Neuroscience
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Traumatic spinal cord injury induces a long-standing inflammatory response in the spinal cord tissue, leading to a progressive apoptotic death of spinal cord neurons and glial cells. We have recently demonstrated that immediate treatment with the antioxidants N-acetyl-cysteine (NAC) and acetyl-l-carnitine (ALC) attenuates neuroinflammation, induces axonal sprouting, and reduces the death of motoneurons in the vicinity of the trauma zone 4weeks after initial trauma. The objective of the current study was to investigate the effects of long-term antioxidant treatment on the survival of descending rubrospinal neurons after spinal cord injury in rats. ⋯ Treatment also decreased the expression of BAX, caspase 3, OX42 and ED1 after 2 weeks. After 8 weeks, treatment decreased immunoreactivity for OX42, whereas it was increased for 5HT. In conclusion, this study provides further insight in the effects of treatment with NAC and ALC on descending pathways, as well as short- and long-term effects on the spinal cord trauma zone.
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Chronic exposure to n-hexane induces peripheral-central axonopathy, mediated by its metabolite 2,5-hexanedione (2,5-HD), in occupational workers and experimental animals, but the underlying mechanism is still unclear. In the current study, we investigated the effects of 2,5-HD on middle-molecular-weight neurofilament (NF-M) axonal transport using live-cell imaging technique in cultured rat dorsal root ganglia (DRG) cells. PA-GFP-NF-M plasmid was transfected into DRG neurons and live-cell imaging was performed to observe the slow axonal transport of NF-M. ⋯ The results showed that 2,5-HD administration resulted in a decrease of NF-M axonal transport and a reduction of three neurofilament subunits levels in DRG cells. Furthermore, 2,5-HD exposure significantly decreased ATP contents and the protein levels of kinesin heavy chain (KHC). These findings indicated that 2,5-HD reduced slow axonal transport, neurofilaments cargoes, motor proteins and ATP energy in rat DRG cells, which may contribute to 2,5-HD-induced neurotoxicity.
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During chronic pain states, peripheral nociceptive stimulation can induce long-term potentiation (LTP) in the spinal dorsal horn, but it is not clear how quickly spinal LTP develops after peripheral noxious stimulation. Furthermore, transient receptor potential vanilloid type 1 (TRPV1) receptors are abundant in spinal cord dorsal horn, especially in the superficial layers, and are thought to be involved in synaptic plasticity. In this study, we investigated the time frame of LTP induction after inflammatory insult and electrical stimulation and the involvement of TRPV1 receptors. ⋯ Topical application of the TRPV1 receptor antagonist capsazepine onto the spinal cord inhibited the induction of spinal LTP by CFA or formalin. Furthermore, capsazepine and another TRPV1 antagonist, (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide, partially or completely blocked the LTP induced by conditioning stimulation with high- and low-frequency electrical stimulation. These results suggest that acute peripheral inflammatory stimulation by CFA or 5% formalin can induce spinal LTP very early after stimulation onset and that TRPV1 receptors in the spinal dorsal horn might contribute to this LTP induction.
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As a consequence of an ischemic episode, energy production is disturbed, leading to neuronal cell death. Despite intensive research, the quest for promising neuroprotective drugs has largely failed, not only because of ineffectiveness, but also because of serious side-effects and dosing difficulties. Acetyl-l-carnitine (ALC) is an essential nutrient which plays a key role in energy metabolism by transporting fatty acids into mitochondria for β-oxidation. ⋯ This finding paralleled the histological analysis: ALC pretreatment resulted in the reappearance of dendritic spines on the CA1 pyramidal cells. Our data demonstrate that ALC administration can restore hippocampal function and spine density. ALC probably acts by enhancing the aerobic metabolic pathway, which is inhibited during and following ischemic attacks.