Abstract:
:High-flow microinfusion is a novel technique for delivery of compounds directly into the brain parenchyma, bypassing the blood-brain barrier. The feasibility of this technique has been demonstrated with low-molecular-weight compounds, macromolecular dyes, and proteins. Delivery of antisense oligonucleotides into the brain parenchyma represents an additional potential application of this technique not previously described. In this report, the authors examined the distribution and disposition of phosphorothioate oligodeoxynucleotide (PS-ODN) infused for this reason. An 18-mer (35)S-PS-ODN (molecular weight approximately 6000) was infused over 1 hour into the caudate putamen of Fischer 344 rats. At 1, 6, 12, 24, and 48 hours after beginning the infusion, the brains were extracted and analyzed using quantitative autoradiographic techniques. Cerebrospinal fluid (CSF) was also aspirated from the cisterna magna and analyzed for radioactivity and stability of the (35)S-PS-ODN. At 1 hour, the infused ODN was uniformly distributed in brain tissue, with a maximum average concentration of 4806.5 +/- 210.5 nCi/g. This represents a tissue concentration of 19.2 +/- 0.84 microM. Extensive spread into surrounding parenchyma was observed over the ensuing 47 hours. The (35)S-PS-ODN radioactivity peaked in the CSF at the end of the 1-hour infusion, containing 10% (50 +/- 20 nCi) of the infused radioactivity. Activity then decayed exponentially over 11 hours, stabilizing at a lower CSF content of 0.2% (1 +/- 0.1 nCi). The volume of distribution (V(d)) was 105 +/- 7.9 mm3 at 1 hour, representing a ratio of V(d)/V(i) (volume of infusion) of 5.2. The V(d) increased to 443.4 +/- 62.3 mm(3) at the end of 48 hours, whereas the average minimum tissue concentration decreased from 15.2 to 3.2 microM. Undegraded 18-mer was seen throughout the 48-hour period using 20% polyacrylamide/7M urea gel electrophoresis. The animals tolerated the infusion without evidence of toxicity, and minimal structural changes in tissue were observed on histological examination. Thus, PS-ODN can be safely delivered in high concentrations to wide areas of the rat brain by using high-flow microinfusion, and the concentrations remain stable even after 48 hours in situ.
journal_name
Neurosurg Focusjournal_title
Neurosurgical focusauthors
Broaddus WC,Prabhu SS,Gillies GT,Neal J,Conrad WS,Chen ZJ,Fillmore H,Young HFdoi
10.3171/foc.1997.3.5.7subject
Has Abstractpub_date
1997-11-15 00:00:00pages
Article4issue
5issn
1092-0684pii
030504journal_volume
3pub_type
杂志文章abstract::OBJECT Cushing's disease (CD) is a potentially lethal neuroendocrinopathy that often requires specialized multidisciplinary treatment to achieve optimized outcomes. The authors analyzed data pertaining to patient, hospital, and admission characteristics as they relate to outcomes following transsphenoidal surgery (TSS...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2014.11.FOCUS14694
更新日期:2015-02-01 00:00:00
abstract:OBJECT:The goal of this study was to evaluate the definition of treatment-resistant depression (TRD), review the literature regarding deep brain stimulation (DBS) for TRD, and identify potential anatomical and functional targets for future widespread clinical application. METHODS:A comprehensive literature review was ...
journal_title:Neurosurgical focus
pub_type: 杂志文章,评审
doi:10.3171/FOC/2008/25/7/E3
更新日期:2008-01-01 00:00:00
abstract:OBJECT:Resorbable polymer implants have become a compelling option in the treatment of acquired and congenital craniofacial deformities. In particular, the resorbable polylactide and polyglycolide polymers have demonstrated excellent safety profiles in multiple in vitro, animal, and clinical studies and are currently b...
journal_title:Neurosurgical focus
pub_type: 临床试验,杂志文章
doi:10.3171/foc.2004.16.3.13
更新日期:2004-03-15 00:00:00
abstract::OBJECTIVEPapers from 2002 to 2017 have highlighted consistent unique socioeconomic challenges and opportunities facing military neurosurgeons. Here, the authors focus on the reserve military neurosurgeon who carries the dual mission of both civilian and military responsibilities.METHODSSurvey solicitation of current a...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2018.9.FOCUS18378
更新日期:2018-12-01 00:00:00
abstract::There has been increasing awareness that glioblastoma, which may seem histopathologically similar across many tumors, actually represents a group of molecularly distinct tumors. Emerging evidence suggests that cells even within the same tumor exhibit wide-ranging molecular diversity. Parallel to the discoveries of mol...
journal_title:Neurosurgical focus
pub_type: 杂志文章,评审
doi:10.3171/2014.9.FOCUS14521
更新日期:2014-12-01 00:00:00
abstract:OBJECT:An experimental study was performed to determine the biomechanical end-mounting configurations that replicate in vivo physiological motion of the cervical spine in a multiple-level human cadaveric model. The vertebral motion response for the modified testing protocol was compared to in vivo motion data and tradi...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:
更新日期:2004-09-15 00:00:00
abstract::The contemporary management of projectile head injuries owes much to the lessons neurosurgeons have distilled from their experiences in war. Through early investigation and an increasingly detailed account of wartime clinical experience, neurosurgeons--including the field's early giants--began to gain a greater unders...
journal_title:Neurosurgical focus
pub_type: 历史文章,杂志文章
doi:10.3171/2010.2.FOCUS1038
更新日期:2010-05-01 00:00:00
abstract:OBJECT:Tumors involving the cervicothoracic junction can have a high propensity for causing instability, with kyphosis and spinal cord compression resulting. Treatment with decompression only can lead to further instability and worsening neurological status. In this article, the authors review their surgical experience...
journal_title:Neurosurgical focus
pub_type: 杂志文章,评审
doi:10.3171/foc.2003.15.5.3
更新日期:2003-11-15 00:00:00
abstract::Microsurgical aspects of clipping of a giant partially thrombosed VA aneurysm in a 57-year-old female are presented and explained in the form of a short video. The presentation includes preparation of the VA, PICA and perforating arteries, the clipping of the aneurysm itself as well as the reduction of the aneurysm ma...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2015.V1.FOCUS14598
更新日期:2015-01-01 00:00:00
abstract::In this article, the author provides a brief description of the role of hypoxia in the tumorigenesis of gliomas and suggests potential ways of exploiting this role to design treatment modalities. Tumor hypoxia predicts the likelihood of metastases, tumor recurrence, resistance to chemotherapy and radiation therapy, in...
journal_title:Neurosurgical focus
pub_type: 杂志文章,评审
doi:10.3171/foc.2006.20.4.16
更新日期:2006-04-15 00:00:00
abstract::There is growing evidence to suggest that pregnancy may increase the risk of hemorrhage from cavernous malformations (CMs). In the present case, a 21-year-old primigravida was admitted to the authors' neurosurgical service after a cesarean section. Three weeks before admission she had experienced rapidly progressive b...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/foc.2006.21.1.13
更新日期:2006-07-15 00:00:00
abstract::The authors present three cases of iatrogenic paracervical abscesses caused by infiltration therapy of pain medications used in conservative treatment in patients with chronic cervicobrachialgia. All three patients had received this therapy several times before presenting with clinical signs of a local infection. The ...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/foc.2004.17.6.13
更新日期:2004-12-15 00:00:00
abstract::Vagus nerve stimulation (VNS) is a key tool in the treatment of patients with medically refractory epilepsy. Although the mechanism of action of VNS remains poorly understood, this modality is now the most widely used nonpharmacological treatment for drug-resistant epilepsy. The goal of this work is to review the hist...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2009.6.FOCUS09126
更新日期:2009-09-01 00:00:00
abstract::Cellular replacement therapy attempts to improve functioning of the diseased human central nervous system (CNS). In this second installment of a 2-part review, the authors discuss the major challenges to the translation of in vitro and animal studies of neural stem cell (NSC) therapy in the clinical setting. This anal...
journal_title:Neurosurgical focus
pub_type: 杂志文章,评审
doi:10.3171/FOC/2008/24/3-4/E22
更新日期:2008-01-01 00:00:00
abstract:OBJECT:Mild traumatic brain injury (MTBI), often referred to as concussion when it occurs in sports, produces persistent cognitive problems in at least 15% of patients. Unfortunately, conventional neuropsychological tests usually yield results within normal limits in this population. The main objective of this event-re...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2012.10.FOCUS12253
更新日期:2012-12-01 00:00:00
abstract::Lumbosacral interbody fusion may be indicated to treat degenerative disc disease at L5-S1, instability or spondylolisthesis at that level, and severe neural foraminal stenosis resulting from loss of disc space height. In addition, L5-S1 interbody fusion may provide anterior support to a long posterior fusion construct...
journal_title:Neurosurgical focus
pub_type: 杂志文章,评审
doi:10.3171/2014.2.FOCUS13467
更新日期:2014-05-01 00:00:00
abstract:OBJECT:The percentage of patients responding to conservative treatment for cervical radiculopathy secondary to nerve root compression is not well quantified. To clarify this question, the authors retrospectively reviewed the records obtained over a 4-year period in patients with cervical radiculopathy to determine thei...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/foc.2002.12.2.4
更新日期:2002-02-15 00:00:00
abstract:OBJECT:Symptomatic adjacent-segment lumbar disease (ASLD) after lumbar fusion often requires subsequent surgical intervention. The authors report utilizing cortical bone trajectory (CBT) pedicle screw fixation with intraoperative CT (O-arm) image-guided navigation to stabilize spinal levels in patients with symptomatic...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2014.1.FOCUS13521
更新日期:2014-03-01 00:00:00
abstract:OBJECT:The object of this study was to compare the effects and complications of manual and computer-aided shaping of titanium meshes for repairing large frontotemporoparietal skull defects following traumatic brain injury. METHODS:From March 2005 to June 2011, 161 patients with frontotemporoparietal skull defects were...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2012.2.FOCUS129
更新日期:2012-07-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to report the etiology, clinical features, microbiology, surgical outcome, and predictors of outcome of spontaneous subdural empyema (SDE). METHODS:The authors conducted a retrospective study in a tertiary hospital. Children up to 18 years of age, with a diagnosis of SDE with infect...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2019.5.FOCUS19268
更新日期:2019-08-01 00:00:00
abstract::In this paper, the authors' aim is to provide an evidence-based review of primary and secondary ischemic stroke prevention guidelines covering most of the common risk factors and stroke etiologies for the practicing neurosurgeon. The key to stroke prevention is in the identification and treatment of the major risk fac...
journal_title:Neurosurgical focus
pub_type: 杂志文章,评审
doi:10.3171/2011.2.FOCUS1164
更新日期:2011-06-01 00:00:00
abstract:OBJECT:Nowadays the role of microsurgical management of intrinsic brain tumors is to maximize the volumetric resection of the tumoral tissue, minimizing the postoperative morbidity. The purpose of this paper was to study the benefits of an original protocol developed for the microsurgical treatment of tumors located in...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2009.11.FOCUS09234
更新日期:2010-02-01 00:00:00
abstract::The development of less invasive methods to evacuate intracerebral hematomas (ICHs) has improved outcome in patients with traumatic brain injury. Eighteen patients with ICHs underwent surgery via one of two methods: stereotactic endoscopic removal (SER) or stereotactic catheter drainage (SCD). The outcome results were...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/foc.1996.1.4.2
更新日期:1996-10-15 00:00:00
abstract:OBJECT:A more comprehensive understanding of the epigenetic abnormalities associated with meningioma tumorigenesis, growth, and invasion may provide useful targets for molecular classification and development of targeted therapies for meningiomas. METHODS:The authors performed a review of the current literature to ide...
journal_title:Neurosurgical focus
pub_type: 杂志文章,评审
doi:10.3171/2013.10.FOCUS13360
更新日期:2013-12-01 00:00:00
abstract::Medulloblastoma and primitive neuroectodermal tumors (PNETs) are the most common malignant brain tumors in children. The concern for late sequelae of neuraxis irradiation and the obligation to improve disease-free survival in children who harbor malignant brain tumors has led to the additional provision of systemic ch...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/foc.1999.7.2.3
更新日期:1999-08-15 00:00:00
abstract::OBJECTIVE The treatment of cervical spinal metastases represents a controversial issue regarding the type, extent, and invasiveness of interventions. In the lumbar and thoracic spine, kypho- and vertebroplasties have been established as minimally invasive procedures for patients with metastases to the vertebral bodies...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2017.5.FOCUS17175
更新日期:2017-08-01 00:00:00
abstract::Arteriovenous malformation (AVM) presenting with epilepsy significantly impacts patient quality of life, and it should be considered very much a seizure disorder. Although hemorrhage prevention is the primary treatment aim of AVM surgery, seizure control should also be at the forefront of therapeutic management. Sever...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2020.1.FOCUS19899
更新日期:2020-04-01 00:00:00
abstract::Although the expectation of monetary compensation has been associated with failures in lumbar discectomy, the issue has not been investigated in patients undergoing cervical disc surgery. The authors analyzed the relationship between economic forms of secondary gain and surgical outcome in a group of patients with a c...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/foc.1998.5.2.9
更新日期:1998-08-15 00:00:00
abstract::OBJECTIVEPatient-reported outcome measures (PROMs) following decompression surgery for lumbar spinal stenosis (LSS) demonstrate considerable heterogeneity. Individualized prediction tools can provide valuable insights for shared decision-making. The authors aim to evaluate the feasibility of predicting short- and long...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/2019.2.FOCUS18723
更新日期:2019-05-01 00:00:00
abstract::Shunt systems with differential pressure valves are prone to the complications of overdrainage. A programmable valve permits adjustment of the opening pressure of the valve. In this paper the authors report the incidence of subdural fluid collections in a randomized trial of programmable compared with conventional val...
journal_title:Neurosurgical focus
pub_type: 杂志文章
doi:10.3171/foc.1999.7.4.2
更新日期:1999-10-15 00:00:00