Abstract:
:Thyrotropin-releasing hormone (TRH) and TRH analogues have been reported to be neuroprotective in experimental models of spinal cord injury and head injury. We have previously shown that a diketopiperazine structurally related to the TRH metabolite cyclo-his-pro reduces neuronal cell death in vitro and in vivo. Here we report the neuroprotective activity of other cyclic dipeptides in multiple in vitro models of neuronal injury and after controlled cortical impact (CCI) in mice. Using primary neuronal cultures, three novel dipeptides were compared to the previously reported diketopiperazine as well as to vehicle controls; each of the compounds reduced cell death after direct physical trauma or trophic withdrawal. Two of these peptides also protected against glutamate toxicity and beta-amyloid-induced injury; the latter also strongly inhibited glutamate-induced increases in intracellular calcium. Treatment with each of the test compounds resulted in highly significant improvement of motor and cognitive recovery after CCI, as well as markedly reducing lesion volumes as shown by high field magnetic resonance imaging. DNA microarray studies following fluid percussion induced traumatic brain injury (TBI) in rats showed that treatment with one of these dipeptides after injury significantly down-regulated expression of mRNAs for cell cycle proteins, aquaporins, cathepsins and calpain in ipsilateral cortex and/or hippocampus, while up-regulating expression of brain-derived neurotrophic factor, hypoxia-inducible factor and several heat-shock proteins. Many of these mRNA expression changes were paralleled at the protein level. The fact that these small peptides modulate multiple mechanisms favoring neuronal cell survival, as well as their ability to improve functional outcome and reduce posttraumatic lesion size, suggests that they may have potential utility in clinical head injury.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Faden AI,Movsesyan VA,Knoblach SM,Ahmed F,Cernak Idoi
10.1016/j.neuropharm.2005.04.001subject
Has Abstractpub_date
2005-09-01 00:00:00pages
410-24issue
3eissn
0028-3908issn
1873-7064pii
S0028-3908(05)00134-6journal_volume
49pub_type
杂志文章abstract::N-Ethyl-maleimide (NEM, 2.5 x 10(-5) M) inhibited the compound action potential of the phrenic nerve and increased the spontaneous release of transmitter from the nerve terminals, recorded as miniature endplate potentials. The first effect was the cause of a blockade of the phrenic nerve diaphragm preparation, during ...
journal_title:Neuropharmacology
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journal_title:Neuropharmacology
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journal_title:Neuropharmacology
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journal_title:Neuropharmacology
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journal_title:Neuropharmacology
pub_type: 杂志文章
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journal_title:Neuropharmacology
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pub_type: 杂志文章
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.10.002
更新日期:2007-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:1983-12-01 00:00:00
abstract::4-Alkylated analogues of homoibotenic acid (HIBO) have previously shown high potency and selectivity at ionotropic and metabotropic glutamic acid receptor (iGluR and mGluR) subtypes. Compounds with different selectivity profiles are valuable pharmacological tools for neuropharmacological studies, and the series of 4-a...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2005.05.007
更新日期:2005-01-01 00:00:00
abstract::Neurotrophins jointly exert various functions in the nervous system, including neuronal differentiation, survival, and regulation of synaptic plasticity. However, the functional interactions of neurotrophins or mechanisms through which neurotrophins regulate each other are still not clear. In the present study, brain-...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(02)00043-6
更新日期:2002-06-01 00:00:00
abstract::The medullary dorsal horn (MDH or Sp5c/C1 region) plays a key role modulating the nociceptive input arriving from craniofacial structures. Some reports suggest that oxytocin could play a role modulating the nociceptive input at the MDH level, but no study has properly tested this hypothesis. Using an electrophysiologi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2017.11.031
更新日期:2018-02-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.10.010
更新日期:2017-02-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2012.05.027
更新日期:2012-09-01 00:00:00
abstract::The increased pro-inflammatory cytokine production was previously observed in Alzheimer's disease (AD). We sought to explore whether acetylcholinesterase inhibitor (AChEI) therapy ameliorates clinical symptoms in AD through down-regulation of inflammation. Expression and release of monocyte chemotactic protein-1 (MCP-...
journal_title:Neuropharmacology
pub_type: 临床试验,杂志文章
doi:10.1016/j.neuropharm.2005.11.006
更新日期:2006-04-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00183-6
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abstract::Ketoprofen is a non-steroidal antiinflammatory drug (NSAID) which provides effective analgesia in situations of pain provoked by tissue inflammation. However, the location of its analgesic effects, (peripheral tissues versus central nervous system), have not been clearly identified and separated. In the present study ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(97)00120-2
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abstract::Acamprosate is clinically used to treat alcohol-dependent patients. While the molecular and pharmacological mechanisms of acamprosate remain unclear, it has been shown to regulate γ-aminobutyric acid (GABA) or glutamate levels in the cortex and striatum. To investigate the effect of acamprosate on brain metabolites in...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2012.02.022
更新日期:2012-06-01 00:00:00
abstract::Long-term consumption of ethanol affects cortical areas that are important for learning and memory, cognition, and decision-making. Deficits in cortical function may contribute to alcohol-abuse disorders by impeding an individual's ability to control drinking. Previous studies from this laboratory show that acute etha...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.03.031
更新日期:2016-08-01 00:00:00
abstract::Serotonin2C (5-HT2C) receptors may influence motivation and reward through effects on the mesocorticolimbic dopamine (DA) system. Previous work from this laboratory indicated that 5-HT2C receptor stimulation does not induce place conditioning when animals are tested in a drug-free state, but does result in decreased l...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.05.006
更新日期:2006-09-01 00:00:00
abstract::Rats were trained to recognize a discriminative stimulus (DS) elicited by the dopamine D(2)/D(3) receptor agonist, PD128,907 (0.16 mg/kg, i.p.), which suppressed frontocortical release of dopamine (DA) but not 5-HT. The selective 5-HT1A receptor agonists, 8-OH-DPAT and flesinoxan, dose-dependently generalized to PD128...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00022-3
更新日期:2001-06-01 00:00:00
abstract::The involvement of metabotropic glutamate receptor group II (mGluRII) in the induction of long-term depression (LTD) was investigated in the medial perforant path of the rat dentate gyrus, a region with a very high density of mGluRII. Perfusion of either of two potent mGluRII agonists, (2S,1R,2R,3R)-2-(2S, 1'R, 2'R, 3...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00168-3
更新日期:1999-01-01 00:00:00
abstract::ɣ-aminobutyric-acid (GABA) functions as the principal inhibitory neurotransmitter in the central nervous system. Imbalances in GABAergic neurotransmission are involved in the pathophysiology of various neurological diseases such as epilepsy, Alzheimer's disease and stroke. GABA transporters (GATs) facilitate the termi...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
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更新日期:2019-12-15 00:00:00
abstract::Stress-related psychiatric disorders, including anxiety, are complex diseases that have genetic, and environmental causes. Stressful experiences increase the release of prefrontal amygdala neurotransmitters, a response that is relevant to cognitive, emotional, and behavioral coping. Moreover, exposure to stress elicit...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.03.044
更新日期:2016-08-01 00:00:00
abstract::Vulnerability to the addictive effects of drugs of abuse varies among individuals, but the biological basis of these differences are poorly known. This work tries to increase this knowledge by comparing the brain proteome of animals with different rate of extinction of cocaine-seeking behaviour. To achieve this goal, ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2009.04.005
更新日期:2009-07-01 00:00:00
abstract::Inhibition in the brain is dominated by the neurotransmitter gamma-aminobutyric acid (GABA); operating through GABA(A) receptors. This form of neural inhibition was presumed to be mediated by synaptic receptors, however recent evidence has highlighted a previously unappreciated role for extrasynaptic GABA(A) receptors...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2008.08.004
更新日期:2009-01-01 00:00:00
abstract::Seldom does a single individual have such a profound effect on the development of a scientific discipline as Erminio Costa had on neuropharmacology. During nearly sixty years of research, Costa and his collaborators helped established many of the basic principles of the pharmacodynamic actions of psychotherapeutics. H...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2010.10.005
更新日期:2011-06-01 00:00:00