Stroke Neuroprotection: Targeting Mitochondria

Overview

Journal Brain Sci

Publisher MDPI

Date 2014 Jun 26

PMID 24961414

Citations 20

Authors

Lora Talley Watts

Reginald Lloyd

Richard Justin Garling

Timothy Duong

Affiliations

Soon will be listed here.

Abstract

Stroke is the fourth leading cause of death and the leading cause of long-term disability in the United States. Blood flow deficit results in an expanding infarct core with a time-sensitive peri-infarct penumbra that is considered salvageable and is the primary target for treatment strategies. The only current FDA-approved drug for treating ischemic stroke is recombinant tissue plasminogen activator (rt-PA). However, this treatment is limited to within 4.5 h of stroke onset in a small subset of patients. The goal of this review is to focus on mitochondrial-dependent therapeutic agents that could provide neuroprotection following stroke. Dysfunctional mitochondria are linked to neurodegeneration in many disease processes including stroke. The mechanisms reviewed include: (1) increasing ATP production by purinergic receptor stimulation, (2) decreasing the production of ROS by superoxide dismutase, or (3) increasing antioxidant defenses by methylene blue, and their benefits in providing neuroprotection following a stroke.

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References

Zheng W, Watts L, Holstein D, Wewer J, Lechleiter J . P2Y1R-initiated, IP3R-dependent stimulation of astrocyte mitochondrial metabolism reduces and partially reverses ischemic neuronal damage in mouse. J Cereb Blood Flow Metab. 2013; 33(4):600-11. PMC: 3618399. DOI: 10.1038/jcbfm.2012.214. View

Tanaka Y, Ishii H, Hiraoka M, Miyasaka N, Kuroiwa T, Hajjar K . Efficacy of recombinant annexin 2 for fibrinolytic therapy in a rat embolic stroke model: a magnetic resonance imaging study. Brain Res. 2007; 1165:135-43. PMC: 2900767. DOI: 10.1016/j.brainres.2007.06.039. View

Jarvis G, Humphries R, Robertson M, Leff P . ADP can induce aggregation of human platelets via both P2Y(1) and P(2T) receptors. Br J Pharmacol. 2000; 129(2):275-82. PMC: 1571831. DOI: 10.1038/sj.bjp.0703046. View

Wu O, Sumii T, Asahi M, Sasamata M, Ostergaard L, Rosen B . Infarct prediction and treatment assessment with MRI-based algorithms in experimental stroke models. J Cereb Blood Flow Metab. 2006; 27(1):196-204. DOI: 10.1038/sj.jcbfm.9600328. View

Shen Q, Fisher M, Sotak C, Duong T . Effects of reperfusion on ADC and CBF pixel-by-pixel dynamics in stroke: characterizing tissue fates using quantitative diffusion and perfusion imaging. J Cereb Blood Flow Metab. 2004; 24(3):280-90. PMC: 2962955. DOI: 10.1097/01.WCB.0000110048.43905.E5. View

Sak K, Webb T . A retrospective of recombinant P2Y receptor subtypes and their pharmacology. Arch Biochem Biophys. 2001; 397(1):131-6. DOI: 10.1006/abbi.2001.2616. View

Cavaliere F, Florenzano F, Amadio S, Fusco F, Viscomi M, DAmbrosi N . Up-regulation of P2X2, P2X4 receptor and ischemic cell death: prevention by P2 antagonists. Neuroscience. 2003; 120(1):85-98. DOI: 10.1016/s0306-4522(03)00228-8. View

Garcia J, Liu K, Ho K . Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke. 1995; 26(4):636-42; discussion 643. DOI: 10.1161/01.str.26.4.636. View

Lu M, Zhang R, Zhang Z, Yang J, Chopp M . Linkage of cell cycle kinetics between embryonic and adult stroke models: an analytical approach. J Neurosci Methods. 2006; 161(2):323-30. DOI: 10.1016/j.jneumeth.2006.10.021. View

10.

Antier D, Carswell H, Brosnan M, Hamilton C, Macrae I, Groves S . Increased levels of superoxide in brains from old female rats. Free Radic Res. 2004; 38(2):177-83. DOI: 10.1080/10715760310001643294. View

11.

Lin A, Poteet E, Du F, Gourav R, Liu R, Wen Y . Methylene blue as a cerebral metabolic and hemodynamic enhancer. PLoS One. 2012; 7(10):e46585. PMC: 3467226. DOI: 10.1371/journal.pone.0046585. View

12.

Reith J, Jorgensen H, Pedersen P, Nakayama H, Raaschou H, Jeppesen L . Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet. 1996; 347(8999):422-5. DOI: 10.1016/s0140-6736(96)90008-2. View

13.

Jin J, Daniel J, Kunapuli S . Molecular basis for ADP-induced platelet activation. II. The P2Y1 receptor mediates ADP-induced intracellular calcium mobilization and shape change in platelets. J Biol Chem. 1998; 273(4):2030-4. DOI: 10.1074/jbc.273.4.2030. View

14.

Friedel F, Lieb D, Ivanovic-Burmazovic I . Comparative studies on manganese-based SOD mimetics, including the phosphate effect, by using global spectral analysis. J Inorg Biochem. 2012; 109:26-32. DOI: 10.1016/j.jinorgbio.2011.12.008. View

15.

James G, Butt A . P2Y and P2X purinoceptor mediated Ca2+ signalling in glial cell pathology in the central nervous system. Eur J Pharmacol. 2002; 447(2-3):247-60. DOI: 10.1016/s0014-2999(02)01756-9. View

16.

Peter C, Hongwan D, Kupfer A, Lauterburg B . Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol. 2000; 56(3):247-50. DOI: 10.1007/s002280000124. View

17.

Wahlgren N, Ahmed N, Davalos A, Ford G, Grond M, Hacke W . Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet. 2007; 369(9558):275-82. DOI: 10.1016/S0140-6736(07)60149-4. View

18.

Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick J . Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004; 363(9411):768-74. DOI: 10.1016/S0140-6736(04)15692-4. View

19.

Miclescu A, Basu S, Wiklund L . Methylene blue added to a hypertonic-hyperoncotic solution increases short-term survival in experimental cardiac arrest. Crit Care Med. 2006; 34(11):2806-13. DOI: 10.1097/01.CCM.0000242517.23324.27. View

20.

Wen Y, Li W, Poteet E, Xie L, Tan C, Yan L . Alternative mitochondrial electron transfer as a novel strategy for neuroprotection. J Biol Chem. 2011; 286(18):16504-15. PMC: 3091255. DOI: 10.1074/jbc.M110.208447. View