Brain research
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Effect of aminoguanidine on post-ischemic brain edema in transient model of focal cerebral ischemia.
Previous experimental studies have shown that aminoguanidine (AG) is beneficial in the late phase of cerebral ischemia. Recently, it has been reported that AG reduces cerebral edema in traumatic brain injury. However, the effects of AG on post-ischemic cerebral edema and blood-brain barrier (BBB) permeability are not clear. ⋯ Additionally, AG at the doses of 75 and 150 mg/kg significantly reduces cortical and striatal infarct volumes (P<0.001), while AG at the dose of 300 mg/kg did not change striatal infarct volumes (P>0.05). Our findings show that AG significantly reduced post-ischemic increase of brain edema with a 3-h therapeutic window in the transient model of focal cerebral ischemia. Moreover, it seems that at least part of the anti-edematous effects of AG is due to decrease of BBB disruption.
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The P3a is an event-related potential (ERP) component believed to reflect an attention-switch to task-irrelevant stimuli or stimulus information. The present study concerns the automaticity of the processes underlying the auditory P3a. More specifically, we investigated whether the auditory P3a is an attention-independent component, that is, whether it can still be elicited under highly-focused selective attention to a different (visual) channel. ⋯ This finding suggests that the elicitation of the auditory P3a does not require available central capacity, and confirms the automatic nature of the processes underlying this ERP component. Moreover, the difficulty of the visual task did not modulate either the mismatch negativity (MMN) or the P3a but did have an effect on a late (350-400 ms) negativity, an ERP deflection perhaps related to a subsequent evaluation of the auditory change. Together, these results imply that the auditory P3a could reflect a strongly-automatic process, one that does not require and is not modulated by attention.
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Intramuscular injection of NGF in human subjects has been reported not to elicit pain, whereas 5% NaCl does. On the other hand, NGF injections induce a long-lasting hyperalgesia. In the present study, the possible neuronal basis of these effects was studied at the spinal level. ⋯ Despite the stronger excitatory effect of 5% NaCl, the sensitization of the dorsal horn neurons after hypertonic saline was less than that after NGF (15.3%). Behavioral experiments showed that NGF injections induced stronger mechanical allodynia and hyperalgesia than hypertonic saline i.m. The data demonstrate that low-frequency activation or even subthreshold potentials in dorsal horn neurons evoked by unmyelinated muscle afferents are an effective means of sensitizing these neurons.
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Delayed paraplegia after operation of the thoracic aorta is considered to be related to vulnerability of motor neurons to ischemia. Recently, endoplasmic reticulum (ER) stress has been reported to participate in neuronal cell death. In the present study, we investigate the expression of ER stress-related molecules and discuss the relationship between neuronal vulnerability and ER stress after transient ischemia in the spinal cord. ⋯ These results indicate that the vulnerability of motor neurons in the spinal cord might be partially attributed to an ER stress response to transient ischemia.
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Paclitaxel (Taxol) is a frontline antineoplastic agent used to treat a variety of solid tumors including breast, ovarian, or lung cancer. The major dose limiting side effect of paclitaxel is a peripheral sensory neuropathy that can last days to a lifetime. To begin to understand the cellular events that contribute to this neuropathy, we examined a marker of cell injury/regeneration (activating transcription factor 3; ATF3), macrophage hyperplasia/hypertrophy; satellite cell hypertrophy in the dorsal root ganglia (DRG) and sciatic nerve as well as astrocyte and microglial activation within the spinal cord at 1, 4, 6 and 10 days following intravenous infusion of therapeutically relevant doses of paclitaxel. ⋯ In contrast, hypertrophy of DRG satellite cells, hypertrophy and hyperplasia of CD68(+) macrophages in the DRG and sciatic nerve, ATF3 expression in S100beta(+) Schwann cells and increased expression of the microglial marker (CD11b) and the astrocyte marker glial fibrillary acidic protein (GFAP) in the spinal cord were not observed until day 6 post-infusion. The present results demonstrate that using the time points and markers examined, DRG neurons show the first sign of injury which is followed days later by other neuropathological changes in the DRG, peripheral nerve and dorsal horn of the spinal cord. Understanding the cellular changes that generate and maintain this neuropathy may allow the development of mechanism-based therapies to attenuate or block this frequently painful and debilitating condition.