Neurochemical research
-
Neurochemical research · Jan 2014
Probenecid protects against transient focal cerebral ischemic injury by inhibiting HMGB1 release and attenuating AQP4 expression in mice.
Stroke results in inflammation, brain edema, and neuronal death. However, effective neuroprotectants are not available. Recent studies have shown that high mobility group box-1 (HMGB1), a proinflammatory cytokine, contributes to ischemic brain injury. ⋯ In addition, HMGB1 release from neurons was significantly diminished and serum HMGB1 levels were substantially reduced following probenecid treatment. Moreover, AQP4 protein expression was downregulated in the cortical penumbra following post-stroke treatment with probenecid. These results suggest that probenecid, a powerful pannexin 1 channel inhibitor, protects against ischemic brain injury by inhibiting cerebral inflammation and edema.
-
Neurochemical research · Jan 2014
Intrathecal miR-96 inhibits Nav1.3 expression and alleviates neuropathic pain in rat following chronic construction injury.
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression post-transcriptionally by binding to their cognate target mRNAs. Emerging evidence suggests that miRNAs are critical regulators of neuronal functions. The expression pattern of miRNAs in the peripheral nervous system after peripheral nerve injury suggest that miRNAs may have important and yet unknown roles in the mechanisms of pain. ⋯ Specifically, Intrathecal administration of miR-96 suppressed the expression of Nav1.3 induced by CCI. Further examination revealed that miR-96 inhibited the Nav1.3 mRNA expression in the embryonic DRG neurons in vitro. Our findings suggest that miR-96 participate in the regulation of neuropathic pain through inhibiting the expression of Nav1.3 in the DRG of CCI rats.
-
Neurochemical research · Nov 2013
Differential proteomic analysis of acute contusive spinal cord injury in rats using iTRAQ reagent labeling and LC-MS/MS.
In this experimental study, differential labeling with isobaric tags for relative and absolute quantitation (iTRAQ) reagents followed by liquid chromatography (LC) and tandem mass spectrometry (MS/MS) proteomic approach was used to investigate differences in the proteome of rat spinal cord at 24 h following a moderate contusion injury. Spinal cord protein samples from the injury epicenter (or from sham controls) were trypsinized and differentially labeled with iTRAQ isotopic reagents. ⋯ The outcome of this analysis revealed that proteins involved in ubiquitination, endocytosis and exocytosis, energy metabolism, inflammatory response, oxidative stress, cytoskeletal disruption, and vascular damage were significantly altered at 24 h following spinal cord injury (SCI). This study demonstrates the utility of the iTRAQ method in proteomic studies and provides further insights into secondary events that occur during acute times following SCI.
-
Neurochemical research · Oct 2013
Decreased expression and role of GRK6 in spinal cord of rats after chronic constriction injury.
Nerve injury and inflammation can both induce neuropathic pain via the production of pro-inflammatory cytokines. In the process, G protein-coupled receptors (GPCRs) were involved in pain signal transduction. GPCR kinase (GRK) 6 is a member of the GRK family that regulates agonist-induced desensitization and signaling of GPCRs. ⋯ In addition, the level of TNF-α underwent the negative pattern of GRK6 in spinal cord. And neutralized TNF-α by antibody intrathecal injection up-regulated GRK6 expression and attenuated the mechanical allodynia and heat hyperalgesia in CCI model. All the data indicated that down-regulation of neuronal GRK6 expression induced by cytokine may be a potential mechanism that contributes to increasing neuronal signaling in neuropathic pain.
-
Neurochemical research · Oct 2013
Tat-collapsin response mediator protein 2 (CRMP2) increases the survival of neurons after NMDA excitotoxity by reducing the cleavage of CRMP2.
Collapsin response mediator protein 2 (CRMP2) is a brain-specific multifunctional adaptor protein involved in neuronal polarity and axonal guidance. Our previous results showed CRMP2 may be involved in the hypoxic preconditioning and ischemic injury, but the mechanism was not clear. This study explored whether CRMP2 was involved in NMDA-induced neural death, and the possible mechanism. ⋯ Thiazolyl blue tetrazolium bromide assay, Hoechst33342/Propidium Iodide staining and Western blot assay showed that Tat-CRMP2 pretreatment increased cell viability compared with the control group against NMDA exposure by decreasing the cleavage of CRMP2. In conclusion, these studies indicated that cleavage of CRMP2 plays an important role involved in the NMDA-induced injury. The cleavage of CRMP2 may be a promising target for excitatory amino acid-related ischemic and hypoxic injury.