Abstract:
:Ischemic insults to the brain in stroke or traumatic brain injury produce excessive release of glutamate from depolarized nerve terminals. This excessive glutamate release in turn stimulates massive calcium entry into nerve cells, activating a biochemical cascade that results in cell death. A major pathway of calcium entry into depolarized nerve cells is through voltage-sensitive, high threshold calcium channels. A large fraction of this calcium entry is mediated through "R-type" calcium channels, channels resistant to blockage by dihydropyridine calcium antagonists such as nimodipine. A newly discovered compound derived from spider venom, CNS 2103, antagonizes both R-type channels and dihydropyridine-sensitive ("L-type") calcium channels. This broad spectrum of action, coupled with selectivity for calcium channels over other classes of voltage-sensitive and ligand-gated ion channels, makes CNS 2103 an interesting lead for development of drugs to treat ischemic brain injury. Activation of presynaptic ("N-type") calcium channels in nerve terminals is a primary cause of excessive neurotransmitter release in brain ischemia. Prevention of glutamate release by blockade of N-type channels in glutamatergic nerve terminals may, at an early stage in the pathophysiological cascade, abort the process leading to nerve cell death. Cambridge NeuroScience has developed a novel rapid kinetic approach for monitoring glutamate release from brain nerve terminals in vitro, and this has led to CNS 1145, a substituted guanidine that selectively blocks a kinetic component of calcium-dependent glutamate release mediated by persistent depolarization. Additional evidence suggests that CNS 1145 antagonizes presynaptic N-type calcium channels, and this may account at least in part for its ability to block glutamate release.
journal_name
J Neurotraumajournal_title
Journal of neurotraumaauthors
McBurney RN,Daly D,Fischer JB,Hu LY,Subbarao K,Knapp AG,Kobayashi K,Margolin L,Reddy NL,Goldin SMsubject
Has Abstractpub_date
1992-05-01 00:00:00pages
S531-43eissn
0897-7151issn
1557-9042journal_volume
9 Suppl 2pub_type
杂志文章,评审abstract::The expression of the heat shock proteins hsp27 and hsp70 was examined in the spinal cord and sciatic nerves of developing rats. Using immunohistochemistry, we found that hsp27 is present in many motoneurones at birth. With development, the intensity of staining increases, reaching adult levels by 21 days, when all sc...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/089771502753754127
更新日期:2002-05-01 00:00:00
abstract::In the present study, long-term and short-term rat preparations were used to develop a model for investigating external anal sphincter (EAS) reflexes in intact and spinal cord-injured (SCI) rats. In this model, EAS distension with an external probe elicits reflex contractions of the EAS in intact, unanesthetized anima...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1998.15.451
更新日期:1998-06-01 00:00:00
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journal_title:Journal of neurotrauma
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abstract::The striatum, together with the hippocampus, is one of the most vulnerable regions in the brain. Recently, genetic abnormalities or mutations have been linked to various neurodegenerative diseases, that is, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), etc., but the processes from gen...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2000.17.251
更新日期:2000-03-01 00:00:00
abstract::Traumatic brain injury (TBI) is known to be accompanied by an increase in intracranial pressure (ICP) and in some cases, by spontaneous generation of cortical spreading depression (CSD) cycles. However, the role of CSD in the pathophysiology of cerebral contusion is still unknown. A multiparametric monitoring assembly...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/089771503322686111
更新日期:2003-12-01 00:00:00
abstract::The rat hippocampus is hypersensitive to secondary cerebral ischemia after mild traumatic brain injury (TBI). An unconfirmed assumption in previous studies of mild TBI followed by forebrain ischemia has been that antecedent TBI did not alter cerebral blood flow (CBF) dynamics in response to secondary ischemia. Using l...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1998.15.615
更新日期:1998-08-01 00:00:00
abstract::Traumatic brain injury (TBI) is a principal cause of long-term physical, cognitive, behavioral, and social deficits in young adults, which frequently coexist with a high incidence of substance abuse disorders. However, few studies have examined the long-term effects of TBI on the neuroendocrine-immune system. TBI was ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2006.23.1802
更新日期:2006-12-01 00:00:00
abstract::Traumatic brain injury (TBI) is associated with enhanced osteogenesis. The aim of this study was to investigate the effect of serum from TBI rats on fracture healing. Results from this study showed that the serum from TBI rats enhanced the expression of bone gamma carboxyglutamate protein (BGLAP), and promoted in vitr...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2012.2442
更新日期:2012-11-20 00:00:00
abstract::Reactive oxygen species have been implicated in the pathogenesis of hypoxic-ischemic injury. It has been shown previously that treating an animal with N-acetyl-L-cysteine (NAC), a scavenger of free radicals, significantly minimizes hypoxic-ischemic-induced brain injury in various acute models. Using a subacute swine m...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2010.1325
更新日期:2010-10-01 00:00:00
abstract::Prevention of the immediate excitotoxic phase occurring in response to spinal cord injury (SCI) is a major issue to reduce the neuronal damage responsible for any ensuing motor deficits. The present study evaluated the neuroprotective efficacy of three noncompetitive NMDA receptor antagonists: Gacyclidine (GK-11), a n...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2000.17.1079
更新日期:2000-11-01 00:00:00
abstract::Severe traumatic brain injury (TBI) results in significant functional disturbances in the hippocampus. Studies support that sodium cromoglycate (CG) induces neuroprotective effects. This study focused on investigating the effects of post-TBI subchronic administration of CG on hippocampal hyperexcitability and damage a...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2019.6975
更新日期:2020-12-01 00:00:00
abstract::Controlled cortical impact (CCI) is a contemporary model of experimental cerebral contusion. We examined the cerebrovascular and neuropathologic effects of a severe CCI in rats. The utility of magnetic resonance imaging (MRI) for the assessment of contusion volume after severe CCI was also established. Severe CCI (3.0...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1995.12.1015
更新日期:1995-12-01 00:00:00
abstract::Traumatic brain injury (TBI) causes damage to the hypothalamo-hypophyseal axis, leading to endocrine dysregulation in up to 40% of TBI patients. Hence, there is an urgent need to identify non-invasive biomarkers for TBI-associated hypothalamo-hypophyseal pathology. Sushi repeat-containing protein X-linked 2 (SRPX2) is...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2019.6739
更新日期:2020-04-01 00:00:00
abstract::In 1990, the Second National Acute Spinal Cord Injury Study reported that high-dosage methylprednisolone improves neurologic recovery in spinal-injured humans. The study showed that patients who received the drug within 8 hr after injury improved, whereas those who received the drug later did not. The drug significant...
journal_title:Journal of neurotrauma
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1992-03-01 00:00:00
abstract::Given the worldwide adverse impact of traumatic brain injury (TBI) on the human population, its diagnosis and prediction are of utmost importance. Historically, many studies have focused on associating head kinematics to brain injury risk. Recently, there has been a push toward using computationally expensive finite e...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.6340
更新日期:2020-04-01 00:00:00
abstract::A better understanding of long-term functional recovery process for patients with traumatic brain injury (TBI) facilitates effective rehabilitations. The aim of this study was to classify and characterize patients with moderate-to-severe TBI based on their functional trajectories up to 5 years post-injury. The study i...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2017.5299
更新日期:2018-07-15 00:00:00
abstract::Severe traumatic brain injury (TBI) leads to an immunocompromised state responsible for an increased morbidity and mortality. Our understanding of the mechanisms responsible for this brain damage is incomplete. Damage maybe mediated by a complex cascade of neuroinflammation, and cytokine activation. In addition, trans...
journal_title:Journal of neurotrauma
pub_type: 杂志文章,随机对照试验
doi:10.1089/neu.2006.23.962
更新日期:2006-06-01 00:00:00
abstract::Traumatic brain injury (TBI) causes high rates of worldwide death and morbidity because of the complex secondary injury cascade. Circular ribonucleic acid (RNA) (circRNA), a type of RNA that forms a covalently closed continuous loop, may be involved in the regulation of secondary injury because it is expressed widely ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.5647
更新日期:2019-04-01 00:00:00
abstract::Pituitary adenylate cyclase activating polypeptide (PACAP) has several different actions in the nervous system. Numerous studies have shown its neuroprotective effects both in vitro and in vivo. Previously, it has been demonstrated that PACAP reduces brain damage in rat models of global and focal cerebral ischemia. Ba...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2006.23.686
更新日期:2006-05-01 00:00:00
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2006.23.1561
更新日期:2006-10-01 00:00:00
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1997.14.211
更新日期:1997-04-01 00:00:00
abstract::The purpose of this study was to investigate the potential neuroprotective efficacy of the mitochondrial uncoupler 2,4-dinitrophenol (DNP) in rats following a mild to moderate spinal cord contusion injury. Animals received intraperitoneal injections of vehicle (DMSO) or 5 mg/mL of DNP prior to injury. Twenty-four hour...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2004.21.1396
更新日期:2004-10-01 00:00:00
abstract::Sports-related concussion is a major public health problem in the United States and yet its biomechanical mechanisms remain unclear. In vitro studies demonstrate axonal elongation as a potential injury mechanism; however, current response-based injury predictors (e.g., maximum principal strain, ε(ep)) typically do not...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2013.3268
更新日期:2015-04-01 00:00:00
abstract::Following a controlled, severe contusion lesion to the lower thoracic spinal cord in adult rats, we found that apoptosis occurred in cells located in both gray and white matter. This suggested that both nonneuronal cells, including astrocytes, oligodendroglia and microglia, as well as neurons, might participate in pro...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1998.15.459
更新日期:1998-07-01 00:00:00
abstract::Several behavioral factors such as violence, impulsivity, and alcohol-related problems are associated with traumatic spinal cord injury (TSCI). Such factors have been associated with inherently low neuronal serotonergic capacity that in turn is reflected in low activity of monoamine oxidase (MAO) as measured in platel...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2016.4462
更新日期:2016-11-01 00:00:00
abstract::Individuals with a mild traumatic brain injury (mTBI) often have executive control deficits; however, the underlying neural mechanisms of such deficits are yet to be clarified. Inhibitory control and cognitive monitoring are two fundamental aspects of executive control processes. This study investigated the executive ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2018.6122
更新日期:2020-01-01 00:00:00
abstract::Visual dysfunction is a common occurrence after traumatic brain injury (TBI). We investigated in this study effects of single or multiple mild TBI on visual function in mice using a closed head injury model that permits unconstrained head movement after impact. Adult mice were briefly anesthetized with isoflurane and ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2019.6602
更新日期:2020-01-15 00:00:00
abstract::We investigated the effect of sports activity on physically-disabled individuals using behavioral and electrophysiological techniques. Visual go/no-go discriminative and simple response tasks were used. Participants included 17 disabled athletes, 9 from open-skill (wheelchair basketball) and eight from closed-skill (s...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2010.1501
更新日期:2010-12-01 00:00:00
abstract::Spinal cord injury (SCI) is less common in children than in adults, but in children it is generally more severe. Spinal loading conditions (speed and displacement) are also thought to affect SCI severity, but the relationship between these parameters is not well understood. This study aimed to investigate the effects ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2012.2725
更新日期:2013-08-01 00:00:00
abstract::Inflammatory cellular responses to brain injury are promoted by proinflammatory messengers. Cyclooxygenases (prostaglandin endoperoxide H synthases [PGH]) are key enzymes in the conversion of arachidonic acid into prostanoids, which mediate immunomodulation, mitogenesis, apoptosis, blood flow, secondary injury (lipid ...
journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/089771501750451802
更新日期:2001-09-01 00:00:00