injury. Thus modulating EGFR signalling represents a potential target for therapies to enhance brain repair from endogenous neural precursors following hypoxic/ischaemic and other brain injuries. PMID:19570028

Effects of irradiation on stem cell response to differentiation inhibitors in the Planarian Dugesia etrusca

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steele, V.E.; Lange, C.S.

1976-07-01

The planarian owes its extensive powers of regeneration to the possession of a totipotential stem cell system. The survival of the animal after irradiation depends mainly upon this system. In this respect the planarian is analogous to mammalian organ systems such as bone marrow or gut epithelium. The differentiated cells control the course of stem cell mediated tissue renewal by the secretion of differentiator and/or inhibitor substances. One such inhibitor substance, present in extracts prepared from homogenized whole planarians, specifically inhibits brain formation. This substance is organ specific, but not species specific. The differentiative integrity of the stem cells aftermore » irradiation is measured by comparing the regenerated brain volumes resulting from the presence or absence of the brain inhibitory extract during the regeneration period. Our data suggest that increasing doses of x irradiation decreases the ability of the stem cells to respond to differentiative substances. The data presented also explore the possibility of altering the postirradiation recovery pattern by shifting the differentiative demands placed on the stem cells. The final proportions of animals (one-half regenerated with, and one-half without, the extract) surviving after 60 days were not significantly different.« less

Segmentation and texture analysis of structural biomarkers using neighborhood-clustering-based level set in MRI of the schizophrenic brain.

PubMed

Latha, Manohar; Kavitha, Ganesan

2018-02-03

Schizophrenia (SZ) is a psychiatric disorder that especially affects individuals during their adolescence. There is a need to study the subanatomical regions of SZ brain on magnetic resonance images (MRI) based on morphometry. In this work, an attempt was made to analyze alterations in structure and texture patterns in images of the SZ brain using the level-set method and Laws texture features. T1-weighted MRI of the brain from Center of Biomedical Research Excellence (COBRE) database were considered for analysis. Segmentation was carried out using the level-set method. Geometrical and Laws texture features were extracted from the segmented brain stem, corpus callosum, cerebellum, and ventricle regions to analyze pattern changes in SZ. The level-set method segmented multiple brain regions, with higher similarity and correlation values compared with an optimized method. The geometric features obtained from regions of the corpus callosum and ventricle showed significant variation (p < 0.00001) between normal and SZ brain. Laws texture feature identified a heterogeneous appearance in the brain stem, corpus callosum and ventricular regions, and features from the brain stem were correlated with Positive and Negative Syndrome Scale (PANSS) score (p < 0.005). A framework of geometric and Laws texture features obtained from brain subregions can be used as a supplement for diagnosis of psychiatric disorders.

Recovery from a possible cytomegalovirus meningoencephalitis-induced apparent brain stem death in an immunocompetent man: a case report.

PubMed

Rahardjo, Theresia Monica; Maskoen, Tinni Trihartini; Redjeki, Ike Sri

2016-08-26

Recovery from cytomegalovirus meningoencephalitis with brain stem death in an immunocompetent patient is almost impossible. We present a remarkable recovery from a possible cytomegalovirus infection in an immunocompetent man who had severe neurological syndromes, suggesting brain stem death complicated by pneumonia and pleural effusion. A 19-year-old Asian man presented at our hospital's emergency department with reduced consciousness and seizures following high fever, headache, confusion, and vomitus within a week before arrival. He was intubated and sent to our intensive care unit. He had nuchal rigidity and tetraparesis with accentuated tendon reflexes. Electroencephalography findings suggested an acute structural lesion at his right temporal area or an epileptic state. A cerebral spinal fluid examination suggested viral infection. A computed tomography scan was normal at the early stage of disease. Immunoglobulin M, immunoglobulin G anti-herpes simplex virus, and immunoglobulin M anti-cytomegalovirus were negative. However, immunoglobulin G anti-cytomegalovirus was positive, which supported a diagnosis of cytomegalovirus meningoencephalitis. His clinical condition deteriorated, spontaneous respiration disappeared, cranial reflexes became negative, and brain stem death was suspected. Therapy included antivirals, corticosteroids, antibiotics, anticonvulsant, antipyretics, antifungal agents, and a vasopressor to maintain hemodynamic stability. After 1 month, he showed a vague response to painful stimuli at his supraorbital nerve and respiration started to appear the following week. After pneumonia and pleural effusion were resolved, he was weaned from the ventilator and moved from the intensive care unit on day 90. This case highlights several important issues that should be considered. First, the diagnosis of brain stem death must be confirmed with caution even if there are negative results of brain stem death test for a long period. Second, cytomegalovirus meningoencephalitis should be considered in the differential diagnosis even for an immunocompetent adult. Third, accurate therapy and simultaneous intensive care have very important roles in the recovery process of patients with cytomegalovirus meningoencephalitis.

Intermittent hypoxia activates peptidylglycine α-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing

PubMed Central

Sharma, Suresh D.; Raghuraman, Gayatri; Lee, Myeong-Seon; Prabhakar, Nanduri R.; Kumar, Ganesh K.

2009-01-01

Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory abnormalities that may involve altered neuropeptide signaling. The effects of IH on neuropeptide synthesis have not been investigated. Peptidylglycine α-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the α-amidation of neuropeptides, which confers biological activity to a large number of neuropeptides. PAM consists of O2-sensitive peptidylglycine α-hydroxylating monooxygenase (PHM) and peptidyl-α-hydroxyglycine α-amidating lyase (PAL) activities. Here, we examined whether IH alters neuropeptide synthesis by affecting PAM activity and, if so, by what mechanisms. Experiments were performed on the brain stem of adult male rats exposed to IH (5% O2 for 15 s followed by 21% O2 for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for 10 days). Analysis of brain stem extracts showed that IH, but not continuous hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM activity was associated with a concomitant elevation in the levels of α-amidated forms of substance P and neuropeptide Y. IH increased the relative abundance of 42- and 35-kDa forms of PHM (∼1.6- and 2.7-fold, respectively), suggesting enhanced proteolytic processing of PHM, which appears to be mediated by an IH-induced increase of endoprotease activity. Kinetic analysis showed that IH increases Vmax but has no effect on Km. IH increased generation of reactive oxygen species in the brain stem, and systemic administration of antioxidant prevented IH-evoked increases of PHM activity, proteolytic processing of PHM, endoprotease activity, and elevations in substance P and neuropeptide Y amide levels. Taken together, these results demonstrate that IH activates PHM in rat brain stem via reactive oxygen species-dependent posttranslational proteolytic processing and further suggest that PAM activation may contribute to IH-mediated peptidergic neurotransmission in rat brain stem. PMID:18818385

Intermittent hypoxia activates peptidylglycine alpha-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing.

PubMed

Sharma, Suresh D; Raghuraman, Gayatri; Lee, Myeong-Seon; Prabhakar, Nanduri R; Kumar, Ganesh K

2009-01-01

Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory abnormalities that may involve altered neuropeptide signaling. The effects of IH on neuropeptide synthesis have not been investigated. Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the alpha-amidation of neuropeptides, which confers biological activity to a large number of neuropeptides. PAM consists of O(2)-sensitive peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) activities. Here, we examined whether IH alters neuropeptide synthesis by affecting PAM activity and, if so, by what mechanisms. Experiments were performed on the brain stem of adult male rats exposed to IH (5% O(2) for 15 s followed by 21% O(2) for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for 10 days). Analysis of brain stem extracts showed that IH, but not continuous hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM activity was associated with a concomitant elevation in the levels of alpha-amidated forms of substance P and neuropeptide Y. IH increased the relative abundance of 42- and 35-kDa forms of PHM ( approximately 1.6- and 2.7-fold, respectively), suggesting enhanced proteolytic processing of PHM, which appears to be mediated by an IH-induced increase of endoprotease activity. Kinetic analysis showed that IH increases V(max) but has no effect on K(m). IH increased generation of reactive oxygen species in the brain stem, and systemic administration of antioxidant prevented IH-evoked increases of PHM activity, proteolytic processing of PHM, endoprotease activity, and elevations in substance P and neuropeptide Y amide levels. Taken together, these results demonstrate that IH activates PHM in rat brain stem via reactive oxygen species-dependent posttranslational proteolytic processing and further suggest that PAM activation may contribute to IH-mediated peptidergic neurotransmission in rat brain stem.

Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

PubMed

Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

2014-01-06

Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

Routine castration in 568 draught colts: incidence of evisceration and omental herniation.

PubMed

Shoemaker, R; Bailey, J; Janzen, E; Wilson, D G

2004-05-01

Castration is one of the most common routine surgical procedures performed in the horse, from which a number of potential complications can arise. We undertook a prospective evaluation of short-term complications associated with castration of draught colts over a 3-year period (1998-2000). To compare castration complications in a large number of draught foals with previously published literature. Five hundred and sixty-eight draught colts, age 4 or 5 months, were castrated in field conditions. Foals were observed for complications for 24 h post operatively. There was no significant difference in complication rates between open and closed surgical techniques. Inguinal/scrotal hernia rate was 4.6% (26/568) prior to surgery, and evisceration of the small intestine occurred in 4.8% (27/568). Foals observed to eviscerate underwent immediate surgical correction with an overall survival rate of 72.2% (13/18). Omental herniation was seen in 2.8% (16/568) of colts. This study showed no difference between the closed and open techniques of castration and the rate of omental herniation or evisceration. The evisceration rate in combination with the omental and presurgical herniation rates approached 12.2%, which is high enough to warrant further examination. Future investigation should help to assess predisposing factors for evisceration. Regardless of the technique employed, herniation appears to pose a significant risk to draught foals undergoing castration.

Orphan nuclear receptor TLX activates Wnt/β-catenin signalling to stimulate neural stem cell proliferation and self-renewal

PubMed Central

Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T.; Gage, Fred H.; Evans, Ronald M.; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/β-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/β-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active β-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a β-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active β-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active β-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active β-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/β-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode. PMID:20010817

Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.

PubMed

Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T; Gage, Fred H; Evans, Ronald M; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active beta-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.

Speculum lumbar extraforaminal microdiscectomy.

PubMed

Obenchain, T G

2001-01-01

Public interest, monetary pressures and improving diagnostic techniques have placed an increasing emphasis on minimalism in lumbar disc excision. Current techniques include microlumbar discectomy and minimally invasive spinal surgery. Both are good techniques but may be painful, require a hospital stay and/or are not widely used because of difficulty acquiring the necessary skills. The author therefore developed a less invasive microscopic technique that may be performed on a consistent outpatient basis with easily acquired skills. The purpose of this study was to describe a variant of minimally invasive lumbar disc excision, while assessing the effects on a small group of patients. The treatment protocol was a prospective community hospital-based case study designed to evaluate a less invasive method of excising herniated lumbar discs residing in the canal, foraminal or far lateral space. This study is comprised of 50 patients with all anatomic forms of lumbar disc herniations, inside or outside the canal, at all levels except the lumbosacral joint. Clinical results were measured by return to work time, the criteria of MacNab and by Prolo et al.'s economic and functional criteria. Selection criteria included adult patients with intractable low back and leg pain, plus an imaging study revealing a lumbar disc herniation consistent with the patient's clinical presentation. Mean patient age was 48 years. The male:female ratio was approximately 2:1. All patients failed at least 3 weeks of conservative therapy. Herniations occurred from the L2-3 space through L4-5, with 30 herniations being within and 20 outside the spinal canal. Both contained and extruded/sequestered herniations were treated. Excluded from the study were patients with herniations inside the spinal canal at the L5-S1 level. Surgical approach was by microscopic speculum transforaminal route for discs residing both within and outside the lumbar canal. The initial 50 consecutive patients had successful technical operations performed on an outpatient basis by this less invasive technique. By the criteria of MacNab (Table 3), 84% (42 of 50) had an excellent or good result, returning to work at a mean time of 3.5 weeks. Per Prolo et al.'s economic scale, 72% were disabled at levels I and II before surgery. Postoperatively, 92% had improved to levels IV and V. Similarly, on his functional scale, 94% functioned at levels I and II before surgery, whereas 88% achieved levels IV and V after surgery. Eighty percent required no pain medications 1 week after surgery. The only complication was an L3 minor nerve root injury as it exited the L3-4 foramen. The author has described a minimally invasive technique for excising herniated discs that is applicable to all types of lumbar herniations, except for those residing in the canal at L5-S1. Clinical outcomes are comparable to those of other forms of discectomy.

Quantitative Assessment of Normal Fetal Brain Myelination Using Fast Macromolecular Proton Fraction Mapping.

PubMed

Yarnykh, V L; Prihod'ko, I Y; Savelov, A A; Korostyshevskaya, A M

2018-05-10

Fast macromolecular proton fraction mapping is a recently emerged MRI method for quantitative myelin imaging. Our aim was to develop a clinically targeted technique for macromolecular proton fraction mapping of the fetal brain and test its capability to characterize normal prenatal myelination. This prospective study included 41 pregnant women (gestational age range, 18-38 weeks) without abnormal findings on fetal brain MR imaging performed for clinical indications. A fast fetal brain macromolecular proton fraction mapping protocol was implemented on a clinical 1.5T MR imaging scanner without software modifications and was performed after a clinical examination with an additional scan time of <5 minutes. 3D macromolecular proton fraction maps were reconstructed from magnetization transfer-weighted, T1-weighted, and proton density-weighted images by the single-point method. Mean macromolecular proton fraction in the brain stem, cerebellum, and thalamus and frontal, temporal, and occipital WM was compared between structures and pregnancy trimesters using analysis of variance. Gestational age dependence of the macromolecular proton fraction was assessed using the Pearson correlation coefficient ( r ). The mean macromolecular proton fraction in the fetal brain structures varied between 2.3% and 4.3%, being 5-fold lower than macromolecular proton fraction in adult WM. The macromolecular proton fraction in the third trimester was higher compared with the second trimester in the brain stem, cerebellum, and thalamus. The highest macromolecular proton fraction was observed in the brain stem, followed by the thalamus, cerebellum, and cerebral WM. The macromolecular proton fraction in the brain stem, cerebellum, and thalamus strongly correlated with gestational age ( r = 0.88, 0.80, and 0.73; P < .001). No significant correlations were found for cerebral WM regions. Myelin is the main factor determining macromolecular proton fraction in brain tissues. Macromolecular proton fraction mapping is sensitive to the earliest stages of the fetal brain myelination and can be implemented in a clinical setting. © 2018 by American Journal of Neuroradiology.

Release of endogenous amino acids from the hippocampus and brain stem from developing and adult mice in ischemia.

PubMed

Oja, Simo S; Saransaari, Pirjo

2009-09-01

The release of neurotransmitters and modulators has been studied mostly using labeled preloaded compounds. For several reasons, however, the estimated release may not reliably reflect the release of endogenous compounds. The basal and K(+)-evoked release of the neuroactive endogenous amino acids GABA, glycine, taurine, L-glutamate and L-aspartate was now studied in slices from the hippocampus and brain stem from 7-day-old and 3-month-old mice under control and ischemic conditions. The release of synaptically not active L-glutamine, L-alanine, L-threonine and L-serine was assessed for comparison. The estimates for the hippocampus and brainstem were markedly different and also different in developing and adult mice. GABA release was much greater in 3-month-old than in 7-day-old mice, whereas with taurine the situation was the opposite, in the hippocampus in particular. K(+) stimulation enhanced glycine release more in the mature than immature brain stem while in the hippocampus the converse was observed. Ischemia enhanced the release of all neuroactive amino acids in both brain regions, the effects being relatively most pronounced in the case of GABA, aspartate and glutamate in the hippocampus in 3-month-old mice, and taurine in 7-day-old and glycine in 3-month-old mice in the brain stem. These results are qualitatively similar to those obtained on earlier experiments with labeled preloaded amino acids. However, the magnitudes of the release cannot be quite correctly estimated using radioactive labels. In developing mice only taurine release may counteract the harmful effects of excitatory amino acids in ischemia in both hippocampus and brain stem.

Stem Cell Technology for (Epi)genetic Brain Disorders.

PubMed

Riemens, Renzo J M; Soares, Edilene S; Esteller, Manel; Delgado-Morales, Raul

2017-01-01

Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).

Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.

PubMed

Gleitz, Hélène Fe; Liao, Ai Yin; Cook, James R; Rowlston, Samuel F; Forte, Gabriella Ma; D'Souza, Zelpha; O'Leary, Claire; Holley, Rebecca J; Bigger, Brian W

2018-06-08

The pediatric lysosomal storage disorder mucopolysaccharidosis type II is caused by mutations in IDS, resulting in accumulation of heparan and dermatan sulfate, causing severe neurodegeneration, skeletal disease, and cardiorespiratory disease. Most patients manifest with cognitive symptoms, which cannot be treated with enzyme replacement therapy, as native IDS does not cross the blood-brain barrier. We tested a brain-targeted hematopoietic stem cell gene therapy approach using lentiviral IDS fused to ApoEII (IDS.ApoEII) compared to a lentivirus expressing normal IDS or a normal bone marrow transplant. In mucopolysaccharidosis II mice, all treatments corrected peripheral disease, but only IDS.ApoEII mediated complete normalization of brain pathology and behavior, providing significantly enhanced correction compared to IDS. A normal bone marrow transplant achieved no brain correction. Whilst corrected macrophages traffic to the brain, secreting IDS/IDS.ApoEII enzyme for cross-correction, IDS.ApoEII was additionally more active in plasma and was taken up and transcytosed across brain endothelia significantly better than IDS via both heparan sulfate/ApoE-dependent receptors and mannose-6-phosphate receptors. Brain-targeted hematopoietic stem cell gene therapy provides a promising therapy for MPS II patients. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Rhythm generation, coordination, and initiation in the vocal pathways of male African clawed frogs

PubMed Central

Cavin Barnes, Jessica; Appleby, Todd

2016-01-01

Central pattern generators (CPGs) in the brain stem are considered to underlie vocalizations in many vertebrate species, but the detailed mechanisms underlying how motor rhythms are generated, coordinated, and initiated remain unclear. We addressed these issues using isolated brain preparations of Xenopus laevis from which fictive vocalizations can be elicited. Advertisement calls of male X. laevis that consist of fast and slow trills are generated by vocal CPGs contained in the brain stem. Brain stem central vocal pathways consist of a premotor nucleus [dorsal tegmental area of medulla (DTAM)] and a laryngeal motor nucleus [a homologue of nucleus ambiguus (n.IX-X)] with extensive reciprocal connections between the nuclei. In addition, DTAM receives descending inputs from the extended amygdala. We found that unilateral transection of the projections between DTAM and n.IX-X eliminated premotor fictive fast trill patterns but did not affect fictive slow trills, suggesting that the fast and slow trill CPGs are distinct; the slow trill CPG is contained in n.IX-X, and the fast trill CPG spans DTAM and n.IX-X. Midline transections that eliminated the anterior, posterior, or both commissures caused no change in the temporal structure of fictive calls, but bilateral synchrony was lost, indicating that the vocal CPGs are contained in the lateral halves of the brain stem and that the commissures synchronize the two oscillators. Furthermore, the elimination of the inputs from extended amygdala to DTAM, in addition to the anterior commissure, resulted in autonomous initiation of fictive fast but not slow trills by each hemibrain stem, indicating that the extended amygdala provides a bilateral signal to initiate fast trills. NEW & NOTEWORTHY Central pattern generators (CPGs) are considered to underlie vocalizations in many vertebrate species, but the detailed mechanisms underlying their functions remain unclear. We addressed this question using an isolated brain preparation of African clawed frogs. We discovered that two vocal phases are mediated by anatomically distinct CPGs, that there are a pair of CPGs contained in the left and right half of the brain stem, and that mechanisms underlying initiation of the two vocal phases are distinct. PMID:27760822

Tumefactive multiple sclerosis requiring emergency craniotomy: case report and literature review.

PubMed

Munarriz, Pablo M; Castaño-Leon, Ana M; Martinez-Perez, Rafael; Hernandez-Lain, Aurelio; Ramos, Ana; Lagares, Alfonso

2013-01-01

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, characterized by focal neurological dysfunction with a relapsing and remitting course. Tumor-like presentation of MS (or "tumefactive"/"pseudotumoral" presentation) has been described before with a certain frequency; it consists of a large single plaque (>2cm) with presence of edema and mass effect and it is hard to distinguish from a brain tumor. However, we present a very rare case of a 53-year-old woman with a right temporal mass that turned out to be a MS plaque, who deteriorated within hours (brain herniation with loss of consciousness and unilateral mydriasis) and required an emergency craniotomy. We also present a review of the literature. It appears that only 4 cases of emergency craniotomy/craniectomy required in a patient with a tumor-like MS plaque have been reported before. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Brain region-selective mechanisms contribute to the progression of cerebral alterations in acute liver failure in rats.

PubMed

Cauli, Omar; López-Larrubia, Pilar; Rodrigo, Regina; Agusti, Ana; Boix, Jordi; Nieto-Charques, Laura; Cerdán, Sebastián; Felipo, Vicente

2011-02-01

Patients with acute liver failure (ALF) often die of intracranial pressure (IP) and cerebral herniation. Main contributors to increased IP are ammonia, glutamine, edema, and blood flow. The sequence of events and underlying mechanisms, as well as the temporal pattern, regional distribution, and contribution of each parameter to the progression of neurologic deterioration and IP, are unclear. We studied rats with ALF to follow the progression of changes in ammonia, glutamine, grade and type (vasogenic or cytotoxic) of edema, blood-brain barrier permeability, cerebral blood flow, and IP. We assessed whether the changes in these parameters were similar between frontal cortex and cerebellum and evaluated the presence, type, and progression of edema in 12 brain areas. ALF was induced by injection of galactosamine. The grade and type of edema was assessed by measuring the apparent diffusion coefficient by magnetic resonance imaging. Cerebral blood flow was measured by magnetic resonance and blood-brain barrier permeability by Evans blue-albumin extravasation. Increased IP arises from an early increase of blood-brain barrier permeability in certain areas (including cerebellum but not frontal cortex) followed by vasogenic edema. Ammonia and glutamine then increase progressively, leading to cytotoxic edema in many areas. Alterations in lactate and cerebral blood flow are later events that further increase IP. Different mechanisms in specific regions of the brain contribute, with different temporal patterns, to the progression of cerebral alterations and IP in ALF. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Brain stem death and organ donation.

PubMed

Davies, C

1996-01-01

Our understanding of the concept and definition of death has changed over time. The British contribution to the body of knowledge on the diagnosis of brain steam death was the publication by the medical royal colleges (1976) of diagnostic criteria. Most literature and research which explores the knowledge and attitudes of nurses towards the concept of brain stem death is from the USA. Several issues which arise from the literature are discussed in relation to organ donation. Further UK-based research is required.

Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: a long-term safety and feasibility study.

PubMed

Elabd, Christian; Centeno, Christopher J; Schultz, John R; Lutz, Gregory; Ichim, Thomas; Silva, Francisco J

2016-09-01

Chronic low back pain due to disc degeneration represents a major social and economic burden worldwide. The current standard of care is limited to symptomatic relief and no current approved therapy promotes disc regeneration. Bone marrow-derived mesenchymal stem cells (MSCs) are easily accessible and well characterized. These MSCs are multipotent and exhibit great tissue regenerative potential including bone, cartilage, and fibrous tissue regeneration. The use of this cell-based biologic for treating protruding disc herniation and/or intervertebral disc degeneration is a promising therapeutic strategy, due to their known regenerative, immuno-modulatory and anti-inflammatory properties. Five patients diagnosed with degenerative disc disease received an intra-discal injection of autologous, hypoxic cultured, bone marrow-derived mesenchymal stem cells (15.1-51.6 million cells) as part of a previous study. These patients were re-consented to participate in this study in order to assess long-term safety and feasibility of intra-discal injection of autologous, hypoxic cultured, bone marrow-derived mesenchymal stem cells 4-6 years post mesenchymal stem cell infusion. The follow-up study consisted of a physical examination, a low back MRI, and a quality of life questionnaire. Patients' lower back MRI showed absence of neoplasms or abnormalities surrounding the treated region. Based on the physical examination and the quality of life questionnaire, no adverse events were reported due to the procedure or to the stem cell treatment 4-6 years post autologous, hypoxic cultured mesenchymal stem cell infusion. All patients self-reported overall improvement, as well as improvement in strength, post stem cell treatment, and four out of five patients reported improvement in mobility. This early human clinical data suggests the safety and feasibility of the clinical use of hypoxic cultured bone marrow-derived mesenchymal stem cells for the treatment of lower back pain due to degenerative disc disorders and support further studies utilizing hypoxic cultured bone marrow-derived stem cells. The overall improvements reported are encouraging, but a larger double-blind, controlled, randomized clinical study with significant number of patients and implementation of validated endpoint measurements are next steps in order to demonstrate efficacy of this cell-based biologic.

Anterior transcorporeal approach of percutaneous endoscopic cervical discectomy for disc herniation at the C4-C5 levels: a technical note.

PubMed

Deng, Zhong-Liang; Chu, Lei; Chen, Liang; Yang, Jun-Song

2016-05-01

With the continuous development of the spinal endoscopic technique in recent years, percutaneous endoscopic cervical discectomy (PECD) has emerged, which bridges the gap between conservative therapy and traditional surgery and has been mainly divided into the anterior transdiscal approach and the posterior interlaminar access. Because of the relatively greater violation to the anterior nucleus pulposus, there is a higher potential of postoperative intervertebral space decrease in the anterior transdiscal approach than in the posterior interlaminar access. In addition, when the herniated lesion is migrated upward or downward behind the vertebral body, both approaches, and even anterior cervical discectomy and fusion, are impractical, and corpectomy is commonly considered as the only efficacious treatment. Anterior transcorporeal approach under endoscopy could enable an individual and adjustable trajectory within the vertebral body under different conditions of disc herniation preserving the motion of adjacent segment, especially in a migrated or sequestered lesion. This report aimed to first describe a novel anterior transcorporeal approach under endoscopy in which we addressed a migrated disc herniation at the C4-C5 levels. A technical report was carried out. A 37-year-old woman presented with posterior neck pain and weakness of extremities for 9 months. On neurologic examination, tingling sensation and numbness were not obvious. However, the power of extremities was dramatically decreased at a level of 3. Hoffmann sign was positive in the bilateral hand. Magnetic resonance imaging (MRI) showed a huge herniation of the C4-C5 disc compressing the median area of the spinal cord. Besides the C4-C5 disc herniation, preoperative computer tomography (CT) also detected that the herniated disc had partial calcification. A novel anterior transcorporeal approach of PECD, through the vertebral body of C5, was performed to address a migrated disc herniation at the C4-C5 levels. The posterior neck pain was measured using the visual analog scale (VAS). A novel anterior transcorporeal approach under endoscopy was performed to address a migrated disc herniation at the C4-C5 levels. This operation was accomplished in 75 minutes. Postoperatively, the drainage tube was retained into the drilling hole for 24 hours to avoid the possibility of hematoma. The patient was advised to wear a neck collar for 3 weeks. Immediately after the operation, the posterior neck pain improved from VAS 7/10 preoperatively to 3/10, and the myodynamia of extremities improved stepwise. At 12 hours postoperatively, the range of motion was also improved. In the further follow-up, the patient has completely recovered from the preoperative symptoms, whose myodynamia of extremities is normal. Besides the postoperative MRI, a total removal of the herniated disc and the transcorporeal drilling tunnel are observed in CT. At postoperative 3-month follow-up, neither disc space narrowing nor instability was observed on CT, in which the bone defect after drilling tunnelwas partially decreased, indicating bone healing. There were no surgery-related complications, such as dysphagia, Horner syndrome, recurrent laryngeal nerve palsy, vagus nerve injury, tracheoesophageal injury, or cervical hematocele. As a supplement to the described surgical approach of PECD, the transcorporeal approach is a novel access for the treatment of cervical intervertebral disc herniation. Among the advantages of this approach are providing a clear visual field during microendoscopic surgery and decreasing the intraoperative iatrogenic injury to, as well as avoiding violation to the discal tissue. Theoretically, the potential of secondary decline of intervertebral height is low. However, as the limitation of one case shows, whether this transcorporeal approach is efficacious and reliable should be verified in a further comparative cohort study with a large volume of patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery from stroke: updates and advances.

PubMed

Boninger, Michael L; Wechsler, Lawrence R; Stein, Joel

2014-11-01

The aim of this study was to describe the current state and latest advances in robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery for stroke. The authors of this summary recently reviewed this work as part of a national presentation. The article represents the information included in each area. Each area has seen great advances and challenges as products move to market and experiments are ongoing. Robotics, stem cells, and brain-computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial.

The direct connections of the C2 dorsal ganglion in the brain stem of the squirrel monkey: a preliminary investigation *

PubMed Central

Fitz-Ritson, Don E.

1979-01-01

The purpose of this investigation was to observe the possible anatomical connections of C2 dorsal root with brain stem nuclei. Labelled amino acids (leucine, glycine, proline), were injected into the dorsal root of C2 of a squirrel monkey. The animal was allowed to survive for 20 hrs. and after, sections of the spinal cord and brain stem were subjected to autoradiographic methods. Direct connections were observed in Lamina II, VII, VIII of the spinal cord; the hypoglossal nucleus, medial vestibular nucleus, lateral cuneatus nucleus and lateral parvocellular reticular formation. Possible anatomical and physiological correlates are explored in relation to the importance of the upper cervical area and its control mechanisms.

Robotics, Stem Cells and Brain Computer Interfaces in Rehabilitation and Recovery from Stroke; Updates and Advances

PubMed Central

Boninger, Michael L; Wechsler, Lawrence R.; Stein, Joel

2014-01-01

Objective To describe the current state and latest advances in robotics, stem cells, and brain computer interfaces in rehabilitation and recovery for stroke. Design The authors of this summary recently reviewed this work as part of a national presentation. The paper represents the information included in each area. Results Each area has seen great advances and challenges as products move to market and experiments are ongoing. Conclusion Robotics, stem cells, and brain computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial PMID:25313662

Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

PubMed

Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

2017-03-01

Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Aluminum overload increases oxidative stress in four functional brain areas of neonatal rats

PubMed Central

2012-01-01

Background Higher aluminum (Al) content in infant formula and its effects on neonatal brain development are a cause for concern. This study aimed to evaluate the distribution and concentration of Al in neonatal rat brain following Al treatment, and oxidative stress in brain tissues induced by Al overload. Methods Postnatal day 3 (PND 3) rat pups (n =46) received intraperitoneal injection of aluminum chloride (AlCl3), at dosages of 0, 7, and 35 mg/kg body wt (control, low Al (LA), and high Al (HA), respectively), over 14 d. Results Aluminum concentrations were significantly higher in the hippocampus (751.0 ± 225.8 ng/g v.s. 294.9 ± 180.8 ng/g; p < 0.05), diencephalon (79.6 ± 20.7 ng/g v.s. 20.4 ± 9.6 ng/g; p < 0.05), and cerebellum (144.8 ± 36.2 ng/g v.s. 83.1 ± 15.2 ng/g; p < 0.05) in the HA group compared to the control. The hippocampus, diencephalon, cerebellum, and brain stem of HA animals displayed significantly higher levels of lipid peroxidative products (TBARS) than the same regions in the controls. However, the average superoxide dismutase (SOD) activities in the cerebral cortex, hippocampus, cerebellum, and brain stem were lower in the HA group compared to the control. The HA animals demonstrated increased catalase activity in the diencephalon, and increased glutathione peroxidase (GPx) activity in the cerebral cortex, hippocampus, cerebellum, and brain stem, compared to controls. Conclusion Aluminum overload increases oxidative stress (H2O2) in the hippocampus, diencephalon, cerebellum, and brain stem in neonatal rats. PMID:22613782

Regional volumes in brain stem and cerebellum are associated with postural impairments in young brain-injured patients.

PubMed

Drijkoningen, David; Leunissen, Inge; Caeyenberghs, Karen; Hoogkamer, Wouter; Sunaert, Stefan; Duysens, Jacques; Swinnen, Stephan P

2015-12-01

Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum-optimized voxel-based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I-IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI. © 2015 Wiley Periodicals, Inc.

Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering.

PubMed

Cheng, Tzu-Yun; Chen, Ming-Hong; Chang, Wen-Han; Huang, Ming-Yuan; Wang, Tzu-Wei

2013-03-01

Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer β-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA(16)-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

T1 hyperintense disc in alkaptonuria.

PubMed

Sag, Alan A; Silbergleit, Richard; Olson, Rick E; Wilson, Jon; Krishnan, Anant

2012-10-01

Case report. To report a rare case of alkaptonuria presenting as a T1-hyperintense disc herniation. A 46-year-old man without previous diagnosis of alkaptonuria underwent evaluation for progressive back pain revealing a T1-hyperintense disc herniation at the L3-L4 level. Discectomy recovered a blackened disc that was pathologically confirmed to be nucleus pulposus with alkaptonuric involvement. The differential diagnosis of a T1-hyperintense, T2-hypointense disc on magnetic resonance imaging is discussed, with emphasis on the pathophysiology of alkaptonuria. A single patient is reported. Pathologically proven patient presentation with radiological and pathological images. We report a rare case of alkaptonuria presenting as a T1-hyperintense disc herniation.

Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone.

PubMed

Domenichini, Florence; Terrié, Elodie; Arnault, Patricia; Harnois, Thomas; Magaud, Christophe; Bois, Patrick; Constantin, Bruno; Coronas, Valérie

2018-05-01

The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Stem Cells 2018;36:761-774. © AlphaMed Press 2018.

Regulation of endogenous neural stem/progenitor cells for neural repair—factors that promote neurogenesis and gliogenesis in the normal and damaged brain

PubMed Central

Christie, Kimberly J.; Turnley, Ann M.

2012-01-01

Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb (OB) and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream (RMS) to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioral outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem/precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation. PMID:23346046

Neural Stem Cells Derived Directly from Adipose Tissue.

PubMed

Petersen, Eric D; Zenchak, Jessica R; Lossia, Olivia V; Hochgeschwender, Ute

2018-05-01

Neural stem cells (NSCs) are characterized as self-renewing cell populations with the ability to differentiate into the multiple tissue types of the central nervous system. These cells can differentiate into mature neurons, astrocytes, and oligodendrocytes. This category of stem cells has been shown to be a promisingly effective treatment for neurodegenerative diseases and neuronal injury. Most treatment studies with NSCs in animal models use embryonic brain-derived NSCs. This approach presents both ethical and feasibility issues for translation to human patients. Adult tissue is a more practical source of stem cells for transplantation therapies in humans. Some adult tissues such as adipose tissue and bone marrow contain a wide variety of stem cell populations, some of which have been shown to be similar to embryonic stem cells, possessing many pluripotent properties. Of these stem cell populations, some are able to respond to neuronal growth factors and can be expanded in vitro, forming neurospheres analogous to cells harvested from embryonic brain tissue. In this study, we describe a method for the collection and culture of cells from adipose tissue that directly, without going through intermediates such as mesenchymal stem cells, results in a population of NSCs that are able to be expanded in vitro and be differentiated into functional neuronal cells. These adipose-derived NSCs display a similar phenotype to those directly derived from embryonic brain. When differentiated into neurons, cells derived from adipose tissue have spontaneous spiking activity with network characteristics similar to that of neuronal cultures.

TGFβ lengthens the G1 phase of stem cells in aged mouse brain.

PubMed

Daynac, Mathieu; Pineda, Jose R; Chicheportiche, Alexandra; Gauthier, Laurent R; Morizur, Lise; Boussin, François D; Mouthon, Marc-André

2014-12-01

Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells. © 2014 AlphaMed Press.

A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination.

PubMed

Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong

2009-04-01

MicroRNAs have been implicated as having important roles in stem cell biology. MicroRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain and may be involved in neural stem cell self-renewal and differentiation. We showed previously that the nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector that is not prone to miR-9 regulation rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses expression of the miR-9 pri-miRNA. By forming a negative regulatory loop with TLX, miR-9 provides a model for controlling the balance between neural stem cell proliferation and differentiation.

A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination

PubMed Central

Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong

2009-01-01

Summary MicroRNAs are important players in stem cell biology. Among them, microRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain. Whether miR-9 plays a role in neural stem cell self-renewal and differentiation is unknown. We showed previously that nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector lacking the miR-9 recognition site rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses miR-9 pri-miRNA expression. MiR-9, by forming a negative regulatory loop with TLX, establishes a model for controlling the balance between neural stem cell proliferation and differentiation. PMID:19330006

Gelatinized Copper–Capillary Alginate Gel Functions as an Injectable Tissue Scaffolding System for Stem Cell Transplants

PubMed Central

Willenberg, Bradley Jay; Zheng, Tong; Meng, Fan-Wei; Meneses, Juan Carlos; Rossignol, Candace; Batich, Christopher D.; Terada, Naohiro; Steindler, Dennis A.; Weiss, Michael D.

2013-01-01

In severe hypoxic–ischemic brain injury, cellular components such as neurons and astrocytes are injured or destroyed along with the supporting extracellular matrix. This presents a challenge to the field of regenerative medicine since the lack of extracellular matrix and supporting structures makes the transplant milieu inhospitable to the transplanted cells. A potential solution to this problem is the use of a biomaterial to provide the extracellular components needed to keep cells localized in cystic brain regions, allowing the cells to form connections and repair lost brain tissue. Ideally, this biomaterial would be combined with stem cells, which have been proven to have therapeutic potentials, and could be delivered via an injection. To study this approach, we derived a hydrogel biomaterial tissue scaffold from oligomeric gelatin and copper–capillary alginate gel (GCCAG). We then demonstrated that our multipotent astrocytic stem cells (MASCs) could be maintained in GCCAG scaffolds for up to 2 weeks in vitro and that the cells retained their multipotency. We next performed a pilot transplant study in which GCCAG was mixed with MASCs and injected into the brain of a neonatal rat pup. After a week in vivo, our results showed that: the GCCAG biomaterial did not cause a significant reactive gliosis; viable cells were retained within the injected scaffolds; and some delivered cells migrated into the surrounding brain tissue. Therefore, GCCAG tissue scaffolds are a promising, novel injectable system for transplantation of stem cells to the brain. PMID:20699061

Distraction manipulation reduction of an L5-S1 disk herniation.

PubMed

Cox, J M; Hazen, L J; Mungovan, M

1993-06-01

A computed tomography (CT)-confirmed L5-S1 disk protrusion is reported to be reduced following chiropractic adjustment, as seen on repeat CT scanning. Correlation of the CT reports with the patient's symptoms before and after manipulation is reported. A 38-yr-old female was treated for low back pain and right lower extremity first sacral dermatome sciatica. CT confirmed disk herniations at both the L4-L5 and L5-S1 levels were found. Motor weakness of the right gluteus maximus muscle was found and extremely tight hamstring muscles accompanying positive straight leg signs were elicited. A clinical and imaging diagnosis of an L5-S1 disk herniation was made. Distraction type chiropractic manipulation, electrical stimulation, exercises, nutrition advice and low back wellness class were administered with complete relief of sciatic pain and nearly complete relief of low back pain. Chiropractic distraction manipulation is an effective treatment of lumbar disk herniation, if the chiropractor is observant during its administration for patient tolerance to manipulation under distraction and any signs of neurological deficit demanding other types of care.

Relationship between fear avoidance beliefs and burnout syndrome in patients with lumbar disc herniation.

PubMed

Taspinar, Ferruh; Taspinar, Betul; Ozkan, Yasemin; Afsar, Emrah; Gul, Canan; Durmaz, Elif Dilara

2016-06-17

Lumbar disc herniation leads to disability by restricting of patients' lives and reducing their quality of life. This situation causes a decrease in motivation of patients by triggering depressive mood. Therefore, the aim of the study was investigation of correlation between fear avoidance beliefs and burnout syndrome in patients with lumbar disc herniation. Totally forty-seven patients (24 male and 23 female patients) diagnosed lumbar disc herniation was included in this study. Maslach II Burnout Inventory (MBI) and Fear Avoidance Beliefs Questionnaire (FABQ) for determining of levels of burnout and fear avoidance level were used, respectively. It was observed that MBI and FABQ scores of the patients were 50.78 ± 10.07 and 36.61 ± 13.91, respectively. Moderate level correlation was found between FABQ and MBI total scores (r= 0.49, p= 0.00). Fear avoidance beliefs of patients with chronic back pain can affect level of burnout syndrome. Therefore, symptoms of burnout syndrome and fear avoidance beliefs of patients should be considered in evaluation and treatment process.

Intraregional differences of perioperative management strategy for lumbar disc herniation: is the Devil really in the details?

PubMed

Zoia, Cesare; Bongetta, Daniele; Poli, Jacopo C; Verlotta, Mariarosaria; Pugliese, Raffaelino; Gaetani, Paolo

2017-01-01

This study intends to evaluate whether regional common habits or differences in case-volume between surgeons are significative variables in the perioperative management of patients undergoing surgery for lumbar disc herniation. An e-mail survey was sent to all neurosurgeons working in Lombardy, Italy's most populated region. The survey consisted of 17 questions about the perioperative management of lumbar disc herniation. Forty-seven percent (47%) out of 206 Lombard neurosurgeons answered the survey. Although in some respects there is clear evidence in current literature on which is the best practice to adopt for an optimal management strategy, we noticed substantial differences between respondents, not only between hospitals but also between surgeons from the same hospital. Still, no differences were evident in a high vs low case-volume comparison. We identified no regional clusterization as for practical principles in the perioperative management of lumbar disc herniation and neither was case-volume a significative variable. Other causes may be relevant in the variability between the perioperative management and the outcomes achieved by different specialists.

Reactive astrocytes as neural stem or progenitor cells: In vivo lineage, In vitro potential, and Genome‐wide expression analysis

PubMed Central

Sirko, Swetlana; Beckers, Johannes; Irmler, Martin

2015-01-01

Here, we review the stem cell hallmarks of endogenous neural stem cells (NSCs) during development and in some niches of the adult mammalian brain to then compare these with reactive astrocytes acquiring stem cell hallmarks after traumatic and ischemic brain injury. Notably, even endogenous NSCs including the earliest NSCs, the neuroepithelial cells, generate in most cases only a single type of progeny and self‐renew only for a rather short time in vivo. In vitro, however, especially cells cultured under neurosphere conditions reveal a larger potential and long‐term self‐renewal under the influence of growth factors. This is rather well comparable to reactive astrocytes in the traumatic or ischemic brain some of which acquire neurosphere‐forming capacity including multipotency and long‐term self‐renewal in vitro, while they remain within their astrocyte lineage in vivo. Both reactive astrocytes and endogenous NSCs exhibit stem cell hallmarks largely in vitro, but their lineage differs in vivo. Both populations generate largely a single cell type in vivo, but endogenous NSCs generate neurons and reactive astrocytes remain in the astrocyte lineage. However, at some early postnatal stages or in some brain regions reactive astrocytes can be released from this fate restriction, demonstrating that they can also enact neurogenesis. Thus, reactive astrocytes and NSCs share many characteristic hallmarks, but also exhibit key differences. This conclusion is further substantiated by genome‐wide expression analysis comparing NSCs at different stages with astrocytes from the intact and injured brain parenchyma. GLIA 2015;63:1452–1468 PMID:25965557

Brain stem representation of thermal and psychogenic sweating in humans.

PubMed

Farrell, Michael J; Trevaks, David; Taylor, Nigel A S; McAllen, Robin M

2013-05-15

Functional MRI was used to identify regions in the human brain stem activated during thermal and psychogenic sweating. Two groups of healthy participants aged 34.4 ± 10.2 and 35.3 ± 11.8 years (both groups comprising 1 woman and 10 men) were either heated by a water-perfused tube suit or subjected to a Stroop test, while they lay supine with their head in a 3-T MRI scanner. Sweating events were recorded as electrodermal responses (increases in AC conductance) from the palmar surfaces of fingers. Each experimental session consisted of two 7.9-min runs, during which a mean of 7.3 ± 2.1 and 10.2 ± 2.5 irregular sweating events occurred during psychogenic (Stroop test) and thermal sweating, respectively. The electrodermal waveform was used as the regressor in each subject and run to identify brain stem clusters with significantly correlated blood oxygen level-dependent signals in the group mean data. Clusters of significant activation were found with both psychogenic and thermal sweating, but a voxelwise comparison revealed no brain stem cluster whose signal differed significantly between the two conditions. Bilaterally symmetric regions that were activated by both psychogenic and thermal sweating were identified in the rostral lateral midbrain and in the rostral lateral medulla. The latter site, between the facial nuclei and pyramidal tracts, corresponds to a neuron group found to drive sweating in animals. These studies have identified the brain stem regions that are activated with sweating in humans and indicate that common descending pathways may mediate both thermal and psychogenic sweating.

Regional variations and age-related changes in arginine metabolism in the rat brain stem and spinal cord.

PubMed

Jing, Y; Fleete, M S; Collie, N D; Zhang, H; Liu, P

2013-11-12

Accumulating evidence suggests that the metabolism of l-arginine, a metabolically versatile amino acid, is critically involved in the aging process. The present study compared the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of l-arginine and its eight down-stream metabolites in the brain stem (pons and medulla) and the cervical spinal cord in 3- (young) and 22- (aged) month-old male Sprague-Dawley rats. Total NOS activity was significantly reduced with age in the spinal cord (but not brain stem), and there were no age-related changes in arginase activity in both regions. Western blot revealed decreased protein expression of endothelial NOS, but not neuronal NOS, with age in both regions. Furthermore, there were significantly decreased l-arginine, glutamate, GABA and spermine levels and increased putrescine and spermidine levels with age in both regions. Although the absolute concentrations of l-arginine and six metabolites were significantly different between the brain stem and spinal cord in both age groups, there were similar clusters between l-arginine and its three main metabolites (l-citrulline, l-ornithine and agmatine) in both regions, which changed as a function of age. These findings, for the first time, demonstrate the regional variations and age-related changes in arginine metabolism in the rat brain stem and spinal cord. Future research is required to understand the functional significance of these changes and the underlying mechanisms. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Brain stem activity changes associated with restored sympathetic drive following CPAP treatment in OSA subjects: a longitudinal investigation

PubMed Central

Lundblad, Linda C.; Fatouleh, Rania H.; McKenzie, David K.; Macefield, Vaughan G.

2015-01-01

Obstructive sleep apnea (OSA) is associated with significantly elevated muscle sympathetic nerve activity (MSNA), leading to hypertension and increased cardiovascular morbidity. Although little is known about the mechanisms responsible for the sympathoexcitation, we have recently shown that the elevated MSNA in OSA is associated with altered neural processing in various brain stem sites, including the dorsolateral pons, rostral ventrolateral medulla, medullary raphe, and midbrain. Given the risk associated with elevated MSNA, we aimed to determine if treatment of OSA with continuous positive airway pressure (CPAP) would reduce the elevated MSNA and reverse the brain stem functional changes associated with the elevated MSNA. We performed concurrent recordings of MSNA and blood oxygen level-dependent (BOLD) signal intensity of the brain stem, using high-resolution functional magnetic resonance imaging, in 15 controls and 13 subjects with OSA, before and after 6 mo CPAP treatment. As expected, 6 mo of CPAP treatment significantly reduced MSNA in subjects with OSA, from 54 ± 4 to 23 ± 3 bursts/min and from 77 ± 7 to 36 ± 3 bursts/100 heart beats. Importantly, we found that MSNA-coupled changes in BOLD signal intensity within the dorsolateral pons, medullary raphe, and rostral ventrolateral medulla returned to control levels. That is, CPAP treatment completely reversed brain stem functional changes associated with elevated MSNA in untreated OSA subjects. These data highlight the effectiveness of CPAP treatment in reducing one of the most significant health issues associated with OSA, that is, elevated MSNA and its associated elevated morbidity. PMID:25995345

Brain stem activity changes associated with restored sympathetic drive following CPAP treatment in OSA subjects: a longitudinal investigation.

PubMed

Lundblad, Linda C; Fatouleh, Rania H; McKenzie, David K; Macefield, Vaughan G; Henderson, Luke A

2015-08-01

Obstructive sleep apnea (OSA) is associated with significantly elevated muscle sympathetic nerve activity (MSNA), leading to hypertension and increased cardiovascular morbidity. Although little is known about the mechanisms responsible for the sympathoexcitation, we have recently shown that the elevated MSNA in OSA is associated with altered neural processing in various brain stem sites, including the dorsolateral pons, rostral ventrolateral medulla, medullary raphe, and midbrain. Given the risk associated with elevated MSNA, we aimed to determine if treatment of OSA with continuous positive airway pressure (CPAP) would reduce the elevated MSNA and reverse the brain stem functional changes associated with the elevated MSNA. We performed concurrent recordings of MSNA and blood oxygen level-dependent (BOLD) signal intensity of the brain stem, using high-resolution functional magnetic resonance imaging, in 15 controls and 13 subjects with OSA, before and after 6 mo CPAP treatment. As expected, 6 mo of CPAP treatment significantly reduced MSNA in subjects with OSA, from 54 ± 4 to 23 ± 3 bursts/min and from 77 ± 7 to 36 ± 3 bursts/100 heart beats. Importantly, we found that MSNA-coupled changes in BOLD signal intensity within the dorsolateral pons, medullary raphe, and rostral ventrolateral medulla returned to control levels. That is, CPAP treatment completely reversed brain stem functional changes associated with elevated MSNA in untreated OSA subjects. These data highlight the effectiveness of CPAP treatment in reducing one of the most significant health issues associated with OSA, that is, elevated MSNA and its associated elevated morbidity. Copyright © 2015 the American Physiological Society.

Modules in the brain stem and spinal cord underlying motor behaviors

PubMed Central

Cheung, Vincent C. K.; Bizzi, Emilio

2011-01-01

Previous studies using intact and spinalized animals have suggested that coordinated movements can be generated by appropriate combinations of muscle synergies controlled by the central nervous system (CNS). However, which CNS regions are responsible for expressing muscle synergies remains an open question. We address whether the brain stem and spinal cord are involved in expressing muscle synergies used for executing a range of natural movements. We analyzed the electromyographic (EMG) data recorded from frog leg muscles before and after transection at different levels of the neuraxis—rostral midbrain (brain stem preparations), rostral medulla (medullary preparations), and the spinal-medullary junction (spinal preparations). Brain stem frogs could jump, swim, kick, and step, while medullary frogs could perform only a partial repertoire of movements. In spinal frogs, cutaneous reflexes could be elicited. Systematic EMG analysis found two different synergy types: 1) synergies shared between pre- and posttransection states and 2) synergies specific to individual states. Almost all synergies found in natural movements persisted after transection at rostral midbrain or medulla but not at the spinal-medullary junction for swim and step. Some pretransection- and posttransection-specific synergies for a certain behavior appeared as shared synergies for other motor behaviors of the same animal. These results suggest that the medulla and spinal cord are sufficient for the expression of most muscle synergies in frog behaviors. Overall, this study provides further evidence supporting the idea that motor behaviors may be constructed by muscle synergies organized within the brain stem and spinal cord and activated by descending commands from supraspinal areas. PMID:21653716

Brain Stem Infarction Due to Basilar Artery Dissection in a Patient with Moyamoya Disease Four Years after Successful Bilateral Revascularization Surgeries.

PubMed

Abe, Takatsugu; Fujimura, Miki; Mugikura, Shunji; Endo, Hidenori; Tominaga, Teiji

2016-06-01

Moyamoya disease (MMD) is a rare cerebrovascular disease with an unknown etiology and is characterized by intrinsic fragility in the intracranial vascular walls such as the affected internal elastic lamina and thinning medial layer. The association of MMD with intracranial arterial dissection is extremely rare, whereas that with basilar artery dissection (BAD) has not been reported previously. A 46-year-old woman developed brain stem infarction due to BAD 4 years after successful bilateral superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis for ischemic-onset MMD. She presented with sudden occipitalgia and subsequently developed transient dysarthria and mild hemiparesis. Although a transient ischemic attack was initially suspected, her condition deteriorated in a manner that was consistent with left hemiplegia with severe dysarthria. Magnetic resonance (MR) imaging revealed brain stem infarction, and MR angiography delineated a double-lumen sign in the basilar artery, indicating BAD. She was treated conservatively and brain stem infarction did not expand. One year after the onset of brain stem infarction, her activity of daily living is still dependent (modified Rankin Scale of 4), and there were no morphological changes associated with BAD or recurrent cerebrovascular events during the follow-up period. The association of MMD with BAD is extremely rare. While considering the common underlying pathology such as an affected internal elastic lamina and fragile medial layer, the occurrence of BAD in a patient with MMD in a stable hemodynamic state is apparently unique. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Analysis of wave III of brain stem auditory evoked potential waveforms during microvascular decompression of cranial nerve VII for hemifacial spasm.

PubMed

Thirumala, Parthasarathy D; Krishnaiah, Balaji; Crammond, Donald J; Habeych, Miguel E; Balzer, Jeffrey R

2014-04-01

Intraoperative monitoring of brain stem auditory evoked potential during microvascular decompression (MVD) prevent hearing loss (HL). Previous studies have shown that changes in wave III (wIII) are an early and sensitive sign of auditory nerve injury. To evaluate the changes of amplitude and latency of wIII of brain stem auditory evoked potential during MVD and its association with postoperative HL. Hearing loss was classified by American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) criteria, based on changes in pure tone audiometry and speech discrimination score. Retrospective analysis of wIII in patients who underwent intraoperative monitoring with brain stem auditory evoked potential during MVD was performed. A univariate logistic regression analysis was performed on independent variables amplitude of wIII and latency of wIII at change max and On-Skin, or a final recording at the time of skin closure. A further analysis for the same variables was performed adjusting for the loss of wave. The latency of wIII was not found to be significantly different between groups I and II. The amplitude of wIII was significantly decreased in the group with HL. Regression analysis did not find any increased odds of HL with changes in the amplitude of wIII. Changes in wave III did not increase the odds of HL in patients who underwent brain stem auditory evoked potential s during MVD. This information might be valuable to evaluate the value of wIII as an alarm criterion during MVD to prevent HL.

Effect of Mobile Phone-Induced Electromagnetic Field on Brain Hemodynamics and Human Stem Cell Functioning: Possible Mechanistic Link to Cancer Risk and Early Diagnostic Value of Electronphotonic Imaging.

PubMed

Bhargav, Hemant; Srinivasan, T M; Varambally, S; Gangadhar, B N; Koka, Prasad

2015-01-01

The mobile phones (MP) are low power radio devices which work on electromagnetic fields (EMFs), in the frequency range of 900-1800 MHz. Exposure to MPEMFs may affect brain physiology and lead to various health hazards including brain tumors. Earlier studies with positron emission tomography (PET) have found alterations in cerebral blood flow (CBF) after acute exposure to MPEMFs. It is widely accepted that DNA double-strand breaks (DSBs) and their misrepair in stem cells are critical events in the multistage origination of various leukemia and tumors, including brain tumors such as gliomas. Both significant misbalance in DSB repair and severe stress response have been triggered by MPEMFs and EMFs from cell towers. It has been shown that stem cells are most sensitive to microwave exposure and react to more frequencies than do differentiated cells. This may be important for cancer risk assessment and indicates that stem cells are the most relevant cellular model for validating safe mobile communication signals. Recently developed technology for recording the human bio-electromagnetic (BEM) field using Electron photonic Imaging (EPI) or Gas Discharge Visualisation (GDV) technique provides useful information about the human BEM. Studies have recorded acute effects of Mobile Phone Electromagnetic Fields (MPEMFs) using EPI and found quantifiable effects on human BEM field. Present manuscript reviews evidences of altered brain physiology and stem cell functioning due to mobile phone/cell tower radiations, its association with increased cancer risk and explores early diagnostic value of EPI imaging in detecting EMF induced changes on human BEM.

Biomechanics of Concussion: The Importance of Neck Tension

NASA Astrophysics Data System (ADS)

Jadischke, Ronald

Linear and angular velocity and acceleration of the head are typically correlated to concussion. Despite improvements in helmet performance to reduce accelerations, a corresponding reduction in the incidence of concussion has not occurred (National Football League [NFL] 1996-present). There is compelling research that forces on and deformation to the brain stem are related to concussion. The brain stem is the center of control for respiration, blood pressure and heart rate and is the root of most cranial nerves. Injury to the brain stem is consistent with most symptoms of concussion reported in the National Football League and the National Hockey League, such as headaches, neck pain, dizziness, and blurred vision. In the Hybrid III anthropomorphic test device (ATD), the upper neck load cell is in close proximity to the human brain stem. This study found that the additional mass of a football helmet onto the Hybrid III headform increases the upper neck forces and moments in response to helmet-to-helmet impact and helmet-to-chest impacts. A new laboratory impactor device was constructed to simulate collisions using two moving Hybrid III ATDs. The impactor was used to recreate on-field collisions (n = 20) in American football while measuring head, neck and upper torso kinematics. A strong correlation between upper neck forces, upper neck power and the estimated strains and strain rates along the axis of the upper cervical spinal cord and brain stem and concussion was found. These biomechanical responses should be added to head kinematic responses for a more comprehensive evaluation of concussion.

Spatio-temporal neural stem cell behavior that leads to both perfect and imperfect structural brain regeneration in adult newts.

PubMed

Urata, Yuko; Yamashita, Wataru; Inoue, Takeshi; Agata, Kiyokazu

2018-06-14

Adult newts can regenerate large parts of their brain from adult neural stem cells (NSCs), but how adult NSCs reorganize brain structures during regeneration remains unclear. In development, elaborate brain structures are produced under broadly coordinated regulations of embryonic NSCs in the neural tube, whereas brain regeneration entails exquisite control of the reestablishment of certain brain parts, suggesting a yet-unknown mechanism directs NSCs upon partial brain excision. Here we report that upon one-quarter excision of the adult newt ( Pleurodeles waltl ) mesencephalon, active participation of local NSCs around specific brain subregions' boundaries leads to some imperfect and some perfect brain regeneration along an individual's rostrocaudal axis. Regeneration phenotypes depend on how the wound closing occurs using local NSCs, and perfect regeneration replicates development-like processes but takes more than one year. Our findings indicate that newt brain regeneration is supported by modularity of boundary-domain NSCs with self-organizing ability in neighboring fields. © 2018. Published by The Company of Biologists Ltd.

Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats.

PubMed

Amini, Naser; Vousooghi, Nasim; Hadjighassem, Mahmoudreza; Bakhtiyari, Mehrdad; Mousavi, Neda; Safakheil, Hosein; Jafari, Leila; Sarveazad, Arash; Yari, Abazar; Ramezani, Sara; Faghihi, Faezeh; Joghataei, Mohammad Taghi

2016-05-01

Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.

Quiescence and activation of stem and precursor cell populations in the subependymal zone of the mammalian brain are associated with distinct cellular and extracellular matrix signals

USDA-ARS?s Scientific Manuscript database

The subependymal zone (SEZ) of the lateral ventricles is one of the areas of the adult brain where new neurons are continuously generated from neural stem cells (NSCs), via rapidly dividing precursors. This neurogenic niche is a complex cellular and extracellular microenvironment, highly vascularize...

Harnessing Autopsied DIPG Tumor Tissues for Orthotopic Xenograft Model Development in the Brain Stems of SCID Mice

DTIC Science & Technology

2012-09-01

patched-1-deficient mouse medulloblastoma . Cancer Res. 2009;69:4682-4690. 14. Mao XG, Zhang X, Xue XY, et al. Brain Tumor Stem-Like Cells Identified by...propagating cells in a mouse model of medulloblastoma . Cancer Cell. 2009;15:135-147. 16. Yagi H, Yanagisawa M, Suzuki Y, et al. HNK-1 epitope-carrying

Effects of segmental traction therapy on lumbar disc herniation in patients with acute low back pain measured by magnetic resonance imaging: A single arm clinical trial.

PubMed

Karimi, Noureddin; Akbarov, Parvin; Rahnama, Leila

2017-01-01

Low Back Pain (LBP) is considered as one of the most frequent disorders, which about 80% of adults experience in their lives. Lumbar disc herniation (LDH) is a cause for acute LBP. Among conservative treatments, traction is frequently used by clinicians to manage LBP resulting from LDH. However, there is still a lack of consensus about its efficacy. The purpose of this study was to evaluate the effects of segmental traction therapy on lumbar discs herniation, pain, lumbar range of motion (ROM), and back extensor muscles endurance in patients with acute LBP induced by LDH. Fifteen patients with acute LBP diagnosed by LDH participated in the present study. Participants undertook 15 sessions of segmental traction therapy along with conventional physiotherapy, 5 times a week for 3 weeks. Lumbar herniated mass size was measured before and after the treatment protocol using magnetic resonance imaging. Furthermore, pain, lumbar ROM and back muscle endurance were evaluated before and after the procedure using clinical outcome measures. Following the treatment protocol, herniated mass size and patients' pain were reduced significantly. In addition, lumbar flexion ROM showed a significant improvement. However, no significant change was observed for back extensor muscle endurance after the treatment procedure. The result of the present study showed segmental traction therapy might play an important role in the treatment of acute LBP stimulated by LDH.

Strain on intervertebral discs after anterior cervical decompression and fusion.

PubMed

Matsunaga, S; Kabayama, S; Yamamoto, T; Yone, K; Sakou, T; Nakanishi, K

1999-04-01

An analysis of the change in strain distribution of intervertebral discs present after anterior cervical decompression and fusion by an original method. The analytical results were compared to occurrence of herniation of the intervertebral disc on magnetic resonance imaging. To elucidate the influence of anterior cervical decompression and fusion on the unfused segments of the spine. There is no consensus regarding the exact significance of the biomechanical change in the unfused segment present after surgery. Ninety-six patients subjected to anterior cervical decompression and fusion for herniation of intervertebral discs were examined. Shear strain and longitudinal strain of intervertebral discs were analyzed on pre- and postoperative lateral dynamic routine radiography of the cervical spine. Thirty of the 96 patients were examined by magnetic resonance imaging before and after surgery, and the relation between alteration in strains and postsurgical occurrence of disc herniation was examined. In the cases of double- or triple-level fusion, shear strain of adjacent segments had increased 20% on average 1 year after surgery. Thirteen intervertebral discs that had an abnormally high degree of strain showed an increase in longitudinal strain after surgery. Eleven (85%) of the 13 discs that showed an abnormal increase in longitudinal strain had herniation in the same intervertebral discs with compression of the spinal cord during the follow-up period. Relief of symptoms was significantly poor in the patients with recent herniation. Close attention should be paid to long-term biomechanical changes in the unfused segment.

Hypovitaminosis D and Cervical Disk Herniation among Adults Undergoing Spine Surgery

PubMed Central

Stoker, Geoffrey E.; Buchowski, Jacob M.; Chen, Christopher T.; Kim, Han Jo; Park, Moon Soo; Riew, K. Daniel

2013-01-01

Study Design Single-center, retrospective study. Objective Suboptimal concentrations of vitamin D have been linked to hip and knee osteoarthritis in large, population-based cohort studies. We sought to examine the association of vitamin D levels with intervertebral disk disease. Methods From January 2010 through May 2011, 91 consecutive, eligible adult spine surgery patients who had undergone cervical magnetic resonance imaging (MRI) and preoperative serum 25-hydroxyvitamin D (s25D) measurement were retrospectively included. MRI was read for C2–T1 disk herniation and degeneration (grades I to V). Logistic regressions were performed. Results Compared with the 384 disks of nondeficient patients, 162 disks of vitamin D-deficient (< 20 ng/mL) patients were more frequently herniated (40% versus 27%, p = 0.004); deficiency was not predictive of individual disk grade (unadjusted odds ratio [uOR] = 0.98, p = 0.817). On regression analysis, deficiency was associated with increased number of herniations per patient (uOR = 2.17, 95% confidence interval [CI] = 1.22 to 3.87, p = 0.009; adjusted odds ratio [aOR] = 2.12, 95% CI = 1.11 to 4.03, p = 0.023). When disks were analyzed individually, and levels (e.g., C5 to C6), additionally controlled for, deficiency correlated with greater likelihood of herniation per disk (uOR = 1.81, 95% CI = 1.22 to 2.66, p = 0.003; aOR = 2.06, 95% CI = 1.25 to 3.41, p = 0.005). Conclusion Among adults undergoing spine surgery at our institution, vitamin D deficiency was associated with cervical disk herniation. Considering the current epidemics of vitamin D insufficiency and neck pain, further investigation is warranted, as these data were retrospectively collected and subject to sampling bias. PMID:24436874

Myeloradicular damage in traumatic cervical disc herniation.

PubMed

Bucciero, A; Carangelo, B; Cerillo, A; Gammone, V; Panagiotopoulos, K; Vizioli, L

1998-12-01

The literature on pure traumatic disc herniation is now voluminous but diversity of opinion exists regarding frequency, pathogenesis and management of this type of lesion. As a further contribution to the solution of the question it is thus justified to report our series of cervical traumatic disc herniation. During the period from January 1986 to December 1994, 41 patients (25 males and 16 females, between the ages of 24 and 51 years) with traumatic cervical disc herniations were operated on by anterior approach. Twenty-six (63.4%) patients presented with radicular syndrome, 3 (7.3%) with medullary symptoms and signs, and 12 (29.3%) with myeloradiculopathy. Disc herniation was at the C3/4 level in 4 (9.7%) cases, at the C4/5 level in 7 (17.1%) cases, at the C5/6 level in 24 (58.5%) cases, and at the C6/7 level in 8 (19.5%) cases. In 6 (40%) patients suffering from myelopathy (with or without radiculopathy) an area of high MR signal intensity was observed within the cervical cord on T2-weighted images; such area corresponded at the level of cord compression by disc and was not demonstrated on T1-weighted images. All patients underwent discectomy without bone grafting. Among patients with radiculopathy, 27 (71%) experienced complete relief of preoperative symptomatology, and 11 (29%) minor pain and/or neurological deficits without interference with work activities. The myelopathy completely disappeared in 11 (73.3%) cases whereas remained unchanged in 3 (20%); 1 patient with myelopathy experienced amelioration of preoperative specific symptoms and signs. The results of surgery for cervical radiculopathy due to traumatic disc herniation are satisfactory since 92 to 100% of the patients postoperatively regain prior activities, an observation we have confirmed with our own series. The results in cases of myelopathy are less satisfactory: although approximately 73% of our patients with myelopathy reported total relief of preoperative symptomatology, published reports indicate that a significant postoperative improvement is seen in 33 to 56% of patients.

[The assessment of the impact of rehabilitation on the pain intensity level in patients with herniated nucleus pulposus of the intervertebral disc].

PubMed

Koszela, Kamil; Krukowska, Sylwia; Woldańska-Okońska, Marta

2017-05-23

Back pain may be caused by many factors. In many cases it is difficult to unambiguously determine a cause of the pathology, which can involve various structures in the spine. In this paper we will discuss the symptoms associated with the degenerative changes of the intervertebral disc, which involve, among others, its bulging, dislocation and pressure on the surrounding structures. These problems require an adequate clinical and imaging diagnostics in order to implement an appropriate treatment. In the first place, it should be based on the conservative methods (such as: pharmacotherapy, rehabilitation and lifestyle changes). Only in the absence of improvement it is recommended to consider a surgical treatment. The aim of the study is to assess the impact of rehabilitation on the pain intensity level in patients with herniated nucleus pulposus of the intervertebral disc. The study was performed in 46 patients (age range: 19-85), including 26 women and 20 men. On the basis of imaging, all patients showed the presence of a slipped disc with disc herniation. The patients were treated conservatively. For pain assessment was used the The Laitinen Modified Questionnaire Indicators of Pain and The Visual- Analogue Scale. The results were statistically analyzed. The results clearly demonstrate the analgesic efficacy of specialized rehabilitation in the spinal pain syndrome in a discopathy with a spinal disc herniation of an intervertebral disc. The rehabilitation of patients with a back pain due to the presence of herniated nucleus pulposus has a significant analgesic effect. In the case of a presence of the herniated nucleus pulposus, the rehabilitation should be considered in a first place. If no improvement, a possible surgery should be considered. An important element of a conservative treatment is an effective rehabilitation, which is of vital economic importance, because a therapy including surgery usually requires subsequent rehabilitation and is much more expensive.

A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

PubMed

Cecchelli, Romeo; Aday, Sezin; Sevin, Emmanuel; Almeida, Catarina; Culot, Maxime; Dehouck, Lucie; Coisne, Caroline; Engelhardt, Britta; Dehouck, Marie-Pierre; Ferreira, Lino

2014-01-01

The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

A history of lumbar disc herniation from Hippocrates to the 1990s.

PubMed

Truumees, Eeric

2015-06-01

In ancient times, a supernatural understanding of the syndrome of lumbar radiculopathy often involved demonic forces vexing the individual with often crippling pain. The ancient Greeks and Egyptians began to take a more naturalistic view and, critically, suspected a relationship between lumbar spinal pathology and leg symptoms. Relatively little then changed for those with sciatica until the classic works by Cotugno and Kocher arrived in the late 18th century. Early lumbar canal explorations were performed in the late 1800s and early 1900s by MacEwen, Horsley, Krause, Taylor, Dandy, and Cushing, among others. In these cases, when compressive pathologies were found and removed, the lesions typically were (mis-)identified as enchondromas or osteochondritis dissecans. To better understand the history, learn more about the first treatments of lumbar disc herniation, and evaluate the impact of the early influences on modern spine practice, searches of PubMed and Embase were performed using the search terms discectomy, medical history, lumbar spine surgery, herniated disc, herniated nucleus pulposus, sciatica, and lumbar radiculopathy. Additional sources were identified from the reference lists of the reviewed papers. Many older and ancient sources including De Ischiade Nervosa are available in English translations and were used. When full texts were not available, English abstracts were used. The first true, intentional discectomy surgery was performed by Mixter and Barr in 1932. Early on, a transdural approach was favored. In 1938, Love described the intralaminar, extradural approach. His technique, although modified with improved lighting, magnification, and retractors, remains a staple approach to disc herniations today. Other modalities such as chymopapain have been investigated. Some remain a part of the therapeutic armamentarium, whereas others have disappeared. By the 1970s, CT scanning after myelography markedly improved the clinical evaluation of patients with lumbar disc herniation. In this era, use of discectomy surgery increased rapidly. Even patients with very early symptoms were offered surgery. Later work, especially by Weber and Hakelius, showed that many patients with lumbar disc herniation would improve without surgical intervention. In the ensuing decades, the debate over operative indications and timing continued, reaching another pivotal moment with the 2006 publication of the initial results of Spine Patient Outcomes Research Trial.

How does accounting for worker productivity affect the measured cost-effectiveness of lumbar discectomy?

PubMed

Koenig, Lane; Dall, Timothy M; Gu, Qian; Saavoss, Josh; Schafer, Michael F

2014-04-01

Back pain attributable to lumbar disc herniation is a substantial cause of reduced workplace productivity. Disc herniation surgery is effective in reducing pain and improving function. However, few studies have examined the effects of surgery on worker productivity. We wished to determine the effect of disc herniation surgery on workers' earnings and missed workdays and how accounting for this effect influences the cost-effectiveness of surgery? Regression models were estimated using data from the National Health Interview Survey to assess the effects of lower back pain caused by disc herniation on earnings and missed workdays. The results were incorporated into Markov models to compare societal costs associated with surgical and nonsurgical treatments for privately insured, working patients. Clinical outcomes and utilities were based on results from the Spine Patient Outcomes Research Trial and additional clinical literature. We estimate average annual earnings of $47,619 with surgery and $45,694 with nonsurgical treatment. The increased earnings for patients receiving surgery as compared with nonsurgical treatment is equal to $1925 (95% CI, $1121-$2728). After surgery, we also estimate that workers receiving surgery miss, on average, 3 fewer days per year than if workers had received nonsurgical treatment (95% CI, 2.4-3.7 days). However, these fewer missed work days only partially offset the assumed 20 workdays missed to recover from surgery. More fully accounting for the effects of disc herniation surgery on productivity reduced the cost of surgery per quality-adjusted life year (QALY) from $52,416 to $35,146 using a 4-year time horizon and from $27,359 to $4186 using an 8-year time horizon. According to a sensitivity analysis, the 4-year cost per QALY varies between $27,921 and $49,787 depending on model assumptions. Increased worker earnings resulting from disc herniation surgery may offset the increased direct medical costs associated with surgery. After accounting for the effects on productivity, disc herniation surgery was found to be a highly cost-effective surgery and may yield net societal savings if the benefits of outpatient and inpatient surgery persist beyond 6 and 12 years, respectively. Level II, economic and decision analysis. See the Instructions for Authors for a complete description of levels of evidence.

Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis.

PubMed

Saito, Kanako; Dubreuil, Veronique; Arai, Yoko; Wilsch-Bräuninger, Michaela; Schwudke, Dominik; Saher, Gesine; Miyata, Takaki; Breier, Georg; Thiele, Christoph; Shevchenko, Andrej; Nave, Klaus-Armin; Huttner, Wieland B

2009-05-19

Although sufficient cholesterol supply is known to be crucial for neurons in the developing mammalian brain, the cholesterol requirement of neural stem and progenitor cells in the embryonic central nervous system has not been addressed. Here we have conditionally ablated the activity of squalene synthase (SQS), a key enzyme for endogenous cholesterol production, in the neural stem and progenitor cells of the ventricular zone (VZ) of the embryonic mouse brain. Mutant embryos exhibited a reduced brain size due to the atrophy of the neuronal layers, and died at birth. Analyses of the E11.5-E15.5 dorsal telencephalon and diencephalon revealed that this atrophy was due to massive apoptosis of newborn neurons, implying that this progeny of the SQS-ablated neural stem and progenitor cells was dependent on endogenous cholesterol biosynthesis for survival. Interestingly, the neural stem and progenitor cells of the VZ, the primary target of SQS inactivation, did not undergo significant apoptosis. Instead, vascular endothelial growth factor (VEGF) expression in these cells was strongly upregulated via a hypoxia-inducible factor-1-independent pathway, and angiogenesis in the VZ was increased. Consistent with an increased supply of lipoproteins to these cells, the level of lipid droplets containing triacylglycerides with unsaturated fatty acyl chains was found to be elevated. Our study establishes a direct link between intracellular cholesterol levels, VEGF expression, and angiogenesis. Moreover, our data reveal a hitherto unknown compensatory process by which the neural stem and progenitor cells of the developing mammalian brain evade the detrimental consequences of impaired endogenous cholesterol biosynthesis.

Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis

PubMed Central

Saito, Kanako; Dubreuil, Veronique; Arai, Yoko; Wilsch-Bräuninger, Michaela; Schwudke, Dominik; Saher, Gesine; Miyata, Takaki; Breier, Georg; Thiele, Christoph; Shevchenko, Andrej; Nave, Klaus-Armin; Huttner, Wieland B.

2009-01-01

Although sufficient cholesterol supply is known to be crucial for neurons in the developing mammalian brain, the cholesterol requirement of neural stem and progenitor cells in the embryonic central nervous system has not been addressed. Here we have conditionally ablated the activity of squalene synthase (SQS), a key enzyme for endogenous cholesterol production, in the neural stem and progenitor cells of the ventricular zone (VZ) of the embryonic mouse brain. Mutant embryos exhibited a reduced brain size due to the atrophy of the neuronal layers, and died at birth. Analyses of the E11.5–E15.5 dorsal telencephalon and diencephalon revealed that this atrophy was due to massive apoptosis of newborn neurons, implying that this progeny of the SQS-ablated neural stem and progenitor cells was dependent on endogenous cholesterol biosynthesis for survival. Interestingly, the neural stem and progenitor cells of the VZ, the primary target of SQS inactivation, did not undergo significant apoptosis. Instead, vascular endothelial growth factor (VEGF) expression in these cells was strongly upregulated via a hypoxia-inducible factor-1–independent pathway, and angiogenesis in the VZ was increased. Consistent with an increased supply of lipoproteins to these cells, the level of lipid droplets containing triacylglycerides with unsaturated fatty acyl chains was found to be elevated. Our study establishes a direct link between intracellular cholesterol levels, VEGF expression, and angiogenesis. Moreover, our data reveal a hitherto unknown compensatory process by which the neural stem and progenitor cells of the developing mammalian brain evade the detrimental consequences of impaired endogenous cholesterol biosynthesis. PMID:19416849

The nuclear receptor tailless is required for neurogenesis in the adult subventricular zone

PubMed Central

Liu, Hai-Kun; Belz, Thorsten; Bock, Dagmar; Takacs, Andrea; Wu, Hui; Lichter, Peter; Chai, Minqiang; Schütz, Günther

2008-01-01

The tailless (Tlx) gene encodes an orphan nuclear receptor that is expressed by neural stem/progenitor cells in the adult brain of the subventricular zone (SVZ) and the dentate gyrus (DG). The function of Tlx in neural stem cells of the adult SVZ remains largely unknown. We show here that in the SVZ of the adult brain Tlx is exclusively expressed in astrocyte-like B cells. An inducible mutation of the Tlx gene in the adult brain leads to complete loss of SVZ neurogenesis. Furthermore, analysis indicates that Tlx is required for the transition from radial glial cells to astrocyte-like neural stem cells. These findings demonstrate the crucial role of Tlx in the generation and maintenance of NSCs in the adult SVZ in vivo. PMID:18794344

Deregulated proliferation and differentiation in brain tumors

PubMed Central

Swartling, Fredrik J; Čančer, Matko; Frantz, Aaron; Weishaupt, Holger; Persson, Anders I

2014-01-01

Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment-resistance, suppress tumor growth, and prevent recurrence in patients. PMID:25416506

Superior herniation of the mediastinum presenting as an anterior neck mass on straining.

PubMed

McDougall, Catherine M; Culham, Gordon; Seear, Michael D; Chilvers, Mark A

2012-07-01

We report an infant with an anterior neck mass present only on straining. Airway fluoroscopy revealed this to be due to superior mediastinal herniation. Neck masses apparent only during Valsalva maneuver are rare and awareness of the differential diagnosis is important to avoid unnecessary investigation or surgery. Copyright © 2012 Wiley Periodicals, Inc.

The neural stem cell fate determinant TLX promotes tumorigenesis and genesis of cells resembling glioma stem cells.

PubMed

Park, Hyo-Jung; Kim, Jun-Kyum; Jeon, Hye-Min; Oh, Se-Yeong; Kim, Sung-Hak; Nam, Do-Hyun; Kim, Hyunggee

2010-11-01

A growing body of evidence indicates that deregulation of stem cell fate determinants is a hallmark of many types of malignancies. The neural stem cell fate determinant TLX plays a pivotal role in neurogenesis in the adult brain by maintaining neural stem cells. Here, we report a tumorigenic role of TLX in brain tumor initiation and progression. Increased TLX expression was observed in a number of glioma cells and glioma stem cells, and correlated with poor survival of patients with gliomas. Ectopic expression of TLX in the U87MG glioma cell line and Ink4a/Arf-deficient mouse astrocytes (Ink4a/Arf(-/-) astrocytes) induced cell proliferation with a concomitant increase in cyclin D expression, and accelerated foci formation in soft agar and tumor formation in in vivo transplantation assays. Furthermore, overexpression of TLX in Ink4a/Arf(-/-) astrocytes inhibited cell migration and invasion and promoted neurosphere formation and Nestin expression, which are hallmark characteristics of glioma stem cells, under stem cell culture conditions. Our results indicate that TLX is involved in glioma stem cell genesis and represents a potential therapeutic target for this type of malignancy.

Distinct roles of neuroepithelial-like and radial glia-like progenitor cells in cerebellar regeneration.

PubMed

Kaslin, Jan; Kroehne, Volker; Ganz, Julia; Hans, Stefan; Brand, Michael

2017-04-15

Zebrafish can regenerate after brain injury, and the regenerative process is driven by resident stem cells. Stem cells are heterogeneous in the vertebrate brain, but the significance of having heterogeneous stem cells in regeneration is not understood. Limited availability of specific stem cells might impair the regeneration of particular cell lineages. We studied regeneration of the adult zebrafish cerebellum, which contains two major stem and progenitor cell types: ventricular zone and neuroepithelial cells. Using conditional lineage tracing we demonstrate that cerebellar regeneration depends on the availability of specific stem cells. Radial glia-like cells are thought to be the predominant stem cell type in homeostasis and after injury. However, we find that radial glia-like cells play a minor role in adult cerebellar neurogenesis and in recovery after injury. Instead, we find that neuroepithelial cells are the predominant stem cell type supporting cerebellar regeneration after injury. Zebrafish are able to regenerate many, but not all, cell types in the cerebellum, which emphasizes the need to understand the contribution of different adult neural stem and progenitor cell subtypes in the vertebrate central nervous system. © 2017. Published by The Company of Biologists Ltd.

Ethical and medical management of a pregnant woman with brain stem death resulting in delivery of a healthy child and organ donation.

PubMed

Gopčević, A; Rode, B; Vučić, M; Horvat, A; Širanović, M; Gavranović, Ž; Košec, V; Košec, A

2017-11-01

Maternal brain death during pregnancy remains an exceedingly complex situation that requires not only a well-considered medical management plan, but also careful decision-making in a legally and ethically delicate situation. Management of brain dead pregnant patients needs to adhere to special strategies that support the mother in a way that she can deliver a viable and healthy child. Brain death in pregnant women is very rare, with only a few published cases. We present a case of a pregnant woman with previously diagnosed multiple brain cavernomas that led to intracranial hemorrhage and brain stem death during the 21st week of pregnancy. The condition that can be proven unequivocally, using tests that do not endanger viability of the fetus, is brain stem death, diagnosed through absence of cranial reflexes. The patient was successfully treated until delivery of a healthy female child at 29weeks of gestation. The patient received continuous hormone substitution therapy, fetal monitoring and extrinsic regulation of maternal homeostasis over 64days. After delivery, the final diagnosis of brain death was established through multi-slice computerized tomography pan-angiography. This challenging case discusses ethical and medical circumstances arising from a diagnosis of maternal brain death, while showing that prolongation of somatic life support in a multidisciplinary setting can result in a successful pregnancy outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain.

PubMed

Hallmann, Anna-Lena; Araúzo-Bravo, Marcos J; Zerfass, Christina; Senner, Volker; Ehrlich, Marc; Psathaki, Olympia E; Han, Dong Wook; Tapia, Natalia; Zaehres, Holm; Schöler, Hans R; Kuhlmann, Tanja; Hargus, Gunnar

2016-05-01

Reprogramming technology enables the production of neural progenitor cells (NPCs) from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs) differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs) and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs. Copyright © 2016 Roslin Cells Ltd. Published by Elsevier B.V. All rights reserved.

Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers

PubMed Central

Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

2014-01-01

Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step‐and‐shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose <45 Gy to spinal cord and <50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5±2.2 Gy and 36.7±14.0 Gy), without significant changes on the other OARs. A marked difference (−15.9±1.9 Gy and −10.1±5.7 Gy) was obtained at the expense of a small difference (−1.3%±0.9%) from initial PTV195% coverage (96.6%±0.9%). Similar difference (−15.7±2.2 Gy and −10.2±6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (−0.3%±0.3% from the initial 98.3%±0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer. PACS number: 87.55.D PMID:24423836

Transmembrane protein CD9 is glioblastoma biomarker, relevant for maintenance of glioblastoma stem cells

PubMed Central

Podergajs, Neža; Motaln, Helena; Rajčević, Uroš; Verbovšek, Urška; Koršič, Marjan; Obad, Nina; Espedal, Heidi; Vittori, Miloš; Herold-Mende, Christel; Miletic, Hrvoje; Bjerkvig, Rolf; Turnšek, Tamara Lah

2016-01-01

The cancer stem cell model suggests that glioblastomas contain a subpopulation of stem-like tumor cells that reproduce themselves to sustain tumor growth. Targeting these cells thus represents a novel treatment strategy and therefore more specific markers that characterize glioblastoma stem cells need to be identified. In the present study, we performed transcriptomic analysis of glioblastoma tissues compared to normal brain tissues revealing sensible up-regulation of CD9 gene. CD9 encodes the transmembrane protein tetraspanin which is involved in tumor cell invasion, apoptosis and resistance to chemotherapy. Using the public REMBRANDT database for brain tumors, we confirmed the prognostic value of CD9, whereby a more than two fold up-regulation correlates with shorter patient survival. We validated CD9 gene and protein expression showing selective up-regulation in glioblastoma stem cells isolated from primary biopsies and in primary organotypic glioblastoma spheroids as well as in U87-MG and U373 glioblastoma cell lines. In contrast, no or low CD9 gene expression was observed in normal human astrocytes, normal brain tissue and neural stem cells. CD9 silencing in three CD133+ glioblastoma cell lines (NCH644, NCH421k and NCH660h) led to decreased cell proliferation, survival, invasion, and self-renewal ability, and altered expression of the stem-cell markers CD133, nestin and SOX2. Moreover, CD9-silenced glioblastoma stem cells showed altered activation patterns of the Akt, MapK and Stat3 signaling transducers. Orthotopic xenotransplantation of CD9-silenced glioblastoma stem cells into nude rats promoted prolonged survival. Therefore, CD9 should be further evaluated as a target for glioblastoma treatment. PMID:26573230

Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells.

PubMed

Yan, Yiping; Shin, Soojung; Jha, Balendu Shekhar; Liu, Qiuyue; Sheng, Jianting; Li, Fuhai; Zhan, Ming; Davis, Janine; Bharti, Kapil; Zeng, Xianmin; Rao, Mahendra; Malik, Nasir; Vemuri, Mohan C

2013-11-01

Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, labor-intensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

The association between sleep-disordered breathing and magnetic resonance imaging findings in a pediatric cohort with Chiari 1 malformation

PubMed Central

Amin, Reshma; Sayal, Priya; Sayal, Aarti; Massicote, Colin; Pham, Robin; Al-Saleh, Suhail; Drake, James; Narang, Indra

2015-01-01

BACKGROUND: The prevalence of sleep-disordered breathing (SDB) reported in the literature for Chiari malformation type 1 (CM1) is uniformly high (24% to 70%). In Canada, there is limited access to pediatric polysomnography (PSG). Therefore, the identification of clinical features would be invaluable for triaging these children. OBJECTIVE: To identify demographic features, clinical symptoms/signs and radiological findings associated with SDB in a large pediatric cohort with CM1. METHODS: A retrospective review was conducted on children with CM1 who underwent baseline PSG. Data were collected on patient demographics (age, sex, weight, height, body mass index), clinical symptoms (chart review and clinical questionnaires), diagnostic imaging of the brain and cervicothoracic spine, and medical history at the time of referral. RESULTS: A total of 68 children were included in the review. The mean (± SD) age of the children at the time of PSG was 7.33±4.01 years; 56% (n=38) were male. There was a 49% prevalence of SDB in this cohort based on the overall apnea-hypopnea index. Obstructive sleep apnea was the predominant type of SDB. Tonsillar herniation was significantly correlated with obstructive apnea-hypopnea index (r=0.24; P=0.036). CONCLUSIONS: A direct relationship between the degree of cerebellar tonsillar herniation and obstructive sleep apnea was demonstrated. However, further prospective studies that include neurophysiological assessment are needed to further translate the central nervous system imaging findings to predict the presence of SDB. PMID:25379655

Exposure to Organophosphates Reduces the Expression of Neurotrophic Factors in Neonatal Rat Brain Regions: Similarities and Differences in the Effects of Chlorpyrifos and Diazinon on the Fibroblast Growth Factor Superfamily

PubMed Central

Slotkin, Theodore A.; Seidler, Frederic J.; Fumagalli, Fabio

2007-01-01

Background The fibroblast growth factor (FGF) superfamily of neurotrophic factors plays critical roles in neural cell development, brain assembly, and recovery from neuronal injury. Objectives We administered two organophosphate pesticides, chlorpyrifos and diazinon, to neonatal rats on postnatal days 1–4, using doses below the threshold for systemic toxicity or growth impairment, and spanning the threshold for barely detectable cholinesterase inhibition: 1 mg/kg/day chlorpyrifos and 1 or 2 mg/kg/day diazinon. Methods Using microarrays, we then examined the regional expression of mRNAs encoding the FGFs and their receptors (FGFRs) in the forebrain and brain stem. Results Chlorpyrifos and diazinon both markedly suppressed fgf20 expression in the forebrain and fgf2 in the brain stem, while elevating brain stem fgfr4 and evoking a small deficit in brain stem fgf22. However, they differed in that the effects on fgf2 and fgfr4 were significantly larger for diazinon, and the two agents also showed dissimilar, smaller effects on fgf11, fgf14, and fgfr1. Conclusions The fact that there are similarities but also notable disparities in the responses to chlorpyrifos and diazinon, and that robust effects were seen even at doses that do not inhibit cholinesterase, supports the idea that organophosphates differ in their propensity to elicit developmental neurotoxicity, unrelated to their anticholinesterase activity. Effects on neurotrophic factors provide a mechanistic link between organophosphate injury to developing neurons and the eventual, adverse neurodevelopmental outcomes. PMID:17589599

Role of the brain stem in tibial inhibition of the micturition reflex in cats.

PubMed

Ferroni, Matthew C; Slater, Rick C; Shen, Bing; Xiao, Zhiying; Wang, Jicheng; Lee, Andy; Roppolo, James R; de Groat, William C; Tai, Changfeng

2015-08-01

This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in α-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (>2 h) poststimulation inhibition that significantly (P < 0.05) increased bladder capacity to 30-60% above control; however, TNS did not produce this effect during AA irritation. TNS applied during CMGs at 5 Hz but not 30 Hz significantly (P < 0.01) increased bladder capacity to 127.3 ± 6.1% of saline control or 187.6 ± 5.0% of AA control. During AA irritation, naloxone (an opioid receptor antagonist) administered intravenously (1 mg/kg) or directly to the surface of the rostral brain stem (300-900 μg) eliminated acute TNS inhibition and significantly (P < 0.05) reduced bladder capacity to 62.8 ± 22.6% (intravenously) or 47.6 ± 25.5% (brain stem application). Results of this and previous studies indicate 1) forebrain circuitry rostral to the pons is not essential for TNS inhibition; and 2) opioid receptors in the brain stem have a critical role in TNS inhibition of overactive bladder reflexes but are not involved in inhibition of normal bladder reflexes. Copyright © 2015 the American Physiological Society.

Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

PubMed

Anselmi, L; Toti, L; Bove, C; Travagli, R A

2017-11-01

Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat

PubMed Central

Jones, Sarah E.

2016-01-01

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. PMID:26888109

Brain stem serotonin protects blood pressure in neonatal rats exposed to episodic anoxia.

PubMed

Yang, Hsiao T; Cummings, Kevin J

2013-12-01

In neonatal rodents, a loss of brain stem serotonin [5-hydroxytryptamine (5-HT)] in utero or at birth compromises anoxia-induced gasping and the recovery of heart rate (HR) and breathing with reoxygenation (i.e., autoresuscitation). How mean arterial pressure (MAP) is influenced after an acute loss of brain stem 5-HT content is unknown. We hypothesized that a loss of 5-HT for ∼1 day would compromise MAP during episodic anoxia. We injected 6-fluorotryptophan (20 mg/kg ip) into rat pups (postnatal days 9-10 or 11-13, n = 22 treated, 24 control), causing a ∼70% loss of brain stem 5-HT. Pups were exposed to a maximum of 15 anoxic episodes, separated by 5 min of room air to allow autoresuscitation. In younger pups, we measured breathing frequency and tidal volume using "head-out" plethysmography and HR from the electrocardiogram. In older pups, we used whole body plethysmography to detect gasping, while monitoring MAP. Gasp latency and the time required for respiratory, HR, and MAP recovery following each episode were determined. Despite normal gasp latency, breathing frequency and a larger tidal volume (P < 0.001), 5-HT-deficient pups survived one-half the number of episodes as controls (P < 0.001). The anoxia-induced decrease in MAP experienced by 5-HT-deficient pups was double that of controls (P = 0.017), despite the same drop in HR (P = 0.48). MAP recovery was delayed ∼10 s by 5-HT deficiency (P = 0.001). Our data suggest a loss of brain stem 5-HT leads to a pronounced, premature loss of MAP in response to episodic anoxia. These data may help explain why some sudden infant death syndrome cases die from what appears to be cardiovascular collapse during apparent severe hypoxia.

Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat.

PubMed

Jones, Sarah E; Dutschmann, Mathias

2016-05-01

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. Copyright © 2016 the American Physiological Society.

Stem cells distribution, cellular proliferation and migration in the adult Austrolebias charrua brain.

PubMed

Torres-Pérez, Maximiliano; Rosillo, Juan Carlos; Berrosteguieta, Ines; Olivera-Bravo, Silvia; Casanova, Gabriela; García-Verdugo, José Manuel; Fernández, Anabel Sonia

2017-10-15

Our previous studies demonstrated that Austrolebias charrua annual fish is an excellent model to study adult brain cell proliferation and neurogenesis due to the presence of active and fast neurogenesis in several regions during its short lifespan. Our main goal was to identify and localize the cells that compose the neurogenic areas throughout the Austrolebias brain. To do this, we used two thymidine halogenated analogs to detect cell proliferation at different survival times: 5-chloro-2'-deoxyuridine (CldU) at 1day and 5-iodo-2'-deoxyuridine (IdU) at 30days. Three types of proliferating cells were identified: I - transient amplifying or fast cycling cells that uptake CldU; II - stem cells or slow cycling cells, that were labeled with both CldU and IdU and did not migrate; and III - migrant cells that uptake IdU. Mapping and 3D-reconstruction of labeled nuclei showed that type I and type II cells were preferentially found close to ventricle walls. Type III cells appeared widespread and migrating in tangential and radial routes. Use of proliferation markers together with Vimentin or Nestin evidenced that type II cells are the putative stem cells that are located at the ventricular lumen. Double label cells with IdU+ and NeuN or HuC/D allowed us identify migrant neurons. Quantitation of labeled nuclei indicates that the proportion of putative stem cells is around 10% in all regions of the brain. This percentage of stem cells suggests the existence of a constant brain cell population in Austrolebias charrua that seems functional to the maintainance of adult neurogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Senescence from glioma stem cell differentiation promotes tumor growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouchi, Rie; Laboratory of Molecular Target Therapy of Cancer, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550; Okabe, Sachiko

Glioblastoma (GBM) is a lethal brain tumor composed of heterogeneous cellular populations including glioma stem cells (GSCs) and differentiated non-stem glioma cells (NSGCs). While GSCs are involved in tumor initiation and propagation, NSGCs' role remains elusive. Here, we demonstrate that NSGCs undergo senescence and secrete pro-angiogenic proteins, boosting the GSC-derived tumor formation in vivo. We used a GSC model that maintains stemness in neurospheres, but loses the stemness and differentiates into NSGCs upon serum stimulation. These NSGCs downregulated telomerase, shortened telomeres, and eventually became senescent. The senescent NSGCs released pro-angiogenic proteins, including vascular endothelial growth factors and senescence-associated interleukins, such asmore » IL-6 and IL-8. Conditioned medium from senescent NSGCs promoted proliferation of brain microvascular endothelial cells, and mixed implantation of GSCs and senescent NSGCs into mice enhanced the tumorigenic potential of GSCs. The senescent NSGCs seem to be clinically relevant, because both clinical samples and xenografts of GBM contained tumor cells that expressed the senescence markers. Our data suggest that senescent NSGCs promote malignant progression of GBM in part via paracrine effects of the secreted proteins. - Highlights: • Non-stem glioma cells (NSGCs) lose telomerase and eventually become senescent. • Senescent NSGCs secrete pro-angiogenic proteins, such as VEGFs, IL-6, and IL-8. • Senescent NSGCs enhance the growth of brain microvascular endothelial cells. • Senescent NSGCs enhance the tumorigenic potential of glioma stem cells in vivo.« less

Neural and mesenchymal stem cells in animal models of Huntington's disease: past experiences and future challenges.

PubMed

Kerkis, Irina; Haddad, Monica Santoro; Valverde, Cristiane Wenceslau; Glosman, Sabina

2015-12-14

Huntington's disease (HD) is an inherited disease that causes progressive nerve cell degeneration. It is triggered by a mutation in the HTT gene that strongly influences functional abilities and usually results in movement, cognitive and psychiatric disorders. HD is incurable, although treatments are available to help manage symptoms and to delay the physical, mental and behavioral declines associated with the condition. Stem cells are the essential building blocks of life, and play a crucial role in the genesis and development of all higher organisms. Ablative surgical procedures and fetal tissue cell transplantation, which are still experimental, demonstrate low rates of recovery in HD patients. Due to neuronal cell death caused by accumulation of the mutated huntingtin (mHTT) protein, it is unlikely that such brain damage can be treated solely by drug-based therapies. Stem cell-based therapies are important in order to reconstruct damaged brain areas in HD patients. These therapies have a dual role: stem cell paracrine action, stimulating local cell survival, and brain tissue regeneration through the production of new neurons from the intrinsic and likely from donor stem cells. This review summarizes current knowledge on neural stem/progenitor cell and mesenchymal stem cell transplantation, which has been carried out in several animal models of HD, discussing cell distribution, survival and differentiation after transplantation, as well as functional recovery and anatomic improvements associated with these approaches. We also discuss the usefulness of this information for future preclinical and clinical studies in HD.

Effect of alpha-tocopherol, pyridoxine and dexpanthenol on the stress in crease of nonesterified fatty acids levels in the brain.

PubMed

Chmela, Z; Sklenovský, A; Dostálová, K; Rypka, M

1993-01-01

The supposed antistress effect of vitamins-alpha-tocopherol, pyridoxine and dexpanthenol (pantothenic acid precursor)--was followed on the model of nociceptive stress in laboratory rats. The decrease of the stress enhancement of nonesterified fatty acids (NEFA), estimated in the brain cortex, hypothalamus and the brain stem, was taken for the indicator of the antistress effect. Nonesterified fatty acids were determined with the help of gas chromatography following the separation performed by thin layer chromatographic method. Five-day application of alpha-tocopherol acetate (per os, 300 mg.kg-1) led to a decrease of the stress enhancement of arachidonic acid level in the brain stem.

MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling

PubMed Central

Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Lang, Ming-Fei; Yang, Su; Li, Wendong; Shi, Yanhong

2010-01-01

Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation. PMID:20133835

MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling.

PubMed

Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Lang, Ming-Fei; Yang, Su; Li, Wendong; Shi, Yanhong

2010-02-02

Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation.

Congenital asymptomatic diaphragmatic hernias in adults: a case series.

PubMed

Bianchi, Enrica; Mancini, Paola; De Vito, Stefania; Pompili, Elena; Taurone, Samanta; Guerrisi, Isabella; Guerrisi, Antonino; D'Andrea, Vito; Cantisani, Vito; Artico, Marco

2013-05-13

Congenital diaphragmatic hernia is a major malformation occasionally found in newborns and babies. Congenital diaphragmatic hernia is defined by the presence of an orifice in the diaphragm, more often to the left and posterolateral, that permits the herniation of abdominal contents into the thorax. The aim of this case series is to provide information on the presentation, diagnosis and outcome of three patients with late-presenting congenital diaphragmatic hernias. The diagnosis of congenital diaphragmatic hernia is based on clinical investigation and is confirmed by plain X-ray films and computed tomography scans. In the present report three cases of asymptomatic abdominal viscera herniation within the thorax are described. The first case concerns herniation of some loops of the large intestine into the left hemi-thorax in a 75-year-old Caucasian Italian woman. The second case concerns a rare type of herniation in the right side of the thorax of the right kidney with a part of the liver parenchyma in a 57-year-old Caucasian Italian woman. The third case concerns herniation of the stomach and bowel into the left side of the chest with compression of the left lung in a 32-year-old Caucasian Italian man. This type of hernia may appear later in life, because of concomitant respiratory or gastrointestinal disease, or it may be an incidental finding in asymptomatic adults, such as in the three cases featured here. Patients who present with late diaphragmatic hernias complain of a wide variety of symptoms, and diagnosis may be difficult. Additional investigation and research appear necessary to better explain the development and progression of this type of disease.

Current evidence of percutaneous nucleoplasty for the cervical herniated disk: a systematic review.

PubMed

Wullems, Jorgen A; Halim, Willy; van der Weegen, Walter

2014-07-01

Although percutaneous cervical nucleoplasty (PCN) has been shown to be both safe and effective, its application is still debated. PCN applied in disk herniation has not been systematically reviewed before, resulting in a limited insight into its effectiveness and safety, and the quality of available evidence. Therefore, we systematically reviewed the evidence on the efficacy and safety of PCN in patients with a (contained) herniated disk. MEDLINE, EMBASE, and the Cochrane Library (Central Register of Controlled Trials) were searched for randomized controlled trials (RCTs) and nonrandomized studies using the following keywords: "Nucleoplasty," "Cervical," "Hernia," "Herniation," "Prolapse," "Protrusion," "Intervertebral disk," and "Percutaneous disk decompression." First, all articles were appraised for methodological quality, and then, RCTs were graded for the level of evidence according a best-evidence synthesis, because a meta-analysis was not possible. Finally, the RCTs' applicability and clinical relevance also was assessed. Of 75 identified abstracts, 10 full-text articles were included (3 RCTs and 7 nonrandomized studies). These studies represented a total of 1021 patients: 823 patients (≥ 892 disks) were treated by PCN. All studies showed low methodological quality, except for two. The level of evidence of the RCTs was graded as moderate, with low to moderate applicability and clinical relevance. All included studies showed PCN to be an effective and safe procedure in the treatment of (contained) herniated disks at short-, mid-, and long-term follow-up. However, the level of evidence is moderate and shows only low to moderate applicability and clinical relevance. © 2013 World Institute of Pain.

Apparent diffusion coefficient mapping in medulloblastoma predicts non-infiltrative surgical planes.

PubMed

Marupudi, Neena I; Altinok, Deniz; Goncalves, Luis; Ham, Steven D; Sood, Sandeep

2016-11-01

An appropriate surgical approach for posterior fossa lesions is to start tumor removal from areas with a defined plane to where tumor is infiltrating the brainstem or peduncles. This surgical approach minimizes risk of damage to eloquent areas. Although magnetic resonance imaging (MRI) is the current standard preoperative imaging obtained for diagnosis and surgical planning of pediatric posterior fossa tumors, it offers limited information on the infiltrative planes between tumor and normal structures in patients with medulloblastomas. Because medulloblastomas demonstrate diffusion restriction on apparent diffusion coefficient map (ADC map) sequences, we investigated the role of ADC map in predicting infiltrative and non-infiltrative planes along the brain stem and/or cerebellar peduncles by medulloblastomas prior to surgery. Thirty-four pediatric patients with pathologically confirmed medulloblastomas underwent surgical resection at our facility from 2004 to 2012. An experienced pediatric neuroradiologist reviewed the brain MRIs/ADC map, assessing the planes between the tumor and cerebellar peduncles/brain stem. An independent evaluator documented surgical findings from operative reports for comparison to the radiographic findings. The radiographic findings were statistically compared to the documented intraoperative findings to determine predictive value of the test in identifying tumor infiltration of the brain stem cerebellar peduncles. Twenty-six patients had preoperative ADC mapping completed and thereby, met inclusion criteria. Mean age at time of surgery was 8.3 ± 4.6 years. Positive predictive value of ADC maps to predict tumor invasion of the brain stem and cerebellar peduncles ranged from 69 to 88 %; negative predictive values ranged from 70 to 89 %. Sensitivity approached 93 % while specificity approached 78 %. ADC maps are valuable in predicting the infiltrative and non-infiltrative planes along the tumor and brain stem interface in medulloblastomas. Inclusion and evaluation of ADC maps in preoperative evaluation can assist in surgical resection planning in patients with medulloblastoma.

Light up the "no-man's land" on the brain stem.

PubMed

Kawase, T

1995-12-01

The ventral surface of the brain stem is anatomically surrounded by the clivus anteriorly, brain stem posteriorly and by the petrous pyramid and cranial nerves from IIIrd to XIIth laterally in the deep posterior cranial fossa. Neurosurgical extra-axial pathologies arising from the area are aneurysms on the vertebro-basilar artery, benign tumors such as clival meningiomas, chordomas, chondromas, trigeminal neurinomas and prepontine epidermoid tumors. Surgical access to the area had been difficult for long years since the neurosurgery was established, because located deeply in such a surgical blindness, so-called "no-man's land". However, recent technical development of "skull base surgery" is opening new doors to light up the surgical darkness of the "no-man's land". This paper reviews the history, development, technique and future prospect of the skull base surgery to open the "no-man's land".

Development and aging of a brain neural stem cell niche.

PubMed

Conover, Joanne C; Todd, Krysti L

2017-08-01

In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear. Here, we review functional and organizational differences in the V-SVZ stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche and its associated functions. Copyright © 2016 Elsevier Inc. All rights reserved.

Gliomagenesis and neural stem cells: Key role of hypoxia and concept of tumor "neo-niche".

PubMed

Diabira, Sylma; Morandi, Xavier

2008-01-01

Gliomas represent the most common primary brain tumors and the most devastating pathology of the central nervous system. Despite progress in conventional treatments, the prognosis remains dismal. Recent studies have suggested that a glioma brain tumor may arise from a "cancer stem cell". To understand this theory we summarize studies of the concepts of neural stem cell, and its specialized microenvironment, namely the niche which can regulate balanced self-renewal, differentiation and stem cell quiescence. We summarize the molecular mechanism known or postulated to be involved in the disregulation of normal stem cells features allowing them to undergo neoplasic transformation. We seek data pointing out the key role of hypoxia in normal homeostasis of stem cells and in the initiation, development and aggressiveness of gliomas. We develop the concept of tumor special microenvironment and we propose the new concept of neo-niche, surrounding the glioma, in which hypoxia could be a key factor to recruit and deregulate different stem cells for gliogenesis process. Substantial advances in treatment would come from obtaining better knowledge of molecular impairs of this disease.

Chymopapain chemonucleolysis: CT changes after treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gentry, L.R.; Turski, P.A.; Strother, C.M.

1985-08-01

Chymopapain chemonucleolysis is now used extensively in this country to treat lumbar disk herniation. Despite increasing experience in patient selection, there continue to be patients who do not respond to treatment and require diagnostic reevaluation. Interpretation of postchemonucleolysis computed tomographic (CT) scans in these patients requires a knowledge of the CT changes that normally occur after treatment with chemonucleolysis. To define these temporal changes, a prospective CT evaluation was performed of 29 treated interspaces in 26 patients who returned for routine postchemonucleolysis follow-up. Despite a successful clinical response in 17 of 21 patients, changes in the size, location, shape, homogeneity,more » and density of the disk herniation were uncommon at the 6 week follow-up. In 24 treated interspaces, the most common changes at 6 week CT follow-up were the development of vacuum phenomenon in three (12.5%) and a slight decrease in the size of two (8.3%) disk herniations. A successful response was noted in 17 of 21 patients scanned at 6 month follow-up, with five (22.7%) of 22 injected interspaces exhibiting vacuum phenomenon and 13 (59.1%) interspaces showing an observable decrease in the size of the disk herniation.« less

[Medical legal issues associated with the evaluation of herniated discs in seafarers to merchant ships].

PubMed

Onofri, E; Salesi, M; Massoni, F; Rosati, M V; Ricci, S

2012-01-01

"Seafarer" means person employed with any job on board a ship offshore, whether publicly or privately, excluding ships of war. Day by day a seafarer is forced to confront a reality in constant motion and live in environments that require awkward movements, and restricting the normal mobility of the person. In order to verify the frequency of herniated discs in this particular category of workers, given the recent introduction of INAIL tabulated diseases, a study was conducted on a sample of seafarers. Data analysis showed that 48.3% of the seafarers of the sample has herniated lumbar disc, and 34.5% of these duties in the deck, and 65.5% of the machine. The study of sample, varied as to age and task being performed, supports the assertion that the individual risk factors, especially age and obesity, are not strongly implicated in the genesis of disk herniation suffered by seafarers while the work factors (vibrations) play a more significant role in the onset of this disease. This consideration is part of a context, that of legal medical evaluation and in particular the causal relationship, which currently seems rather lacking in terms of literature and scientific production.

[Surgical treatment of thoracic disc herniation].

PubMed

Hrabálek, L; Kalita, O; Langová, K

2010-08-01

The aim of this study was to compare the efficiency of different surgical approaches to thoracic disc herniation, and to show the role of segmental fusion and selection of an appropriate microsurgical decompression technique for the successful outcome of surgery. A group of 27 patients, 10 men and 17 women, between 31 and 70 years (average age, 49.33 years) were included in this prospective study. They underwent surgery for thoracic degeneration disc disease in the period from June 1994 to August 2008. In all patients, the severity of myelopathy was assessed using the grading Frankel system and JOA score, axial and radicular pain intensity was evaluated with VAS and ODI rating systems. The diagnosis was established on the basis of thoracic spine radiography, thoracic spine MRI and a CT scan of the segment. A total of 30 thoracic segments, in the range of Th4/Th5 to Th12/L1, were indicated for surgery. Localisation of the hernia was medial at 19 segments, mediolateral at three and lateral at eight segments. Soft disc herniation was found in 17 cases and hard disc protrusion at the remaining 13 segments. Surgery for significant myelopathy was carried out in 23 patients and for pain in four patients. According to the surgical procedure used, the patients were allocated to two groups: group A comprised 10 patients treated without disc replacement through a laminectomy or a costotransversectomy exposure, and group B consisted of 17 patients undergo- ing intersomatic fusion via a thoracotomy. Clinical and radiographic examinations were made at regular intervals for at least 1 year of follow-up. The results of clinical assessment, including JOA scores, JOA Recovery Rate, VAS scores at rest and after exercise and ODI, were statistically analysed for each group and compared. There was a statistically significant difference in JOA evaluation of myelopathy between the groups in group A, the mean JOA score declined from 7.9 to 7.0, i.e., -0.9 point, while in group B it increased from 6.71 to 9.12, i.e., +2.41 points. The mean JOA Recovery Rate did not reach a plus value in group A, while in group B it improved by 55 %. JOA Recovery Rate: Of the seven patients in group A evaluated for myelopathy, a fair result was in one, unchanged in two and worse in four patients. Of the 16 patients evaluated for myelopathy in group B, the results were excellent in four, good in six, fair in four and unchanged in two patients. Frankel grade function: In group A, one patient improved by one grade, two remained unchanged, two deteriorated by one grade and two by two grades. In group B, five patients improved by one grade, two patients by two grades and two patients by three grades. Eight patients remained unchanged and no patient deteriorated. The post-operative pain intensity, as assessed by the mean VAS score, was lower at rest and after exercise in both groups; the score was better in group B, but the difference was not statistically significant. The ODI was evaluated only in group B its mean value improved from 41.4% to 26.1%, i.e., by 15.3%. Between 7 to 15 % of the patients have asymptomatic thoracic disc herniation, while symptomatic herniation is very rare and accounts for only 0.25 % to 0.57 % of herniated discs in the whole spine. Severe or progressive myelopathy is a clear indication for surgical intervention in thoracic disc herniation, but the role of surgery in pain control is controversial. There are five approaches for thoracic disc herniation. Transpleural anterolateral thoracotomy has an advantage over the other methods because it permits the treatment of all types of herniation, whether localised centrally, laterally or contralaterally, i.e., soft, calcified or sequestered intradural disc herniation. The results of treatment will depend on the outcome of surgical spinal cord decompression and the degree of spinal stabilisation achieved. The surgical procedure via thoracotomy with intersomatic fusion resulted in a statistically more significant improvement of myelopathy than the posterior approach without disc replacement, and it provided greater pain relief. The authors recommend to treat thoracic disc herniation by discectomy via a thoracotomy and by intersomatic fusion.

Consecutive light microscopy, scanning-transmission electron microscopy and transmission electron microscopy of traumatic human brain oedema and ischaemic brain damage.

PubMed

Castejon, O J; Castejon, H V; Diaz, M; Castellano, A

2001-10-01

Cortical biopsies of 11 patients with traumatic brain oedema were consecutively studied by light microscopy (LM) using thick plastic sections, scanning-transmission electron microscopy ((S)TEM) using semithin plastic sections and transmission electron microscopy (TEM) using ultrathin sections. Samples were glutaraldehyde-osmium fixed and embedded in Araldite or Epon. Thick sections were stained with toluidine-blue for light microscopy. Semithin sections were examined unstained and uncoated for (S)TEM. Ultrathin sections were stained with uranyl and lead. Perivascular haemorrhages and perivascular extravasation of proteinaceous oedema fluid were observed in both moderate and severe oedema. Ischaemic pyramidal and non-pyramidal nerve cells appeared shrunken, electron dense and with enlargement of intracytoplasmic membrane compartment. Notably swollen astrocytes were observed in all samples examined. Glycogen-rich and glycogen-depleted astrocytes were identified in anoxic-ischaemic regions. Dark and hydropic satellite, interfascicular and perivascular oligodendrocytes were also found. The status spongiosus of severely oedematous brain parenchyma observed by LM and (S)TEM was correlated with the enlarged extracellular space and disrupted neuropil observed by TEM. The (S)TEM is recommended as a suitable technique for studying pathological processes in the central nervous system and as an informative adjunct to LM and TEM.

Management of Lumbar Conditions in the Elite Athlete.

PubMed

Hsu, Wellington K; Jenkins, Tyler James

2017-07-01

Lumbar disk herniation, degenerative disk disease, and spondylolysis are the most prevalent lumbar conditions that result in missed playing time. Lumbar disk herniation has a good prognosis. After recovery from injury, professional athletes return to play 82% of the time. Surgical management of lumbar disk herniation has been shown to be a viable option in athletes in whom nonsurgical measures have failed. Degenerative disk disease is predominately genetic but may be accelerated in athletes secondary to increased physiologic loading. Nonsurgical management is the standard of care for lumbar degenerative disk disease in the elite athlete. Spondylolysis is more common in adolescent athletes with back pain than in adult athletes. Nonsurgical management of spondylolysis is typically successful. However, if surgery is required, fusion or direct pars repair can allow the patient to return to sports.

Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain.

PubMed

Green, Claudia; Minassian, Anuka; Vogel, Stefanie; Diedenhofen, Michael; Beyrau, Andreas; Wiedermann, Dirk; Hoehn, Mathias

2018-02-14

Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft ex vivo However, an assessment of the long-term functional and structural improvement in vivo is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event. SIGNIFICANCE STATEMENT In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of their influence on the whole-brain networks. Here, we have longitudinally and noninvasively monitored the structural and functional network alterations in the mouse model of focal cerebral ischemia. Structural changes of fiber-density increases are stimulated in the endogenous tissue without further modulation by the stem cells, while functional networks are stabilized by the stem cells via a paracrine effect. These results will help decipher the underlying networks of brain plasticity in response to cerebral lesions and offer clues to unravelling the mystery of how stem cells mediate regeneration. Copyright © 2018 the authors 0270-6474/18/381648-14$15.00/0.

Go with the Flow: Cerebrospinal Fluid Flow Regulates Neural Stem Cell Proliferation.

PubMed

Kaneko, Naoko; Sawamoto, Kazunobu

2018-06-01

Adult neural stem cells in the wall of brain ventricles make direct contact with cerebrospinal fluid. In this issue of Cell Stem Cell, Petrik et al. (2018) demonstrate that these neural stem cells sense the flow of cerebrospinal fluid through a transmembrane sodium channel, ENaC, which regulates their proliferation. Copyright © 2018 Elsevier Inc. All rights reserved.

Diagnosis and treatment of hyponatraemia in neurosurgical patients.

PubMed

Cuesta, Martín; Hannon, Mark J; Thompson, Christopher J

2016-05-01

Hyponatraemia is the most common electrolyte imbalance in neurosurgical patients. Acute hyponatraemia is particularly common in neurosurgical patients after any type of brain insult, including brain tumours and their treatment, pituitary surgery, subarachnoid haemorrhage or traumatic brain injury. Acute hyponatraemia is an emergency condition, as it leads to cerebral oedema due to passive osmotic movement of water from the hypotonic plasma to the relatively hypertonic brain which ultimately is the cause of the symptoms associated with hyponatraemia. These include decreased level of consciousness, seizures, non-cardiogenic pulmonary oedema or transtentorial brain herniation. Prompt treatment is mandatory to prevent such complications, minimize permanent brain damage and therefore permit rapid recovery after brain insult. The infusion of 3% hypertonic saline is the treatment of choice with different rates of administration based on the severity of symptoms and the rate of drop in plasma sodium concentration. The pathophysiology of hyponatraemia in neurotrauma is multifactorial; although the syndrome of inappropriate antidiuresis (SIADH) and central adrenal insufficiency are the commonest causes encountered. Fluid restriction has historically been the classical treatment for SIADH, although it is relatively contraindicated in some neurosurgical patients such as those with subarachnoid haemorrhage. Furthermore, many cases admitted have acute onset hyponatraemia, who require hypertonic saline infusion. The recently developed vasopressin receptor 2 antagonist class of drug is a promising and effective tool but more evidence is needed in neurosurgical patients. Central adrenal insufficiency may also cause acute hyponatraemia in neurosurgical patients; this responds clinically and biochemically to hydrocortisone. The rare cerebral salt wasting syndrome is treated with large volume normal saline infusion. In this review, we summarize the current evidence based on the clinical presentation, causes and treatment of different types of hyponatraemia in neurosurgical patients. Copyright © 2016. Published by Elsevier España, S.L.U.

A Double-Edged Sword Role for Ubiquitin-Proteasome System in Brain Stem Cardiovascular Regulation During Experimental Brain Death

PubMed Central

Wu, Carol H. Y.; Chan, Julie Y. H.; Chan, Samuel H. H.; Chang, Alice Y. W.

2011-01-01

Background Brain stem cardiovascular regulatory dysfunction during brain death is underpinned by an upregulation of nitric oxide synthase II (NOS II) in rostral ventrolateral medulla (RVLM), the origin of a life-and-death signal detected from blood pressure of comatose patients that disappears before brain death ensues. Furthermore, the ubiquitin-proteasome system (UPS) may be involved in the synthesis and degradation of NOS II. We assessed the hypothesis that the UPS participates in brain stem cardiovascular regulation during brain death by engaging in both synthesis and degradation of NOS II in RVLM. Methodology/Principal Findings In a clinically relevant experimental model of brain death using Sprague-Dawley rats, pretreatment by microinjection into the bilateral RVLM of proteasome inhibitors (lactacystin or proteasome inhibitor II) antagonized the hypotension and reduction in the life-and-death signal elicited by intravenous administration of Escherichia coli lipopolysaccharide (LPS). On the other hand, pretreatment with an inhibitor of ubiquitin-recycling (ubiquitin aldehyde) or ubiquitin C-terminal hydrolase isozyme L1 (UCH-L1) potentiated the elicited hypotension and blunted the prevalence of the life-and-death signal. Real-time polymerase chain reaction, Western blot, electrophoresis mobility shift assay, chromatin immunoprecipitation and co-immunoprecipitation experiments further showed that the proteasome inhibitors antagonized the augmented nuclear presence of NF-κB or binding between NF-κB and nos II promoter and blunted the reduced cytosolic presence of phosphorylated IκB. The already impeded NOS II protein expression by proteasome inhibitor II was further reduced after gene-knockdown of NF-κB in RVLM. In animals pretreated with UCH-L1 inhibitor and died before significant increase in nos II mRNA occurred, NOS II protein expression in RVLM was considerably elevated. Conclusions/Significance We conclude that UPS participates in the defunct and maintained brain stem cardiovascular regulation during experimental brain death by engaging in both synthesis and degradation of NOS II at RVLM. Our results provide information on new therapeutic initiatives against this fatal eventuality. PMID:22110641

Medical diagnosis imaging systems: image and signal processing applications aided by fuzzy logic

NASA Astrophysics Data System (ADS)

Hata, Yutaka

2010-04-01

First, we describe an automated procedure for segmenting an MR image of a human brain based on fuzzy logic for diagnosing Alzheimer's disease. The intensity thresholds for segmenting the whole brain of a subject are automatically determined by finding the peaks of the intensity histogram. After these thresholds are evaluated in a region growing, the whole brain can be identified. Next, we describe a procedure for decomposing the obtained whole brain into the left and right cerebral hemispheres, the cerebellum and the brain stem. Our method then identified the whole brain, the left cerebral hemisphere, the right cerebral hemisphere, the cerebellum and the brain stem. Secondly, we describe a transskull sonography system that can visualize the shape of the skull and brain surface from any point to examine skull fracture and some brain diseases. We employ fuzzy signal processing to determine the skull and brain surface. The phantom model, the animal model with soft tissue, the animal model with brain tissue, and a human subjects' forehead is applied in our system. The all shapes of the skin surface, skull surface, skull bottom, and brain tissue surface are successfully determined.

An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy.

PubMed

Kreiner, D Scott; Hwang, Steven W; Easa, John E; Resnick, Daniel K; Baisden, Jamie L; Bess, Shay; Cho, Charles H; DePalma, Michael J; Dougherty, Paul; Fernand, Robert; Ghiselli, Gary; Hanna, Amgad S; Lamer, Tim; Lisi, Anthony J; Mazanec, Daniel J; Meagher, Richard J; Nucci, Robert C; Patel, Rakesh D; Sembrano, Jonathan N; Sharma, Anil K; Summers, Jeffrey T; Taleghani, Christopher K; Tontz, William L; Toton, John F

2014-01-01

The objective of the North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Lumbar Disc Herniation with Radiculopathy is to provide evidence-based recommendations to address key clinical questions surrounding the diagnosis and treatment of lumbar disc herniation with radiculopathy. The guideline is intended to reflect contemporary treatment concepts for symptomatic lumbar disc herniation with radiculopathy as reflected in the highest quality clinical literature available on this subject as of July 2011. The goals of the guideline recommendations are to assist in delivering optimum efficacious treatment and functional recovery from this spinal disorder. To provide an evidence-based educational tool to assist spine specialists in the diagnosis and treatment of lumbar disc herniation with radiculopathy. Systematic review and evidence-based clinical guideline. This guideline is a product of the Lumbar Disc Herniation with Radiculopathy Work Group of NASS' Evidence-Based Guideline Development Committee. The work group consisted of multidisciplinary spine care specialists trained in the principles of evidence-based analysis. A literature search addressing each question and using a specific search protocol was performed on English-language references found in Medline, Embase (Drugs and Pharmacology), and four additional evidence-based databases to identify articles. The relevant literature was then independently rated using the NASS-adopted standardized levels of evidence. An evidentiary table was created for each of the questions. Final recommendations to answer each clinical question were developed via work group discussion, and grades were assigned to the recommendations using standardized grades of recommendation. In the absence of Level I to IV evidence, work group consensus statements have been developed using a modified nominal group technique, and these statements are clearly identified as such in the guideline. Twenty-nine clinical questions were formulated and addressed, and the answers are summarized in this article. The respective recommendations were graded by strength of the supporting literature, which was stratified by levels of evidence. The clinical guideline has been created using the techniques of evidence-based medicine and best available evidence to aid practitioners in the care of patients with symptomatic lumbar disc herniation with radiculopathy. The entire guideline document, including the evidentiary tables, suggestions for future research, and all the references, is available electronically on the NASS Web site at http://www.spine.org/Pages/PracticePolicy/ClinicalCare/ClinicalGuidlines/Default.aspx and will remain updated on a timely schedule. Copyright © 2014 Elsevier Inc. All rights reserved.

A role for adult TLX-positive neural stem cells in learning and behaviour.

PubMed

Zhang, Chun-Li; Zou, Yuhua; He, Weimin; Gage, Fred H; Evans, Ronald M

2008-02-21

Neurogenesis persists in the adult brain and can be regulated by a plethora of external stimuli, such as learning, memory, exercise, environment and stress. Although newly generated neurons are able to migrate and preferentially incorporate into the neural network, how these cells are molecularly regulated and whether they are required for any normal brain function are unresolved questions. The adult neural stem cell pool is composed of orphan nuclear receptor TLX-positive cells. Here, using genetic approaches in mice, we demonstrate that TLX (also called NR2E1) regulates adult neural stem cell proliferation in a cell-autonomous manner by controlling a defined genetic network implicated in cell proliferation and growth. Consequently, specific removal of TLX from the adult mouse brain through inducible recombination results in a significant reduction of stem cell proliferation and a marked decrement in spatial learning. In contrast, the resulting suppression of adult neurogenesis does not affect contextual fear conditioning, locomotion or diurnal rhythmic activities, indicating a more selective contribution of newly generated neurons to specific cognitive functions.

The Emerging Role of Epigenetics in Stroke

PubMed Central

Qureshi, Irfan A.; Mehler, Mark F.

2013-01-01

The transplantation of exogenous stem cells and the activation of endogenous neural stem and progenitor cells (NSPCs) are promising treatments for stroke. These cells can modulate intrinsic responses to ischemic injury and may even integrate directly into damaged neural networks. However, the neuroprotective and neural regenerative effects that can be mediated by these cells are limited and may even be deleterious. Epigenetic reprogramming represents a novel strategy for enhancing the intrinsic potential of the brain to protect and repair itself by modulating pathologic neural gene expression and promoting the recapitulation of seminal neural developmental processes. In fact, recent evidence suggests that emerging epigenetic mechanisms are critical for orchestrating nearly every aspect of neural development and homeostasis, including brain patterning, neural stem cell maintenance, neurogenesis and gliogenesis, neural subtype specification, and synaptic and neural network connectivity and plasticity. In this review, we survey the therapeutic potential of exogenous stem cells and endogenous NSPCs and highlight innovative technological approaches for designing, developing, and delivering epigenetic therapies for targeted reprogramming of endogenous pools of NSPCs, neural cells at risk, and dysfunctional neural networks to rescue and restore neurologic function in the ischemic brain. PMID:21403016

SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions.

PubMed

Akiguchi, Ichiro; Pallàs, Mercè; Budka, Herbert; Akiyama, Haruhiko; Ueno, Masaki; Han, Jingxian; Yagi, Hideo; Nishikawa, Tomohumi; Chiba, Yoichi; Sugiyama, Hiroshi; Takahashi, Ryoya; Unno, Keiko; Higuchi, Keiichi; Hosokawa, Masanori

2017-08-01

Senescence accelerated mice P8 (SAMP8) show significant age-related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age-associated increase of PAS-positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4-8 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem. β/A4(Aβ) protein-like immunoreactive granular structures are observed in various regions and increase in number markedly with age. Other age-associated histological changes include cortical atrophy, neuronal cell loss in locus coeruleus and lateral tegmental nuclei, intraneuronal accumulation of lipopigments in Purkinje cells and eosinophilic inclusion bodies in thalamic neurons. A blood-brain barrier dysfunction and astrogliosis are also prominent with advancing age in the hippocampus. These changes are generally similar to the pathomorphology of aging human brains and characterized by their association with some specific glioneuronal reactions. As for the hallmarks of Alzheimer brains, tau morphology has not yet been confirmed regardless of the age-related increase in phosphorylated tau in SAMP8 mice brains, but early age-related Aβ deposition in the hippocampus has recently been published. SAMP8 mice are, therefore, not only a senescence-accelerated model but also a promising model for Alzheimer's disease and other cognitive disorders. © 2017 Japanese Society of Neuropathology.

Wiring Pathways to Replace Aggression

ERIC Educational Resources Information Center

Bath, Howard

2006-01-01

The previous article in this series introduced the triune brain, the three components of which handle specialized life tasks. The survival brain, or brain stem, directs automatic physiological functions, such as heartbeat and breathing, and mobilizes fight/flight behaviour in times of threat. The emotional (or limbic) brain activates positive or…

A GIANT RETROPERITONEAL LIPOMA PRESENTING AS A SCIATIC HERNIA: MRI FINDINGS.

PubMed

Duran, S; Cavusoglu, M; Elverici, E; Unal, T D

2015-01-01

Sciatic hernia is a rare condition and its clinical diagnosis is uneasy. Herniation of pelvic organs as well as of retroperitoneal neoplasm has been reported in the literature. Sciatica occurs as a result of compression of the sciatic nerve by the herniated sac. We present a case of retroperitoneal lipoma in a patient who had lower leg complaint and describe the imaging findings.

Prognostic value of magnetic resonance imaging findings in patients with sciatica.

PubMed

El Barzouhi, Abdelilah; Verwoerd, Annemieke J H; Peul, Wilco C; Verhagen, Arianne P; Lycklama À Nijeholt, Geert J; Van der Kallen, Bas F; Koes, Bart W; Vleggeert-Lankamp, Carmen L A M

2016-06-01

OBJECTIVE This study aimed to determine the prognostic value of MRI variables to predict outcome in patients with herniated disc-related sciatica, and whether MRI could facilitate the decision making between early surgery and prolonged conservative care in these patients. METHODS A prospective observational evaluation of patients enrolled in a randomized trial with 1-year follow-up was completed. A total of 283 patients with sciatica who had a radiologically confirmed disc herniation were randomized either to surgery or to prolonged conservative care with surgery if needed. Outcome measures were recovery and leg pain severity. Recovery was registered on a 7-point Likert scale. Complete/near complete recovery was considered a satisfactory outcome. Leg pain severity was measured on a 0- to 100-mm visual analog scale. Multiple MRI characteristics of the degenerated disc herniation were independently scored by 3 spine experts. Cox models were used to study the influence of MRI variables on rate of recovery, and linear mixed models were used to determine the predictive value of MRI variables for leg pain severity during follow-up. The interaction of each MRI predictor with treatment allocation was tested. There were no study-specific conflicts of interest. RESULTS Baseline MRI variables associated with less leg pain severity were the reader's assessment of presence of nerve root compression (p < 0.001), and assessment of extrusion compared with protrusion of the disc herniation (p = 0.006). Both variables tended to be associated, but not significantly, with satisfactory outcome during follow-up (HR 1.45, 95% CI 0.93-2.24, and HR 1.24, 95% CI 0.96-1.61, respectively). The size of disc herniation at baseline was not associated with outcome. There was no significant change in the effects between treatment groups. CONCLUSIONS MRI assessment of the presence of nerve root compression and extrusion of a herniated disc at baseline was associated with less leg pain during 1-year follow-up, irrespective of a surgical or conservative treatment. MRI findings seem not to be helpful in determining which patients might fare better with early surgery compared with a strategy of prolonged conservative care. Clinical trial registration no.: ISRCTN26872154 ( controlled-trials.com ).

Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

PubMed Central

Zhou, Hai-xiao; Liu, Zhi-gang; Liu, Xiao-jiao; Chen, Qian-xue

2016-01-01

Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO) treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid (2.5–3.0 atm impact force). The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions. PMID:26981097

Knowledge and attitudes of nurses on a regional neurological intensive therapy unit towards brain stem death and organ donation.

PubMed

Davies, C

1997-01-01

The study aimed to explore nurses knowledge and attitudes towards brain stem death and organ donation. An ex post facto research design was used to determine relationships between variables. A 16 item questionnaire was used to collect data. Statistical analysis revealed one significant result. The limitations of the sample size is acknowledged and the conclusion suggests a larger study is required.

Novel Regenerative Therapies Based on Regionally Induced Multipotent Stem Cells in Post-Stroke Brains: Their Origin, Characterization, and Perspective.

PubMed

Takagi, Toshinori; Yoshimura, Shinichi; Sakuma, Rika; Nakano-Doi, Akiko; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-12-01

Brain injuries such as ischemic stroke cause severe neural loss. Until recently, it was believed that post-ischemic areas mainly contain necrotic tissue and inflammatory cells. However, using a mouse model of cerebral infarction, we demonstrated that stem cells develop within ischemic areas. Ischemia-induced stem cells can function as neural progenitors; thus, we initially named them injury/ischemia-induced neural stem/progenitor cells (iNSPCs). However, because they differentiate into more than neural lineages, we now refer to them as ischemia-induced multipotent stem cells (iSCs). Very recently, we showed that putative iNSPCs/iSCs are present within post-stroke areas in human brains. Because iNSPCs/iSCs isolated from mouse and human ischemic tissues can differentiate into neuronal lineages in vitro, it is possible that a clearer understanding of iNSPC/iSC profiles and the molecules that regulate iNSPC/iSC fate (e.g., proliferation, differentiation, and survival) would make it possible to perform neural regeneration/repair in patients following stroke. In this article, we introduce the origin and traits of iNSPCs/iSCs based on our reports and recent viewpoints. We also discuss their possible contribution to neurogenesis through endogenous and exogenous iNSPC/iSC therapies following ischemic stroke.

Neuronal sources of hedgehog modulate neurogenesis in the adult planarian brain.

PubMed

Currie, Ko W; Molinaro, Alyssa M; Pearson, Bret J

2016-11-19

The asexual freshwater planarian is a constitutive adult, whose central nervous system (CNS) is in a state of constant homeostatic neurogenesis. However, very little is known about the extrinsic signals that act on planarian stem cells to modulate rates of neurogenesis. We have identified two planarian homeobox transcription factors, Smed-nkx2.1 and Smed-arx , which are required for the maintenance of cholinergic, GABAergic, and octopaminergic neurons in the planarian CNS. These very same neurons also produce the planarian hedgehog ligand ( Smed-hh ), which appears to communicate with brain-adjacent stem cells to promote normal levels of neurogenesis. Planarian stem cells nearby the brain express core hh signal transduction genes, and consistent hh signaling levels are required to maintain normal production of neural progenitor cells and new mature cholinergic neurons, revealing an important mitogenic role for the planarian hh signaling molecule in the adult CNS.

A Case of Myxedema Coma Presenting as a Brain Stem Infarct in a 74-Year-Old Korean Woman

PubMed Central

Ahn, Ji Yun; Kwon, Hyuk-Sool; Ahn, Hee Chol

2010-01-01

Myxedema coma is the extreme form of untreated hypothyroidism. In reality, few patients present comatose with severe myxedema. We describe a patient with myxedema coma which was initially misdiagnosed as a brain stem infarct. She presented to the hospital with alteration of the mental status, generalized edema, hypothermia, hypoventilation, and hypotension. Initially her brain stem reflexes were absent. After respiratory and circulatory support, her neurologic status was not improved soon. The diagnosis of myxedema coma was often missed or delayed due to various clinical findings and concomitant medical condition and precipitating factors. It is more difficult to diagnose when a patient has no medical history of hypothyroidism. A high index of clinical suspicion can make a timely diagnosis and initiate appropriate treatment. We report this case to alert clinicians considering diagnosis of myxedema coma in patients with severe decompensated metabolic state including mental change. PMID:20808690

A case of myxedema coma presenting as a brain stem infarct in a 74-year-old Korean woman.

PubMed

Ahn, Ji Yun; Kwon, Hyuk-Sool; Ahn, Hee Chol; Sohn, You Dong

2010-09-01

Myxedema coma is the extreme form of untreated hypothyroidism. In reality, few patients present comatose with severe myxedema. We describe a patient with myxedema coma which was initially misdiagnosed as a brain stem infarct. She presented to the hospital with alteration of the mental status, generalized edema, hypothermia, hypoventilation, and hypotension. Initially her brain stem reflexes were absent. After respiratory and circulatory support, her neurologic status was not improved soon. The diagnosis of myxedema coma was often missed or delayed due to various clinical findings and concomitant medical condition and precipitating factors. It is more difficult to diagnose when a patient has no medical history of hypothyroidism. A high index of clinical suspicion can make a timely diagnosis and initiate appropriate treatment. We report this case to alert clinicians considering diagnosis of myxedema coma in patients with severe decompensated metabolic state including mental change.

Early awareness of cerebrospinal fluid hypovolemia after craniotomy for microsurgical aneurysmal clipping.

PubMed

Kawahara, Ichiro; Tsutsumi, Keisuke; Matsunaga, Yuki; Takahata, Hideaki; Ono, Tomonori; Toda, Keisuke; Baba, Hiroshi

2013-08-01

Mild cerebrospinal fluid (CSF) hypovolemia is a well-known clinical entity, but critical CSF hypovolemia that can cause transtentorial herniation is an unusual and rare clinical entity that occurs after craniotomy. We investigated CSF hypovolemia after microsurgical aneurysmal clipping for subarachnoid hemorrhage (SAH). This study included 144 consecutive patients with SAH. Lumbar drainage (LD) was inserted after general anesthesia or postoperatively as a standard perioperative protocol. CSF hypovolemia diagnosis was based on three criteria. Eleven patients (7.6%) were diagnosed with CSF hypovolemia according to diagnostic criteria in a postoperative range of 0-8 days. In all patients, signs or symptoms of CSF hypovolemia improved within 24 hours by clamping LD and using the Trendelenburg position. As a cause of acute clinical deterioration after aneurysmal clipping, CSF hypovolemia is likely under-recognized, and may actually be misdiagnosed as vasospasm or brain swelling. We should always take the etiology of CSF hypovolemia into consideration, and especially pay attention in patients with pneumocephalus and subdural fluid collection alongside brain sag on computed tomography. These patients are at higher risk developing of pressure gradients between their cranial and spinal compartments, and therefore, brain sagging after LD, than after ventricular drainage. We should be vigilant to strictly manage LD so as not to produce high pressure gradients.

Intracerebral hemorrhage with a favorable outcome in a patient with childhood primary angiitis of the central nervous system.

PubMed

Silva, Marco Felipe; Feitosa, Ana Raquel; Paz, José A; Aikawa, Nádia Emi; Silva, Clovis A

2016-01-01

Childhood primary angiitis of the central nervous system (cPACNS) is a rare inflammatory brain disease of unknown etiology. Of note, brain hemorrhage has been rarely reported in cPACNS patients, generally associated with a delayed clinical diagnosis, or with a diagnosis only at necropsy. We present the case of a boy with cPACNS that previously suffered an ischemic stroke. At the age of 7 years and 10 months, he presented a sudden and severe headache, vomiting and reduction in consciousness level (Glasgow coma scale 7), requiring prompt tracheal intubation. Brain computed tomography demonstrated intraparenchymal hematoma in the right parieto-occipital lobe and a small focus of bleeding in the right frontal lobe, vasogenic edema, herniation of the uncus and a 10mm deviation to the left from the midline. C-reactive protein (9.2mg/dL) and von Willebrand factor (vWF) antigen (202%) were elevated. Decompressive craniotomy was performed and methylprednisolone and cyclophosphamide were administered. One week later, the patient had left hemiparesis without other sequelae. Importantly, motor deficits have been improving progressively. Our case reinforces the inclusion of this vasculitis as a differential diagnosis in children and adolescents with CNS hemorrhage. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Congenital asymptomatic diaphragmatic hernias in adults: a case series

PubMed Central

2013-01-01

Introduction Congenital diaphragmatic hernia is a major malformation occasionally found in newborns and babies. Congenital diaphragmatic hernia is defined by the presence of an orifice in the diaphragm, more often to the left and posterolateral, that permits the herniation of abdominal contents into the thorax. The aim of this case series is to provide information on the presentation, diagnosis and outcome of three patients with late-presenting congenital diaphragmatic hernias. The diagnosis of congenital diaphragmatic hernia is based on clinical investigation and is confirmed by plain X-ray films and computed tomography scans. Case presentations In the present report three cases of asymptomatic abdominal viscera herniation within the thorax are described. The first case concerns herniation of some loops of the large intestine into the left hemi-thorax in a 75-year-old Caucasian Italian woman. The second case concerns a rare type of herniation in the right side of the thorax of the right kidney with a part of the liver parenchyma in a 57-year-old Caucasian Italian woman. The third case concerns herniation of the stomach and bowel into the left side of the chest with compression of the left lung in a 32-year-old Caucasian Italian man. This type of hernia may appear later in life, because of concomitant respiratory or gastrointestinal disease, or it may be an incidental finding in asymptomatic adults, such as in the three cases featured here. Conclusions Patients who present with late diaphragmatic hernias complain of a wide variety of symptoms, and diagnosis may be difficult. Additional investigation and research appear necessary to better explain the development and progression of this type of disease. PMID:23668793

Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation

PubMed Central

Dong, Dayong; Xue, Jinbiao; Zheng, Xiaoting

2018-01-01

Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group (n = 35) and control group (n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group (P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups (P < 0.05) also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications. PMID:29785195

Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation.

PubMed

Cai, Chunyue; Gong, Yuefeng; Dong, Dayong; Xue, Jinbiao; Zheng, Xiaoting; Zhong, Zhangfeng; Shao, Jialong; Mi, Daguo

2018-01-01

Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group ( n = 35) and control group ( n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group ( P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups ( P < 0.05) also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications.

Reliability of cervical radiculopathy, its congruence between patient history and medical imaging evidence of disc herniation and its role in surgical decision.

PubMed

Mostofi, Keyvan; Khouzani, Reza Karimi

2016-10-01

The incidence of cervical disc herniation is estimated about 5.5/100,000, and they lead to surgical intervention in 26 %. Cervical disc herniation causes radiculopathy, which defines by radicular pain and sensory deficit and maybe weakness following the path of the affected nerves. Classically, cervical radiculopathy is expected to follow its specific dermatome-C4, C5, C6, C7 and C8. We investigate patients who present with discrepancy between classical radiculopathy and imaging findings in the daily practice of our profession. We reviewed the medical records of 102 patients with cervical radiculopathy, caused by cervical disc herniation. All patients had surgery. We found an apparent discrepancy between clinical and radiological findings, patients complained of radiculopathy on one side, and magnetic resonance imaging (MRI) scan or CT scan finding on the other side in ten patients (10.2 %). We did not found any other abnormalities in preoperative and post-operative period. All patients underwent cervical diskectomy via anterior approach. Six weeks after surgery eight patients (80 %) recovered completely, and 3 months after all ten patients (100 %) had been relieved totally. The aim of this paper is review of this medical concept and management of radiculopathy in patients with this discrepancy. As far as we know, the subject has not yet been touched in this light in medical literature. The discrepancy between clinical radiculopathy and disc herniation level on MRI or on CT scan is not rare. Management of this discrepancy requires further investigation to avoid missing diagnosis and treatment failure.

Cervical disc hernia operations through posterior laminoforaminotomy.

PubMed

Yolas, Coskun; Ozdemir, Nuriye Guzin; Okay, Hilmi Onder; Kanat, Ayhan; Senol, Mehmet; Atci, Ibrahim Burak; Yilmaz, Hakan; Coban, Mustafa Kemal; Yuksel, Mehmet Onur; Kahraman, Umit

2016-01-01

The most common used technique for posterolateral cervical disc herniations is anterior approach. However, posterior cervical laminotoforaminomy can provide excellent results in appropriately selected patients with foraminal stenosis in either soft disc prolapse or cervical spondylosis. The purpose of this study was to present the clinical outcomes following posterior laminoforaminotomy in patients with radiculopathy. We retrospectively evaluated 35 patients diagnosed with posterolateral cervical disc herniation and cervical spondylosis with foraminal stenosis causing radiculopathy operated by the posterior cervical keyhole laminoforaminotomy between the years 2010 and 2015. The file records and the radiographic images of the 35 patients were assessed retrospectively. The mean age was 46.4 years (range: 34-66 years). Of the patients, 19 were males and 16 were females. In all of the patients, the neurologic deficit observed was radiculopathy. The posterolaterally localized disc herniations and the osteophytic structures were on the left side in 18 cases and on the right in 17 cases. In 10 of the patients, the disc level was at C5-6, in 18 at C6-7, in 2 at C3-4, in 2 at C4-5, in 1 at C7-T1, in 1 patient at both C5-6 and C6-7, and in 1 at both C4-5 and C5-6. In 14 of these 35 patients, both osteophytic structures and protruded disc herniation were present. Intervertebral foramen stenosis was present in all of the patients with osteophytes. Postoperatively, in 31 patients the complaints were relieved completely and four patients had complaints of neck pain and paresthesia radiating to the arm (the success of operation was 88.5%). On control examinations, there was no finding of instability or cervical kyphosis. Posterior cervical laminoforaminotomy is an alternative appropriate choice in both cervical soft disc herniations and cervical stenosis.

Transforaminal epidural steroid injections followed by mechanical diagnosis and therapy to prevent surgery for lumbar disc herniation.

PubMed

van Helvoirt, Hans; Apeldoorn, Adri T; Ostelo, Raymond W; Knol, Dirk L; Arts, Mark P; Kamper, Steven J; van Tulder, Maurits W

2014-07-01

Prospective cohort study. To report the clinical course of patients with MRI-confirmed lumbar disc herniation-related radicular noncentralizing pain who received transforaminal epidural steroid injections (TESIs) and mechanical diagnosis and therapy (MDT). Noncentralizing symptoms in patients with lumbar disc herniation are associated with poor outcome. Commonly used treatments for these patients include TESIs and MDT. No study has evaluated the outcome of combining both strategies. Consecutive candidates for herniated lumbar disc surgery with noncentralizing chronic pain were eligible. Patients received TESIs followed by MDT. The primary outcomes were pain severity in the leg, disability (Roland-Morris Disability Questionnaire for Sciatica), and global perceived effect (GPE). Outcomes were measured at baseline, discharge, and 12 months. Linear mixed-models and McNemar's tests were used to analyze outcome data. Sixty-nine patients receive TESIs. After TESIs, symptoms were resolved completely in 11 patients (16%). In these patients, symptom resolution was maintained at 12 months. A second subgroup of 32 patients (46%) reported significantly less pain after TESIs and showed centralization with MDT reassessment (significant reductions in leg pain and disability [P < 0.001]) and a satisfaction rate of 90% at 12 months. A third subgroup of 11 patients (16%) reported significantly less pain after TESIs but still showed noncentralization with MDT reassessment (significant reductions in leg pain and disability [P < 0.05] and a satisfaction rate of 50% at 12 months). A fourth subgroup of 15 patients (22%) did not respond on TESIs and received an operative intervention. The results indicate that a course of TESIs followed by MDT may be able to avoid surgery in a substantial proportion of candidates for herniated lumbar disc surgery. Wiley Periodicals, Inc.

Emergency Medicine Myths: Computed Tomography of the Head Prior to Lumbar Puncture in Adults with Suspected Bacterial Meningitis - Due Diligence or Antiquated Practice?

PubMed

April, Michael D; Long, Brit; Koyfman, Alex

2017-09-01

Various sources purport an association between lumbar puncture and brainstem herniation in patients with intracranial mass effect lesions. Several organizations and texts recommend head computed tomography (CT) prior to lumbar puncture in selected patients. To review the evidence regarding the utility of obtaining head CT prior to lumbar puncture in adults with suspected bacterial meningitis. Observational studies report a risk of post-lumbar puncture brainstem herniation in the presence of intracranial mass effect (1.5%) that is significantly lower than that reported among all patients with bacterial meningitis (up to 13.3%). It is unclear from existing literature whether identifying patients with intracranial mass effect decreases herniation risk. Up to 80% of patients with bacterial meningitis experiencing herniation have no CT abnormalities, and approximately half of patients with intracranial mass effect not undergoing lumbar puncture herniate. Decision rules to selectively perform CT on only those individuals most likely to have intracranial mass effect lesions have not undergone validation. Despite recommendations for immediate antimicrobial therapy prior to imaging, data indicate an association between pre-lumbar puncture CT and antibiotic delays. Recent data demonstrate shortened door-to-antibiotic times and lower mortality from bacterial meningitis after implementation of new national guidelines, which restricted generally accepted CT indications by removing impaired mental status as imaging criterion. Data supporting routine head CT prior to lumbar puncture are limited. Physicians should consider selective CT for those patients at risk for intracranial mass effect lesions based on decision rules or clinical gestalt. Patients undergoing head CT must receive immediate antibiotic therapy. Published by Elsevier Inc.

Imaging Determinants of Clinical Effectiveness of Lumbar Transforaminal Epidural Steroid Injections.

PubMed

Maus, Timothy P; El-Yahchouchi, Christine A; Geske, Jennifer R; Carter, Rickey E; Kaufmann, Timothy J; Wald, John T; Diehn, Felix E

2016-12-01

To examine associations between imaging characteristics of compressive lesions and patient outcomes after lumbar transforaminal epidural steroid injections (TFESIs) stratified by steroid formulation (solution versus suspension). Retrospective observational study, academic radiology practice. A 516-patient sample was selected from 2,634 consecutive patients receiving lumbar TFESI for radicular pain. The advanced imaging study(s) preceding sampled TFESI were reviewed. Compressive lesions were described by a) nature of the lesion [disc herniation, fixed stenosis, synovial cyst, epidural fibrosis, no lesion] b) degree of neural compression [4 part scale], and c) presence of a tandem lesion. Associations between 2-month categorical outcomes (responder rates for pain, functional recovery) and imaging characteristics, stratified by steroid formulation, were examined with chi-squared tests of categorical outcomes and multivariable logistic regression models. Disc herniation patients had more responders for functional recovery than patients with fixed lesions (54% versus 38%, P = 0.01). Patients with fixed lesions receiving steroid solution (dexamethasone) had more responders for pain relief, with a similar trend for functional recovery, than patients receiving suspensions (59% versus 40%, P = 0.01). Outcomes for patients with fixed lesions treated with dexamethasone were not statistically different from those for disc herniation patients. Patients with single compressive lesions had more responders than those with tandem lesions (55% versus 41%, P = 0.03). In the entire sample, outcomes for disc herniations were more favorable than for fixed lesions. However, fixed lesions treated with dexamethasone had outcomes indistinguishable from disc herniations. Single lesions had better outcomes than tandem lesions. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Anterior herniation of lumbar disc induces persistent visceral pain: discogenic visceral pain: discogenic visceral pain.

PubMed

Tang, Yuan-Zhang; Shannon, Moore-Langston; Lai, Guang-Hui; Li, Xuan-Ying; Li, Na; Ni, Jia-Xiang

2013-01-01

Visceral pain is a common cause for seeking medical attention. Afferent fibers innervating viscera project to the central nervous system via sympathetic nerves. The lumbar sympathetic nerve trunk lies in front of the lumbar spine. Thus, it is possible for patients to suffer visceral pain originating from sympathetic nerve irritation induced by anterior herniation of the lumbar disc. This study aimed to evaluate lumbar discogenic visceral pain and its treatment. Twelve consecutive patients with a median age of 56.4 years were enrolled for investigation between June 2012 and December 2012. These patients suffered from long-term abdominal pain unresponsive to current treatment options. Apart from obvious anterior herniation of the lumbar discs and high signal intensity anterior to the herniated disc on magnetic resonance imaging, no significant pathology was noted on gastroscopy, vascular ultrasound, or abdominal computed tomography (CT). To prove that their visceral pain originated from the anteriorly protruding disc, we evaluated whether pain was relieved by sympathetic block at the level of the anteriorly protruding disc. If the block was effective, CT-guided continuous lumbar sympathetic nerve block was finally performed. All patients were positive for pain relief by sympathetic block. Furthermore, the average Visual Analog Scale of visceral pain significantly improved after treatment in all patients (P < 0.05). Up to 11/12 patients had satisfactory pain relief at 1 week after discharge, 8/12 at 4 weeks, 7/12 at 8 weeks, 6/12 at 12 weeks, and 5/12 at 24 weeks. It is important to consider the possibility of discogenic visceral pain secondary to anterior herniation of the lumbar disc when forming a differential diagnosis for seemingly idiopathic abdominal pain. Continuous lumbar sympathetic nerve block is an effective and safe therapy for patients with discogenic visceral pain.

Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas

ClinicalTrials.gov

2015-12-14

Adult Brain Tumor; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Melanocytic Lesion; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma; Adult Pineocytoma; Recurrent Adult Brain Tumor

[Clinical-neuropsychological study of patients with hematomas, cavernomas and arteriovenous malformations of the brain stem].

PubMed

Buklina, S B; Gavriushin, A V; Okishev, D N

2009-01-01

A clinical-neuropsychological study of 25 patients with hematomas, cavernomas and arteriovenous malformations of different brain stem regions has been performed. Patients with hydrocephalic-hypertensive and dislocation syndromes as well as a history of neurological diseases were excluded from the study. All patients had hemorrhages in different brain stem regions, most of which had occurred several weeks ago. Hematomas were located in different regions of the pons (14 patients) and midbrain (7 patients) and spread to both regions in 4 patients. All patients underwent MRI study of the brain and complex neuropsychological investigation using the A.R. Luria's method. Neuropsychological symptoms before the surgery were found in 20 patients. Cognitive disturbances similar by the lesion of frontal lobes, in particular the promoter zone, that manifested themselves in disturbances of dynamic praxis, writing, verbal memory, were observed most often. Cognitive disturbances similar by the lesion of occipital hemisphere regions, i.e. disturbances of visual gnosis and spatial defects, were found less often. The most severe symptoms were observed in the lesion of the midbrain and upper regions of the pons.

Astrocyte-Secreted Factors Selectively Alter Neural Stem and Progenitor Cell Proliferation in the Fragile X Mouse

PubMed Central

Sourial, Mary; Doering, Laurie C.

2016-01-01

An increasing body of evidence indicates that astrocytes contribute to the governance and fine tuning of stem and progenitor cell production during brain development. The effect of astrocyte function in cell production in neurodevelopmental disorders is unknown. We used the Neural Colony Forming Cell assay to determine the effect of astrocyte conditioned media (ACM) on the generation of neurospheres originating from either progenitor cells or functional stem cells in the knock out (KO) Fragile X mouse model. ACM from both normal and Fmr1-KO mice generated higher percentages of smaller neurospheres indicative of restricted proliferation of the progenitor cell population in Fmr1-KO brains. Wild type (WT) neurospheres, but not KO neurospheres, showed enhanced responses to ACM from the Fmr1-KO mice. In particular, Fmr1-KO ACM increased the percentage of large neurospheres generated, representative of spheres produced from neural stem cells. We also used 2D DIGE to initiate identification of the astrocyte-secreted proteins with differential expression between Fmr1-KO and WT cortices and hippocampi. The results further support the critical role of astrocytes in governing neural cell production in brain development and point to significant alterations in neural cell proliferation due to astrocyte secreted factors from the Fragile X brain. Highlights: • We studied the proliferation of neural stem and progenitor cells in Fragile X. • We examined the role of astrocyte-secreted factors in neural precursor cell biology. • Astrocyte-secreted factors with differential expression in Fragile X identified. PMID:27242437

[Fetal magnetic resonance imaging evaluation of congenital diaphragmatic hernia].

PubMed

Sebastià, C; Garcia, R; Gomez, O; Paño, B; Nicolau, C

2014-01-01

A diaphragmatic hernia is defined as the protrusion of abdominal viscera into the thoracic cavity through a normal or pathological orifice. The herniated viscera compress the lungs, resulting in pulmonary hypoplasia and secondary pulmonary hypertension, which are the leading causes of neonatal death in patients with congenital diaphragmatic hernia. Congenital diaphragmatic hernia is diagnosed by sonography in routine prenatal screening. Although magnetic resonance imaging is fundamentally used to determine whether the liver is located within the abdomen or has herniated into the thorax, it also can provide useful information about other herniated structures and the degree of pulmonary hypoplasia. The aim of this article is to review the fetal magnetic resonance findings for congenital diaphragmatic hernia and the signs that enable us to establish the neonatal prognosis when evaluating pulmonary hypoplasia. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling.

PubMed

Dong, Huimin; Lin, Xi; Li, Yuntao; Hu, Ronghua; Xu, Yang; Guo, Xiaojie; La, Qiong; Wang, Shun; Fang, Congcong; Guo, Junli; Li, Qi; Mao, Shanping; Liu, Baohui

2017-10-31

Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro , resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.

STEM Tones Pre-Activate Suffixes in the Brain

ERIC Educational Resources Information Center

Söderström, Pelle; Horne, Merle; Roll, Mikael

2017-01-01

Results from the present event-related potentials (ERP) study show that tones on Swedish word stems can rapidly pre-activate upcoming suffixes, even when the word stem does not carry any lexical meaning. Results also show that listeners are able to rapidly restore suffixes which are replaced with a cough. Accuracy in restoring suffixes correlated…

A PITX3-EGFP Reporter Line Reveals Connectivity of Dopamine and Non-dopamine Neuronal Subtypes in Grafts Generated from Human Embryonic Stem Cells.

PubMed

Niclis, Jonathan C; Gantner, Carlos W; Hunt, Cameron P J; Kauhausen, Jessica A; Durnall, Jennifer C; Haynes, John M; Pouton, Colin W; Parish, Clare L; Thompson, Lachlan H

2017-09-12

Development of safe and effective stem cell-based therapies for brain repair requires an in-depth understanding of the in vivo properties of neural grafts generated from human stem cells. Replacing dopamine neurons in Parkinson's disease remains one of the most anticipated applications. Here, we have used a human PITX3-EGFP embryonic stem cell line to characterize the connectivity of stem cell-derived midbrain dopamine neurons in the dopamine-depleted host brain with an unprecedented level of specificity. The results show that the major A9 and A10 subclasses of implanted dopamine neurons innervate multiple, developmentally appropriate host targets but also that the majority of graft-derived connectivity is non-dopaminergic. These findings highlight the promise of stem cell-based procedures for anatomically correct reconstruction of specific neuronal pathways but also emphasize the scope for further refinement in order to limit the inclusion of uncharacterized and potentially unwanted cell types. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Reduction in nerve root compression by the nucleus pulposus after Feng's Spinal Manipulation☆

PubMed Central

Feng, Yu; Gao, Yan; Yang, Wendong; Feng, Tianyou

2013-01-01

Ninety-four patients with lumbar intervertebral disc herniation were enrolled in this study. Of these, 48 were treated with Feng's Spinal Manipulation, hot fomentation, and bed rest (treatment group). The remaining 46 patients were treated with hot fomentation and bed rest only (control group). After 3 weeks of treatment, clinical parameters including the angle of straight-leg raising, visual analogue scale pain score, and Japanese Orthopaedic Association score for low back pain were improved. The treatment group had significantly better improvement in scores than the control group. Magnetic resonance myelography three-dimensional reconstruction imaging of the vertebral canal demonstrated that filling of the compressed nerve root sleeve with cerebrospinal fluid increased significantly in the treatment group. The diameter of the nerve root sleeve was significantly larger in the treatment group than in the control group. However, the sagittal diameter index of the herniated nucleus pulposus and the angle between the nerve root sleeve and the thecal sac did not change significantly in either the treatment or control groups. The effectiveness of Feng's Spinal Manipulation for the treatment of symptoms associated with lumbar intervertebral disc herniation may be attributable to the relief of nerve root compression, without affecting the herniated nucleus pulposus or changing the morphology or position of the nerve root. PMID:25206408

Chemonucleolysis for relief of sciatica due to a herniated intervertebral disc.

PubMed Central

McCulloch, J A

1981-01-01

Chemonucleolysis is the nonoperative chemical removal of displaced lumbar disc material. The enzyme chymopapain, which has a wide margin of safety between its effective therapeutic and toxic doses, is effective in the management of sciatica due to a herniated intervertebral disc. The patient will have leg pain as the dominant symptom and a 50% reduction in straight-leg raising with or without bowstring discomfort and crossover pain. Neurologic symptoms and signs are usual, as are abnormal results of contrast studies, which will verify the level of involvement. In 220 randomly selected patients who met criteria for the diagnosis of sciatica due to a herniated intervertebral disc and did not have psychogenic or nonorganic spinal pain, a spinal stenosis or a history of a previous, unsuccessful operation to relieve the sciatica, chemonucleolysis had a success rate of 80%. The only complications were a severe anaphylactic reaction in two patients and lesser, delayed reactions in five others. All of the reactions were successfully treated. Of the 45 patients in whom chemonucleolysis was unsuccessful, 38 underwent a laminectomy. In 3 of the 38 the results of chemonucleolysis were initially good, but later the disc herniation recurred; thus, the long-term treatment failure rate was 1.4%. PMID:7011530

The number of stem cells in the subependymal zone of the adult rodent brain is correlated with the number of ependymal cells and not with the volume of the niche.

PubMed

Kazanis, Ilias; Ffrench-Constant, Charles

2012-05-01

The mammalian subependymal zone (SEZ; often called subventricular) situated at the lateral walls of the lateral ventricles of the brain contains a pool of relatively quiescent adult neural stem cells whose neurogenic activity persists throughout life. These stem cells are positioned in close proximity both to the ependymal cells that provide the cerebrospinal fluid interface and to the blood vessel endothelial cells, but the relative contribution of these 2 cell types to stem cell regulation remains undetermined. Here, we address this question by analyzing a naturally occurring example of volumetric scaling of the SEZ in a comparison of the mouse SEZ with the larger rat SEZ. Our analysis reveals that the number of stem cells in the SEZ niche is correlated with the number of ependymal cells rather than with the volume, thereby indicating the importance of ependymal-derived factors in the formation and function of the SEZ. The elucidation of the factors generated by ependymal cells that regulate stem cell numbers within the SEZ is, therefore, of importance for stem cell biology and regenerative neuroscience.

Adult human neural stem cell therapeutics: Current developmental status and prospect.

PubMed

Nam, Hyun; Lee, Kee-Hang; Nam, Do-Hyun; Joo, Kyeung Min

2015-01-26

Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as cell therapeutics for neurological disease. Compared with other types of stem cells, aNSCs have clinical advantages, such as limited proliferation, inborn differentiation potential into functional neural cells, and no ethical issues. In spite of the merits of aNSCs, difficulties in the isolation from the normal brain, and in the in vitro expansion, have blocked preclinical and clinical study using aNSCs. However, several groups have recently developed novel techniques to isolate and expand aNSCs from normal adult brains, and showed successful applications of aNSCs to neurological diseases. With new technologies for aNSCs and their clinical strengths, previous hurdles in stem cell therapies for neurological diseases could be overcome, to realize clinically efficacious regenerative stem cell therapeutics.

Syringe needle skull penetration reduces brain injuries and secondary inflammation following intracerebral neural stem cell transplantation.

PubMed

Gao, Mou; Dong, Qin; Zhang, Hongtian; Yang, Yang; Zhu, Jianwei; Yang, Zhijun; Xu, Minhui; Xu, Ruxiang

2017-03-01

Intracerebral neural stem cell (NSC) transplantation is beneficial for delivering stem cell grafts effectively, however, this approach may subsequently result in brain injury and secondary inflammation. To reduce the risk of promoting brain injury and secondary inflammation, two methods were compared in the present study. Murine skulls were penetrated using a drill on the left side and a syringe needle on the right. Mice were randomly divided into three groups (n=84/group): Group A, receiving NSCs in the left hemisphere and PBS in the right; group B, receiving NSCs in the right hemisphere and PBS in the left; and group C, receiving equal NSCs in both hemispheres. Murine brains were stained for morphological analysis and subsequent evaluation of infiltrated immune cells. ELISA was performed to detect neurotrophic and immunomodulatory factors in the brain. The findings indicated that brain injury and secondary inflammation in the left hemisphere were more severe than those in the right hemisphere, following NSC transplantation. In contrast to the left hemisphere, more neurotrophic factors but less pro-inflammatory cytokines were detected in the right hemisphere. In addition, increased levels of neurotrophic factors and interleukin (IL)-10 were observed in the NSC transplantation side when compared with the PBS-treated hemispheres, although lower levels of IL-6 and tumor necrosis factor-α were detected. In conclusion, the present study indicated that syringe needle skull penetration vs. drill penetration is an improved method that reduces the risk of brain injury and secondary inflammation following intracerebral NSC transplantation. Furthermore, NSCs have the potential to modulate inflammation secondary to brain injuries.

A Brain Unfixed: Unlimited Neurogenesis and Regeneration of the Adult Planarian Nervous System

PubMed Central

Brown, David D. R.; Pearson, Bret J.

2017-01-01

Powerful genetic tools in classical laboratory models have been fundamental to our understanding of how stem cells give rise to complex neural tissues during embryonic development. In contrast, adult neurogenesis in our model systems, if present, is typically constrained to one or a few zones of the adult brain to produce a limited subset of neurons leading to the dogma that the brain is primarily fixed post-development. The freshwater planarian (flatworm) is an invertebrate model system that challenges this dogma. The planarian possesses a brain containing several thousand neurons with very high rates of cell turnover (homeostasis), which can also be fully regenerated de novo from injury in just 7 days. Both homeostasis and regeneration depend on the activity of a large population of adult stem cells, called neoblasts, throughout the planarian body. Thus, much effort has been put forth to understand how the flatworm can continually give rise to the diversity of cell types found in the adult brain. Here we focus on work using single-cell genomics and functional analyses to unravel the cellular hierarchies from stem cell to neuron. In addition, we will review what is known about how planarians utilize developmental signaling to maintain proper tissue patterning, homeostasis, and cell-type diversity in their brains. Together, planarians are a powerful emerging model system to study the dynamics of adult neurogenesis and regeneration. PMID:28588444

Control of adult neurogenesis by programmed cell death in the mammalian brain.

PubMed

Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

2016-04-21

The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases.

Bioreactivity: Studies on a Simple Brain Stem Reflex in Behaving Animals

DTIC Science & Technology

1990-08-10

problem in attempting to understand complex physiological processes, such as brain neuromodulation , or complex behavioral processes, such as arousal...containing only one synapse in brain, and receives dense inputs from two neurochemical systems important in neuromodulation and arousal. Initial

Bioreactivity: Studies on a Simple Brain Stem Reflex in Behaving Animals

DTIC Science & Technology

1990-01-04

attempting to understand complex physiological processes, such as brain neuromodulation , or complex behavioral processes, such as arousal, is finding a...one synapse in brain, and receives dense inputs from two neurochemical systems important in neuromodulation and arousal. Initial pharmacologic studies

Brain stem/brain stem occipital bone ratio and the four-line view in nuchal translucency images of fetuses with open spina bifida.

PubMed

Iuculano, Ambra; Zoppi, Maria Angelica; Piras, Alessandra; Arras, Maurizio; Monni, Giovanni

2014-09-10

Abstract Objective: Brain stem depth/brain stem occipital bone distance (BS/BSOB ratio) and the four-line view, in images obtained for nuchal translucency (NT) screening in fetuses with open spina bifida (OSB). Methods: Single center, retrospective study based on the assessment of NT screening images of fetuses with OSB. A ratio between the BS depth and the BSOB distance was calculated (BS/BSOB ratio) and the four-line view observed, and the sensitivity for a BS/BSOB ratio superior/equal to 1, and for the lack of detection of the four-line view were calculated. Results: There were 17 cases of prenatal diagnosis OSB. In six cases, the suspicion on OSB was raised during NT screening, in six cases, the diagnosis was made before 20 weeks and in five cases during anomaly scan. The BS/BSOB ratio was superior/equal to 1 in all 17 cases, and three lines, were visualized in 15/17 images of the OSB cases, being the sensitivity 100% (95% CI, 81 to 100%) and 88% (95% CI, 65 to 96%). Conclusion: Assessment of BS/BSOB ratio and four-line view in NT images is feasible detecting affected by OSB with high sensitivity. The presence of associated anomalies or of an enlarged NT enhances the early detection.

Brain stem venous congestion due to dural arteriovenous fistulas of the cavernous sinus.

PubMed

Kai, Y; Hamada, J I; Morioka, M; Yano, S; Ushio, Y

2004-10-01

Venous congestion of the brain stem due to dural arteriovenous fistulas (DAVFs) in the cavernous sinus is rare and presents therapeutic challenges. To assess the prognosis of patients with symptomatic DAVFs and brain stem dysfunction, we evaluated the degree of venous ischemia by examining pre- and post-treatment magnetic resonance images (MRI) in 2 patients presenting with venous congestion of the brain stem. A 56-year-old woman with left hemiparesis and a 70-year-old woman with gait disturbance attributable to right cavernous sinus DAVFs were referred to our hospital. In both cases, T2-weighted magnetic resonance imaging (MRI) disclosed a hyperintensity lesion in the brainstem due to venous congestion. Both patients underwent open surgery for direct embolization of the cavernous sinus because there were no approach routes for transvenous embolization. The patient whose pretreatment MRI demonstrated Gd enhancement continued to manifest neurological deficits and persistence of the abnormal hyperintensity on post-treatment T2-weighted MRI. In the other patient whose pretreatment MRI showed no Gd enhancement, treatment produced a complete response of her neurological deficit and disappearance of the abnormal hyperintensity area. We tentatively conclude that lesions corresponding to hyperintensity areas on non-Gd-enhanced, T2-weighted MRI may reflect a reversible condition whereas lesions identified as hyperintense areas on GD-enhanced T2-weighted MRI may be indicative of irreversibility.

[Distribution of human enterovirus 71 in brainstem of infants with brain stem encephalitis and infection mechanism].

PubMed

Hao, Bo; Gao, Di; Tang, Da-Wei; Wang, Xiao-Guang; Liu, Shui-Ping; Kong, Xiao-Ping; Liu, Chao; Huang, Jing-Lu; Bi, Qi-Ming; Quan, Li; Luo, Bin

2012-04-01

To explore the mechanism that how human enterovirus 71 (EV71) invades the brainstem and how intercellular adhesion molecules-1 (ICAM-1) participates by analyzing the expression and distribution of human EV71, and ICAM-1 in brainstem of infants with brain stem encephalitis. Twenty-two brainstem of infants with brain stem encephalitis were collected as the experimental group and 10 brainstems of fatal congenital heart disease were selected as the control group. The sections with perivascular cuffings were selected to observe EV71-VP1 expression by immunohistochemistry method and ICAM-1 expression was detected for the sections with EV71-VP1 positive expression. The staining image analysis and statistics analysis were performed. The experiment and control groups were compared. (1) EV71-VP1 positive cells in the experimental group were mainly astrocytes in brainstem with nigger-brown particles, and the control group was negative. (2) ICAM-1 positive cells showed nigger-brown. The expression in inflammatory cells (around blood vessels of brain stem and in glial nodules) and gliocytes increased. The results showed statistical difference comparing with control group (P < 0.05). The brainstem encephalitis can be used to diagnose fatal EV71 infection in infants. EV71 can invade the brainstem via hematogenous route. ICAM-1 may play an important role in the pathogenic process.

Signaling mechanisms regulating adult neural stem cells and neurogenesis

PubMed Central

Faigle, Roland; Song, Hongjun

2012-01-01

Background Adult neurogenesis occurs throughout life in discrete regions of the mammalian brain and is tightly regulated via both extrinsic environmental influences and intrinsic genetic factors. In recent years, several crucial signaling pathways have been identified in regulating self-renewal, proliferation, and differentiation of neural stem cells, as well as migration and functional integration of developing neurons in the adult brain. Scope of review Here we review our current understanding of signaling mechanisms, including Wnt, notch, sonic hedgehog, growth and neurotrophic factors, bone morphogenetic proteins, neurotransmitters, transcription factors, and epigenetic modulators, and crosstalk between these signaling pathways in the regulation of adult neurogenesis. We also highlight emerging principles in the vastly growing field of adult neural stem cell biology and neural plasticity. Major conclusions Recent methodological advances have enabled the field to identify signaling mechanisms that fine-tune and coordinate neurogenesis in the adult brain, leading to a better characterization of both cell-intrinsic and environmental cues defining the neurogenic niche. Significant questions related to niche cell identity and underlying regulatory mechanisms remain to be fully addressed and will be the focus of future studies. General significance A full understanding of the role and function of individual signaling pathways in regulating neural stem cells and generation and integration of newborn neurons in the adult brain may lead to targeted new therapies for neurological diseases in humans. PMID:22982587

Myoclonus

MedlinePlus

... injury, stroke, brain tumors, kidney or liver failure, lipid storage disease, chemical or drug poisoning, or other ... example, is in the brain stem close to structures that are responsible for the startle response, an ...

Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation

PubMed Central

St. John, James A.; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W.; Batzloff, Michael R.

2016-01-01

Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. PMID:27382023

Involvement of PI3K and ROCK signaling pathways in migration of bone marrow-derived mesenchymal stem cells through human brain microvascular endothelial cell monolayers.

PubMed

Lin, Mei-Na; Shang, De-Shu; Sun, Wei; Li, Bo; Xu, Xin; Fang, Wen-Gang; Zhao, Wei-Dong; Cao, Liu; Chen, Yu-Hua

2013-06-04

Bone marrow-derived mesenchymal stem cells (MSC) represent an important and easily available source of stem cells for potential therapeutic use in neurological diseases. The entry of circulating cells into the central nervous system by intravenous administration requires, firstly, the passage of the cells across the blood-brain barrier (BBB). However, little is known of the details of MSC transmigration across the BBB. In the present study, we employed an in vitro BBB model constructed using a human brain microvascular endothelial cell monolayer to study the mechanism underlying MSC transendothelial migration. Transmigration assays, transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) flux assays showed that MSC could transmigrate through human brain microvascular endothelial cell monolayers by a paracellular pathway. Cell fractionation and immunofluorescence assays confirmed the disruption of tight junctions. Inhibition assays showed that a Rho-kinase (ROCK) inhibitor (Y27632) effectively promoted MSC transendothelial migration; conversely, a PI3K inhibitor (LY294002) blocked MSC transendothelial migration. Interestingly, adenovirus-mediated interference with ROCK in MSC significantly increased MSC transendothelial migration, and overexpression of a PI3K dominant negative mutant in MSC cells could block transendothelial migration. Our findings provide clear evidence that the PI3K and ROCK pathways are involved in MSC migration through human brain microvascular endothelial cell monolayers. The information yielded by this study may be helpful in constructing gene-modified mesenchymal stem cells that are able to penetrate the BBB effectively for cell therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

Controlling Differentiation of Stem Cells for Developing Personalized Organ-on-Chip Platforms.

PubMed

Geraili, Armin; Jafari, Parya; Hassani, Mohsen Sheikh; Araghi, Behnaz Heidary; Mohammadi, Mohammad Hossein; Ghafari, Amir Mohammad; Tamrin, Sara Hasanpour; Modarres, Hassan Pezeshgi; Kolahchi, Ahmad Rezaei; Ahadian, Samad; Sanati-Nezhad, Amir

2018-01-01

Organ-on-chip (OOC) platforms have attracted attentions of pharmaceutical companies as powerful tools for screening of existing drugs and development of new drug candidates. OOCs have primarily used human cell lines or primary cells to develop biomimetic tissue models. However, the ability of human stem cells in unlimited self-renewal and differentiation into multiple lineages has made them attractive for OOCs. The microfluidic technology has enabled precise control of stem cell differentiation using soluble factors, biophysical cues, and electromagnetic signals. This study discusses different tissue- and organ-on-chip platforms (i.e., skin, brain, blood-brain barrier, bone marrow, heart, liver, lung, tumor, and vascular), with an emphasis on the critical role of stem cells in the synthesis of complex tissues. This study further recaps the design, fabrication, high-throughput performance, and improved functionality of stem-cell-based OOCs, technical challenges, obstacles against implementing their potential applications, and future perspectives related to different experimental platforms. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differentiation and characteristics of the enhanced green fluorescent protein gene transgenic goat neural stem cells cultured in attached and non-attached plates.

PubMed

Zheng, Yue-Mao; Dang, Yong-Hui; Qiu, Shuang; Qi, Ying-Pei; Xu, Yong-Ping; Sai, Wu-Jia-Fu

2011-08-01

The aims of this study were (i) to determine whether NSCs (neural stem cells) could be isolated from the brain of embryonic day 98 fetal goat, (ii) to determine if these stem cells have the capability of multipotent differentiation following transfection with a reporter gene, EGFP (enhanced green fluorescent protein) and (iii) to study the characteristics of the stem cells cultured in attached and non-attached plates. NSCs were isolated from embryonic day 98 fetal goat brain, transfected with EGFP gene using lipofection, and subcultured in attached and non-attached plates respectively. The transgenic stem cells were induced to differentiate into osteogenic and endothelial cells in vitro respectively. Markers associated with undifferentiated NSCs and their differentiated cells were tested by RT-PCR (reverse transcription-PCR). The results demonstrated that stem cells could be isolated from embryonic day 98 fetal goat brain, and EGFP gene could be transfected into the cells. The transgenic NSCs were capable of self-renewal, a defining property of stem cells, and were grown as free-floating neurospheres in non-attached plates. When the neurospheres were transferred and cultured in attached plates, cells migrate from the neurospheres and are grown as spindle cells. The stem cells were grown as quasi-circular cells when the single stem cells were cultured in attached plates. Both the NSCs cultured in non-attached and attached plates could express Hes1 (hairy and enhancer of split 1), Oct4 (octamer-binding protein 4), Nanog, Sox2 [SRY (sex-determining region Y)-box 2] and Nestin, while following differentiation cells expressed markers for osteogenic cells (Osteocalcin+ and Osteonectin+) and endothelium (CD34+ and eNOS+). The results demonstrated that the goat EGFP gene transgenic NSCs have the capability of multipotent differentiation, which means that the transgenic NSCs may be useful in cell transplantation studies in future.

Magnetic Enhancement of Stem Cell-Targeted Delivery into the Brain Following MR-Guided Focused Ultrasound for Opening the Blood-Brain Barrier.

PubMed

Shen, Wei-Bin; Anastasiadis, Pavlos; Nguyen, Ben; Yarnell, Deborah; Yarowsky, Paul J; Frenkel, Victor; Fishman, Paul S

2017-07-01

Focused ultrasound (FUS)-mediated blood-brain barrier disruption (BBBD) can enable even large therapeutics such as stem cells to enter the brain from the bloodstream. However, the efficiency is relatively low. Our previous study showed that human neural progenitor cells (hNPCs) loaded with superparamagnetic iron oxide nanoparticles (SPIONs) in culture were attracted by an external magnetic field. In vivo, enhanced brain retention was observed near a magnet mounted on the skull in a rat model of traumatic brain injury, where BBBD also occurs. The goal of the current study was to determine whether magnetic attraction of SPION-loaded hNPCs would also enhance their retention in the brain after FUS-mediated BBBD. A small animal magnetic resonance imaging (MRI)-guided FUS system operating at 1.5 MHz was used to treat rats (∼120 g) without tissue damage or hemorrhage. Evidence of successful BBBD was validated with both radiologic enhancement of gadolinium on postsonication TI MRI and whole brain section visualization of Evans blue dye. The procedure was then combined with the application of a powerful magnet to the head directly after intravenous injection of the hNPCs. Validation of cells within the brain was performed by staining with Perls' Prussian blue for iron and by immunohistochemistry with a human-specific antigen. By injecting equal numbers of iron oxide (SPIONs) and noniron oxide nanoparticles-loaded hNPCs, each labeled with a different fluorophore, we found significantly greater numbers of SPIONs-loaded cells retained in the brain at the site of BBBD as compared to noniron loaded cells. This result was most pronounced in regions of the brain closest to the skull (dorsal cortex) in proximity to the magnet surface. A more powerful magnet and a Halbach magnetic array resulted in more effective retention of SPION-labeled cells in even deeper brain regions such as the striatum and ventral cortex. There, up to 90% of hNPCs observed contained SPIONs compared to 60% to 70% with the less powerful magnet. Fewer cells were observed at 24 h posttreatment compared to 2 h (primarily in the dorsal cortex). These results demonstrate that magnetic attraction can substantially enhance the retention of stem cells after FUS-mediated BBBD. This procedure could provide a safer and less invasive approach for delivering stem cells to the brain, compared to direct intracranial injections, substantially reducing the risk of bleeding and infection.

Symmetrical Curvilinear Cytotoxic Edema Along the Surface of the Brain Stem: A Probable New Magnetic Resonance Imaging Finding of Leptomeningeal Carcinomatosis.

PubMed

Khil, Eun Kyung; Lee, A Leum; Chang, Kee-Hyun; Yun, Tae Jin; Hong, Hyun Sook

2015-07-01

Lung cancer is one of the most common neoplasms to appear leptomeningeal metastasis (LM). Contrast-enhanced magnetic resonance imaging (MRI) is better diagnostic choice for LM and usually shows focal nodular or diffuse linear enhancement on the leptomeninges along the sulci and tentorium in the brain. We experienced atypical 2 cases of lung cancer in patients who showed unusual brain MRI finding of symmetrical curvilinear or band-like, nonenhancing cytotoxic edema along the surface of the brain stem. This finding is unique and different from the general findings of leptomeningeal metastasis. This unique imaging finding of symmetric curvilinear nonenhancing cytotoxic edema along the brainstem is extremely rare and represents a new presentation of leptomeningeal carcinomatosis.

Stereotactic Radiosurgery in Treating Patients With Brain Tumors

ClinicalTrials.gov

2012-03-21

Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease.

PubMed

Linares, Gabriel R; Chiu, Chi-Tso; Scheuing, Lisa; Leng, Yan; Liao, Hsiao-Mei; Maric, Dragan; Chuang, De-Maw

2016-07-01

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone marrow-derived mesenchymal stem cells (MSCs) with lithium and VPA prior to intranasal delivery to the brain would enhance their therapeutic efficacy, and thereby facilitate functional recovery in N171-82Q HD transgenic mice. MSCs were treated in the presence or absence of combined lithium and VPA, and were then delivered by brain-targeted single intranasal administration to eight-week old HD mice. Histological analysis confirmed the presence of MSCs in the brain. Open-field test revealed that ambulatory distance and mean velocity were significantly improved in HD mice that received preconditioned MSCs, compared to HD vehicle-control and HD mice transplanted with non-preconditioned MSCs. Greater benefits on motor function were observed in HD mice given preconditioned MSCs, while HD mice treated with non-preconditioned MSCs showed no functional benefits. Moreover, preconditioned MSCs reduced striatal neuronal loss and huntingtin aggregates in HD mice. Gene expression profiling of preconditioned MSCs revealed a robust increase in expression of genes involved in trophic effects, antioxidant, anti-apoptosis, cytokine/chemokine receptor, migration, mitochondrial energy metabolism, and stress response signaling pathways. Consistent with this finding, preconditioned MSCs demonstrated increased survival after transplantation into the brain compared to non-preconditioned cells. Our results suggest that preconditioning stem cells with the mood stabilizers lithium and VPA before transplantation may serve as an effective strategy for enhancing the therapeutic efficacy of stem cell-based therapies. Copyright © 2016. Published by Elsevier Inc.

Fallopian Tube Herniation through Left Sided Abdominal Drain Site.

PubMed

Hussain, Khalid; Masood, Jovaria

2016-06-01

Intra-abdominal drains have been used since long to prevent intra-abdominal collection, and detect any anastomotic leaks. We report a case of left sided fallopian tube herniation from a left lower abdominal drain site in a 27-year female who underwent caesarian section for breach presentation. Several complications related to drain usage has been described but left sided fallopian tube prolapse through drain site has not been reported in literature.

Diffusion-weighted imaging and diffusion tensor imaging of asymptomatic lumbar disc herniation.

PubMed

Sakai, Toshinori; Miyagi, Ryo; Yamabe, Eiko; Fujinaga, Yasunari; N Bhatia, Nitin; Yoshioka, Hiroshi

2014-01-01

Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) were performed on a healthy 31-year-old man with asymptomatic lumbar disc herniation. Although the left S1 nerve root was obviously entrapped by a herniated mass, neither DWI nor DTI showed any significant findings for the nerve root. Decreased apparent diffusion coefficient (ADC) values and increased fractional anisotropy (FA) values were found. These results are contrary to those in previously published studies of symptomatic patients, in which a combination of increased ADC and decreased FA seem to have a relationship with nerve injury and subsequent symptoms, such as leg pain or palsy. Our results seen in an asymptomatic subject suggest that the compressed nerve with no injury, such as edema, demyelination, or persistent axonal injury, may be indicated by a combination of decreased ADC and increased FA. ADC and FA could therefore be potential tools to elucidate the pathomechanism of radiculopathy.

Two-year comprehensive medical management of degenerative lumbar spine disease (lumbar spondylolisthesis, stenosis, or disc herniation): a value analysis of cost, pain, disability, and quality of life: clinical article.

PubMed

Parker, Scott L; Godil, Saniya S; Mendenhall, Stephen K; Zuckerman, Scott L; Shau, David N; McGirt, Matthew J

2014-08-01

Current health care reform calls for a reduction of procedures and treatments that are less effective, more costly, and of little value (high cost/low quality). The authors assessed the 2-year cost and effectiveness of comprehensive medical management for lumbar spondylolisthesis, stenosis, and herniation by utilizing a prospective single-center multidisciplinary spine center registry in a real-world practice setting. Analysis was performed on a prospective longitudinal quality of life spine registry. Patients with lumbar spondylolisthesis (n = 50), stenosis (n = 50), and disc herniation (n = 50) who had symptoms persisting after 6 weeks of medical management and who were eligible for surgical treatment were entered into a prospective registry after deciding on nonsurgical treatment. In all cases, comprehensive medical management included spinal steroid injections, physical therapy, muscle relaxants, antiinflammatory medication, and narcotic oral agents. Two-year patient-reported outcomes, back-related medical resource utilization, and occupational work-day losses were prospectively collected and used to calculate Medicare fee-based direct and indirect costs from the payer and societal perspectives. The maximum health gain associated with medical management was defined as the improvement in pain, disability, and quality of life experienced after 2 years of medical treatment or at the time a patient decided to cross over to surgery. The maximum health gain in back pain, leg pain, disability, quality of life, depression, and general health state did not achieve statistical significance by 2 years of medical management, except for pain and disability in patients with disc herniation and back pain in patients with lumbar stenosis. Eighteen patients (36%) with spondylolisthesis, 11 (22%) with stenosis, and 17 (34%) with disc herniation eventually required surgical management due to lack of improvement. The 2-year improvement did not achieve a minimum clinically important difference in any outcome measure. The mean 2-year total cost (direct plus indirect) of medical management was $6606 for spondylolisthesis, $7747 for stenosis, and $7097 for herniation. In an institution-wide, prospective, longitudinal quality of life registry that measures cost and effectiveness of all spine care provided, comprehensive medical management did not result in sustained improvement in pain, disability, or quality of life for patients with surgically eligible degenerative lumbar spondylolisthesis, stenosis, or disc herniation. From both the societal and payer perspective, continued medical management of patients with these lumbar pathologies in whom 6 weeks of conservative therapy failed was of minimal value given its lack of health utility and effectiveness and its health care costs. The findings from this real-world practice setting may more accurately reflect the true value and effectiveness of nonoperative care in surgically eligible patient populations.

Brain abscess in children.

PubMed

Atiq, Mehnaz; Ahmed, Umair Syed; Allana, Salman Saleem; Chishti, Khalid N

2006-05-01

Brain abscess is a serious life-threatening complication of several diseases. The objective of this study was to look at the clinical profile of patients, predisposing conditions, microbiology and outcome of children suffering from brain abscess. Thirty children aged less than 15 years were reviewed. There were 15 males and 15 females. The mean age of presentation was 5.6+/-4.4 years. The duration of illness at the time of admission was 17.6+/-24.6 days. Typically patients presented with fever, vomiting, headache and seizures. The predisposing conditions found were cyanotic congenital heart disease in 11 (37%) of children, meningitis in 6 (20%), septicemia in 7 (23%) and no underlying cause was found in 5 (17%) children. The most common microbe in children with cyanotic congenital heart disease was of the Streptococcus milleri group (52%). Computerized tomography confirmed the diagnosis and the most common location of the abscess was the parietal lobe of the cerebral hemisphere. All abscesses were large, more than 2 cm in diameter and were aspirated surgically. Excision was performed in 6 children. Five children expired, one due to a intracranial bleeding and the others due to severe cerebral edema and tentorial herniation. Complications were seen in 20 children and 16 had sequelae, hemiparesis in 11 and seizure disorder in 5. Brain abscess is a serious infection with poor outcome if diagnosed late. Delayed surgical drainage has high morbidity and mortality. The threshold for diagnosis should be low, particularly in children with a predisposing condition like cyanotic congenital heart disease.

Disease and Stem Cell-Based Analysis of the 2014 ASNTR Meeting

PubMed Central

Eve, David J.

2015-01-01

A wide variety of subjects are presented at the annual American Society of Neural Therapy and Repair meeting every year, as typified by this summary of the 2014 meeting. Parkinson’s disease-related presentations were again the most popular topic, with traumatic brain injury, spinal cord injury, and stroke being close behind. Other disorders included Huntington’s disease, brain cancer, and bipolar disorders. Several studies were related to multiple diseases, and many studies attempted to reveal more about the disease process. The use of scaffolds, drugs, and gene therapy as disease models and/or potential therapies were also featured. An increasing proportion of presentations related to stem cells, with the study of multiple stem cell types being the most common. Induced pluripotent stem cells were increasingly popular, including two presentations each on a muscle-derived dedifferentiated cell type and cells derived from bipolar patients. Other stem cells, including neural stem cells, mesenchymal stem cells, umbilical cord blood cells, and embryonic stem cells, were featured. More than 55% of the stem cell studies involved transplantation, with human-derived cells being the most frequently transplanted, while rats were the most common recipient. Two human autologous studies for spinal cord injury and hypoxia-derived encephalopathy, while a further three allogenic studies for stroke and spinal cord injury, were also featured. This year’s meeting highlights the increasing promise of stem cells and other therapies for the treatment of neurodegenerative disorders. PMID:26858901

Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22

ClinicalTrials.gov

2018-01-26

Glioblastoma Multiforme; Fibrillary Astrocytoma of Brain; Glioma of Brainstem; Anaplastic Astrocytoma; Pilomyxoid Astrocytoma; Mixed Oligodendroglioma-Astrocytoma; Brain Stem Glioma; Diffuse Intrinsic Pontine Glioma

Proliferation versus Differentiation: Redefining Retinoic Acid's Role.

PubMed

Mosher, Kira Irving; Schaffer, David V

2018-06-05

Retinoic acid is commonly used in culture to differentiate stem cells into neurons and has established neural differentiation functions in vivo in developing and adult organisms. In this issue of Stem Cell Reports, Mishra et al. (2018) broaden its role in stem cell functions, showing that retinoic acid is necessary for stem and progenitor cell proliferation in the adult brain. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

A preclinical murine model for the early detection of radiation-induced brain injury using magnetic resonance imaging and behavioral tests for learning and memory: with applications for the evaluation of possible stem cell imaging agents and therapies.

PubMed

Ngen, Ethel J; Wang, Lee; Gandhi, Nishant; Kato, Yoshinori; Armour, Michael; Zhu, Wenlian; Wong, John; Gabrielson, Kathleen L; Artemov, Dmitri

2016-06-01

Stem cell therapies are being developed for radiotherapy-induced brain injuries (RIBI). Magnetic resonance imaging (MRI) offers advantages for imaging transplanted stem cells. However, most MRI cell-tracking techniques employ superparamagnetic iron oxide particles (SPIOs), which are difficult to distinguish from hemorrhage. In current preclinical RIBI models, hemorrhage occurs concurrently with other injury markers. This makes the evaluation of the recruitment of transplanted SPIO-labeled stem cells to injury sites difficult. Here, we developed a RIBI model, with early injury markers reflective of hippocampal dysfunction, which can be detected noninvasively with MRI and behavioral tests. Lesions were generated by sub-hemispheric irradiation of mouse hippocampi with single X-ray beams of 80 Gy. Lesion formation was monitored with anatomical and contrast-enhanced MRI and changes in memory and learning were assessed with fear-conditioning tests. Early injury markers were detected 2 weeks after irradiation. These included an increase in the permeability of the blood-brain barrier, demonstrated by a 92 ± 20 % contrast enhancement of the irradiated versus the non-irradiated brain hemispheres, within 15 min of the administration of an MRI contrast agent. A change in short-term memory was also detected, as demonstrated by a 40.88 ± 5.03 % decrease in the freezing time measured during the short-term memory context test at this time point, compared to that before irradiation. SPIO-labeled stem cells transplanted contralateral to the lesion migrated toward the lesion at this time point. No hemorrhage was detected up to 10 weeks after irradiation. This model can be used to evaluate SPIO-based stem cell-tracking agents, short-term.

Brain, Behavior, and Immunity: Biobehavioral influences on recovery following hematopoietic stem cell transplantation

Cancer.gov

Review of hematopoietic stem cell transplantation and its potential “window of opportunity” during which interventions targeting stress-related behavioral factors can influence the survival, health, and well-being of recipients.

Expression of Idh1R132H in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis.

PubMed

Bardella, Chiara; Al-Dalahmah, Osama; Krell, Daniel; Brazauskas, Pijus; Al-Qahtani, Khalid; Tomkova, Marketa; Adam, Julie; Serres, Sébastien; Lockstone, Helen; Freeman-Mills, Luke; Pfeffer, Inga; Sibson, Nicola; Goldin, Robert; Schuster-Böeckler, Benjamin; Pollard, Patrick J; Soga, Tomoyoshi; McCullagh, James S; Schofield, Christopher J; Mulholland, Paul; Ansorge, Olaf; Kriaucionis, Skirmantas; Ratcliffe, Peter J; Szele, Francis G; Tomlinson, Ian

2016-10-10

Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1 R132H in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced α-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1 R132H mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oka, Naoki; Soeda, Akio; Inagaki, Akihito

2007-08-31

There is increasing evidence for the presence of cancer stem cells (CSCs) in malignant brain tumors, and these CSCs may play a pivotal role in tumor initiation, growth, and recurrence. Vascular endothelial growth factor (VEGF) promotes the proliferation of vascular endothelial cells (VECs) and the neurogenesis of neural stem cells. Using CSCs derived from human glioblastomas and a retrovirus expressing VEGF, we examined the effects of VEGF on the properties of CSCs in vitro and in vivo. Although VEGF did not affect the property of CSCs in vitro, the injection of mouse brains with VEGF-expressing CSCs led to the massivemore » expansion of vascular-rich GBM, tumor-associated hemorrhage, and high morbidity, suggesting that VEGF promoted tumorigenesis via angiogenesis. These results revealed that VEGF induced the proliferation of VEC in the vascular-rich tumor environment, the so-called stem cell niche.« less

Genetic strategies to investigate neuronal circuit properties using stem cell-derived neurons

PubMed Central

Garcia, Isabella; Kim, Cynthia; Arenkiel, Benjamin R.

2012-01-01

The mammalian brain is anatomically and functionally complex, and prone to diverse forms of injury and neuropathology. Scientists have long strived to develop cell replacement therapies to repair damaged and diseased nervous tissue. However, this goal has remained unrealized for various reasons, including nascent knowledge of neuronal development, the inability to track and manipulate transplanted cells within complex neuronal networks, and host graft rejection. Recent advances in embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) technology, alongside novel genetic strategies to mark and manipulate stem cell-derived neurons, now provide unprecedented opportunities to investigate complex neuronal circuits in both healthy and diseased brains. Here, we review current technologies aimed at generating and manipulating neurons derived from ESCs and iPSCs toward investigation and manipulation of complex neuronal circuits, ultimately leading to the design and development of novel cell-based therapeutic approaches. PMID:23264761

Neural Stem Cells: Implications for the Conventional Radiotherapy of Central Nervous System Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barani, Igor J.; Benedict, Stanley H.; Lin, Peck-Sun

Advances in basic neuroscience related to neural stem cells and their malignant counterparts are challenging traditional models of central nervous system tumorigenesis and intrinsic brain repair. Neurogenesis persists into adulthood predominantly in two neurogenic centers: subventricular zone and subgranular zone. Subventricular zone is situated adjacent to lateral ventricles and subgranular zone is confined to the dentate gyrus of the hippocampus. Neural stem cells not only self-renew and differentiate along multiple lineages in these regions, but also contribute to intrinsic brain plasticity and repair. Ionizing radiation can depopulate these exquisitely sensitive regions directly or impair in situ neurogenesis by indirect, dose-dependentmore » and inflammation-mediated mechanisms, even at doses <2 Gy. This review discusses the fundamental neural stem cell concepts within the framework of cumulative clinical experience with the treatment of central nervous system malignancies using conventional radiotherapy.« less

A High-Content Small Molecule Screen Identifies Sensitivity of Glioblastoma Stem Cells to Inhibition of Polo-Like Kinase 1

PubMed Central

Danovi, Davide; Folarin, Amos; Gogolok, Sabine; Ender, Christine; Elbatsh, Ahmed M. O.; Engström, Pär G.; Stricker, Stefan H.; Gagrica, Sladjana; Georgian, Ana; Yu, Ding; U, Kin Pong; Harvey, Kevin J.; Ferretti, Patrizia; Paddison, Patrick J.; Preston, Jane E.; Abbott, N. Joan; Bertone, Paul; Smith, Austin; Pollard, Steven M.

2013-01-01

Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS) cells and genetically normal neural stem (NS) cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101) as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1) (phospho T210), with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364) phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF−/−, or p53−/−), as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value. PMID:24204733

Magnetoencephalographic accuracy profiles for the detection of auditory pathway sources.

PubMed

Bauer, Martin; Trahms, Lutz; Sander, Tilmann

2015-04-01

The detection limits for cortical and brain stem sources associated with the auditory pathway are examined in order to analyse brain responses at the limits of the audible frequency range. The results obtained from this study are also relevant to other issues of auditory brain research. A complementary approach consisting of recordings of magnetoencephalographic (MEG) data and simulations of magnetic field distributions is presented in this work. A biomagnetic phantom consisting of a spherical volume filled with a saline solution and four current dipoles is built. The magnetic fields outside of the phantom generated by the current dipoles are then measured for a range of applied electric dipole moments with a planar multichannel SQUID magnetometer device and a helmet MEG gradiometer device. The inclusion of a magnetometer system is expected to be more sensitive to brain stem sources compared with a gradiometer system. The same electrical and geometrical configuration is simulated in a forward calculation. From both the measured and the simulated data, the dipole positions are estimated using an inverse calculation. Results are obtained for the reconstruction accuracy as a function of applied electric dipole moment and depth of the current dipole. We found that both systems can localize cortical and subcortical sources at physiological dipole strength even for brain stem sources. Further, we found that a planar magnetometer system is more suitable if the position of the brain source can be restricted in a limited region of the brain. If this is not the case, a helmet-shaped sensor system offers more accurate source estimation.

Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy.

PubMed

Wei, Zheng Z; Zhu, Yan-Bing; Zhang, James Y; McCrary, Myles R; Wang, Song; Zhang, Yong-Bo; Yu, Shan-Ping; Wei, Ling

2017-10-05

Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: "stem cells," "hypoxic preconditioning," "ischemic preconditioning," and "cell transplantation." Original articles and critical reviews on the topics were selected. Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.

Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

PubMed Central

Wang, Shih-Min; Lei, Huan-Yao; Liu, Ching-Chuan

2012-01-01

Enterovirus 71 (EV71) is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS). Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema. PMID:22956971

Clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells

PubMed Central

Deng, Peter; Torrest, Audrey; Pollock, Kari; Dahlenburg, Heather; Annett, Geralyn; Nolta, Jan A.; Fink, Kyle D.

2016-01-01

Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC) to secrete brain-derived neurotrophic factor (BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease (HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system. PMID:27335539

Methionine PET/CT Studies In Patients With Cancer

ClinicalTrials.gov

2018-06-15

Brain Tumors and/or Solid Tumors Including; Brain Stem Glioma; High Grade CNS Tumors; Ependymoma; Medulloblastoma; Craniopharyngioma; Low Grade CNS Tumors; Hodgkin Lymphoma; Non Hodgkin Lymphoma; Ewing Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Other

Evaluation of common vaginal tunic ligation during field castration in draught colts.

PubMed

Carmalt, J L; Shoemaker, R W; Wilson, D G

2008-09-01

The objective of this study was to determine if ligation of the common vaginal tunic could prevent or reduce the incidence of omental herniation and eventration in draught colts undergoing routine field castration. It was found that common vaginal tunic ligation, while not completely preventing omental herniation and evisceration, significantly reduced the incidence of these complications and should be considered in those males deemed at increased risk of significant post castration complications.

Brain and eyes of Kerygmachela reveal protocerebral ancestry of the panarthropod head.

PubMed

Park, Tae-Yoon S; Kihm, Ji-Hoon; Woo, Jusun; Park, Changkun; Lee, Won Young; Smith, M Paul; Harper, David A T; Young, Fletcher; Nielsen, Arne T; Vinther, Jakob

2018-03-09

Recent discoveries of fossil nervous tissue in Cambrian fossils have allowed researchers to trace the origin and evolution of the complex arthropod head and brain based on stem groups close to the origin of the clade, rather than on extant, highly derived members. Here we show that Kerygmachela from Sirius Passet, North Greenland, a primitive stem-group euarthropod, exhibits a diminutive (protocerebral) brain that innervates both the eyes and frontal appendages. It has been surmised, based on developmental evidence, that the ancestor of vertebrates and arthropods had a tripartite brain, which is refuted by the fossil evidence presented here. Furthermore, based on the discovery of eyes in Kerygmachela, we suggest that the complex compound eyes in arthropods evolved from simple ocelli, present in onychophorans and tardigrades, rather than through the incorporation of a set of modified limbs.

Tumor necrosis factor-α-dependent infiltration of macrophages into the dorsal root ganglion in a rat disc herniation model.

PubMed

You, Changcheng; Zhu, Kai; Liu, Xiaoqi; Xi, Chunyang; Zhang, Zhipeng; Xu, Gongping; Yan, Jinglong

2013-11-01

A prospective molecular mechanism of macrophages infiltration in experimental disc herniation. To investigate the mechanisms of macrophages infiltration into the dorsal root ganglion (DRG) in a rat model of disc herniation. Macrophages infiltrate the DRG after application of nucleus pulposus (NP) on the DRG, and may play an important role in radiculopathy. However, the mechanisms of macrophages infiltration after NP application remain poorly understood. After experimental disc herniation in this study, we investigated changes in the expression of ED1 (a marker of macrophages) and vascular cell adhesion molecule-1 (VCAM-1) in DRG using immunofluorescence. We also investigated the expression of ED1 and VCAM-1 in DRG by treatment with tumor necrosis factor-α (TNF-α) inhibitor at the time of surgery. We found a massive ED1-positive macrophages infiltrated the DRG, and VCAM-1-like immunoreactivity vessels became evident after NP application. Furthermore, both macrophage infiltration and VCAM-1 expression were prevented by treatment with TNF-α inhibitor at the time of surgery. These findings indicated that macrophages infiltration into the DRG was TNF-α-dependent, and might be partly mediated by VCAM-1 in the early stage of experimental lumbar disc herination. Taken together, this study provides important preliminary data suggesting that TNF-α plays an important role in the macrophage infiltration. N/A.

Role of brain-derived neurotrophic factor during the regenerative response after traumatic brain injury in adult zebrafish.

PubMed

Cacialli, Pietro; Palladino, Antonio; Lucini, Carla

2018-06-01

Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The brain of adult zebrafish, a teleost fish widely used as vertebrate model, possesses high regenerative properties after injury due to the presence of numerous stem cells niches. The ventricular lining of the zebrafish dorsal telencephalon is the most studied neuronal stem cell niche because its dorso-lateral zone is considered the equivalent to the hippocampus of mammals which contains one of the two constitutive neurogenic niches of mammals. To mimic TBI, stab wound in the dorso-lateral telencephalon of zebrafish was used in studies devoted to fish regenerative properties. Brain-derived neurotrophic factor, which is known to play key roles in the repair process after traumatic brain lesions, persists around the lesioned area of injured telencephalon of adult zebrafish. These results are extensively compared to reparative processes in rodent brain. Considering the complete repair of the damaged area in fish, it could be tempting to consider brain-derived neurotrophic factor as a factor contributing to create a permissive environment that enables the establishment of new neuronal population in damaged brain.

Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation.

PubMed

St John, James A; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W; Ulett, Glen C; Batzloff, Michael R; Beacham, Ifor R; Ekberg, Jenny A K

2016-09-01

Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Postnatal Development of Brain-Derived Neurotrophic Factor (BDNF) and Tyrosine Protein Kinase B (TrkB) Receptor Immunoreactivity in Multiple Brain Stem Respiratory-Related Nuclei of the Rat

PubMed Central

Liu, Qiuli; Wong-Riley, Margaret T.T.

2013-01-01

Previously, we found a transient imbalance between suppressed excitation and enhanced inhibition in the respiratory network of the rat around postnatal days (P) 12–13, a critical period when the hypoxic ventilatory response is at its weakest. The mechanism underlying the imbalance is poorly understood. Brain-derived neurotrophic factor (BDNF) and its tyrosine protein kinase B (TrkB) receptors are known to potentiate glutamatergic and attenuate gamma-aminobutyric acid (GABA)ergic neurotransmission, and BDNF is essential for respiratory development. We hypothesized that the excitation-inhibition imbalance during the critical period stemmed from a reduced expression of BDNF and TrkB at that time within respiratory-related nuclei of the brain stem. An in-depth, semiquantitative immunohistochemical study was undertaken in seven respiratory-related brain stem nuclei and one nonrespiratory nucleus in P0–21 rats. The results indicate that the expressions of BDNF and TrkB: 1) in the pre-Bötzinger complex, nucleus ambiguus, commissural and ventrolateral subnuclei of solitary tract nucleus, and retrotrapezoid nucleus/parafacial respiratory group were significantly reduced at P12, but returned to P11 levels by P14; 2) in the lateral paragigantocellular nucleus and parapyramidal region were increased from P0 to P7, but were strikingly reduced at P10 and plateaued thereafter; and 3) in the nonrespiratory cuneate nucleus showed a gentle plateau throughout the first 3 post-natal weeks, with only a slight decline of BDNF expression after P11. Thus, the significant downregulation of both BDNF and TrkB in respiratory-related nuclei during the critical period may form the basis of, or at least contribute to, the inhibitory-excitatory imbalance within the respiratory network during this time. PMID:22678720

Leukemia inhibitory factor in the neuroimmune communication pathways in allergic asthma.

PubMed

Lin, Min-Juan; Lao, Xue-Jun; Liu, Sheng-Ming; Xu, Zhen-Hua; Zou, Wei-Feng

2014-03-20

In the pathogenesis of asthma, central sensitization is suggested to be an important neural mechanism, and neurotrophins and cytokines are likely to be the major mediators in the neuroimmune communication pathways of asthma. However, their impact on the central nervous system in allergic asthma remains unclear. We hypothesize that central neurogenic inflammation develops in the pathogenesis of allergic asthma, and nerve growth factor (NGF) and leukemia inhibitory factor (LIF) are important mediators in its development. An asthma model of rats was established by sensitization and challenged with ovalbumin (OVA). For further confirmation of the role of LIF in neurogenic inflammation, a subgroup was pretreated with intraperitoneally (i.p.) LIF antibody before OVA challenge. The levels of LIF and NGF were measured with reverse transcription and polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry stain in lung tissue, airway-specific dorsal root ganglia (DRG, C7-T5) and brain stem of asthmatic rats, anti-LIF pretreated rats and controls. A significantly increased number of LIF- and NGF-immunoreactive cells were detected in lung tissue, DRG and the brain stem of asthmatic rats. In the asthma group a significantly increase level of mRNA encoding LIF and NGF in lung tissue was detected, but not in DRG and the brain stem. Pretreatment with LIF antibody decreased the level of LIF and NGF in all tissues. LIF is an important mediator in the crosstalk between nerve and immune systems. Our study demonstrate that the increased level of LIF and NGF in DRG and brain stem may be not based on result from de novo synthesis, but rather on result from retrograde nerve transport or passage across the blood-brain-barrier. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Imaging transplanted stem cells in real time using an MRI dual-contrast method

PubMed Central

Ngen, Ethel J.; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

2015-01-01

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies. PMID:26330231

Stem cells technology: a powerful tool behind new brain treatments.

PubMed

Duru, Lucienne N; Quan, Zhenzhen; Qazi, Talal Jamil; Qing, Hong

2018-06-18

Stem cell research has recently become a hot research topic in biomedical research due to the foreseen unlimited potential of stem cells in tissue engineering and regenerative medicine. For many years, medicine has been facing intense challenges, such as an insufficient number of organ donations that is preventing clinicians to fulfill the increasing needs. To try and overcome this regrettable matter, research has been aiming at developing strategies to facilitate the in vitro culture and study of stem cells as a tool for tissue regeneration. Meanwhile, new developments in the microfluidics technology brought forward emerging cell culture applications that are currently allowing for a better chemical and physical control of cellular microenvironment. This review presents the latest developments in stem cell research that brought new therapies to the clinics and how the convergence of the microfluidics technology with stem cell research can have positive outcomes on the fields of regenerative medicine and high-throughput screening. These advances will bring new translational solutions for drug discovery and will upgrade in vitro cell culture to a new level of accuracy and performance. We hope this review will provide new insights into the understanding of new brain treatments from the perspective of stem cell technology especially regarding regenerative medicine and tissue engineering.

Imaging transplanted stem cells in real time using an MRI dual-contrast method.

PubMed

Ngen, Ethel J; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

2015-09-02

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies.

Neurophysiologic intraoperative monitoring of the vestibulocochlear nerve.

PubMed

Simon, Mirela V

2011-12-01

Neurosurgical procedures involving the skull base and structures within can pose a significant risk of damage to the brain stem and cranial nerves. This can have life-threatening consequences and/or result in devastating neurologic deficits. Over the past decade, intraoperative neurophysiology has significantly evolved and currently offers a great tool for live monitoring of the integrity of nervous structures. Thus, dysfunction can be identified early and prompt modification of the surgical management or operating conditions, leads to avoidance of permanent structural damage.Along these lines, the vestibulocochlear nerve (CN VIII) and, to a greater extent, the auditory pathways as they pass through the brain stem are especially at risk during cerebelopontine angle (CPA), posterior/middle fossa, or brain stem surgery. CN VIII can be damaged by several mechanisms, from vascular compromise to mechanical injury by stretch, compression, dissection, and heat injury. Additionally, cochlea itself can be significantly damaged during temporal bone drilling, by noise, mechanical destruction, or infarction, and because of rupture, occlusion, or vasospasm of the internal auditory artery.CN VIII monitoring can be successfully achieved by live recording of the function of one of its parts, the cochlear or auditory nerve (AN), using the brain stem auditory evoked potentials (BAEPs), electrocochleography (ECochG), and compound nerve action potentials (CNAPs) of the cochlear nerve.This is a review of these techniques, their principle, applications, methodology, interpretation of the evoked responses, and their change from baseline, within the context of surgical and anesthesia environments, and finally the appropriate management of these changes.

The brain stem saccadic burst generator encodes gaze in three-dimensional space.

PubMed

Van Horn, Marion R; Sylvestre, Pierre A; Cullen, Kathleen E

2008-05-01

When we look between objects located at different depths the horizontal movement of each eye is different from that of the other, yet temporally synchronized. Traditionally, a vergence-specific neuronal subsystem, independent from other oculomotor subsystems, has been thought to generate all eye movements in depth. However, recent studies have challenged this view by unmasking interactions between vergence and saccadic eye movements during disconjugate saccades. Here, we combined experimental and modeling approaches to address whether the premotor command to generate disconjugate saccades originates exclusively in "vergence centers." We found that the brain stem burst generator, which is commonly assumed to drive only the conjugate component of eye movements, carries substantial vergence-related information during disconjugate saccades. Notably, facilitated vergence velocities during disconjugate saccades were synchronized with the burst onset of excitatory and inhibitory brain stem saccadic burst neurons (SBNs). Furthermore, the time-varying discharge properties of the majority of SBNs (>70%) preferentially encoded the dynamics of an individual eye during disconjugate saccades. When these experimental results were implemented into a computer-based simulation, to further evaluate the contribution of the saccadic burst generator in generating disconjugate saccades, we found that it carries all the vergence drive that is necessary to shape the activity of the abducens motoneurons to which it projects. Taken together, our results provide evidence that the premotor commands from the brain stem saccadic circuitry, to the target motoneurons, are sufficient to ensure the accurate control shifts of gaze in three dimensions.

Individual Differences in Working Memory, Nonverbal IQ, and Mathematics Achievement and Brain Mechanisms Associated with Symbolic and Nonsymbolic Number Processing

ERIC Educational Resources Information Center

Gullick, Margaret M.; Sprute, Lisa A.; Temple, Elise

2011-01-01

Individual differences in mathematics performance may stem from domain-general factors like working memory and intelligence. Parietal and frontal brain areas have been implicated in number processing, but the influence of such cognitive factors on brain activity during mathematics processing is not known. The relationship between brain mechanisms…

Copine1 regulates neural stem cell functions during brain development.

PubMed

Kim, Tae Hwan; Sung, Soo-Eun; Cheal Yoo, Jae; Park, Jae-Yong; Yi, Gwan-Su; Heo, Jun Young; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong

2018-01-01

Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

Stem Cell Therapy for the Central Nervous System in Lysosomal Storage Diseases.

PubMed

Siddiqi, Faez; Wolfe, John H

2016-10-01

Neurological diseases with genetic etiologies result in the loss or dysfunction of neural cells throughout the CNS. At present, few treatment options exist for the majority of neurogenetic diseases. Stem cell transplantation (SCT) into the CNS has the potential to be an effective treatment modality because progenitor cells may replace lost cells in the diseased brain, provide multiple trophic factors, or deliver missing proteins. This review focuses on the use of SCT in lysosomal storage diseases (LSDs), a large group of monogenic disorders with prominent CNS disease. In most patients the CNS disease results in intellectual disability that is refractory to current standard-of-care treatment. A large amount of preclinical work on brain-directed SCT has been performed in rodent LSD models. Cell types that have been used for direct delivery into the CNS include neural stem cells, embryonic and induced pluripotent stem cells, and mesenchymal stem cells. Hematopoietic stem cells have been an effective therapy for the CNS in a few LSDs and may be augmented by overexpression of the missing gene. Current barriers and potential strategies to improve SCT for translation into effective patient therapies are discussed.

Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells

PubMed Central

Varela, Christine; Denis, Jérôme Alexandre; Polentes, Jérôme; Feyeux, Maxime; Aubert, Sophie; Champon, Benoite; Piétu, Geneviève; Peschanski, Marc; Lefort, Nathalie

2012-01-01

Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor clinical outcome. Neural stem cells carrying the 1q defect implanted into the brains of rats failed to integrate and expand, whereas normal cells engrafted. Our results call for additional quality controls to be implemented to ensure genomic integrity not only of undifferentiated pluripotent stem cells, but also of hESC derivatives that form cell therapy end products, particularly neural lines. PMID:22269325

Prion diseases and adult neurogenesis: how do prions counteract the brain's endogenous repair machinery?

PubMed

Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

2014-01-01

Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process, however it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies.

Neural stem cells in the immature, but not the mature, subventricular zone respond robustly to traumatic brain injury.

PubMed

Goodus, Matthew T; Guzman, Alanna M; Calderon, Frances; Jiang, Yuhui; Levison, Steven W

2015-01-01

Pediatric traumatic brain injury is a significant problem that affects many children each year. Progress is being made in developing neuroprotective strategies to combat these injuries. However, investigators are a long way from therapies to fully preserve injured neurons and glia. To restore neurological function, regenerative strategies will be required. Given the importance of stem cells in repairing damaged tissues and the known persistence of neural precursors in the subventricular zone (SVZ), we evaluated regenerative responses of the SVZ to a focal brain lesion. As tissues repair more slowly with aging, injury responses of male Sprague Dawley rats at 6, 11, 17, and 60 days of age and C57Bl/6 mice at 14 days of age were compared. In the injured immature animals, cell proliferation in the dorsolateral SVZ more than doubled by 48 h. By contrast, the proliferative response was almost undetectable in the adult brain. Three approaches were used to assess the relative numbers of bona fide neural stem cells, as follows: the neurosphere assay (on rats injured at postnatal day 11, P11), flow cytometry using a novel 4-marker panel (on mice injured at P14) and staining for stem/progenitor cell markers in the niche (on rats injured at P17). Precursors from the injured immature SVZ formed almost twice as many spheres as precursors from uninjured age-matched brains. Furthermore, spheres formed from the injured brain were larger, indicating that the neural precursors that formed these spheres divided more rapidly. Flow cytometry revealed a 2-fold increase in the percentage of stem cells, a 4-fold increase in multipotential progenitor-3 cells and a 2.5-fold increase in glial-restricted progenitor-2/multipotential-3 cells. Analogously, there was a 2-fold increase in the mitotic index of nestin+/Mash1- immunoreactive cells within the immediately subependymal region. As the early postnatal SVZ is predominantly generating glial cells, an expansion of precursors might not necessarily lead to the production of many new neurons. On the contrary, many BrdU+/doublecortin+ cells were observed streaming out of the SVZ into the neocortex 2 weeks after injuries to P11 rats. However, very few new mature neurons were seen adjacent to the lesion 28 days after injury. Altogether, these data indicate that immature SVZ cells mount a more robust proliferative response to a focal brain injury than adult cells, which includes an expansion of stem cells, primitive progenitors and neuroblasts. Nonetheless, this regenerative response does not result in significant neuronal replacement, indicating that new strategies need to be implemented to retain the regenerated neurons and glia that are being produced. © 2014 S. Karger AG, Basel.

The role of fluoroscopic interlaminar epidural injections in managing chronic pain of lumbar disc herniation or radiculitis: a randomized, double-blind trial.

PubMed

Manchikanti, Laxmaiah; Singh, Vijay; Cash, Kimberly A; Pampati, Vidyasagar; Falco, Frank J E

2013-09-01

There is continued debate on the effectiveness, indications, and medical necessity of epidural injections in managing pain and disability from lumbar disc herniation, despite extensive utilization. There is paucity of literature on interlaminar epidural injections in managing lumbar disc herniation or radiculitis in contemporary interventional pain management settings utilizing fluoroscopy. A randomized, double-blind, active-control trial was undertaken to assess the effectiveness of lumbar interlaminar epidural injections with or without steroids for disc herniation and radiculitis. The primary outcome was defined as pain relief and functional status improvement of ≥ 50%. One hundred twenty patients were randomly assigned to 1 of the 2 groups. Group I patients received lumbar interlaminar injections containing a local anesthetic (lidocaine 0.5%, 6 mL), whereas Group II patients received lumbar interlaminar epidural injections of 0.5% lidocaine, 5 mL, mixed with 1 mL of non-particulate betamethasone. In the patients who responded with initial 2 procedures with at least 3 weeks of relief, significant improvement was seen in 80% of the patients in the local anesthetic group and 86% of the patients in the local anesthetic and steroid group. The overall average procedures per year were 3.6 in the local anesthetic group and 4.1 in the local anesthetic and steroid group, with an average relief of 33.7 ± 18.1 weeks in the local anesthetic group and 39.1 ± 12.2 weeks in the local anesthetic and steroid group over a period of 52 weeks in the overall population. Lumbar interlaminar epidural injections of local anesthetic with or without steroids might be effective in patients with disc herniation or radiculitis, with potential superiority of steroids compared with local anesthetic alone at 1 year follow-up. © 2012 The Authors Pain Practice © 2012 World Institute of Pain.

A randomized, controlled, double-blind trial of fluoroscopic caudal epidural injections in the treatment of lumbar disc herniation and radiculitis.

PubMed

Manchikanti, Laxmaiah; Singh, Vijay; Cash, Kimberly A; Pampati, Vidyasagar; Damron, Kim S; Boswell, Mark V

2011-11-01

A randomized, controlled, double-blind trial. To assess the effectiveness of fluoroscopically directed caudal epidural injections in managing chronic low back and lower extremity pain in patients with disc herniation and radiculitis with local anesthetic with or without steroids. The available literature on the effectiveness of epidural injections in managing chronic low back pain secondary to disc herniation is highly variable. One hundred twenty patients suffering with low back and lower extremity pain with disc herniation and radiculitis were randomized to one of the two groups: group I received caudal epidural injections with an injection of local anesthetic, lidocaine 0.5%, 10 mL; group II patients received caudal epidural injections with 0.5% lidocaine, 9 mL, mixed with 1 mL of steroid. The Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake were utilized with assessment at 3, 6, and 12 months posttreatment. The percentage of patients with significant pain relief of 50% or greater and/or improvement in functional status with 50% or more reduction in ODI scores was seen in 70% and 67% in group I and 77% and 75% in group II with average procedures per year of 3.8 ± 1.4 in group I and 3.6 + 1.1 in group II. However, the relief with first and second procedures was significantly higher in the steroid group. The number of injections performed was also higher in local anesthetic group even though overall relief was without any significant difference among the groups. There was no difference among the patients receiving steroids. Caudal epidural injection with local anesthetic with or without steroids might be effective in patients with disc herniation or radiculitis. The present evidence illustrates potential superiority of steroids compared with local anesthetic at 1-year follow-up.

[Results of percutaneous discectomy in the management of lumbar disc herniation].

PubMed

Lima-Ramírez, P G; Montiel-Jarquín, A J; Barragán-Hervella, R G; Sánchez-Durán, M A; Ochoa-Neri, A; Loria-Castellanos, J; Vázquez-Rodríguez, C; Villatoro-Martínez, A; Castillo-Pérez, J J

2016-01-01

Percutaneous discectomy is a disc decompression technique approved by the FDA that is useful to improve pain caused by a herniated disc. However, its practice is under discussion because the benefits of the technique are controversial. To describe the clinical course of patients with low lumbar disc herniation (L4-L5, L5-S1) treated by percutaneous surgery within one year of surgery and prove that it is a useful surgical option for the relief of symptoms caused by this pathological entity. Cohort study; the clinical course of 21 patients with lumbar disc herniation treated with percutaneous discectomy manually during March 2011-November 2013, is presented. The evaluation was made before surgery and at four, 30, 180 and 365 days after surgery by numerical pain scale (NPS), Oswestry (IDO) and MacNab criteria. We used nonparametric inferential statistics (Wilcoxon) for differences in proportions. n = 21, six (28.57%) men, 15 (71.42%) women; average age: 37.95, (14-56) ± 10.60 years; the most affected vertebral level was L4-L5 in 57.14% of the patients; the NPS preoperative average was 7.75 (5-9) ± 1.12; at 365 days: average 2.14 (0-7) ± 2.37. The IDO preoperative average was 37% (28-40%) ± 3.06, and at 365 days: 9.52% (0-40%) ± 13.92. The prognosis (IDO) in the presurgical was good to zero (0%) patients and in 15 (71.42%) at 365 days, regular in five (23.80%) and poor in one (4.78%) (p = 0.00, CI 95% 0.00 to 0.13, Wilcoxon); according to MacNab criteria, in 15 (71.42%) patients were excellent and good, poor in four (19.04%) and bad in two (9.52%) (p = 0.00). Percutaneous discectomy provides good results for the treatment of lumbar disc herniation (L4-L5, L5-S1) at 365 days after surgery.

Diagnosis and operatory treatment of the patients with failed back surgery caused by herniated disk relapse.

PubMed

Bodiu, A

2014-01-01

THE OBJECT OF STUDY: Analysis of surgical treatment results in patients with recurrent lumbar disc herniation by transforaminal lumbar interbody fusion (TLIF) and repeated laminotomy and discectomy for the improvement of pain and disability. Data analysis was performed on a complex diagnosis and treatment of 56 patients with recurrent lumbar disc herniation who had previously underwent 1-3 lumbar disc surgeries. An MRI investigation with paramagnetic contrast agent (gadolinium) was used for the diagnosis and differentiation of epidural fibrosis, and a dynamic lateral X-ray investigation was carried out for the identification of segmental instability. The evolution period after the previous surgery was between 1 and 3 years after the index surgery. Pain expression degree and dynamics were assessed with the pain visual analog scale (VAS) in early and late postoperative periods. Postoperative success was assessed by using a modified MacNab scale. The follow-up recording period after the last operation was of at least 1 year, ranging from 1 to 4 years. The surgical treatment was effective in most cases, recording a reduction in pain expression level from 7.2-7.7 points on the VAS scale to 1.7-2.1 in the early period and 2.2-2.6 in the late period (1 year). Repeated surgery was effective in 21 of 30 (70%) cases who underwent decompression surgery without fusion and in 20 of 26 (76.9%) cases who underwent repeated surgery with transforaminal lumbar interbody fusion (TLIF). Overall, postoperative success was assessed by using a modified MacNab scale. Repeated surgery is a viable option for patients who have clinical manifestations of recurrent disc herniation. Investigation with contrast agent by MRI allows differentiating disk herniation recurrences from epidural fibrosis. Supplementing repeated discectomies and decompression with intervertebral transforaminal fusion provide superior clinical outcomes, especially in patients with clinical and radiological signs of lumbar segment instability.

Biomechanical testing of a polymer-based biomaterial for the restoration of spinal stability after nucleotomy

PubMed Central

Hegewald, Aldemar A; Knecht, Sven; Baumgartner, Daniel; Gerber, Hans; Endres, Michaela; Kaps, Christian; Stüssi, Edgar; Thomé, Claudius

2009-01-01

Background Surgery for disc herniations can be complicated by two major problems: painful degeneration of the spinal segment and re-herniation. Therefore, we examined an absorbable poly-glycolic acid (PGA) biomaterial, which was lyophilized with hyaluronic acid (HA), for its utility to (a) re-establish spinal stability and to (b) seal annulus fibrosus defects. The biomechanical properties range of motion (ROM), neutral zone (NZ) and a potential annulus sealing capacity were investigated. Methods Seven bovine, lumbar spinal units were tested in vitro for ROM and NZ in three consecutive stages: (a) intact, (b) following nucleotomy and (c) after insertion of a PGA/HA nucleus-implant. For biomechanical testing, spinal units were mounted on a loading-simulator for spines. In three cycles, axial loading was applied in an excentric mode with 0.5 Nm steps until an applied moment of ± 7.5 Nm was achieved in flexion/extension. ROM and NZ were assessed. These tests were performed without and with annulus sealing by sewing a PGA/HA annulus-implant into the annulus defect. Results Spinal stability was significantly impaired after nucleotomy (p < 0.001). Intradiscal implantation of a PGA-HA nucleus-implant, however, restored spinal stability (p < 0.003). There was no statistical difference between the stability provided by the nucleus-implant and the intact stage regarding flexion/extension movements (p = 0.209). During the testing sequences, herniation of biomaterial through the annulus defect into the spinal canal regularly occurred, resulting in compression of neural elements. Sewing a PGA/HA annulus-implant into the annulus defect, however, effectively prevented herniation. Conclusion PGA/HA biomaterial seems to be well suited for cell-free and cell-based regenerative treatment strategies in spinal surgery. Its abilities to restore spinal stability and potentially close annulus defects open up new vistas for regenerative approaches to treat intervertebral disc degeneration and for preventing implant herniation. PMID:19604373

Cervical disc hernia operations through posterior laminoforaminotomy

PubMed Central

Yolas, Coskun; Ozdemir, Nuriye Guzin; Okay, Hilmi Onder; Kanat, Ayhan; Senol, Mehmet; Atci, Ibrahim Burak; Yilmaz, Hakan; Coban, Mustafa Kemal; Yuksel, Mehmet Onur; Kahraman, Umit

2016-01-01

Objective: The most common used technique for posterolateral cervical disc herniations is anterior approach. However, posterior cervical laminotoforaminomy can provide excellent results in appropriately selected patients with foraminal stenosis in either soft disc prolapse or cervical spondylosis. The purpose of this study was to present the clinical outcomes following posterior laminoforaminotomy in patients with radiculopathy. Materials and Methods: We retrospectively evaluated 35 patients diagnosed with posterolateral cervical disc herniation and cervical spondylosis with foraminal stenosis causing radiculopathy operated by the posterior cervical keyhole laminoforaminotomy between the years 2010 and 2015. Results: The file records and the radiographic images of the 35 patients were assessed retrospectively. The mean age was 46.4 years (range: 34-66 years). Of the patients, 19 were males and 16 were females. In all of the patients, the neurologic deficit observed was radiculopathy. The posterolaterally localized disc herniations and the osteophytic structures were on the left side in 18 cases and on the right in 17 cases. In 10 of the patients, the disc level was at C5-6, in 18 at C6-7, in 2 at C3-4, in 2 at C4-5, in 1 at C7-T1, in 1 patient at both C5-6 and C6-7, and in 1 at both C4-5 and C5-6. In 14 of these 35 patients, both osteophytic structures and protruded disc herniation were present. Intervertebral foramen stenosis was present in all of the patients with osteophytes. Postoperatively, in 31 patients the complaints were relieved completely and four patients had complaints of neck pain and paresthesia radiating to the arm (the success of operation was 88.5%). On control examinations, there was no finding of instability or cervical kyphosis. Conclusion: Posterior cervical laminoforaminotomy is an alternative appropriate choice in both cervical soft disc herniations and cervical stenosis. PMID:27217655

The NEtherlands Cervical Kinematics (NECK) trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study.

PubMed

Arts, Mark P; Brand, Ronald; van den Akker, Elske; Koes, Bart W; Peul, Wilco C

2010-06-16

Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prosthesis is necessary and cost-effective will be determined by this trial. Netherlands Trial Register NTR1289.

Minimally Invasive versus Open Spine Surgery: What Does the Best Evidence Tell Us?

PubMed

McClelland, Shearwood; Goldstein, Jeffrey A

2017-01-01

Spine surgery has been transformed significantly by the growth of minimally invasive surgery (MIS) procedures. Easily marketable to patients as less invasive with smaller incisions, MIS is often perceived as superior to traditional open spine surgery. The highest quality evidence comparing MIS with open spine surgery was examined. A systematic review of randomized controlled trials (RCTs) involving MIS versus open spine surgery was performed using the Entrez gateway of the PubMed database for articles published in English up to December 28, 2015. RCTs and systematic reviews of RCTs of MIS versus open spine surgery were evaluated for three particular entities: Cervical disc herniation, lumbar disc herniation, and posterior lumbar fusion. A total of 17 RCTs were identified, along with six systematic reviews. For cervical disc herniation, MIS provided no difference in overall function, arm pain relief, or long-term neck pain. In lumbar disc herniation, MIS was inferior in providing leg/low back pain relief, rehospitalization rates, quality of life improvement, and exposed the surgeon to >10 times more radiation in return for shorter hospital stay and less surgical site infection. In posterior lumbar fusion, MIS transforaminal lumbar interbody fusion (TLIF) had significantly reduced 2-year societal cost, fewer medical complications, reduced time to return to work, and improved short-term Oswestry Disability Index scores at the cost of higher revision rates, higher readmission rates, and more than twice the amount of intraoperative fluoroscopy. The highest levels of evidence do not support MIS over open surgery for cervical or lumbar disc herniation. However, MIS TLIF demonstrates advantages along with higher revision/readmission rates. Regardless of patient indication, MIS exposes the surgeon to significantly more radiation; it is unclear how this impacts patients. These results should optimize informed decision-making regarding MIS versus open spine surgery, particularly in the current advertising climate greatly favoring MIS.

The NEtherlands Cervical Kinematics (NECK) Trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study

PubMed Central

2010-01-01

Background Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Methods/Design Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Discussion Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prothesis is necessary and cost-effective will be determined by this trial. Trial Registration Netherlands Trial Register NTR1289 PMID:20553591

Caspase inhibitors increase the rate of recovery of neural stem/progenitor cells from post-mortem rat brains stored at room temperature.

PubMed

Hasegawa, Atsuko; Yamada, Chikako; Tani, Miho; Hirano, Shun-ichiro; Tokumoto, Yasuhito; Miyake, Jun

2009-06-01

To match the demand of regenerative medicine for nerve system, collection of stem cells from the post-mortem body is one of the most practical ways. In this study, the storage condition of the post-mortem body was examined. We prepared neural stem/progenitor cells (NSPCs) from post-mortem rat brains stored at different temperatures. When brains were stored at 4 degrees C, for one week, we were able to obtain neurospheres (a spheroid body containing NSPCs) by stimulation of cells with epidermal growth factor (EGF). Incremental increases in storage temperature decreased the rate of appearance of neurospheres. Within 48 h at 15 degrees C, 24 h at 25 degrees C, in both condition, we were able to recover NSPCs from post-mortem rat brains. At 15 degrees C, 90% of neurosphere-forming activity was lost within 24 h. However, even after 24 h at 25 degrees C, 2% neurosphere-forming activity remained. After 6 h of death, there was very little difference between the rates of NSPC recovery at 4 degrees C and 25 degrees C. Addition of caspase inhibitors to both the rat brain storage solution and the NSPC culture medium increased the rate of neurosphere-forming activity. In particular, an inhibitor of caspase-8 activity increased the NSPC recovery rate approximately three-fold, with no accompanying detrimental effects on neural differentiation in vitro.

miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells

PubMed Central

Sun, GuoQiang; Ye, Peng; Murai, Kiyohito; Lang, Ming-Fei; Li, Shengxiu; Zhang, Heying; Li, Wendong; Fu, Chelsea; Yin, Jason; Wang, Allen; Ma, Xiaoxiao; Shi, Yanhong

2012-01-01

miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 plays an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that histone demethylase LSD1, a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development. PMID:22068596

How Stem Cells Speak with Host Immune Cells in Inflammatory Brain Diseases

PubMed Central

Pluchino, Stefano; Cossetti, Chiara

2014-01-01

Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases. PMID:23633288

Poland syndrome involving the left hemithorax with dextrocardia and herniation of the spleen

PubMed Central

Panda, Shasanka Shekhar; Bajpai, Minu; Singh, Amit; Jana, Manisha

2014-01-01

Poland syndrome is characterised by unilateral absence of the large pectoral muscle, ipsilateral symbrachydactyly and occasionally other malformations of the anterior chest wall and breast. The condition is more frequent among men and usually occurs on the right hemithorax in the unilateral form. This case is unique because we believe it is a rare case of Poland syndrome involving the left hemithorax along with dextrocardia and herniation of the spleen from the left subcostal region. PMID:24567179

Poland syndrome involving the left hemithorax with dextrocardia and herniation of the spleen.

PubMed

Panda, Shasanka Shekhar; Bajpai, Minu; Singh, Amit; Jana, Manisha

2014-02-23

Poland syndrome is characterised by unilateral absence of the large pectoral muscle, ipsilateral symbrachydactyly and occasionally other malformations of the anterior chest wall and breast. The condition is more frequent among men and usually occurs on the right hemithorax in the unilateral form. This case is unique because we believe it is a rare case of Poland syndrome involving the left hemithorax along with dextrocardia and herniation of the spleen from the left subcostal region.

[Survey on the use of mannitol in prehospital care in Paris area].

PubMed

Duchateau, F X; Burnod, A; Chollet, C; Ricard-Hibon, A; Samain, E; Marty, J

2004-09-01

To evaluate the use of mannitol in prehospital care in Paris area. Survey using telephone interviews. Emergency physicians on duty in the 37 emergency departments in charge of prehospital care in Paris area were called by one investigator. They were asked to answer a questionnaire about their own use of mannitol in the prehospital setting. Ninety-six questionnaires were recorded. Physicians were anaesthesiologists (9%) or emergency physicians (87%). In three departments, mannitol was not available in the ambulances. Thirty-five per cent (n = 34) reported no use of mannitol and 17% (n = 16) just once. Fourteen physicians (15%) did not want to use it. The reasons for not using mannitol were lack of knowledge about efficacy for five, need for previous brain imaging for seven or neurosurgeon's agreement before using mannitol for three. For those who had already used mannitol or were ready to use it, the main indication was increased intracranial pressure with clinical signs of brain herniation after severe brain injury for 92% of physicians. Thirty-one % reported not knowing the dose of mannitol, 33% having a memorandum immediately available and among those who answered the question, 63% gave a value compatible with guidelines. A significant percentage of physicians tacking part in the French prehospital care system, do not follow published guidelines on the use of mannitol. Actions improving implementation of those guidelines should be supported.

Cerebral Infarction after Traumatic Brain Injury: Incidence and Risk Factors

PubMed Central

Bae, Dong-Hyeon; Choi, Kyu-Sun; Chun, Hyoung-Joon; Ko, Yong; Bak, Koang Hum

2014-01-01

Objective Post-traumatic cerebral infarction (PTCI) is one of the most severe secondary insults after traumatic brain injury (TBI), and is known to be associated with poor outcome and high mortality rate. We assessed the practical incidence and risk factors for the development of PTCI. Methods We conducted retrospective study on 986 consecutive patients with TBI from the period May 2005 to November 2012 at our institution. The definition of PTCI was made on non-enhanced CT scan based on a well-demarcated or fairly discernible region of low attenuation following specific vascular territory with normal initial CT. Clinical and radiological findings that related to patients' outcome were reviewed and statistically compared. Results PTCI was observed in 21 (2.1%) patients. Of various parameters, age (p=0.037), initial Glasgow coma scale score (p<0.01), brain herniation (p=0.044), and decompressive craniectomy (p=0.012) were significantly higher in patients with PTCI than patients who do not have PTCI. Duration between accident and PTCI, patterns of TBI and vascular territory of PTCI were not specific. The mortality rates were significantly higher in patients with PTCI than without PTCI. Conclusion The development of PTCI is rare after TBI, but it usually results in serious outcome and high mortality. Early recognition for risks and aggressive managements is mandatory to prevent PTCI. PMID:27169031

Direct and efficient transfection of mouse neural stem cells and mature neurons by in vivo mRNA electroporation.

PubMed

Bugeon, Stéphane; de Chevigny, Antoine; Boutin, Camille; Coré, Nathalie; Wild, Stefan; Bosio, Andreas; Cremer, Harold; Beclin, Christophe

2017-11-01

In vivo brain electroporation of DNA expression vectors is a widely used method for lineage and gene function studies in the developing and postnatal brain. However, transfection efficiency of DNA is limited and adult brain tissue is refractory to electroporation. Here, we present a systematic study of mRNA as a vector for acute genetic manipulation in the developing and adult brain. We demonstrate that mRNA electroporation is far more efficient than DNA electroporation, and leads to faster and more homogeneous protein expression in vivo Importantly, mRNA electroporation allows the manipulation of neural stem cells and postmitotic neurons in the adult brain using minimally invasive procedures. Finally, we show that this approach can be efficiently used for functional studies, as exemplified by transient overexpression of the neurogenic factor Myt1l and by stably inactivating Dicer nuclease in vivo in adult born olfactory bulb interneurons and in fully integrated cortical projection neurons. © 2017. Published by The Company of Biologists Ltd.

Blood-brain barrier-supported neurogenesis in healthy and diseased brain.

PubMed

Pozhilenkova, Elena A; Lopatina, Olga L; Komleva, Yulia K; Salmin, Vladimir V; Salmina, Alla B

2017-05-24

Adult neurogenesis is one of the most important mechanisms contributing to brain development, learning, and memory. Alterations in neurogenesis underlie a wide spectrum of brain diseases. Neurogenesis takes place in highly specialized neurogenic niches. The concept of neurogenic niches is becoming widely accepted due to growing evidence of the important role of the microenvironment established in the close vicinity to stem cells in order to provide adequate control of cell proliferation, differentiation, and apoptosis. Neurogenic niches represent the platform for tight integration of neurogenesis and angiogenesis supported by specific properties of cerebral microvessel endothelial cells contributing to establishment of partially compromised blood-brain barrier (BBB) for the adjustment of local conditions to the current metabolic needs of stem and progenitor cells. Here, we review up-to-date data on microvascular dynamics in activity-dependent neurogenesis, specific properties of BBB in neurogenic niches, endothelial-driven mechanisms of clonogenic activity, and future perspectives for reconstructing the neurogenic niches in vitro.

Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain.

PubMed

Emborg, Marina E; Liu, Yan; Xi, Jiajie; Zhang, Xiaoqing; Yin, Yingnan; Lu, Jianfeng; Joers, Valerie; Swanson, Christine; Holden, James E; Zhang, Su-Chun

2013-03-28

The generation of induced pluripotent stem cells (iPSCs) opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Grounded understanding of abstract concepts: The case of STEM learning.

PubMed

Hayes, Justin C; Kraemer, David J M

2017-01-01

Characterizing the neural implementation of abstract conceptual representations has long been a contentious topic in cognitive science. At the heart of the debate is whether the "sensorimotor" machinery of the brain plays a central role in representing concepts, or whether the involvement of these perceptual and motor regions is merely peripheral or epiphenomenal. The domain of science, technology, engineering, and mathematics (STEM) learning provides an important proving ground for sensorimotor (or grounded) theories of cognition, as concepts in science and engineering courses are often taught through laboratory-based and other hands-on methodologies. In this review of the literature, we examine evidence suggesting that sensorimotor processes strengthen learning associated with the abstract concepts central to STEM pedagogy. After considering how contemporary theories have defined abstraction in the context of semantic knowledge, we propose our own explanation for how body-centered information, as computed in sensorimotor brain regions and visuomotor association cortex, can form a useful foundation upon which to build an understanding of abstract scientific concepts, such as mechanical force. Drawing from theories in cognitive neuroscience, we then explore models elucidating the neural mechanisms involved in grounding intangible concepts, including Hebbian learning, predictive coding, and neuronal recycling. Empirical data on STEM learning through hands-on instruction are considered in light of these neural models. We conclude the review by proposing three distinct ways in which the field of cognitive neuroscience can contribute to STEM learning by bolstering our understanding of how the brain instantiates abstract concepts in an embodied fashion.

Ochratoxin A at nanomolar concentration perturbs the homeostasis of neural stem cells in highly differentiated but not in immature three-dimensional brain cell cultures.

PubMed

Zurich, Marie-Gabrielle; Honegger, Paul

2011-08-28

Ochratoxin A (OTA), a fungal contaminant of basic food commodities, is known to be highly cytotoxic, but the pathways underlying adverse effects at subcytotoxic concentrations remain to be elucidated. Recent reports indicate that OTA affects cell cycle regulation. Therefore, 3D brain cell cultures were used to study OTA effects on mitotically active neural stem/progenitor cells, comparing highly differentiated cultures with their immature counterparts. Changes in the rate of DNA synthesis were related to early changes in the mRNA expression of neural stem/progenitor cell markers. OTA at 10nM, a concentration below the cytotoxic level, was ineffective in immature cultures, whereas in mature cultures it significantly decreased the rate of DNA synthesis together with the mRNA expression of key transcriptional regulators such as Sox2, Mash1, Hes5, and Gli1; the cell cycle activator cyclin D2; the phenotypic markers nestin, doublecortin, and PDGFRα. These effects were largely prevented by Sonic hedgehog (Shh) peptide (500ngml(-1)) administration, indicating that OTA impaired the Shh pathway and the Sox2 regulatory transcription factor critical for stem cell self-renewal. Similar adverse effects of OTA in vivo might perturb the regulation of stem cell proliferation in the adult brain and in other organs exhibiting homeostatic and/or regenerative cell proliferation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

ADHD Experts Fear Brain-Growth Study Being Misconstrued

ERIC Educational Resources Information Center

Viadero, Debra

2007-01-01

This article reports on the results of a groundbreaking brain-imaging study suggesting that attention deficit hyperactivity disorder stems from delayed brain maturation. Implicit in some of the news coverage was the hopeful idea that many--even most--children eventually grow out of the disorder. But that's not exactly true, according to a…

Mind, Brain and Education: A Decade of Evolution

ERIC Educational Resources Information Center

Schwartz, Marc

2015-01-01

This article examines the evolution of Mind, Brain, and Education (MBE), the field, alongside that of the International Mind, Brain and Education Society (IMBES). The reflections stem mostly from my observations while serving as vice president, president-elect, and president of IMBES during the past 10 years. The article highlights the evolution…

Syngeneic Transplantation of Olfactory Ectomesenchymal Stem Cells Restores Learning and Memory Abilities in a Rat Model of Global Cerebral Ischemia.

PubMed

Veron, Antoine D; Bienboire-Frosini, Cécile; Girard, Stéphane D; Sadelli, Kevin; Stamegna, Jean-Claude; Khrestchatisky, Michel; Alexis, Jennifer; Pageat, Patrick; Asproni, Pietro; Mengoli, Manuel; Roman, François S

2018-01-01

Stem cells are considered as promising tools to repair diverse tissue injuries. Among the different stem cell types, the "olfactory ectomesenchymal stem cells" (OE-MSCs) located in the adult olfactory mucosa stand as one of the best candidates. Here, we evaluated if OE-MSC grafts could decrease memory impairments due to ischemic injury. OE-MSCs were collected from syngeneic F344 rats. After a two-step global cerebral ischemia, inducing hippocampal lesions, learning abilities were evaluated using an olfactory associative discrimination task. Cells were grafted into the hippocampus 5 weeks after injury and animal's learning abilities reassessed. Rats were then sacrificed and the brains collected for immunohistochemical analyses. We observed significant impairments in learning and memory abilities following ischemia. However, 4 weeks after OE-MSC grafts, animals displayed learning and memory performances similar to those of controls, while sham rats did not improve them. Immunohistochemical analyses revealed that grafts promoted neuroblast and glial cell proliferation, which could permit to restore cognitive functions. These results demonstrated, for the first time, that syngeneic transplantations of OE-MSCs in rats can restore cognitive abilities impaired after brain injuries and provide support for the development of clinical studies based on grafts of OE-MSCs in amnesic patients following brain injuries.

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions

PubMed Central

Ming, Guo-li; Song, Hongjun

2011-01-01

Summary Adult neurogenesis, a process of generating functional neurons from adult neural precursors, occurs throughout life in restricted brain regions in mammals. The past decade has witnessed tremendous progress in addressing questions related to almost every aspect of adult neurogenesis in the mammalian brain. Here we review major advances in our understanding of adult mammalian neurogenesis in the dentate gyrus of the hippocampus and from the subventricular zone of the lateral ventricle, the rostral migratory stream to the olfactory bulb. We highlight emerging principles that have significant implications for stem cell biology, developmental neurobiology, neural plasticity, and disease mechanisms. We also discuss remaining questions related to adult neural stem cells and their niches, underlying regulatory mechanisms and potential functions of newborn neurons in the adult brain. Building upon the recent progress and aided by new technologies, the adult neurogenesis field is poised to leap forward in the next decade. PMID:21609825

Visualization of migration of human cortical neurons generated from induced pluripotent stem cells.

PubMed

Bamba, Yohei; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

2017-09-01

Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly. Our system needs no viable brain tissue, which is usually used in slice culture. Migratory behavior of human cortical neuron can be observed more easily and more vividly by its fluorescence and glial scaffold than that by earlier methods. Our in vitro experimental system provides a new platform for investigating development of the human central nervous system and brain malformation. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain Abscess.

PubMed

Davis; Baldwin

1999-05-01

Optimal treatment of a brain abscess requires early clinical suspicion, and the diagnosis is usually made by identification of the abscess on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The immediate first step is to reduce the potentially life-threatening brain mass (abscess and surrounding cerebral edema) and secure the diagnosis with culture specimens. This is usually accomplished by reducing the increased intracranial pressure (ICP) through surgical aspiration with or without drainage of the abscess pus. The surgical procedure chosen depends on several factors, including the location and type of abscess, multiplicity, and the medical condition of the patient. In addition, dexamethasone and hyperventilation may be required if brain herniation is imminent. The dexamethasone dose should be reduced as soon as the ICP is reduced because steroid administration may retard abscess capsule formation and decrease antibiotic concentrations within the abscess cavity. Antibiotic therapy should be started as soon as the diagnosis is made. Penicillin G or third-generation cephalosporins plus metronidazole are commonly given to treat both anaerobic and aerobic bacteria. The initial choice of antibiotic will vary on the basis of the suspected source of the brain organisms, which is most often either contiguous spread from a sinus or mastoid infection or hematogenous spread from a pulmonary, gastrointestinal, cardiac, or dental infection. Isolation and determination of the antibiotic sensitivities of the organism from abscess pus allow definitive antibiotic therapy. Patients should be managed in an intensive care unit. Phenytoin is often given to prevent seizures, which could further elevate the ICP. The duration of antimicrobial treatment is 4 to 8 weeks, during which time the patient should be monitored clinically and with repeated neuroimaging studies to ensure abscess resolution.

miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4

PubMed Central

Okuda, Hiroshi; Xing, Fei; Pandey, Puspa R; Sharma, Sambad; Watabe, Misako; Pai, Sudha K.; Mo, Yin-Yuan; Iiizumi-Gairani, Megumi; Hirota, Shigeru; Liu, Yin; Wu, Kerui; Pochampally, Radhika; Watabe, Kounosuke

2012-01-01

Despite significant improvement in survival rates of breast cancer patients, prognosis of metastatic disease is still dismal. Cancer stem-like cells (CSCs) are considered to play a role in metastatic progression of breast cancer; however, the exact pathological role of CSCs is yet to be elucidated. In this report, we found that CSCs (CD24−/CD44+/ESA+) isolated from metastatic breast cell lines are significantly more metastatic than non-CSC populations in an organ specific manner. The results of our microRNA profile analysis for these cells revealed that CSCs that are highly metastatic to bone and brain expressed significantly lower level of miR-7 and that this microRNA was capable of modulating one of the essential genes for induced pluripotent stem cell, KLF4. Interestingly, high expression of KLF4 was significantly and inversely correlated to brain- but not bone-metastasis free survival of breast cancer patients, and we indeed found that the expression of miR-7 significantly suppressed the ability of CSCs to metastasize to brain but not to bone in our animal model. We also examined the expression of miR-7 and KLF4 in brain-metastatic lesions and found that these genes were significantly down- or up-regulated, respectively, in the tumor cells in brain. Furthermore, the results of our in vitro experiments indicate that miR-7 attenuates the abilities of invasion and self-renewal of CSCs by modulating KLF4 expression. These results suggest that miR-7 and KLF4 may serve as biomarkers or therapeutic targets for brain metastasis of breast cancer. PMID:23384942

Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy

PubMed Central

Wei, Zheng Z; Zhu, Yan-Bing; Zhang, James Y; McCrary, Myles R; Wang, Song; Zhang, Yong-Bo; Yu, Shan-Ping; Wei, Ling

2017-01-01

Objective: Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. Data Sources: This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: “stem cells,” “hypoxic preconditioning,” “ischemic preconditioning,” and “cell transplantation.” Study Selection: Original articles and critical reviews on the topics were selected. Results: Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. Conclusions: In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications. PMID:28937044

No pain, no gain: lack of exercise obstructs neurogenesis.

PubMed

Watson, Nate; Ji, Xunming; Yasuhara, Takao; Date, Isao; Kaneko, Yuji; Tajiri, Naoki; Borlongan, Cesar V

2015-01-01

Bedridden patients develop atrophied muscles, their daily activities greatly reduced, and some display a depressive mood. Patients who are able to receive physical rehabilitation sometimes show surprising clinical improvements, including reduced depression and attenuation of other stress-related behaviors. Regenerative medicine has advanced two major stem cell-based therapies for CNS disorders, namely, transplantation of exogenous stem cells and amplification of endogenous neurogenesis. The latter strategy embraces a natural way of reinnervating the damaged brain and correcting the neurological impairments. In this study, we discussed how immobilization-induced disuse atrophy, using the hindlimb suspension model, affects neurogenesis in rats. The overarching hypothesis is that immobilization suppresses neurogenesis by reducing the circulating growth or trophic factors, such as vascular endothelial growth factor or brain-derived neurotrophic factor. That immobilization alters neurogenesis and stem cell differentiation in the CNS requires characterization of the stem cell microenvironment by examining the trophic and growth factors, as well as stress-related proteins that have been implicated in exercise-induced neurogenesis. Although accumulating evidence has revealed the contribution of "increased" exercise on neurogenesis, the reverse paradigm involving "lack of exercise," which mimics pathological states (e.g., stroke patients are often immobile), remains underexplored. This novel paradigm will enable us to examine the effects on neurogenesis by a nonpermissive stem cell microenvironment likely produced by lack of exercise. BrdU labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid and brain levels of trophic factors, growth factors, and stress-related proteins are proposed as indices of neurogenesis, while quantitative measurements of spontaneous movements will reveal psychomotor components of immobilization. Studies designed to reveal how in vivo stimulation, or lack thereof, alters the stem cell microenvironment are needed to begin to develop treatment strategies for enhancing neurogenesis in bedridden patients.

Insights into the Biology and Therapeutic Applications of Neural Stem Cells

PubMed Central

Harris, Lachlan; Zalucki, Oressia; Piper, Michael; Heng, Julian Ik-Tsen

2016-01-01

The cerebral cortex is essential for our higher cognitive functions and emotional reasoning. Arguably, this brain structure is the distinguishing feature of our species, and yet our remarkable cognitive capacity has seemingly come at a cost to the regenerative capacity of the human brain. Indeed, the capacity for regeneration and neurogenesis of the brains of vertebrates has declined over the course of evolution, from fish to rodents to primates. Nevertheless, recent evidence supporting the existence of neural stem cells (NSCs) in the adult human brain raises new questions about the biological significance of adult neurogenesis in relation to ageing and the possibility that such endogenous sources of NSCs might provide therapeutic options for the treatment of brain injury and disease. Here, we highlight recent insights and perspectives on NSCs within both the developing and adult cerebral cortex. Our review of NSCs during development focuses upon the diversity and therapeutic potential of these cells for use in cellular transplantation and in the modeling of neurodevelopmental disorders. Finally, we describe the cellular and molecular characteristics of NSCs within the adult brain and strategies to harness the therapeutic potential of these cell populations in the treatment of brain injury and disease. PMID:27069486

Inequality in leg length is important for the understanding of the pathophysiology of lumbar disc herniation

PubMed Central

Balik, Mehmet Sabri; Kanat, Ayhan; Erkut, Adem; Ozdemir, Bulent; Batcik, Osman Ersagun

2016-01-01

Objective: Inequality in leg length may lead to to abnormal transmission of load across the endplates and degeneration lumbar spine and the disc space. There has been no study focusing on lumbar disc herniation (LDH) and leg length discrepancy. This subject was investigated in this study. Materials and Methods: Consecutive adult patients with leg length discrepancy and low back pain (LBP) admitted to our department were respectivelly studied. Results: A total number of 39 subjects (31 women and eight men) with leg length discrepancy and LBP and 43 (25 females and 18 males) patients with LBP as a control group were tested. Occurrence of disc herniation is statistically different between patients with hip dysplasia and control groups (P < 0.05). Conclusion: The results of this study showed a statistically significant association between leg length discrepancy and occurrence of LDH. The changes of spine anatomy with leg length discrepancy in hip dysplastic patients are of importance in understanding the nature of LDH. PMID:27217654

Delayed diaphragmatic herniation masquerading as a complicated parapneumonic effusion.

PubMed

Tsang, J; Ryan, F

1999-01-01

Injury to the diaphragm following blunt or penetrating thoracoabdominal trauma is not uncommon. Recognition of this important complication of trauma continues to be a challenge because of the lack of specific clinical and plain radiographic features, the frequent presence of other serious injuries and the potential for delayed presentation. Delayed diaphragmatic herniation often presents with catastrophic bowel obstruction or strangulation. Early recognition of diaphragmatic injury is required to avoid this potentially lethal complication. The case of a 35-year-old man with a history of a knife wound to the left flank 15 years previously, who presented with unexplained acute hypoxemic respiratory failure and a unilateral exudative pleural effusion that was refractory to tube thoracostomy drainage, is reported. After admission to hospital, he developed gross dilation of his colon; emergency laparotomy revealed an incarcerated colonic herniation into the left hemithorax. Interesting clinical features of this patient's case included the patient's hobby of weightlifting, a persistently deviated mediastinum despite drainage of the pleural effusion and deceptive pleural fluid biochemical indices.

Terminal ileum gangrene secondary to a type IV paraesophageal hernia.

PubMed

Hsu, Ching Tsai; Hsiao, Po Jen; Chiu, Chih Chien; Chan, Jenq Shyong; Lin, Yee Fung; Lo, Yuan Hung; Hsiao, Chia Jen

2016-02-28

Type IV paraesophageal hernia (PEH) is very rare, and is characterized by the intrathoracic herniation of the abdominal viscera other than the stomach into the chest. We describe a 78-year-old woman who presented at our emergency department because of epigastric pain that she had experienced over the past 24 h. On the day after admission, her pain became severe and was accompanied by right chest pain and dyspnea. Chest radiography revealed an intrathoracic intestinal gas bubble occupying the right lower lung field. Emergency explorative laparotomy identified a type IV PEH with herniation of only the terminal ileum through a hiatal defect into the right thoracic cavity. In this report, we also present a review of similar cases in the literature published between 1980 and 2015 in PubMed. There were four published cases of small bowel herniation into the thoracic cavity during this period. Our patient represents a rare case of an individual diagnosed with type IV PEH with incarceration of only the terminal ileum.

Naturally Occurring Disk Herniation in Dogs: An Opportunity for Pre-Clinical Spinal Cord Injury Research

PubMed Central

Levine, Gwendolyn J.; Porter, Brian F.; Topp, Kimberly; Noble-Haeusslein, Linda J.

2011-01-01

Abstract Traumatic spinal cord injuries represent a significant source of morbidity in humans. Despite decades of research using experimental models of spinal cord injury to identify candidate therapeutics, there has been only limited progress toward translating beneficial findings to human spinal cord injury. Thoracolumbar intervertebral disk herniation is a naturally occurring disease that affects dogs and results in compressive/contusive spinal cord injury. Here we discuss aspects of this disease that are analogous to human spinal cord injury, including injury mechanisms, pathology, and metrics for determining outcomes. We address both the strengths and weaknesses of conducting pre-clinical research in these dogs, and include a review of studies that have utilized these animals to assess efficacy of candidate therapeutics. Finally, we consider a two-species approach to pre-clinical data acquisition, beginning with a reproducible model of spinal cord injury in the rodent as a tool for discovery with validation in pet dogs with intervertebral disk herniation. PMID:21438715

Surgical resection of large encephalocele: a report of two cases and consideration of resectability based on developmental morphology.

PubMed

Ohba, Hideo; Yamaguchi, Satoshi; Sadatomo, Takashi; Takeda, Masaaki; Kolakshyapati, Manish; Kurisu, Kaoru

2017-03-01

The first-line treatment of encephalocele is reduction of herniated structures. Large irreducible encephalocele entails resection of the lesion. In such case, it is essential to ascertain preoperatively if the herniated structure encloses critical venous drainage. Two cases of encephalocele presenting with large occipital mass underwent magnetic resonance (MR) imaging. In first case, the skin mass enclosed the broad space containing cerebrospinal fluid and a part of occipital lobe and cerebellum. The second case had occipital mass harboring a large portion of cerebrum enclosing dilated ventricular space. Both cases had common venous anomalies such as split superior sagittal sinus and high-positioned torcular herophili. They underwent resection of encephalocele without subsequent venous congestion. We could explain the pattern of venous anomalies in encephalocele based on normal developmental theory. Developmental theory connotes that major dural sinuses cannot herniate into the sac of encephalocele. Irrespective to its size, encephalocele can be resected safely at the neck without subsequent venous congestion.

"Laparoscopic excision of a large ovarian cyst herniating into the inguinal canal: a rare presentation".

PubMed

Machado, Norman Oneil; Machado, Lovina S M; Al Ghafri, Wadha

2011-08-01

Inguinal hernia repair is one of the most common operation in surgical practice. Despite its common occurrence, hernia often poses a surgical dilemma even for a skilled surgeon. The unexpected hernial content constitutes one of these cases. Although the often-reported, unusual contents of a hernia sac include ovary, fallopian tube, vermiform appendix, Meckel diverticulum, and urinary bladder, the herniation of a large ovarian cyst into the inguinal canal has been hardly reported. Majority of the ovarian cysts are asymptomatic or present with vague lower abdominal pain, whereas the presentation of a large ovarian cyst as an inguinolabial swelling as in our patient is extremely rare. We present here one of the few reported cases of a laparoscopic excision of a large ovarian cyst herniating into the inguinal canal and discuss the pathogenesis of an ovarian cyst as hernial content, the advantages and concerns of a laparoscopic approach in resecting large ovarian cysts, and simultaneous management of the inguinal hernia.

Pro-life role for c-Jun N-terminal kinase and p38 mitogen-activated protein kinase at rostral ventrolateral medulla in experimental brain stem death.

PubMed

Chang, Alice Y W

2012-11-17

Based on an experimental brain stem death model, we demonstrated previously that activation of the mitogen-activated protein kinase kinase 1/2 (MEK1/2)/extracellular signal-regulated kinase 1/2 (ERK1/2)/ mitogen-activated protein kinase signal-interacting kinase 1/2 (MNK1/2) cascade plays a pro-life role in the rostral ventrolateral medulla (RVLM), the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life) and decreases (pro-death) to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients. The present study assessed the hypothesis that, in addition to ERK1/2, c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK), the other two mammalian members of MAPKs that are originally identified as stress-activated protein kinases, are activated specifically by MAPK kinase 4 (MAP2K4) or MAP2K6 and play a pro-life role in RVLM during experimental brain stem death. We further delineated the participation of phosphorylating activating transcriptional factor-2 (ATF-2) and c-Jun, the classical transcription factor activated by JNK or p38MAPK, in this process. An experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol) bilaterally into RVLM of Sprague-Dawley rats was used, alongside cardiovascular, pharmacological and biochemical evaluations. Results from ELISA showed that whereas the total JNK, p38MAPK, MAP2K4 and MAP2K6 were not affected, augmented phosphorylation of JNK at Thr183 and Tyr185 and p38MAPK at Thr180 and Tyr182, accompanied by phosphorylation of their upstream activators MAP2K4 at Ser257 and Thr261 and MAP2K6 at Ser207 and Thr211 in RVLM occurred preferentially during the pro-life phase of experimental brain stem death. Moreover, the activity of transcription factors ATF-2 at Thr71 and c-Jun at Ser73, rather than Elk-1 at Ser383 in RVLM were also augmented during the pro-life phase. Furthermore, pretreatment by microinjection into the bilateral RVLM of specific JNK inhibitors, JNK inhibitor I (100 pmol) or SP600125 (5 pmol), or specific p38MAPK inhibitors, p38MAPK inhibitor III (500 pmol) or SB203580 (2 nmol), exacerbated the depressor effect and blunted the augmented life-and-death signal exhibited during the pro-life phase. On the other hand, pretreatment with the negative control for JNK or p38MAPK inhibitor, JNK inhibitor I negative control (100 pmol) or SB202474 (2 nmol), was ineffective in the vehicle-controls and Mev-treatment groups. Our results demonstrated that activation of JNK or p38MAPK in RVLM by their upstream activators MAP2K4 or MAP2K6 plays a preferential pro-life role by sustaining the central cardiovascular regulatory machinery during experimental brain stem death via phosphorylation and activation of nuclear transcription factor ATF-2 or c-Jun.

Distribution of calcium channel Ca(V)1.3 immunoreactivity in the rat spinal cord and brain stem.

PubMed

Sukiasyan, N; Hultborn, H; Zhang, M

2009-03-03

The function of local networks in the CNS depends upon both the connectivity between neurons and their intrinsic properties. An intrinsic property of spinal motoneurons is the presence of persistent inward currents (PICs), which are mediated by non-inactivating calcium (mainly Ca(V)1.3) and/or sodium channels and serve to amplify neuronal input signals. It is of fundamental importance for the prediction of network function to determine the distribution of neurons possessing the ion channels that produce PICs. Although the distribution pattern of Ca(V)1.3 immunoreactivity (Ca(V)1.3-IR) has been studied in some specific central nervous regions in some species, so far no systematic investigations have been performed in both the rat spinal cord and brain stem. In the present study this issue was investigated by immunohistochemistry. The results indicated that the Ca(V)1.3-IR neurons were widely distributed across different parts of the spinal cord and the brain stem although with variable labeling intensities. In the spinal gray matter large neurons in the ventral horn (presumably motoneurons) tended to display higher levels of immunoreactivity than smaller neurons in the dorsal horn. In the white matter, a subset of glial cells labeled by an oligodendrocyte marker was also Ca(V)1.3-positive. In the brain stem, neurons in the motor nuclei appeared to have higher levels of immunoreactivity than those in the sensory nuclei. Moreover, a number of nuclei containing monoaminergic cells, for example the locus coeruleus, were also strongly immunoreactive. Ca(V)1.3-IR was consistently detected in the neuronal perikarya regardless of the neuronal type. However, in the large neurons in the spinal ventral horn and the cranial motor nuclei the Ca(V)1.3-IR was clearly detectable in first and second order dendrites. These results indicate that in the rat spinal cord and brain stem Ca(V)1.3 is probably a common calcium channel used by many kinds of neurons to facilitate the neuronal information processing via certain intracellular mechanisms, for instance, PICs.

Blockade of brain stem gap junctions increases phrenic burst frequency and reduces phrenic burst synchronization in adult rat.

PubMed

Solomon, Irene C; Chon, Ki H; Rodriguez, Melissa N

2003-01-01

Recent investigations have examined the influence of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in vitro using transverse medullary slice and en bloc brain stem-spinal cord preparations obtained from neonatal (1-5 days postnatal) mice. Gap junction proteins, however, have been identified in both neurons and glia in brain stem regions implicated in respiratory control in both neonatal and adult rodents. Here, we used an in vitro arterially perfused rat preparation to examine the role of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents. We recorded rhythmic inspiratory motor activity from one or both phrenic nerves before and during pharmacological blockade (i.e., uncoupling) of brain stem gap junctions using carbenoxolone (100 microM), 18alpha-glycyrrhetinic acid (25-100 microM), 18beta-glycyrrhetinic acid (25-100 microM), octanol (200-300 microM), or heptanol (200 microM). During perfusion with a gap junction uncoupling agent, we observed an increase in the frequency of phrenic bursts (~95% above baseline frequency; P < 0.001) and a decrease in peak amplitude of integrated phrenic nerve discharge (P < 0.001). The increase in frequency of phrenic bursts resulted from a decrease in both T(I) (P < 0.01) and T(E) (P < 0.01). In addition, the pattern of phrenic nerve discharge shifted from an augmenting discharge pattern to a "bell-shaped" or square-wave discharge pattern in most experiments. Spectral analyses using a fast Fourier transform (FFT) algorithm revealed a reduction in the peak power of both the 40- to 50-Hz peak (corresponding to the MFO) and 90- to 110-Hz peak (corresponding to the HFO) although spurious higher frequency activity (> or =130 Hz) was observed, suggesting an overall loss or reduction in inspiratory-phase synchronization. Although additional experiments are required to identify the specific brain stem regions and cell types (i.e., neurons, glia) mediating the observed modulations in phrenic motor output, these findings suggest that gap junction communication modulates generation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents in vitro.

Outcome of nucleoplasty in patients with radicular pain due to lumbar intervertebral disc herniation

PubMed Central

Ogbonnaya, Sunny; Kaliaperumal, Chandrasekaran; Qassim, Abdulla; O’Sullivan, Michael

2013-01-01

Background: Nucleoplasty (percutaneous lumbar disc decompression) is a minimally invasive procedure that utilizes radiofrequency energy as a treatment for symptomatic lumbar disc herniation, against open microdiscectomy, which would be the mainstay treatment modality. The literature reports a favorable outcome in up to 77% of patients at 6 months. Aim: To evaluate the effectiveness of nucleoplasty in the management of discogenic radicular pain. Materials and Methods: The medical notes of 33 patients, admitted for nucleoplasty between June 2006 and September 2007, were reviewed retrospectively. All had radicular pain, and contained herniated disc as seen on magnetic resonance imaging (MRI) of lumbosacral spine. Patients were followed up at 1 and 3 months post-procedure. The outcome measures employed in this study were satisfaction with symptoms and self-reported improvement. Results: Thirty-three cases were examined (18 males and 15 females). Twenty-seven procedures were performed with no complications and six were abandoned due to anatomical reasons. There were 18 and 15 cases of disc herniation at L5/S1 and L4/5 levels, respectively. Four weeks following the procedure, 13 patients reported improvement in symptoms, and 14 remained symptomatically the same and subsequently had open microdiscectomy. Conclusion: Nucleoplasty has been shown to be a safe and minimal-access procedure. Less than half of our selected cohort of patients reported symptomatic improvement at 1-month follow-up. We no longer offer this procedure to our patients. Possible reasons are discussed. PMID:23633860

Conservatively treated massive prolapsed discs: a 7-year follow-up

PubMed Central

Benson, RT; Tavares, SP; Robertson, SC; Sharp, R; Marshall, RW

2010-01-01

INTRODUCTION The natural history of a lumbar hernia of the nucleus pulposus (HNP) is not fully known and clear indications for operative intervention cannot be established from the literature. Several studies have shown that the largest discs appear to have the greatest tendency to resolve. The aim of this study was to investigate whether massive prolapsed discs can be safely managed conservatively once clinical improvement has occurred. PATIENTS AND METHODS Thirty-seven patients were studied by clinical assessments and serial magnetic resonance imaging (MRI) over 2 years. Patients had severe sciatica at first, but began to show clinical improvement despite the large disc hernia-tions. Clinical assessment included the Lasegue test and neurological appraisal. The Oswestry Disability Index was used to measure function and changes in function. Serial MRI studies allowed measurement of volume changes of the herniated disc material over a period of time. RESULTS Initial follow-up at an average of 23.2 months revealed that 83% had a complete and sustained recovery at the initial follow-up. Only four patients required a discectomy. The average Oswestry disability index improved from 58% to 15%. Volumetric analysis of serial MRI scans found an average reduction of 64% in disc size. There was a poor correlation between clinical improvement and the extent of disc resolution. CONCLUSIONS A massive disc herniation can pursue a favourable clinical course. If early progress is shown, the long-term prognosis is very good and even massive disc herniations can be treated conservatively. PMID:19887021

Safe and sustainable: the extracranial approach toward frontoethmoidal meningoencephalocele repair.

PubMed

Heidekrueger, Paul I; Thu, Myat; Mühlbauer, Wolfgang; Holm-Mühlbauer, Charlotte; Schucht, Philippe; Anderl, Hans; Schoeneich, Heinrich; Aung, Kyawzwa; Mg Ag, Mg; Thu Soe Myint, Ag; Juran, Sabrina; Aung, Thiha; Ehrl, Denis; Ninkovic, Milomir; Broer, P Niclas

2017-10-01

OBJECTIVE Although rare, frontoethmoidal meningoencephaloceles continue to pose a challenge to neurosurgeons and plastic reconstructive surgeons. Especially when faced with limited infrastructure and resources, establishing reliable and safe surgical techniques is of paramount importance. The authors present a case series in order to evaluate a previously proposed concise approach for meningoencephalocele repair, with a focus on sustainability of internationally driven surgical efforts. METHODS Between 2001 and 2016, a total of 246 patients with frontoethmoidal meningoencephaloceles were treated using a 1-stage extracranial approach by a single surgeon in the Department of Neurosurgery of the Yangon General Hospital in Yangon, Myanmar, initially assisted by European surgeons. Outcomes and complications were evaluated. RESULTS A total of 246 patients (138 male and 108 female) were treated. Their ages ranged from 75 days to 32 years (median 8 years). The duration of follow-up ranged between 4 weeks and 16 years (median 4 months). Eighteen patients (7.3%) showed signs of increased intracranial pressure postoperatively, and early CSF rhinorrhea was observed in 27 patients (11%), with 5 (2%) of them requiring operative dural repair. In 8 patients, a decompressive lumbar puncture was performed. There were 8 postoperative deaths (3.3%) due to meningitis. In 15 patients (6.1%), recurrent herniation of brain tissue was observed; this herniation led to blindness in 1 case. The remaining patients all showed good to very good aesthetic and functional results. CONCLUSIONS A minimally invasive, purely extracranial approach to frontoethmoidal meningoencephalocele repair may serve well, especially in middle- and low-income countries. This case series points out how the frequently critiqued lack of sustainability in the field of humanitarian surgical missions, as well as the often-cited missing aftercare and dependence on foreign supporters, can be circumvented by meticulous training of local surgeons.

Repair of bony lateral skull base defects equal to or larger than 10 mm by extracorporeally sewed unit-sandwich graft.

PubMed

Indorewala, Shabbir; Nemade, Gaurav; Indorewala, Abuzar; Mahajan, Gauri

2018-06-23

To see effectiveness of the senior author's repair technique for repair of large (equal to or larger than 10 mm) bony lateral skull base defects. Retrospective. Secondary/tertiary care center. We performed retrospective review of 9 surgeries done in our institution between January 2010 and December 2013 for repair of large lateral bony skull base defects. We defined skull base defects extra-cranially and repaired them intra-cranially. We made an extracorporeal sandwich of autologous fascia-bone-fascia (fascia lata and nasal septal bone) and sewed it together to make it into a unit-sandwich graft. This extracorporeally sewed unit-sandwich graft was then inserted to close the large skull base defects either via (1) a cranial slit-window, or (2) the skull base defect itself. Since skull base is bony, bony repair is preferred. Bone plates that are easily available for skull base repair are calvarial and nasal septal bone. Occasionally, harvest of split calvarial bone carries risk of major complications. We preferred nasal septal bone. Harvesting of septal bone even in children using a posterior incision should not disturb the cartilage growth centers. All nine patients were operated by this technique. We had four patients with cerebrospinal fluid leak, and five patients with brain herniation. All these patients had complete reversal of herniation of cranial contents and cessation of cerebrospinal fluid leak. On imaging, in 6 cases the bone graft remained in original intended position after 12 months of surgery. The bone graft was not identifiable in 3 cases. The senior author's technique using autologous multi-layered graft is simple to master, repeatable and very effective.

Survival rates and prognostic predictors of high grade brain stem gliomas in childhood: a systematic review and meta-analysis.

PubMed

Hassan, Hadeel; Pinches, Anne; Picton, Susan V; Phillips, Robert S

2017-10-01

Diagnosis of a pediatric high grade brain stem glioma is devastating with dismal outcomes. This systematic review and meta-analysis was undertaken to determine the survival rates and assess potential prognostic factors including selected interventions. Studies included involved pediatric participants with high grade brain stem gliomas diagnosed by magnetic resonance imaging or biopsy reporting overall survival rates. Meta-analysis was undertaken using a binomial random effects model. Sixty-five studies (2336 participants) were included. Meta-analysis showed 1 year overall survival (OS) of 41% (95% confidence interval (CI) 38-44%, I-sq 52%, 2083 participants), 2 year OS of 15.3% (95% confidence interval 12-20%, I-sq 73.1%, 1329 participants) and 3 year OS of 7.3% (95% confidence interval 5.2-10%, I-sq 26%, 584 participants). Meta-analyses of median overall survival results was not possible due to the lack of reported measures of variance. Subgroup analysis comparing date of study, classification of tumor, use of temozolomide, non-standard interventions or phase 1/2 versus other studies demonstrated no difference in survival outcomes. There was insufficient data to undertake subgroup meta-analysis of patient age, duration of symptoms, K27M histone mutations and AVCR1 mutations. Survival outcomes of high grade brain stem gliomas have remained very poor, and do not clearly vary according to classification, phase of study or use of different therapeutic interventions. Future studies should harmonize outcome and prognostic variable reporting to enable accurate meta-analysis and better exploration of prognosis.

Brain Stem Cavernous Malformations: Operative Nuances of a Less-Invasive Resection Technique.

PubMed

Singh, Harminder; Elarjani, Turki; da Silva, Harley Brito; Shetty, Rakshith; Kim, Louis; Sekhar, Laligam N

2017-12-08

Different operative techniques are reported for the resection of brainstem cavernous malformations (BSCMs). The senior author has previously reported on a less-invasive technique of entering the brain stem with piecemeal removal of BSCMs, especially the deep-seated ones. To present a larger series of these lesions, emphasizing the approach to the brain stem via case selection. We discuss the nuances of the less-invasive operative technique through case illustrations and intraoperative videos. A retrospective review of 46 consecutive cases of BSCMs, with their clinical and radiographic data, was performed. Nine cases were selected to illustrate 7 different operative approaches, and discuss surgical nuances of the less-invasive technique unique to each. Postoperative morbidity, defined as an increase in modified Rankin Scale, was observed in 5 patients (10.9%). A residual BSCM was present in 2 patients (4.3%); both underwent reoperation to remove the remainder. At follow-up of 31.1 ± 27.8 mo, 3 patients experienced recurrence (6.5%). Overall, 65% of our patients improved, 20% stayed the same, and 11% worsened postsurgery. Two patients died, yielding a mortality of 4.3%. Using the less-invasive resection technique for piecemeal BSCM removal, in appropriately selected patients, has yielded comparable to improved patient outcomes over existing large series. In our experience, lateral, anterolateral, and posterolateral approaches are favorable over direct midline (dorsal or ventral) approaches. A thorough understanding of brain-stem safe-entry zones, in conjunction with appropriate approach selection, is key to a good outcome in challenging cases. Copyright © 2017 by the Congress of Neurological Surgeons

Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study

PubMed Central

Monuki, Edwin S.; Powers, James; Schwartz, Phillip H.; Watkins, Paul A.; Shi, Yang; Moser, Ann; Shrier, David A.; Waterham, Hans R.; Nugent, Diane J.; Abdenur, Jose E.

2015-01-01

Objective Acyl-CoA oxidase (ACOX1) deficiency is a rare disorder of peroxisomal very-long chain fatty acid oxidation. No reports detailing attempted treatment, longitudinal imaging, or neuropathology exist. We describe the natural history of clinical symptoms and brain imaging in two siblings with ACOX1 deficiency, including the younger sibling's response to allogeneic unrelated donor hematopoietic stem cell transplantation (HSCT). Methods We conducted retrospective chart review to obtain clinical history, neuro-imaging, and neuropathology data. ACOX1 genotyping were performed to confirm the disease. In vitro fibroblast and neural stem cell fatty acid oxidation assays were also performed. Results Both patients experienced a fatal neurodegenerative course, with late-stage cerebellar and cerebral gray matter atrophy. Serial brain magnetic resonance imaging in the younger sibling indicated demyelination began in the medulla and progressed rostrally to include the white matter of the cerebellum, pons, midbrain, and eventually subcortical white matter. The successfully engrafted younger sibling had less brain inflammation, cortical atrophy, and neuronal loss on neuroimaging and neuropathology compared to the untreated older sister. Fibroblasts and stem cells demonstrated deficient very long chain fatty acid oxidation. Interpretation Although HSCT did not halt the course of ACOX1 deficiency, it reduced the extent of white matter inflammation in the brain. Demyelination continued because of ongoing neuronal loss, which may be due to inability of transplant to prevent progression of gray matter disease, adverse effects of chronic corticosteroid use to control graft-versus-host disease, or intervention occurring beyond a critical point for therapeutic efficacy. PMID:24619150

Mouse embryonic stem cell-derived cells reveal niches that support neuronal differentiation in the adult rat brain.

PubMed

Maya-Espinosa, Guadalupe; Collazo-Navarrete, Omar; Millán-Aldaco, Diana; Palomero-Rivero, Marcela; Guerrero-Flores, Gilda; Drucker-Colín, René; Covarrubias, Luis; Guerra-Crespo, Magdalena

2015-02-01

A neurogenic niche can be identified by the proliferation and differentiation of its naturally residing neural stem cells. However, it remains unclear whether "silent" neurogenic niches or regions suitable for neural differentiation, other than the areas of active neurogenesis, exist in the adult brain. Embryoid body (EB) cells derived from embryonic stem cells (ESCs) are endowed with a high potential to respond to specification and neuralization signals of the embryo. Hence, to identify microenvironments in the postnatal and adult rat brain with the capacity to support neuronal differentiation, we transplanted dissociated EB cells to conventional neurogenic and non-neurogenic regions. Our results show a neuronal differentiation pattern of EB cells that was dependent on the host region. Efficient neuronal differentiation of EB cells occurred within an adjacent region to the rostral migratory stream. EB cell differentiation was initially patchy and progressed toward an even distribution along the graft by 15-21 days post-transplantation, giving rise mostly to GABAergic neurons. EB cells in the striatum displayed a lower level of neuronal differentiation and derived into a significant number of astrocytes. Remarkably, when EB cells were transplanted to the striatum of adult rats after a local ischemic stroke, increased number of neuroblasts and neurons were observed. Unexpectedly, we determined that the adult substantia nigra pars compacta, considered a non-neurogenic area, harbors a robust neurogenic environment. Therefore, neurally uncommitted cells derived from ESCs can detect regions that support neuronal differentiation within the adult brain, a fundamental step for the development of stem cell-based replacement therapies. © 2014 AlphaMed Press.