Abstract:
OBJECT:Although traumatic brain injury (TBI) is the leading cause of death and morbidity in young adults, no effective pharmaceutical treatment is available. By inhibiting glycogen synthase kinase-3 (GSK-3) and histone deacetylases (HDACs), respectively, lithium and valproate (VPA) have beneficial effects in diverse neurodegenerative diseases. Furthermore, in an excitotoxic neuronal model and in animal models of amyotrophic lateral sclerosis, Huntington disease, and stroke, combined treatment with lithium and VPA produces more robust neuroprotective effects than treatment with either agent alone. Building on previous work that establishes that therapeutic doses of either lithium or VPA have beneficial effects in mouse models of TBI, this study evaluated the effects of combined treatment with subeffective doses of lithium and VPA in a mouse model of TBI. METHODS:Male C57BL/6 mice underwent TBI and were subsequently treated with lithium, VPA, or a combination of lithium and VPA 15 minutes post-TBI and once daily thereafter for up to 3 weeks; all doses were subeffective (1 mEq/kg of lithium and 200 mg/kg of VPA). Assessed parameters included lesion volume via H & E staining; blood-brain barrier (BBB) integrity via immunoglobulin G extravasation; neurodegeneration via Fluoro-Jade B staining; motor coordination via a beam-walk test; and protein levels of acetylhistone H3, phospho-GSK-3β, and β-catenin via Western blotting. RESULTS:Posttrauma treatment with combined subeffective doses of lithium and VPA significantly reduced lesion volume, attenuated BBB disruption, and mitigated hippocampal neurodegeneration 3 days after TBI. As expected, subeffective doses of lithium or VPA alone did not have these beneficial effects. Combined treatment also improved motor coordination starting from Day 7 and persisting at least 21 days after TBI. Acetylation of histone H3, an index of HDAC inhibition, was robustly increased by the combined treatment 3 days after TBI. CONCLUSIONS:Cotreatment with subeffective doses of lithium and VPA significantly attenuated TBI-induced brain lesion, BBB disruption, and neurodegeneration, and robustly improved long-term functional recovery. These findings suggest that potentiating histone acetylation by HDAC inhibition is probably part of the mechanism underlying the beneficial effects associated with this combined treatment for TBI. Because both lithium and VPA have a long history of safe clinical use, the results suggest that using a combination of these 2 agents at subtherapeutic doses to treat patients with TBI may also reduce side effects and enhance tolerability.
journal_name
J Neurosurgjournal_title
Journal of neurosurgeryauthors
Yu F,Wang Z,Tanaka M,Chiu CT,Leeds P,Zhang Y,Chuang DMdoi
10.3171/2013.6.JNS13135subject
Has Abstractpub_date
2013-09-01 00:00:00pages
766-73issue
3eissn
0022-3085issn
1933-0693journal_volume
119pub_type
杂志文章abstract::A patient with hydrocephalus due to aqueductal stenosis suffered facial pain which was relieved after the insertion of a ventriculoperitoneal shunt. The trigeminal somatosensory evoked response (TSER) of the affected side showed lower amplitudes and longer latencies as compared to the unaffected side. Following surger...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1982.57.2.0267
更新日期:1982-08-01 00:00:00
abstract::The neurological and neuroradiological manifestations of pediatric achondroplasia are analyzed on the basis of 10 cases. In addition to the classical symptomatology of an enlarging head, with or without increased intracranial pressure, several patients presented symptoms related to a small foramen magnum. Respiratory ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1981.54.1.0049
更新日期:1981-01-01 00:00:00
abstract::The effect of suppression of postischemic reactive hyperemia on the blood-brain barrier (BBB) and ischemic brain edema after temporary focal cerebral ischemia was studied in cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow (rCBF) was measured by a thermal diffusion method and a hydroge...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1989.70.1.0073
更新日期:1989-01-01 00:00:00
abstract::The authors report on a 17-year-old boy with cervical myelopathy from dilated epidural veins due to cerebrospinal fluid (CSF) overdrainage. The patient had a long-standing subdural-peritoneal shunt and presented with incapacitating spastic tetraparesis. Magnetic resonance imaging revealed significant cervical spinal c...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/ped.2007.106.3.227
更新日期:2007-03-01 00:00:00
abstract::A study was designed to investigate hyperperfusion syndrome after the restoration of normal cerebral blood flow in a chronically cerebral ischemic state resulting from high-flow arteriovenous malformations or severe carotid stenosis. A fistula between the left distal common carotid artery and the jugular vein was crea...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1992.76.3.0478
更新日期:1992-03-01 00:00:00
abstract::A case of chronic diploic hematoma of the parietal bone is reported. This lesion is considered to have developed over several years following minor head trauma. Clinical, radiological, and pathological findings of this rare lesion are described. To the authors' knowledge, this is the first reported case of such an unc...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1994.80.6.1112
更新日期:1994-06-01 00:00:00
abstract::The effect of intrathecal fibrinolysis on cerebrospinal fluid (CSF) absorption was investigated after experimental subarachnoid hemorrhage (SAH). In 11 cats, SAH was induced by intracisternal application of 1 to 4 ml of fresh autologous blood. Thirty minutes after the experimental SAH, the CSF outflow resistance was f...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1991.74.5.0789
更新日期:1991-05-01 00:00:00
abstract:OBJECTIVE:Perilesional edema is a predominant mechanism underlying secondary brain injury after traumatic brain injury (TBI). Perilesional edema is characterized by inflammation, production of proinflammatory cytokines, and migration of peripheral immune cells into the brain. The nucleotide-binding domain and leucine-r...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2019.6.JNS1954
更新日期:2019-09-27 00:00:00
abstract:OBJECT:This study was conducted to evaluate the value of postoperative CT scans in determining the probability of return to the operating room (OR) and the optimal time to obtain such scans to determine the effects of surgery. METHODS:Between January and December 2006 (12 months), all postoperative head CT scans obtai...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2009.11.JNS081048
更新日期:2010-11-01 00:00:00
abstract::A comprehensive review of the literature has shown that the treatment of choice for cerebellar astrocytomas has primarily been gross-total resection of the mass and gross-total resection of the enhancing portion of pilocytic astrocytomas. Most large scale studies of postresection survival rates of patients with cerebe...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1997.87.2.0257
更新日期:1997-08-01 00:00:00
abstract::Cerebrospinal fluid (CSF) was collected preoperatively (by lumbar puncture) or perioperatively (by lumbar or ventricular drain) from 32 patients with subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms. Samples were also obtained from six control patients without evidence of subarachnoid blood. Smooth-m...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1984.60.5.0927
更新日期:1984-05-01 00:00:00
abstract::Morning glory syndrome is a congenital anomaly of the optic disc in which the disc is enlarged and excavated, with white glial tissue in the center. A case is presented of morning glory syndrome associated with sphenoid encephalocele, median cleft lip, and agenesis of the corpus callosum. A 22-day-old boy was referred...
journal_title:Journal of neurosurgery
pub_type: 杂志文章,评审
doi:10.3171/jns.1992.77.6.0949
更新日期:1992-12-01 00:00:00
abstract::OBJECTIVE Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) (World Federation of Neurosurgical Societies Grade IV or V) are often considered for decompressive craniectomy (DC) as a rescue therapy for refractory intracranial hypertension. The authors performed a systematic review and meta-analysis to a...
journal_title:Journal of neurosurgery
pub_type: 杂志文章,meta分析
doi:10.3171/2016.9.JNS161383
更新日期:2017-12-01 00:00:00
abstract::To determine the risk of intracranial hemorrhage in patients with malignant gliomas who are treated with anticoagulant drugs for late postoperative venous thromboembolism, the authors retrospectively reviewed the computerized data base of all patients with primary brain tumors seen at the University of California, San...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1987.66.3.0357
更新日期:1987-03-01 00:00:00
abstract::The authors determined the landmarks and coordinates for intraoperative ventricular puncture directly from the supraorbital craniotomy opening via an eyebrow incision. Fifty magnetic resonance (MR) imaging studies were obtained from patients with no pathological cerebral characteristics or ventricular distortion. The ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2006.105.3.485
更新日期:2006-09-01 00:00:00
abstract::The author describes a new technique for exposure of the cervical spine laminae in which the attachments of the semispinalis cervicis and multifidus muscles to the spinous processes are left untouched. It provides a conservative exposure through which a diverse range of posterior cervical surgeries can be performed. I...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/spi.2002.96.1.0122
更新日期:2002-01-01 00:00:00
abstract::OBJECTIVE Outpatient craniotomy has many advantages to the psychological and physical well-being of patients, as well as benefits to the health care system. Its efficacy and safety have been well demonstrated, but barriers to its widespread adoption remain. Among the challenges is a perception that its application is ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2015.11.JNS152151
更新日期:2016-11-01 00:00:00
abstract::The authors report the first case of vasogenic cerebral edema due to a cell-mediated hypersensitivity reaction to a nickel-containing aneurysm clip. The patient initially presented for elective clipping of a right middle cerebral artery aneurysm, and on long-term follow-up she demonstrated relapsing-remitting cerebral...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2014.6.JNS132405
更新日期:2014-10-01 00:00:00
abstract::The authors demonstrate the use of cottonoid as a marker for ultrasound localization of a subcortical tumor. ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1984.60.2.0438
更新日期:1984-02-01 00:00:00
abstract:OBJECT:Skull bone regeneration induced by transforming growth factor-beta1 (TGFbeta1)-containing gelatin hydrogels (TGFbeta1-hydrogels) was investigated using a rabbit skull defect model. Different strengths of TGFbeta1 were examined and compared: different TGFbeta1 doses in gelatin hydrogels with a fixed water content...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2000.92.2.0315
更新日期:2000-02-01 00:00:00
abstract::Surgical sacrifice of the carotid artery is a frequently anticipated event during the treatment of certain aneurysms and tumors. The ability to predict tolerance to carotid artery occlusion is therefore of benefit when planning procedures in which the carotid artery is at risk. A trial of carotid artery occlusion usin...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1994.81.1.0015
更新日期:1994-07-01 00:00:00
abstract::The authors report on a 17-year-old boy who suffered from slowly progressive and long-standing symptoms of ataxia, neck pain, and headache. Computerized tomography (CT) and magnetic resonance (MR) imaging revealed a tumor arising from the floor of the fourth ventricle that resulted in a moderate hydrocephalus. A parti...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1999.91.3.0506
更新日期:1999-09-01 00:00:00
abstract::The diagnosis of CSF hypovolemia remains controversial. The primary diagnostic factor relies on confirmation of leakage of the CSF based on reduced spinal fluid pressure. Determining the specific leakage site is the most important issue for effective treatment but remains a difficult task. Although CT myelography, rad...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2015.2.JNS142746
更新日期:2016-02-01 00:00:00
abstract::A new aneurysm clip has been developed specifically for internal carotid artery (ICA) aneurysms. This fenestrated clip's occluding blades deviate laterally, since the majority of ICA aneurysms protrude posterolateral to the parent artery. The clip was applied safely in seven recent patients with ICA aneurysms. ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1986.65.1.0122
更新日期:1986-07-01 00:00:00
abstract::Symptomatic cysts of the septum pellucidum are rare. Up to 1969, 17 published cases were considered to be symptomatic. In the case report here, a 9-week-old girl was hospitalized because of disproportionate progressive enlargement of the head, lumbar myelomeningocele, and a history of generalized seizures. A giant sep...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1981.55.4.0646
更新日期:1981-10-01 00:00:00
abstract:OBJECT:Functional neurosurgical interventions such as deep brain stimulation (DBS) are traditionally performed with the aid of a stereotactic frame. Although frameless techniques have been perceived as less accurate, data from a recent phantom study of a modified frameless approach demonstrated a laboratory accuracy ex...
journal_title:Journal of neurosurgery
pub_type: 临床试验,杂志文章
doi:10.3171/jns.2005.103.3.0404
更新日期:2005-09-01 00:00:00
abstract::Angiograms obtained prior to treatment in 53 cases of deep-seated cerebral arteriovenous malformations (AVM's) were retrospectively analyzed with particular attention to the topography of the AVM nidus and the venous drainage. The location of the lesion was determined by a combination of angiography and computerized t...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1985.63.2.0180
更新日期:1985-08-01 00:00:00
abstract::In 1964, a 51-year-old man experienced a right abducens nerve palsy, which resolved spontaneously. In 1978, he developed painful ophthalmoplegia on the right with paresis of the right oculomotor and trigeminal nerves. Neuroradiographic evaluation was reported unremarkable, and the painful ophthalmoplegia was attribute...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1981.54.1.0113
更新日期:1981-01-01 00:00:00
abstract::Age-related norms for the regional cerebral blood flow (rCBF) response to Diamox (acetazolamide) were based on studies of 55 normal subjects at rest and on studies of 33 of these 55 normal subjects following an intravenous injection of Diamox (22 mg/kg). After the Diamox injection, rCBF increased at all locations meas...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1987.67.4.0525
更新日期:1987-10-01 00:00:00
abstract:OBJECT:It is unclear if there is a relationship between Chiari malformation Type I (CM-I) and body mass index (BMI). The aim of this study was to identify the relationship between BMI and cerebellar tonsil position in a random sample of people. METHODS:Cerebellar tonsil position in 2400 subjects from a cohort of patie...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2014.10.JNS141317
更新日期:2015-07-01 00:00:00