Heng Zhao Lab Publications


Ischemic Tolerance: In Situ and Remote Pre- and Postconditioning. Zhao H. In: Primer on Cerebrovascular Diseases. United Kingdom: Mara Conner (Elsevier); 2017. 202-5. (Chapters can be downloaded here: http://www.sciencedirect.com/science/book/9780128030585)

Preconditioning in neuroprotection: From hypoxia to ischemia. Li S, Hafeez A, Noorulla F, Geng X, Shao G, Ren C, Lu G, Zhao H, Ding Y, Ji X. Progress in Neurobiology. 2017 Jan 18. pii: S0301-0082(15)30071-X. doi: 10.1016/j.pneurobio.2017.01.001. [Epub ahead of print] Review.

Characterization of mouse serum exosomal small RNA content: The origins and their roles in modulating inflammatory response. Zhou X, Jiao Z, Ji J, Li S, Huang X, Lu X, Zhao H, Peng J, Chen X, Ji Q, Ji Y. Oncotarget. 2017 Apr 27. doi: 10.18632/oncotarget.17448. [Epub ahead of print]


The Role of Spleen-Derived Immune Cells in Ischemic Brain Injury. Zhao H. In: Zhao H. Zhang J, Chen J, Hu X, ed. Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke. Switzerland: Springer; 2016: 189-99. link.springer.com/content/pdf/10.1007%2F978-3-319-32337-4_10.pdf

Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients. Ji Q, Ji Y, Peng J, Zhou X, Chen X, Zhao H, Xu T, Chen L, Xu Y. PloS One. 2016 Sep 23;11(9):e0163645. doi: 10.1371/journal.pone.0163645. eCollection 2016

Glycyrrhizin protects against focal cerebral ischemia via inhibition of T cell activity and HMGB1-mediated mechanisms. Xiong X, Gu L, Wang Y, Luo Y, Zhang H, Lee J, Krams S, Zhu S, Zhao H. Journal of Neuroinflammation. 2016 Sep 8;13(1):241. doi: 10.1186/s12974-016-0705-5.

MKEY, a Peptide Inhibitor of CXCL4-CCL5 Heterodimer Formation, Protects Against Stroke in Mice. Fan Y, Xiong X, Zhang Y, Yan D, Jian Z, Xu B, Zhao H. Journal of the American Heart Association. 2016 Sep 15;5(9). pii: e003615. doi: 10.1161/JAHA.116.003615.


Perylene-diimide-based nanoparticles as highly efficient photoacoustic agents for deep brain tumor imaging in living mice. Fan Q, Cheng K, Yang Z, Zhang R, Yang M, Hu X, Ma X, Bu L, Lu X, Xiong X, Huang W, Zhao H, Cheng Z. Advanced Materials 2015 Feb 4;27(5):843-7. doi: 10.1002/adma.201402972. Epub 2014 Nov 6.

Mechanisms and therapies for acute CNS insults. Vemuganti R, Zhao H. Metabolic Brain Disease. 2015 Apr;30(2):353. doi: 10.1007/s11011-014-9585-5.

Tim-3 cell signaling and iNOS are involved in the protective effects of ischemic postconditioning against focal ischemia in rats. Wei D, Xiong X, Zhao H. Metabolic Brain Disease. 2015 Apr;30(2):483-90. doi: 10.1007/s11011-014-9543-2. Epub 2014 Apr 29.

Docosahexaenoic acid attenuates hyperglycemia-enhanced hemorrhagic transformation after transient focal cerebral ischemia in rats. Lin Y, Xu M, Wan J, Wen S, Sun J, Zhao H, Lou M. Neuroscience. 2015 Aug 20;301:471-9. doi: 10.1016/j.neuroscience.2015.06.024. Epub 2015 Jun 20.


PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and mTOR pathways. Xiong X, Xie R, Zhang H, Gu L, Xie W, Cheng M, Jian Z, Kovacina K, Zhao H. Neurobiology of Disease. 2014 Jun;66:43-52. doi: 10.1016/j.nbd.2014.02.006. Epub 2014 Feb 27.

Intrastriatal transplantation of retinal pigment epithelial cells for the treatment of Parkinson disease: in vivo longitudinal molecular imaging with 18F-P3BZA PET/CT. Bu L, Li R, Liu H, Feng W, Xiong X, Zhao H, Vollrath D, Shen B, Cheng Z. Radiology. 2014 Jul;272(1):174-83. doi: 10.1148/radiol.14132042. Epub 2014 Apr 20.

Mammalian target of rapamycin cell signaling pathway contributes to the protective effects of ischemic postconditioning against stroke. Xie R, Wang P, Cheng M, Sapolsky R, Ji X, Zhao H. Stroke. 2014 Sep;45(9):2769-76. doi: 10.1161/STROKEAHA.114.005406. Epub 2014 Jul 10.



Moderate Hypothermia Inhibits Brain Inflammation and Attenuates Peripheral Immunosuppression Caused by Stroke in Rats. Gu, L, Xiong, X, Lee, J, Xu,B, Krams, S, Steinberg, G.K., Zhao, H*. CNS Neuroscience & Therapeutics 2013 Aug 24. doi: 10.1111/cns.12160

Akt isoforms differentially protect against stroke-induced neuronal injury by regulating mTOR activities. Xie, R, Cheng, M, Li, M, Xiong, X, Daadi, M, Sapolsky, R, Zhao, H.
Journal of Cerebral Blood Flow & Metabolism 2013 Aug 14. oi:10.1038/jcbfm.2013.132

Ischemic postconditioning protects against focal cerebral ischemia by inhibiting brain inflammation while attenuating peripheral lymphopenia in mice. Joo SP, Xie W, Xiong X, Xu B, Zhao H. Neuroscience 2013 Jul 23; 243:149-57.

Ischemic postconditioning facilitates brain recovery after stroke by promoting Akt/mTOR activity in nude rats. Xie, R, Wang, P, Ji, X, Zhao, H*. Journal of Neurochemistry 2013 Jun 18. doi: 10.1111/jnc.12342.

Using hormetic strategies to improve ischemic preconditioning and postconditioning against stroke. Zhao, H, Joo, SP, Xie, W, Ji, X. International Journal of Physiology, Pathophysiology & Pharmacology 2013 May 27; 5(2):61-72.

T cells contribute to stroke-induced lymphopenia in rats. Gu, L, Xiong, X, Wei, D, Gao, X, Krams, S, Zhao, H*.  PLoS One. 2013 Mar 15; 8(3):e59602.

Hurdles to clear before clinical translation of ischemic postconditioning against stroke.
Zhao H. Translational Stroke Research, 2013, 2013 Feb 1; 4(1):63-70.


The protective effects of T cell deficiency against brain injury are ischemic model-dependent in rats. Xiong X, Gu L, Zhang H, Xu B, Zhu S, Zhao H*. Neurochemistry International. 2012 Dec 8. doi:pii: S0197-0186(12)00389-0. 10.1016/j.neuint.2012.11.016.

Distinctive effects of T cell subsets in neuronal injury induced by co-cultured splenocytes in vitro and by in vivo stroke in mice. Gu, L, Xiong, X, Zhang, H, Xu, B, Zhao, H*. Stroke, 2012 Jul 2; 43(7):1941-6.

Lithium treatment reduces brain injury induced by focal ischemia with partial reperfusion and the protective mechanisms dispute the importance of Akt activity. Takahashi, T, Steinberg, GK, Zhao H*. Aging and Disease, 2012 Jun; 3(3):226-33.

Phosphorylated MAPK/ERK1/2 may not always represent its kinase activity in a rat model of focal cerebral ischemia with or without ischemic preconditioning. Takahashi, T, Steinberg, GK, Zhao H* Neuroscience, 2012 May 3; 209:155-60

Prokineticin 2 is a novel endangering mediator in cerebral ischemic injury. Cheng, M, Lee, A, Sun, G, Culbertson, C, Zhao, H, Lyons, D, Zhou, Q, Steinberg, GK, Sapolsky, RM Proceedings of the National Academy of Sciences U S A, 2012 Apr 3; 109(14):5475-80.

The chronic protective effects of limb remote preconditioning and the underlying mechanisms involved in inflammatory factors in focal cerebral ischemia in rats.
Wei, D, Ren, C, Chen, X, Zhao, H*. PLoS One, 2012 Feb 1; 7(2):e30892

From Rapid to Delayed and Remote Postconditioning: the Evolving Concept of Ischemic Postconditioning in Brain Ischemia. Zhao, H*, Ren, C, Chen X, Shen J
Current Drug Targets, 2012 Feb 1; 13(2):173-87


Limited therapeutic time windows of mild to moderate hypothermia in a focal ischemia model in rats. Zhao, H*, Steinberg, G.K. Stroke Research and Treatment, 2011 May 2:131834.

The protective effects of ischemic postconditioning against stroke: from rapid to delayed and remote postconditioning (Review). Zhao, H*. The Open Drug Discovery Journal, 2011 Dec 24, 2, 138-147


The protective effects of rapid ischemic preconditioning on the Akt pathway in focal ischemia in Rats. Gao, X, Zhang, H, Steinberg, G, Zhao, H*. Translational Stroke Research, (2010) 1:202–209


Remote postconditioning reduces infarct size after focal ischemia in rats. Ren, C, Ran, Z, Gao, X, Wei, D, Chen X, Zhao, H*. Brain Research, 2009 Sep 8; 1288:88-94. Epub 2009 Jul 23

Preservation of ROS caused dephosphorylation of PTEN may contribute to neuroprotective effect of post-ischemic hypothermia. Lee, S, Zhao, H, Steinberg, GK. Journal of Cerebral Blood Flow & Metabolism, 2009 Sep;29(9):1589-600. Epub 2009 Jun 24.

High dose of simvastatin induces hyperlocomotive and anxiolytic-like activities: the association with the up-regulation of NMDA receptor binding inthe rat brain. Wang, D, Zengin A, Deng C, Li,Y, Newell,KA, Yang, GY, Lu,Y, Wilder-Smith, EP, Zhao,H, Huang, XF, Experimental Neurology. 2009 Mar; 216(1):132-8. Epub 2008 Dec 3

Ischemic postconditioning as a novel avenue to protect against brain injury after stroke. Zhao, H*, Journal of Cerebral Blood Flow & Metabolism, 2009 May; 29(5):873-85. Epub 2009 Feb 25.


Blocking glucocorticoid and enhancing estrogenic genomic signaling protects against cerebral ischemia. Cheng M, Sun GH, Jin M, Zhao H, Steinberg GK, Sapolsky RM Journal of Cerebral Blood Flow & Metabolism, 2009 Jan; 29(1): 130–136. doi:10.1038/jcbfm.2008.105

Delayed postconditioning protects against focal ischemic brain injury in rats. Ren, C, Gao, X, Gang, Niu, Zhimin Yan, Chen X, Zhao, H*. PLoS ONE.; 2008 Dec 10: 3(12):e3851. Epub. 2008 Dec 10.

δPKC activation antagonizes the protective effect of ERK1/2 inhibition but it conversely reduces ERK1/2 phosphorylation after stroke. Castaneda, D, Zhao, H, Mochly-Rosen, D, Steinberg, GK, Brain Research, 2008 Nov 27. [Epub ahead of print].

PET imaging of VEGFR after stroke. Cai, W, Guzaman R, Chen K, Hsu A, Bliss, T, Sun G, Wang H, He L, Li, Z, Zhao H, Steinberg GK, Chen X Stroke, 2008 Oct 23. [Epub ahead of print].

Protective effects of ischemic postconditioning compared to gradual reperfusion or preconditioning. Gao, X, Ren, C, Zhao, H, * Journal of Neuroscience Research, 2008 Aug 15; 86(11):2505-11.

Inhibiting caspase-3 activity blocks β-catenin degradation after focal ischemia in rat. Zhang, H, Gao, X, Ren, C, Steinberg, GK, Zhao, H*. Neuroreport, 2008 May 28; 19(8):821-4.

Synthesis of a potent and selective 18F-Labeled delta-opioid receptor antagonist derived from the dmt-tic pharmacophore for positron emission tomography imaging. Ryu, EK, Wu, Z, Chen, K, Lazarus, LH, Marczak, ED, Sasaki, Y, Ambo, A, Salvador, S, Ren C,Zhao, H, Balboni, J, Chen, X, Journal of Medicinal Chemistry, 2008 Mar 27;51(6):1817-23. Epub 2008 Mar 1.

Hypothermia blocks β-catenin degradation after focal Ischemia in rat. Zhang, H, Ren, C, Gao, X, Takahashi, T, Sapolsky, RM, Steinberg, GK, Zhao, H*. Brain Research, 2 2008 Mar 10; 1198:182-7. Epub 2008 Jan 14.

The Akt, MAPK and PKC cell signaling pathways regulate the protection of ischemic postconditioning against focal cerebral ischemia in rats. Gao, X, Zhang, H, Takahashi, T, Steinberg, GK, Zhao, H*. Journal of Neurochemistry, 2008 May; 105(3):943-55. Epub 2008 Jan 7.

Dual Roles of the MAPK/ERK1/2 Pathway after Stroke (Review). Sawe, N, Steinberg, GK, Zhao, H*. Journal of Neuroscience Research, 2008 Jun; 86(8):1659-69.

Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning. Ren, C, Gao, X, Steinberg, GK, Zhao, H*. Neuroscience, 2008 Feb 19; 151(4):1099-1103. Epub 2007 Dec 15.

Molecular Imaging as the Main Part of Our Decision-Making and Treatment Strategies in Stroke (review). Kashefi A, Zhao H, Chen X. Frontiers in Bioscience, 2008 Jan 1; 13:1535-56.


The protective effect of ischemic postconditioning against ischemic injury: from the heart to the brain (Review). Zhao, H*. Journal of Neuroimmune Pharmacology, 2007 Dec; 2(4):313-8. Epub 2007 Sep 18.

Conditions of protection by hypothermia and effects on apoptotic pathways in a model of permanent middle cerebral artery occlusion. Zhao, H, Wang, J, Shimohata, T, Sun, G, Yenari, MA, Sapolsky R.M, Steinberg, G.K. Journal of Neurosurgery, 2007 Sep;107(3):636-41.

General versus specific actions of mild-moderate hypothermia in protecting against cerebral ischemic damage (review). Zhao, H*, Sapolsky, R.M, Steinberg, G.K. Journal of Cerebral Blood Flow & Metabolism, 2007 Dec;27(12):1879-94. Epub 2007 Aug 8.

Viralcaspase inhibitor p35, but not crmA, is neuroprotective in theischemic penumbra following experimental stroke. Sung, JH, Zhao, H, Roy, M, Sapolsky, M. R, Steinberg, G. K, Neuroscience, 2007 Nov 23;149(4):804-12. Epub 2007 Jul 26.

Suppression of δPKC activation after focal cerebral ischemia contributes to the protective effect of hypothermia. Shimohata, T, Zhao, H, Sung, JH, Sun, G, Mochly-Rosen, D, Steinberg, GK, J Journal of Cerebral Blood Flow & Metabolism. 2007 Feb 7; [Epub ahead of print]

εPKCmay contribute to the protective effect of hypothermia in a rat focal cerebral ischemia model. Shimohata, T, Zhao, H, Steinberg, GK. Stroke, 2007 Feb; 38(2):375-80. Epub 2007 Jan 4.

Gene therapy using SOD1 protects striatal neurons from experimental stroke. Davis, A.S, Zhao, H,Guo Hua Sun, G, Robert M. Sapolsky, R.M, Steinberg, GK Neuroscience Letters. 2007 Jan 3; 411(1):32-6. Epub 2006 Nov 15.


PI3K/Akt survival signal pathways are implicated in neuronal survival after stroke (Review). Zhao, H*, Sapolsky, R.M, Steinberg, G.K. Molecular Neurobiology. 2006 Dec; 34(3):249-70.

Hypothermia blocks ischemic changes in ubiquitin distribution and levels following stroke. Liu J, Zhao, H, Sung, J, Sun, GH, and Steinberg, G.K. Neuroreport. 2006 Nov 6; 17(16):1691-5.

Interrupting reperfusion as a stroke therapy - Ischemic postconditioning reduces infarct size after focal ischemia in rats. Zhao, H*, Sapolsky, R.M, Steinberg, G.K.,
Journal of Cerebral Blood Flow & Metabolism, 2006 Sep;26(9):1114-21.


Akt Contributes to Neuroprotection by Hypothermia against Cerebral Ischemia in Rats. Zhao, H, Shimohata, T, Wang, J, Sun, G, Sapolsky, R.M, Steinberg, G.K. Journal of Neuroscience, 2005 Oct; 25 9794-9806

Biphasic cytochrome c release after transient global ischemia and its inhibition by hypothermia. Zhao, H,Yenari, M. A., Cheng, D, Sapolsky, R. M., Steinberg, G.K. Journal of Cerebral Blood Flow & Metabolism, 2005 Sep; 25(9):1119-29.


Chaperones, protein aggregation, and brain protection from hypoxic/ischemic injury.
Giffard, RG, Xu, L, Zhao, H, Carrico, W, Ouyang, Y, Qiao, Y, Sapolsky, R, Steinberg, G.K., Hu, B, Yenari, MA. Journal of Experimental Biology. 2004 Aug 15; 207(Pt 18):3213-20.

Glycogen synthase kinase 3β inhibitor Chir025 reduces neuronal death resulting from oxygen-glucose deprivation, glutamate excitotoxicity and cerebral ischemia. Kelly, S, Zhao, H, Sun, G.H., Cheng, D, Qiao, Y, Luo, J, Martin, K, Steinberg, G.K., Harrison, S.D., Yenari, M.A. Experimental Neurology. 2004 Aug; 188(2):378-86.

Bcl-2 transfection via herpes simplex virus blocks AIF translocation after focal ischemia in rat. Zhao, H, Yenari, M. A., Cheng, D, Sapolsky, R.M., Steinberg, G.K. Journal of Cerebral Blood Flow & Metabolism. 2004 Jun; 24(6):681-92.

Catalase overexpression protects striatal neurons from transient focal cerebral ischemia. Gu, W, Zhao, H, Yenari, M. A., Sapolsky, R.M., Steinberg, G.K Neuroreport, 2004 Mar 1; 15(3):413-6.

Mild post-ischemic hypothermia prolongs the time window for gene therapy by inhibiting cytochrome c release. Zhao, H, Yenari, M.A., Sapolsky, R.M., Steinberg, G.K.
Stroke. 2004 Feb; 35(2):572-7


Cellular and Molecular Events underlying Ischemia-Induced Neuronal Apoptosis. Zheng, Z, Zhao, H, Steinberg, G.K and Yenari, M.A. Drug News & Perspectives, 2003 Oct, 16 (9): 497-503

Prospects for the treatment of stroke using gene therapy. Zhao, H, Yenari, M. A., Sapolsky, R. M., Steinberg, G.K. Expert Review of Neurotherapeutics 2003 May, 3(3)

Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity. Zhao, H, Yenari, M. A., Sapolsky, R. M., Steinberg, G.K. Journal of Neurochemistry. 2003 May; 85(4):1026-36.

Gene therapy and hypothermia for stroke treatment. Yenari, M.A., Zhao, H, Giffard, R.G., Sobel, R.A., Sapolsky, R.M., Steinberg, G.K. Annals of the New York Academy of Science 2003 May; 993:54-68; discussion 79-81.


Gene transfer of HSP72 protects cornuammonis 1 region of the hippocampus neurons from global ischemia: influence of Bcl-2. Kelly, S, Zhang, Z.J., Zhao, H, Xu, L, Giffard, R.G., Sapolsky, R.M., Yenari M.A., Steinberg G.K. Annals of Neurology 2002 Aug; 52(2):160-7

Extracellular glutamate changes in rat striatum during ischemia determined by a novel dialysis electrode and conventional microdialysis. Sugahara, M, Asai, S, Zhao, H, Nagata, T, Kunimatsu, T, Ishii, Y, Kohno, T, Ishikawa, K. Neurochemistry International 2001 Jul; 39(1):65-73.

Two distinct components of initial glutamate release synchronized with anoxic depolarization in rat global brain ischemia. Asai, S, Kunimatsu, T, Zhao, H, Nagata, T, Takahashi, Y, Ishii, Y, Kohno, T, Ishikawa, K. Neuroreport. 2000 Sep 11; 11(13):2947-52.

Quantitative evaluation of extracellular glutamate concentration in postischemic glutamate re-uptake, dependent on brain temperature, in the rat following severe global brain ischemia. Asai, S, Zhao, H, Kohno, T, Takahashi, Y, Nagata, T, Ishikawa, K. Brain Research 2000 May 2; 864(1):60-8.

Phosphorylation of c-Jun and its localization with heme oxygenase-1 and cyclooxygenase-2 in CA1 pyramidal neurons after transient forebrain ischemia.
Matsuoka, Y, Okazaki, M, Zhao, H, Asai, S, Ishikawa, K, Kitamura, Y. Journal of Cerebral Blood Flow & Metabolism 1999 Nov; 19(11):1247-55.

Nicergoline enhances glutamate re-uptake and protects against brain damage in rat global brain ischemia. Asai, S, Zhao, H, Yamashita, A, Jike, T, Kunimatsu, T, Nagata, T, Kohno, T, Ishikawa, K. European Journal of Pharmacology 1999 Nov 3:383(3): 267-74.

Transient in vivo membrane depolarization and glutamate release before anoxic depolarization in rat striatum. Kunimatsu, T, Asai, S, Kanematsu, K, Zhao, H, Kohno, T, Misaki, T, Ishikawa, K. Brain Research 1999 Jun 12; 831(1-2):273-82.

Neither L-NAME nor L-arginine changes extracellular glutamate elevation and anoxic depolarization during global ischemia and reperfusion in rat. Zhao, H*, Asai, S, Ishikawa, K. Neuroreport. 1999 Feb 5; 10(2):313-8.

Minimal effect of brain temperature changes on glutamate release in rat following severe global brain ischemia: a dialysis electrode study. Asai, S, Zhao, H, Takahashi, Y, Nagata, T, Kohno, T, Ishikawa, K, Neuroreport. 1998 Dec 1; 9(17):3863-8.

Effects of brain temperature on CBF thresholds for extracellular glutamate release and reuptake in the striatum in a rat model of graded global ischemia. Zhao, H, Asai, S, Kohno, T, Ishikawa, K, Neuroreport. 1998 Oct 5; 9(14):3183-8.

Real-time monitoring of the effects of normothermia and hypothermia on extracellular glutamate re-uptake in the rat following global brain ischemia. Zhao, H, Asai, S, Kanematsu, K, Kunimatsu, T, Kohno, T, Ishikawa, K, Neuroreport. 1997 Jul 7; 8(9-10):2389-93.

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