Neuroscience letters
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Neuroscience letters · Sep 2009
Neuroprotective effects of group II metabotropic glutamate receptor agonist DCG-IV on hippocampal neurons in transient forebrain ischemia.
Activation of group II metabotropic glutamate receptor (mGluR) inhibits the excessive release of glutamate that may be crucial in the pathogenesis of cerebral ischemia. This study investigated the protective effects of the group II mGluR agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), against cerebral ischemia by examining extracellular glutamate concentration ([Glu]e) and neuronal damage in a rat model of transient forebrain ischemia. Cerebral ischemia was induced by 5 min of bilateral carotid artery occlusion and hypotension. ⋯ The intraventricular injection of DCG-IV (250 pmol) significantly attenuated the [Glu]e increase and significantly increased the survival rate of CA1 neurons. Co-injection of LY341495 reversed the protective effects of DCG-IV. These results suggest that pretreatment with DCG-IV has neuroprotective effects against ischemic neuronal injuries through the inhibition of the glutamate release via the activation of group II mGluR.
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Neuroscience letters · Sep 2009
Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat.
The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB(1) receptor. This study evaluates the anticonvulsant activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB(1) antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation - MDA) in the rat. ⋯ Our data suggest the involvement of the CB system in the inhibitory control of hyperexcitability phenomena in a model of acute partial epilepsy. Although the MDA model per se does not induce a basal activation of CB(1) receptors, as suggested by the lack of efficacy of AM251 when administered alone, the partial suppression of WIN55,212-2-induced effects in rats pre-treated with AM251 allows to hypothesise that the WIN55,212-2-induced antiepileptic effect is strictly linked to an increased CB(1) receptor activation or to the involvement of further receptor subtypes.
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Neuroscience letters · Sep 2009
Lactation is a natural model of hippocampus neuroprotection against excitotoxicity.
Lactation is a temporary but complex physiological condition in which hormones and neurogenic stimulation from suckling cause maternal brain plasticity. It has been shown that lactation prevents cell damage induced by excitotoxicity in the dorsal hippocampus of the dam after peripheral administration of kainic acid (KA). The aim of this study was to determine whether lactation protects the maternal hippocampus against damage induced by intracerebral application (ICV) of KA and if lactation decreases, or only delays, this damaging effect of KA. ⋯ Lactation prevented cell damage of the pyramidal layers of the hippocampus (CA1, CA3, and CA4), as compared to virgin rats. The longer period of KA exposure increased the difference in cell damage between these two conditions. The present results confirm that lactation is a natural model for neuroprotection, since it effectively prevents acute and chronic cell damage of the hippocampus induced by exposure to KA.
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In the present offering, the authors provide evidence for the role of the hypoglossal motonucleus in causing a cranial nerve hyperactivity syndrome, namely hemilingual spasm. During a microvascular decompression operation to treat hemilingual spasm, transcranial stimulation elicited a delayed electromyographic (EMG) response from the tongue. This late volley of EMG activity occurred with a latency of approximately 40 ms, lasted approximately 50 ms, and disappeared when the offending vessel was displaced away from the exit zone of the hypoglossal nerve root along medulla oblongata. ⋯ This abnormal response, known as the lateral spread response, is a characteristic sign for hemifacial spasm that disappears after the offending vessel is moved off the facial nerve root. The results of the present study indicate that the EMG signs of hemilingual spasm are similar to those of HFS and that the tongue spasms are most likely caused by hyperactivity of the hypoglossal motonucleus. Based on the authors' knowledge, the above detailed electrophysiological findings related to hemilingual spasm have not been previously reported in the literature.
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Neuroscience letters · Sep 2009
Signaling pathway involved in hypoxia-inducible factor-1alpha regulation in hypoxic-ischemic cortical neurons in vitro.
Hypoxia-inducible factor-1alpha (HIF-1alpha) is a key transciptional regulator of cellular and systemic oxygen homeostasis. Previous studies have shown that the regulation of HIF-1alpha is involved in the activation of PI3K/Akt pathway in some cells. However, whether this pathway plays a role in modulating HIF-1alpha in cultured cortical neurons during hypoxia-ischemia (HI) remains unclear. ⋯ Meanwhile, p-Akt increased and peaked at 4h after reperfusion, preceding HIF-1alpha expression. Pretreatment with wortmannin, a PI3K/Akt pathway inhibitor, significantly inhibited p-Akt expression and further attenuated both transcription and translation of HIF-1alpha and VEGF. Collectively, our findings suggested that PI3K/Akt signaling pathway might be involved in HIF-1alpha regulation after OGD in cultured cortical neurons.