Abstract:
:Clinical studies indicate that phenytoin prevents acute post-traumatic seizures but not subsequent post-traumatic epilepsy. We explored this phenomenon using organotypic hippocampal slice cultures as a model of severe traumatic brain injury. Hippocampal slices were cultured for up to eight weeks, during which acute and chronic electrical recordings revealed a characteristic evolution of spontaneous epileptiform discharges, including interictal spikes, seizure activity and electrical status epilepticus. Cell death exhibited an early peak immediately following slicing, and a later secondary peak that coincided with the peak of seizure-like activity. The secondary peak in neuronal death was abolished by either blockade of glutamatergic transmission with kynurenic acid or by elimination of ictal activity and status epilepticus with phenytoin. Withdrawal of kynurenic acid or phenytoin was followed by a sharp increase in spontaneous seizure activity. Phenytoin's anticonvulsant and neuroprotective effects failed after four weeks of continuous administration. These data support the clinical findings that after brain injury, anticonvulsants prevent seizures but not epilepsy or the development of anticonvulsant resistance. We extend the clinical data by showing that secondary neuronal death is correlated with ictal but not interictal activity, and that blocking all three of these sequelae of brain injury does not prevent epileptogenesis in this in vitro model.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Berdichevsky Y,Dzhala V,Mail M,Staley KJdoi
10.1016/j.nbd.2011.11.001subject
Has Abstractpub_date
2012-02-01 00:00:00pages
774-85issue
2eissn
0969-9961issn
1095-953Xpii
S0969-9961(11)00370-6journal_volume
45pub_type
杂志文章abstract::Lyme disease, caused by the bacterium Borrelia burgdorferi, can cause multi-systemic signs and symptoms, including peripheral and central nervous system disease. This review examines the evidence for and mechanisms of inflammation in neurologic Lyme disease, with a specific focus on the central nervous system, drawing...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2009.11.016
更新日期:2010-03-01 00:00:00
abstract::Neuropeptide Y (NPY) and NPY receptors are widely expressed in the mammalian central nervous system. Studies in both humans and rodent models revealed that brain NPY levels are altered in some neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Machado-Joseph disease...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2016.07.022
更新日期:2016-11-01 00:00:00
abstract::Schizophrenia is a complex neuropsychiatric disorder that involves disturbances in neural circuitry and synaptic function. The exquisite network architecture and capacity for discreet post-synaptic remodeling of neurons requires coordination by an elaborate intracellular network of molecular signal transduction system...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2011.12.029
更新日期:2012-05-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) are reported to possess immunomodulatory properties. Previous reports have demonstrated the beneficial effects of MSC-transplantation in focal cerebral ischemia animal models. In this study, we have investigated the neuroimmunomodulatory functions of human MSCs, transplanted in a rat foca...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.12.009
更新日期:2011-03-01 00:00:00
abstract::In addition to the substantial biological diversity among humans, our limited ability to reliably measure expression changes of small magnitude significantly reduces our capacity to obtain convergent sets of transcriptome data in postmortem brain. In particular, differences in the structure and sensitivity/reproducibi...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2004.10.020
更新日期:2005-04-01 00:00:00
abstract::Twelve- to sixteen-month-old (G2019S) LRRK2 transgenic mice prepared by us displayed progressive neuronal death of substantia nigra pars compacta (SNpc) dopaminergic cells. In the present study, we hypothesized that prior to a late-phase death of SNpc dopaminergic neurons, (G2019S) LRRK2 also causes an early-phase neu...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.04.021
更新日期:2014-08-01 00:00:00
abstract::The identification of novel molecular targets crucially involved in motor neuron degeneration/survival is a necessary step for the development of hopefully more effective therapeutic strategies for amyotrophic lateral sclerosis (ALS) patients. In this view, S1R, an endoplasmic reticulum (ER)-resident receptor with cha...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.10.010
更新日期:2014-02-01 00:00:00
abstract::Dravet syndrome is a severe infantile-onset epileptic encephalopathy which begins with febrile seizures and is caused by heterozygous loss-of-function mutations of the voltage-gated sodium channel gene SCN1A. We designed a CRISPR-based gene therapy for Scn1a-haplodeficient mice using multiple guide RNAs (gRNAs) in the...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2020.104954
更新日期:2020-07-01 00:00:00
abstract::Necroptosis is a regulated form of necrosis that is mediated by a variety of proteins including tumor necrosis factor-α (TNF-α) and receptor-interacting proteins (RIPs). TNF-α, a critical inflammatory molecule, is one of the initiating signals in the necroptosis pathway, and RIP3 acts as a switch that commits the cell...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.05.004
更新日期:2019-09-01 00:00:00
abstract::Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whe...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2015.12.004
更新日期:2016-03-01 00:00:00
abstract::Optic neuritis is a frequent and early symptom of multiple sclerosis (MS). Conventional magnetic resonance (MR) techniques provide means to assess multiple MS-related pathologies, including axonal injury, demyelination, and inflammation. A method to directly and non-invasively probe white-matter function could further...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.02.007
更新日期:2014-07-01 00:00:00
abstract::Rare de novo mutations in genes associated with inherited Mendelian disorders are potential contributors to sporadic disease. DYT1 dystonia is an autosomal dominant, early-onset, generalized dystonia associated with an in-frame, trinucleotide deletion (n. delGAG, p. ΔE 302/303) in the Tor1a gene. Here we examine the s...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.05.003
更新日期:2016-09-01 00:00:00
abstract::The developing rodent brain is vulnerable to pharmacological blockade of N-methyl-d-aspartate (NMDA) receptors which can lead to severe and disseminated apoptotic neurodegeneration. Here, we show that systemic administration of the NMDA receptor antagonist MK801 to 7-day-old rats leads to impaired activity of extracel...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2004.03.013
更新日期:2004-07-01 00:00:00
abstract::Sex differences are a well-known phenomenon in Alzheimer's disease (AD), with women having a higher risk for AD than men. Many AD mouse models display a similar sex-dependent pattern, with females showing earlier cognitive deficits and more severe neuropathology than males. However, whether those differences are relev...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.08.009
更新日期:2016-12-01 00:00:00
abstract::Multiple sclerosis (MS) is a chronic, inflammatory autoimmune disease that affects the central nervous system (CNS) for which there is no cure. In MS, encephalitogenic T cells infiltrate the CNS causing demyelination and neuroinflammation; however, little is known about the role of regulatory T cells (Tregs) in CNS ti...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2020.104868
更新日期:2020-07-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by the progressive loss of motor neurons, leading to profound weakness and eventual death of affected individuals. For the vast majority of patients with ALS, the etiology of the disorder is unknown, and although multiple clinical...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1006/nbdi.1999.0266
更新日期:1999-10-01 00:00:00
abstract::Fragile X syndrome (FXS) patients do not make the fragile X mental retardation protein (FMRP). The absence of FMRP causes dysregulated translation, abnormal synaptic plasticity and the most common form of inherited intellectual disability. But FMRP loss has minimal effects on memory itself, making it difficult to unde...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.01.003
更新日期:2016-04-01 00:00:00
abstract::In this review, we highlight critical unresolved questions in the etiology and mechanisms causing preterm brain injury. Involvement of neurons, glia, endogenous factors and exogenous exposures is considered. The structural and functional correlates of interrupted development and injury in the premature brain are under...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2015.10.012
更新日期:2016-08-01 00:00:00
abstract::Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 gene mutation in vascular smooth muscle cells (VSMCs), leading to ischemic stroke and vascular dementia. To date, the pathogenesis of CADASIL remains poorly understo...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.104561
更新日期:2019-12-01 00:00:00
abstract::Pituitary adenylate cyclase activating polypeptide (PACAP) and its complementary receptor, PAC1, are crucial in central respiratory control. PACAP Knockout (KO) mice exhibit a SIDS-like phenotype, with an inability to overcome noxious insults, compression of baseline ventilation, and death in the early post-neonatal p...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.04.002
更新日期:2017-07-01 00:00:00
abstract::Excitotoxicity plays a central role in the neuronal damage during ischemic stroke. Although growing evidence suggests that activation of extrasynaptic NMDA receptors initiates neuronal death, no direct evidence demonstrated their activation during ischemia. Using rat hippocampal slices, we detected oxygen-glucose depr...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.05.005
更新日期:2013-10-01 00:00:00
abstract::Mutations in vacuolar protein sorting 35 (VPS35) have been linked to familial Parkinson's disease (PD). VPS35, a component of the retromer, mediates the retrograde transport of cargo from the endosome to the trans-Golgi network. Here we showed that retromer depletion increases the lysosomal turnover of the mannose 6-p...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.07.014
更新日期:2014-11-01 00:00:00
abstract:OBJECTIVE:In Parkinson's disease, chronic striatal dopamine depletion results in over-activity and under-activity of the indirect and direct striatal output pathways respectively. In this study, we investigated changes in the function of glutamatergic cortico-striatal synapses that contribute to abnormalities in striat...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.10.013
更新日期:2011-03-01 00:00:00
abstract::Failure of cell cycle regulation in neurons might be critically involved in the process of neurodegeneration in Alzheimer's disease (AD). We present here evidence to support the hypothesis that cell cycle alterations occur in cells other than neurons in AD sufferers. Lymphocytes from AD patients immortalized with Epst...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/s0969-9961(03)00040-8
更新日期:2003-08-01 00:00:00
abstract::Huntington's disease (HD) is a neurodegenerative disorder involving progressive motor disturbances, cognitive decline, and desynchronized sleep-wake rhythms. Recent studies revealed that restoring normal sleep-wake cycles can improve cognitive function in HD mice, suggesting that some sleep/wake systems remain operati...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2011.02.006
更新日期:2011-06-01 00:00:00
abstract:PURPOSE:Generalized spike and wave discharges (SWD) are generated within the cortico-thalamo-cortical system. However the exact interactions between cortex and different thalamic nuclei needed for the generation and maintenance of SWD are still to be elucidated. This study aims to shed more light on these interactions ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.03.023
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND/INTRODUCTION:The neuroinflammatory response plays a major role in the secondary injury cascade after traumatic spinal cord injury (SCI). To date, systemic anti-inflammatory medications such as methylprednisolone sodium succinate (MPSS) have shown promise in SCI. However, systemic immunosuppression can have d...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2020.105187
更新日期:2021-01-01 00:00:00
abstract::Neuropeptide Y (NPY) is an important 36 amino acid peptide that is abundantly expressed in the mammalian CNS and is known to be an endogenous modulator of seizure activity, including in rat models of Genetic Generalised Epilepsy (GGE) with absence seizures. Studies have shown that viral-mediated "gene therapy" with ov...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.01.016
更新日期:2018-05-01 00:00:00
abstract::GPNMB is a glycoprotein observed upon tissue damage and inflammation and is associated with astrocytes, microglia, and macrophages. Gene variations in GPNMB are linked with Parkinson's disease (PD) risk, and changes in protein levels of GPNMB have been found in lysosomal storage disorders, including Gaucher's disease ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.08.013
更新日期:2018-12-01 00:00:00
abstract::Neural stem cells (NSCs) are multipotent, self-renewing progenitors that generate progeny that differentiate into neurons and glia. NSCs in the adult mammalian brain are generally quiescent. Environmental stimuli such as learning or exercise can activate quiescent NSCs, inducing them to proliferate and produce new neu...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2017.01.010
更新日期:2017-11-01 00:00:00