Brain research bulletin
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Brain research bulletin · Jul 2013
Nobiletin protects against cerebral ischemia via activating the p-Akt, p-CREB, BDNF and Bcl-2 pathway and ameliorating BBB permeability in rat.
There is cumulative evidence that the serine-threonine kinase Akt and its downstream nuclear transcription factor CREB are involved in neuronal survival and protection. The Akt activates and phosphorylates CREB at Ser133, resulting in the up-regulation of pro-survival CREB target genes such as BDNF and Bcl-2. Thus, Akt/CREB signaling pathway may be one propitious target for treatment of ischemic cerebral injury. ⋯ Immunohistochemistry, western blot and RT-qPCR analysis indicated that NOB dramatically promoted the activities of Akt, CREB, BDNF and Bcl-2 (P<0.05). Meanwhile, claudin-5 expression was also enhanced. On the basis of these findings, we concluded that NOB protected the brain from ischemic damage and it maybe through activating the Akt/CREB signaling pathway and ameliorating BBB permeability.
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Brain research bulletin · Jul 2013
Src/p38 MAPK pathway in spinal microglia is involved in mechanical allodynia induced by peri-sciatic administration of recombinant rat TNF-α.
Our previous work has shown that peri-sciatic administration of recombinant rat TNF-α (rrTNF) induces mechanical allodynia and up-regulation of TNF-α in the spinal dorsal horn of rats; however, the underlying mechanisms remain unknown. In the current study, we found that the levels of phosphorylated Src-family kinases (p-SFKs) and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were significantly increased in bilateral lumbar spinal dorsal horn on day 3 after rrTNF administration. Double immunofluorescence staining revealed that p-SFKs and p-p38 MAPK were nearly restricted to the microglia. ⋯ Moreover, PP2 inhibited the up-regulation of p-p38 MAPK induced by rrTNF. We also found that intrathecal injection of TNF-α neutralization antibody alleviated mechanical allodynia in bilateral hind paws and suppressed up-regulation of p-SFKs and p-p38 MAPK. These results suggest that activation of the SFKs/p38 MAPK pathway in microglia and subsequent TNF-α expression in the spinal dorsal horn may contribute to the mechanical hyperalgesic state induced by peri-sciatic administered rrTNF.
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Brain research bulletin · Jul 2013
Pronociceptive changes in the activity of rostroventromedial medulla (RVM) pain modulatory cells in the streptozotocin-diabetic rat.
Neuropathic pain is one of the most frequent complications of diabetes. The increased neuronal activity of primary afferents and spinal cord neurons in streptozotocin (STZ)-diabetic rats increases the recruitment of the nociceptive ascending pathways, which may affect the activity of pain control circuits in the brain. This study aimed to characterize the electrophysiological responses of neurons of the rostroventromedial medulla (RVM), a key brainstem area involved in descending modulation of nociceptive neurotransmission at the spinal cord, in STZ-diabetic rats. ⋯ On the contrary, the number of active antinociceptive OFF-like cells was significantly lower in the STZ-diabetic rats and their spontaneous activity was decreased when compared with CTRL. Overall, the changes in the activity of RVM pain modulatory cells in STZ-diabetic rats point to enhancement of descending pain facilitation. Based on similar results obtained at the RVM in traumatic neuropathic pain models, the changes in the electrophysiological responses of RVM in STZ-diabetic rats may account for exacerbated pain-like behaviors in diabetic neuropathy.