Neurochemistry international
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Searching for effective pharmacological agents for traumatic brain injury (TBI) treatment has largely been unsuccessful. The transient receptor potential melastatin 7 (TRPM7), a TRP channel that is essential for embryonic development, has been shown to mediate ischemic neuronal injury in vivo and in vitro, but global deletion of TRPM7 in mice is lethal. Here, carvacrol was used to investigate the protective effect of TRPM7 inhibition in an in vitro traumatic neuronal injury model. ⋯ The involvement of TRPM7 sensitive calcium influx in our in vitro model was confirmed by the results that bradykinin induced calcium influx was prevented by carvacrol in neurons. Furthermore, carvacrol significantly inhibited the induction of neuronal nitric oxide synthase (nNOS) after traumatic injury, and treatment with carvacrol and the nNOS inhibitor NLPA together had no extra effect on calcium concentration and neuronal injury. Thus, inhibition of TRPM7 function by carvacrol protects against traumatic neuronal injury, and might be a potential drug development strategy for the treatment of TBI.
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Although numerous studies demonstrated a neuroprotective potency of unspecific group III mGluR agonists in in vitro and in vivo models of excitotoxicity, little is known about the protective role of group III mGlu receptor activation against neuronal cell injury evoked by ischemic conditions. The aim of the present study was to assess neuroprotective potential of the allosteric agonist of mGlu7 receptor, N,N'-Bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082) against oxygen-glucose deprivation (OGD)- and kainate (KA)-evoked neuronal cell damage in primary neuronal cultures, with special focus on its efficacy after delayed application. We demonstrated that in cortical neuronal cultures exposed to a 180 min OGD, AMN082 (0.01-1 µM) in a concentration- and time-dependent way attenuated the OGD-induced changes in the LDH release and MTT reduction assays. ⋯ Next, we showed that AMN082 (0.5 and 1 µM) attenuated the OGD-induced increase in the number of necrotic nuclei as well inhibited the OGD-evoked calpain activation, suggesting the participation of these processes in the mechanism of AMN082-mediated protection. Additionally, we showed that protection evoked by AMN082 (1 µM) in KA model was connected with the inhibition of toxin-induced caspase-3 activity, and this effect was abolished by the mGlu7 receptor antagonist. The obtained results indicated that the activation of mGlu7 receptors may be a promising target for neuroprotection against ischemic and excitotoxic insults.
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The present study was designed to examine whether somatostatin analog octreotide (OCT) was involved in antinociception in the ventrolateral orbital cortex (VLO) and determine whether this effect had a sex difference between male and female rats. The radiant heat-evoked tail flick (TF) reflex was used as an index of acute nociceptive response in lightly anesthetized rats. The number of flinches evoked by formalin injection into the hindpaw was used to evaluate inflammatory persistent pain in conscious rats. ⋯ Pretreatment with c-SOM (25.0 µg in 0.5 µl) into the VLO totally antagonized the 10 ng OCT-induced inhibition of the flinches in both phases in female rats. Additionally, single administration of c-SOM into the VLO failed to alter tail reflex latencies and formalin-induced nociceptive behaviors in female rats. The results provide the first valuable evidence that somatostatin and its receptors are involved in antinociception in acute heat-evoked nociception and inflammatory persistent pain only in female rats, not male rats, in the VLO.
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Sulfur dioxide (SO2) is a common air pollutant and can cause harmful insults on neurons. Microglial activation has been implicated in the signaling cascades that contribute to neuronal cell death in various neurological disorders. In the present study, we found that SO2 derivatives decreased cell viability via inducing oxidative stress, inflammatory responses and apoptotic cell death in BV2 microglial cells. ⋯ CHPG increased the expression of TNF-α stimulated gene/protein 6 (TSG-6), but decreased the activation of nuclear factor-κB (NF-κB) after SO2 derivatives treatment in BV2 cells. In addition, knockdown of TSG-6 expression by specific targeted short interfering RNA (siRNA) partially reversed the protection induced by CHPG. Therefore, our findings reveal a mechanistic basis for exploring the association between SO2 exposure and neurological disorders, and also for opening up therapeutic approaches of ameliorating neuronal injury resulting from exposure in atmospheric polluting environment.
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Brain abscesses frequently cause symptoms such as seizures, delirium, paresis and sensory deficits that could reflect brain edema, increased intracranial pressure, or tissue destruction. However, it is also possible that pus constituents could disturb neuronal function in the surrounding brain tissue. In pus from 16 human brain abscesses, extracellular potassium ([K(+)]o) was 10.6 ± 4.8 mmol/L (mean ± SD; maximum value 22.0 mmol/L). ⋯ Pus from 10 extracerebral abscesses (empyemas) also had higher [K(+)]o, zinc, iron, calcium, copper, manganese, and chromium than did CSF. Brain abscess [K(+)]o was significantly higher than serum potassium (3.8 ± 0.5 mmol/L; p = 0.0001), indicating that the elevated abscess [K(+)]o originated from damaged cells (e.g. brain cells and leukocytes), not from serum. High [K(+)]o could depolarize neurons, high levels of zinc could inhibit glutamate and GABA receptors, and high levels of iron and copper could cause oxidative damage, all of which could contribute to neuronal dysfunction in brain abscess patients.