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Nrf2 activation in astrocytes contributes to spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning.
J Neurotrauma. 2014 Aug 01; 31(15):1343-53.JN

Abstract

In this study, we investigated whether nuclear factor erythroid 2-related factor 2 (Nrf2) activation in astrocytes contributes to the neuroprotection induced by a single hyperbaric oxygen preconditioning (HBO-PC) against spinal cord ischemia/reperfusion (SCIR) injury. In vivo: At 24 h after a single HBO-PC at 2.5 atmospheres absolute for 90 min, the male ICR mice underwent SCIR injury by aortic cross-clamping surgery and observed for 48 h. HBO-PC significantly improved hindlimb motor function, reduced secondary spinal cord edema, ameliorated the reactivity of spinal motor-evoked potentials, and slowed down the process of apoptosis to exert neuroprotective effects against SCIR injury. At 12 h or 24 h after HBO-PC without aortic cross-clamping surgery, Western blot, enzyme-linked immunosorbent assay, realtime-polymerase chain reaction and double-immunofluorescence staining were used to detect the Nrf2 activity of spinal cord tissue, such as mRNA level, protein content, DNA binding activity, and the expression of downstream gene, such as glutamate-cysteine ligase, γ-glutamyltransferase, multidrug resistance protein 1, which are key proteins for intracellular glutathione synthesis and transit. The Nrf2 activity and downstream genes expression were all enhanced in normal spinal cord with HBO-PC. Glutathione content of spinal cord tissue with HBO-PC significantly increased at all time points after SCIR injury. Moreover, Nrf2 overexpression mainly occurs in astrocytes. In vitro: At 24 h after HBO-PC, the primary spinal astrocyte-neuron co-cultures from ICR mouse pups were subjected to oxygen-glucose deprivation (OGD) for 90 min to simulate the ischemia-reperfusion injury. HBO-PC significantly increased the survival rate of neurons and the glutathione content in culture medium, which was mainly released from asctrocytes. Moreover, the Nrf2 activity and downstream genes expression induced by HBO-PC were mainly enhanced in astrocytes, but not in neurons. In conclusion, our findings demonstrated that spinal cord ischemic tolerance induced by HBO-PC may be mainly related to Nrf2 activation in astrocytes.

Authors+Show Affiliations

1 Department of Diving and Hyperbaric Medicine, College of Naval Medicine, the Second Military Medical University , Shanghai, China .No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24716787

Citation

Xu, Jiajun, et al. "Nrf2 Activation in Astrocytes Contributes to Spinal Cord Ischemic Tolerance Induced By Hyperbaric Oxygen Preconditioning." Journal of Neurotrauma, vol. 31, no. 15, 2014, pp. 1343-53.
Xu J, Huang G, Zhang K, et al. Nrf2 activation in astrocytes contributes to spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning. J Neurotrauma. 2014;31(15):1343-53.
Xu, J., Huang, G., Zhang, K., Sun, J., Xu, T., Li, R., Tao, H., & Xu, W. (2014). Nrf2 activation in astrocytes contributes to spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning. Journal of Neurotrauma, 31(15), 1343-53. https://doi.org/10.1089/neu.2013.3222
Xu J, et al. Nrf2 Activation in Astrocytes Contributes to Spinal Cord Ischemic Tolerance Induced By Hyperbaric Oxygen Preconditioning. J Neurotrauma. 2014 Aug 1;31(15):1343-53. PubMed PMID: 24716787.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nrf2 activation in astrocytes contributes to spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning. AU - Xu,Jiajun, AU - Huang,Guoyang, AU - Zhang,Kun, AU - Sun,Jinchuan, AU - Xu,Tao, AU - Li,Runping, AU - Tao,Hengyi, AU - Xu,Weigang, Y1 - 2014/07/11/ PY - 2014/4/11/entrez PY - 2014/4/11/pubmed PY - 2015/4/22/medline KW - Nrf2 KW - astrocyte KW - hyperbaric oxygen preconditioning KW - neuroprotection KW - oxygen-glucose deprivation KW - spinal cord ischemia/reperfusion SP - 1343 EP - 53 JF - Journal of neurotrauma JO - J. Neurotrauma VL - 31 IS - 15 N2 - In this study, we investigated whether nuclear factor erythroid 2-related factor 2 (Nrf2) activation in astrocytes contributes to the neuroprotection induced by a single hyperbaric oxygen preconditioning (HBO-PC) against spinal cord ischemia/reperfusion (SCIR) injury. In vivo: At 24 h after a single HBO-PC at 2.5 atmospheres absolute for 90 min, the male ICR mice underwent SCIR injury by aortic cross-clamping surgery and observed for 48 h. HBO-PC significantly improved hindlimb motor function, reduced secondary spinal cord edema, ameliorated the reactivity of spinal motor-evoked potentials, and slowed down the process of apoptosis to exert neuroprotective effects against SCIR injury. At 12 h or 24 h after HBO-PC without aortic cross-clamping surgery, Western blot, enzyme-linked immunosorbent assay, realtime-polymerase chain reaction and double-immunofluorescence staining were used to detect the Nrf2 activity of spinal cord tissue, such as mRNA level, protein content, DNA binding activity, and the expression of downstream gene, such as glutamate-cysteine ligase, γ-glutamyltransferase, multidrug resistance protein 1, which are key proteins for intracellular glutathione synthesis and transit. The Nrf2 activity and downstream genes expression were all enhanced in normal spinal cord with HBO-PC. Glutathione content of spinal cord tissue with HBO-PC significantly increased at all time points after SCIR injury. Moreover, Nrf2 overexpression mainly occurs in astrocytes. In vitro: At 24 h after HBO-PC, the primary spinal astrocyte-neuron co-cultures from ICR mouse pups were subjected to oxygen-glucose deprivation (OGD) for 90 min to simulate the ischemia-reperfusion injury. HBO-PC significantly increased the survival rate of neurons and the glutathione content in culture medium, which was mainly released from asctrocytes. Moreover, the Nrf2 activity and downstream genes expression induced by HBO-PC were mainly enhanced in astrocytes, but not in neurons. In conclusion, our findings demonstrated that spinal cord ischemic tolerance induced by HBO-PC may be mainly related to Nrf2 activation in astrocytes. SN - 1557-9042 UR - https://www.unboundmedicine.com/medline/citation/24716787/Nrf2_activation_in_astrocytes_contributes_to_spinal_cord_ischemic_tolerance_induced_by_hyperbaric_oxygen_preconditioning_ L2 - https://www.liebertpub.com/doi/full/10.1089/neu.2013.3222?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -