Abstract:
:Neural transplantation has been investigated experimentally and clinically for the purpose of developing new treatment options for intractable epilepsy. In the present study we assessed the anticonvulsant efficacy and safety of bilateral allotransplantation of genetically engineered striatal GABAergic rat cell lines into the substantia nigra pars reticulata (SNr). Rats with previously-established seizures, induced by amygdala kindling, were used as a model of temporal lobe epilepsy. Three cell lines were transplanted: (1) immortalized GABAergic cells (M213-2O) derived from embryonic rat striatum; (2) M213-2O cells (CL4) transfected with human GAD67 cDNA to obtain higher GABA synthesis than the parent cell line; and (3) control cells (121-1I), also derived from embryonic rat striatum, but which did not show GAD expression. A second control group received injections of medium alone. Transplantation of M213-2O cells into the SNr of kindled rats resulted in significant but transient anticonvulsant effects. Neither control cells nor medium induced anticonvulsant effects. Strong tissue reactions were, however, induced in the host brain of kindled but not of non-kindled rats, and only in animals that received grafts of genetically modified CL4 cells. These tissue reactions included graft rejection, massive infiltration of inflammatory immune cells, and gliosis. The anticonvulsant effect of M213-2O cells emphasizes the feasibility of local manipulations of seizures by intranigral transplantation of GABA-producing cells. On the other hand, the present data suggest that kindling-induced activation of microglia in the SNr can enhance immune reactions to transplanted cells. In this case, under conditions of further immunological stimulation by CL4 cells, transfected with a human cDNA, substantial immune reactions occurred. Thus, it appears that the condition of the host brain and the production of foreign proteins by transplanted cells have to be considered in estimating the risks of rejection of transplants into the brain.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Nolte MW,Löscher W,Herden C,Freed WJ,Gernert Mdoi
10.1016/j.nbd.2008.05.010subject
Has Abstractpub_date
2008-09-01 00:00:00pages
342-54issue
3eissn
0969-9961issn
1095-953Xpii
S0969-9961(08)00102-2journal_volume
31pub_type
杂志文章abstract::Signs or symptoms of impaired autonomic regulation of circulation often attend Parkinson disease (PD). This review covers biomarkers and mechanisms of autonomic cardiovascular abnormalities in PD and related alpha-synucleinopathies. The clearest clinical laboratory correlate of dysautonomia in PD is loss of myocardial...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2011.10.025
更新日期:2012-06-01 00:00:00
abstract::Several reports indicate that the activity of the hypothalamic–pituitary–adrenal axis (HPA) is increased after a brain insult and that its down-regulation can improve detrimental outcomes associated with ischemic brain injuries.Granulocyte-colony stimulating factor (G-CSF) is a neuroprotective drug shown in the naïve ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.03.021
更新日期:2012-07-01 00:00:00
abstract::Astrocytes are abundant neuron-supporting glial cells that harbor a powerful arsenal of neuroprotective antioxidative molecules and neurotrophic factors. Here we examined whether enrichment with healthy striatal astrocytes can provide neuroprotection against progressive dopaminergic neurodegeneration. Serotonin 1A (5-...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.08.003
更新日期:2013-11-01 00:00:00
abstract::Seizures occur in the basal ganglia (BG) of epileptic patients and in animal models of epilepsy, but there is relatively little known about how these events are gated and/or propagated through this structure. Here, we present and characterize a model of in vitro seizure-like events (SLEs) in the striatum by applying c...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.11.019
更新日期:2013-04-01 00:00:00
abstract::Aminoglycosides force read through of premature stop codon mutations and introduce new mutation-specific gene-corrective strategies in Duchenne muscular dystrophy. A chronic treatment with gentamicin (32 mg/kg/daily i.p., 8-12 weeks) was performed in exercised mdx mice with the dual aim to clarify the dependence on dy...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2008.07.009
更新日期:2008-11-01 00:00:00
abstract::Symptoms in Parkinson's Disease (PD) have been linked to oscillatory activity within the basal ganglia. In humans, such activity has been detected mainly in the local field potentials (LFPs) recorded from electrode contacts used for deep brain stimulation. Although most studies have focused on activity within the subt...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.01.020
更新日期:2013-06-01 00:00:00
abstract::Infection of immunocompetent adult rats with Borna disease virus (BDV) causes severe encephalitis and neural dysfunction. The expression of COX-2 and CGRP, genes previously shown to be implicated in CNS disease and peripheral inflammation, was dramatically upregulated in the cortical neurons of acutely BDV-infected ra...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.1998.0225
更新日期:1999-02-01 00:00:00
abstract::Injury to retinal ganglion cell (RGC) axons triggers rapid activation of Jun N-terminal kinase (JNK) signaling, a major prodeath pathway in injured RGCs. Of the multiple kinases that can activate JNK, dual leucine kinase (Dlk) is known to regulate both apoptosis and Wallerian degeneration triggered by axonal insult. H...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.05.015
更新日期:2014-09-01 00:00:00
abstract::We have previously shown that increases in blood-brain barrier permeability represent an important component of ischemia-reperfusion related brain injury in the fetus. Pro-inflammatory cytokines could contribute to these abnormalities in blood-brain barrier function. We have generated pharmacological quantities of mou...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.09.007
更新日期:2015-01-01 00:00:00
abstract::The disruption of the blood-spinal cord barrier (BSCB) by matrix metalloprotease (MMP) activation is a detrimental event that leads to blood cell infiltration, inflammation, and apoptosis, thereby contributing to permanent neurological disability after spinal cord injury (SCI). However, the molecular mechanisms underl...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.07.015
更新日期:2016-11-01 00:00:00
abstract::Photoreceptor cell death is an irreversible, pathologic event in many blinding retinal diseases including retinitis pigmentosa, age-related macular disease, and retinal detachment. Light exposure can exacerbate a variety of human retinal diseases by increasing the rate of photoreceptor cell death. In the present study...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.08.017
更新日期:2006-03-01 00:00:00
abstract::Charcot-Marie-Tooth disease (CMT) is a genetic disorder that can be caused by aberrations in >80 genes. CMT has heterogeneous modes of inheritance, including autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive. Over 95% of cases are dominantly inherited. In this study, we investigated wh...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.01.006
更新日期:2017-04-01 00:00:00
abstract::Dietary or pharmacological manipulation of plasma lipids markedly influences amyloid deposition in animal models of Alzheimer's Disease (AD). However, it is not known whether baseline plasma lipids in AD models differ from wild-type littermates throughout the natural history of disease. To address this question, we me...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.06.007
更新日期:2006-10-01 00:00:00
abstract::Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce great...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.06.016
更新日期:2014-10-01 00:00:00
abstract::Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder caused by a (GCG)n trinucleotide repeat expansion in the poly(A) binding protein nuclear-1 (PABPN1) gene, which in turn leads to an expanded polyalanine tract in the protein. We generated transgenic mice expressing either the wild type or the expanded ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2004.09.021
更新日期:2005-04-01 00:00:00
abstract::To thoroughly understand the function and regulation of neurotransmitter systems in the brain, as well as the underlying disease mechanisms, it is important to comprehensively analyze the expression patterns of genes participating in such systems. Using functional annotated cDNA clones (FANTOM), we examined the gene e...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.01.021
更新日期:2005-08-01 00:00:00
abstract::Neurodegeneration is a common neuropathological feature of prion diseases. Although evidence of apoptosis was found in natural and experimental prion diseases, the precise mechanisms by which neurons die are poorly understood. The pro-apoptotic BAX protein, a key factor of the mitochondrial pathway, plays a central ro...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.05.013
更新日期:2006-09-01 00:00:00
abstract::Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra and a marked reduction of dopamine (DA) levels in the striatum. Binding to its specific receptors, DA switches on a complex program of intracellular signaling that regulates gene ex...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.05.014
更新日期:2005-12-01 00:00:00
abstract::This paper presents a novel model of tremor in Parkinson's disease (PD) based on extensive literature review as well as novel results stemming from functional stereotactic neurosurgery for the alleviation of tremor in PD. Specifically, evidence that suggests the basal ganglia induces PD tremor via excessive inhibitory...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2015.10.009
更新日期:2016-01-01 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::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::DYT1 dystonia is an inherited disease linked to mutation in the TOR1A gene encoding for the protein torsinA. Although the mechanism by which this genetic alteration leads to dystonia is unclear, multiple lines of clinical evidence suggest a link between dystonia and a reduced dopamine D2 receptor (D2R) availability. B...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.03.003
更新日期:2010-06-01 00:00:00
abstract::Huntington's disease (HD) is a genetic neurodegenerative disease characterized by movement disorders, cognitive decline and neuropsychiatric symptoms. HD is caused by expanded CAG tract within the coding region of Huntingtin protein. Despite major insights into the molecular mechanisms leading to HD, no effective cure...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.04.007
更新日期:2012-08-01 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::Although the incidence of seizures after a cerebrovascular event including intracerebral hemorrhage has been widely recognized, the present studies have demonstrated that generalized convulsive seizures can cause multifocal amygdaloallocortical hemorrhage and tissue necrosis, the origin of which remains to be establis...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.01.029
更新日期:2005-08-01 00:00:00
abstract::Sleep plays a critical role in the process of memory consolidation. In particular, during non-rapid eye movement (NREM) slow wave sleep, slow-oscillations, spindles, hippocampal sharp wave ripples, and their phase coupling are involved in the process of transferring and consolidating information recently encoded and t...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2020.104865
更新日期:2020-07-01 00:00:00
abstract::The dysregulation of glycogen synthase kinase-3 (GSK3) has been implicated in Alzheimer disease (AD) pathogenesis and in Abeta-induced neurotoxicity, leading us to investigate it as a therapeutic target in an intracerebroventricular Abeta infusion model. Infusion of a specific GSK3 inhibitor SB216763 (SB) reduced a do...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2008.10.007
更新日期:2009-02-01 00:00:00
abstract::Copper is an essential trace metal which plays a fundamental role in the biochemistry of the human nervous system. Menkes disease and Wilson disease are inherited disorders of copper metabolism and the dramatic neurodegenerative phenotypes of these two diseases underscore the essential nature of copper in nervous syst...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1006/nbdi.1999.0250
更新日期:1999-08-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease, caused by the loss of motor neurons in the brain and spinal cord. Although 10% of ALS cases are familial (FALS), the majority are sporadic (SALS) and probably associated to a multifactorial etiology. Currently ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.12.002
更新日期:2015-02-01 00:00:00
abstract::NMDA receptor dysfunction is central to the encephalopathies caused by missense mutations in the NMDA receptor subunit genes. Missense variants of GRIN1, GRIN2A, and GRIN2B cause similar syndromes with varying severity of intellectual impairment, autism, epilepsy, and motor dysfunction. To gain insight into possible b...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.104527
更新日期:2019-12-01 00:00:00