Published Online
on September 23, 2004

A more recent version of this article appeared on November 1, 2004

This Article Full Text (PDF) All Versions of this Article: 35/11_suppl_1/2748    most recent 01.STR.0000143325.25610.acv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chan, P. H. Search for Related Content PubMed PubMed Citation Articles by Chan, P. H. Pubmed/NCBI databases Medline Plus Health Information Stroke Related Collections Apoptosis Genetically altered mice Ischemic biology - basic studies

Submitted on June 3, 2004
Revised on July 30, 2004
Accepted on August 5, 2004

Future Targets and Cascades for Neuroprotective Strategies

Pak H. Chan PhD^*

From the Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, Calif.

^* To whom correspondence should be addressed. E-mail: phchan{at}stanford.edu.

Abstract--Cumulative evidence suggests that apoptosis plays a pivotal role in neuronal death after cerebral ischemia in various experimental animal models. The time-dependent molecular and biochemical sequelae that lead to apoptotic cell death after the interruption of cerebral blood flow have been established. Many neuroprotective agents that target cell death pathways have been failures, and alternative strategies need to be considered. One such strategy is to target the neuronal survival signaling pathway, which involves the phosphatidylinositol 3-kinase (PI3-K)/Akt (protein kinase B) pathway. It has been demonstrated that PI3-K/Akt and downstream phosphorylated Bad and proline-rich Akt substrate survival signaling cascades are upregulated in surviving neurons in the ischemic brain that overexpresses copper-zinc superoxide dismutase activity. These studies provide an impetus for novel therapeutic targets in neuroprotective strategies in stroke.

Key words: apoptosis • cell survival signaling • mitochondria • neuroprotection • stroke

This article has been cited by other articles:

				J. A. Zivin, G. W. Albers, N. Bornstein, T. Chippendale, B. Dahlof, T. Devlin, M. Fisher, W. Hacke, W. Holt, S. Ilic, et al. Effectiveness and Safety of Transcranial Laser Therapy for Acute Ischemic Stroke Stroke, April 1, 2009; 40(4): 1359 - 1364. [Abstract] [Full Text] [PDF]

				S. Guo, W. J. Kim, J. Lok, S.-R. Lee, E. Besancon, B.-H. Luo, M. F. Stins, X. Wang, S. Dedhar, and E. H. Lo Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons PNAS, May 27, 2008; 105(21): 7582 - 7587. [Abstract] [Full Text] [PDF]

				X. N. Tang, Q. Wang, M. A. Koike, D. Cheng, M. L. Goris, F. G. Blankenberg, and M. A. Yenari Monitoring the Protective Effects of Minocycline Treatment with Radiolabeled Annexin V in an Experimental Model of Focal Cerebral Ischemia J. Nucl. Med., November 1, 2007; 48(11): 1822 - 1828. [Abstract] [Full Text] [PDF]

				J. Yu, S. A. Novgorodov, D. Chudakova, H. Zhu, A. Bielawska, J. Bielawski, L. M. Obeid, M. S. Kindy, and T. I. Gudz JNK3 Signaling Pathway Activates Ceramide Synthase Leading to Mitochondrial Dysfunction J. Biol. Chem., August 31, 2007; 282(35): 25940 - 25949. [Abstract] [Full Text] [PDF]

				S. V. Madhunapantula, A. Sharma, and G. P. Robertson PRAS40 Deregulates Apoptosis in Malignant Melanoma Cancer Res., April 15, 2007; 67(8): 3626 - 3636. [Abstract] [Full Text] [PDF]

				T. Tsubokawa, V. Jadhav, I. Solaroglu, Y. Shiokawa, Y. Konishi, and J. H. Zhang Lecithinized Superoxide Dismutase Improves Outcomes and Attenuates Focal Cerebral Ischemic Injury via Antiapoptotic Mechanisms in Rats Stroke, March 1, 2007; 38(3): 1057 - 1062. [Abstract] [Full Text] [PDF]

				P. E. Bickler and C. S. Fahlman The inhaled anesthetic, isoflurane, enhances Ca2+-dependent survival signaling in cortical neurons and modulates MAP kinases, apoptosis proteins and transcription factors during hypoxia. Anesth. Analg., August 1, 2006; 103(2): 419 - 29, table of contents. [Abstract] [Full Text] [PDF]

				E. H. Lo, M. A. Moskowitz, and T. P. Jacobs Exciting, Radical, Suicidal: How Brain Cells Die After Stroke Stroke, February 1, 2005; 36(2): 189 - 192. [Full Text] [PDF]