Abstract:
:These experiments were completed as part of an NIH "Facilities of Research Excellence in Spinal Cord Injury" contract to support independent replication of published studies that could be considered for eventual clinical testing. Recent studies have reported that selective inhibition of the P2X7 receptor improves both the functional and histopathological consequences of a contusive spinal cord injury (SCI) in rats. We repeated two published studies reporting the beneficial effects of pyridoxal-5'-phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS) or Brilliant blue G (BBG) treatment after SCI (Wang et al., 2004 and Peng et al., 2009). Mild thoracic SCI was first produced in Experiment 1 by means of the MASCIS impactor at T10 (height 6.25 mm, weight 10 g) followed by intraspinal administration of a P2X7 antagonist (2 μl/10 mM) after injury. Treatment with PPADS or another highly selective P2X7R antagonist Brilliant Blue G (BBG) (2 μl/02 mM) did not improve locomotive (BBB rating scale) over a 7 week period compared to vehicle treated rats. Also, secondary histopathological changes in terms of overall lesion and cavity volume were not significantly different between the PPADS, BBG, and vehicle treated animals. In the second experiment, the systemic administration of BBG (10 or 50 mg/kg, iv) 15 min, 24 and 72 h after moderate (12.5 mm) SCI failed to significantly improve motor recovery or histopathological outcome over the 6 week observational period. Although we cannot conclude that there will be no long-term beneficial effects in other spinal cord injury models using selective P2X7 receptor antagonists at different doses or treatment durations, we caution researchers that this potentially exciting therapy requires further preclinical investigations before the implementation of clinical trials targeting severe SCI patients.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Marcillo A,Frydel B,Bramlett HM,Dietrich WDdoi
10.1016/j.expneurol.2011.06.008subject
Has Abstractpub_date
2012-02-01 00:00:00pages
687-92issue
2eissn
0014-4886issn
1090-2430pii
S0014-4886(11)00230-5journal_volume
233pub_type
杂志文章abstract::For the past 15 years, patients with Parkinson's disease have participated in clinical trials evaluating the efficacy of intrastriatal dopamine transplants. Principally, two donor tissues have been employed, the chromaffin cells of the adrenal medulla and fetal ventral mesencephalon. The clinical response following ea...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1006/exnr.1996.6386
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abstract::To determine if phenytoin reduces depolarization-linked acetylcholine release from synaptosomes solely by interacting with Na+, the effect of phenytoin (100 to 200 microM) and/or tetrodotoxin (1 microM) on ACh release was assayed in synaptosomes depolarized with either KCl 56 mM or veratridine 10 microM. Phenytoin red...
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pub_type: 杂志文章
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6426
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abstract::The glial cell-derived neurotrophic factor (GDNF) precursor contains several putative sites for prohormone convertase-mediated excision of short peptides. Here, we show that one of the predicted peptides, named BEP (brain excitatory peptide), induces a substantial increase in the synaptic excitability in rat CA1 pyram...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2007.12.018
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(84)90065-7
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.03.011
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abstract::Frontotemporal dementia (FTD) is the second most common cause of presenile dementia. Here we have investigated the frequency of the epsilon4 allele of the Apolipoprotein (APOE) gene in FTD and in other non-Alzheimer forms of dementia related to FTD such as Motor Neurone disease dementia, semantic dementia, progressive...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2000.7387
更新日期:2000-06-01 00:00:00
abstract::Grafts of embryonic ventral mesencephalic tissue placed in the striatum of 6-hydroxydopamine-lesioned rats survive, and make and receive connections to and from the host brain. The dopaminergic neurons of the graft can grow processes into the host brain, and thereby alleviate many of the behavioral deficits of this fo...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1006/exnr.1996.0141
更新日期:1996-09-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1998.6886
更新日期:1998-10-01 00:00:00
abstract::The respiratory central pattern generator must respond to chemosensory cues to maintain oxygen (O2) and carbon dioxide (CO2) homeostasis in the blood and tissues. To do this, sensorial cells located in the periphery and central nervous system monitor the arterial partial pressure of O2 and CO2 and initiate respiratory...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2016.05.036
更新日期:2017-01-01 00:00:00
abstract::Neuropathic pain is common after traumatic injuries to the cauda equina/conus medullaris and brachial plexus. Clinically, this pain is difficult to treat and its mechanisms are not well understood. Lesions to the ventral roots are common in these injuries, but are rarely considered as potential contributors to pain. W...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2006.11.003
更新日期:2007-03-01 00:00:00
abstract::Alpha-synuclein (alphaSN) is implicated in Parkinson's disease (PD) and is the major component of Lewy bodies (LBs). Although alphaSN is mainly expressed in neuronal cells and exists as a cytoplasmic protein, it has been found in body fluids including cerebrospinal fluid and blood. This study explored plasma alphaSN a...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2006.12.006
更新日期:2007-04-01 00:00:00
abstract::Epidermal growth factor responsive (EGFr) neural progenitor (NP) cells have been shown to be a potential alternative tissue source for neural transplantation and for developmental study. We have shown that nonpassaged EGFr NP cells can self-renew for 2 years in neurospheres and can robustly differentiate into glia and...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2000.7425
更新日期:2000-07-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2020.113391
更新日期:2020-10-01 00:00:00
abstract::Sympathetic innervation of lymphoid tissues is localized to specific tissue compartments, but little is known of the "factors" that are important in establishing this pattern during development. Numerous studies have shown interactions of nerve growth factor (NGF) with the immune system, which may include modulation o...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6711
更新日期:1998-01-01 00:00:00
abstract::Breathing is a vital homeostatic behavior and must be precisely regulated throughout life. Clinical conditions commonly associated with inflammation, undermine respiratory function may involve plasticity in respiratory control circuits to compensate and maintain adequate ventilation. Alternatively, other clinical cond...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2016.07.022
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal mo...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2017.05.005
更新日期:2017-09-01 00:00:00
abstract::The vanilloid receptor TRPV(1) is a key nociceptive molecule located in primary afferent nociceptive neurons in dorsal root ganglia (DRG) for initiating neurogenic inflammation and pain. Our recent study demonstrates that up-regulation of TRPV(1) receptors by intradermal injection of capsaicin is modulated by activati...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2009.12.011
更新日期:2010-03-01 00:00:00
abstract::No current therapy for Parkinson disease has been shown to slow or reverse the progressive course of the disease. As a departure from traditional treatments, gene therapy approaches provide a new hope for realizing this long-sought goal; but before they can be widely employed for use in patients, they must first be su...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2007.08.012
更新日期:2008-01-01 00:00:00
abstract::Nitrosative stress contributes to nerve conduction slowing, thermal hypoalgesia, and impaired nitrergic innervation in animal models of Type 1 diabetes. The role for reactive nitrogen species in Type 2 diabetes-associated neuropathy remains unexplored. This study evaluated the role for nitrosative stress in functional...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2007.03.019
更新日期:2007-06-01 00:00:00
abstract::Proximal axotomy in adult animals results in delayed death of motor neurons. Features characteristic of both necrosis and apoptosis have been described in motor neurons of the spinal cord following proximal avulsion of the ventral roots. We have previously demonstrated that a genomic herpes simplex virus (HSV)-based v...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2000.7597
更新日期:2001-04-01 00:00:00
abstract::Huntington's disease is an autosomal dominant neurogenetic disorder leading to striatal atrophy, characterized by involuntary movements. Voluntary movements also deteriorate, but the neurophysiological mechanisms are less understood. We investigated voluntary movement execution and its neural correlates by means of mo...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.11.018
更新日期:2009-03-01 00:00:00
abstract::The extensive period of retinal ganglion cell (RGC) neurogenesis in the rat is associated with a protracted sequence of arrival of their axons into central targets such as the superior colliculus (SC) (Dallimore et al., 2002). Using in utero 5-bromo-2'-deoxyrudine (BrdU) injections to label early (embryonic day (E) 15...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2010.07.007
更新日期:2010-10-01 00:00:00
abstract::Rat axial muscle previously has not been studied histochemically. We were interested in determining the fiber composition and fiber distribution in rat lateral longissimus (LL), the large epaxial dorsiflexor muscle active during sexual posturing in the female rat and to determine if estrogen replacement in ovariectomi...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(83)90229-7
更新日期:1983-02-01 00:00:00
abstract::The sciatic nerve of adult mice was transected and proximal and distal nerve stumps were sutured into a nontoxic bioresorbable nerve guide. Nerve guide lumens were either empty or filled with a gel containing 80% laminin and additional extracellular matrix components. Two weeks later cells in the L3 through L5 dorsal ...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(85)90087-1
更新日期:1985-06-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1997.6497
更新日期:1997-07-01 00:00:00
abstract::The retrograde axonal transport mechanism of motor neurons has been exploited to deliver the gene encoding Glial cell line-derived neurotrophic factor (GDNF) into the central nervous system to provide trophic support following injury. A nonviral gene delivery system, consisting of a monoclonal antibody (MC192) that bi...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2006.05.027
更新日期:2006-11-01 00:00:00
abstract::A single fourth lumbar dorsal rootlet was transected at the entry point into the spinal cord. The nerve fibres were labelled with biotin dextran injected into the rootlet. An endogenous matrix containing olfactory-ensheathing cells (OECs) labelled with green fluorescent protein was applied to the opposing cut surfaces...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.04.021
更新日期:2004-08-01 00:00:00
abstract::Excessive synchronization of basal ganglia neuronal activity at ~20 Hz is characteristic of patients with untreated Parkinson's disease (PD). Correlative evidence suggests that this activity may contribute to bradykinesia. Attempts to demonstrate causality through stimulation imposed synchronization at 20 Hz in the re...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2011.05.018
更新日期:2011-09-01 00:00:00