Skip to main content
Top
Published in: Translational Stroke Research 4/2014

Open Access 01-08-2014 | Original Article

Remote Ischemic Perconditioning is Effective After Embolic Stroke in Ovariectomized Female Mice

Authors: Md Nasrul Hoda, Kanchan Bhatia, Sherif S. Hafez, Maribeth H. Johnson, Shahneela Siddiqui, Adviye Ergul, Syed Kashif Zaidi, Susan C. Fagan, David C. Hess

Published in: Translational Stroke Research | Issue 4/2014

Login to get access

Abstract

Remote ischemic conditioning is neuroprotective in young male rodents after experimental stroke. However, it has never been tested in females whom remain at higher risk of stroke injury after menopause. We tested remote ischemic perconditioning therapy (RIPerC) at 2 h after embolic stroke in ovariectomized (OVX) female mice with and without intravenous tissue plasminogen activator (IV-tPA) treatment. We assessed cerebral blood flow (CBF), neurobehavioral outcomes, infarction, hemorrhage, edema, and survival. RIPerC therapy with and without IV-tPA improved the CBF and neurobehavioral outcomes and reduced the infarction, hemorrhage, and edema significantly. Late IV-tPA alone at 4 h post-stroke neither improved the neurobehavior nor reduced the infarction but aggravated hemorrhage and mortality in OVX mice. RIPerC therapy prevented the increased mortality during late IV-tPA. Our study demonstrates for the first time that RIPerC therapy is effective in OVX females.
Literature
1.
go back to reference Hess DC, Hoda MN, Bhatia K. Remote limb preconditioning and postconditioning: will it translate into a promising treatment for acute stroke? Stroke; J Cereb Circ. 2013;44:1191–7.CrossRef Hess DC, Hoda MN, Bhatia K. Remote limb preconditioning and postconditioning: will it translate into a promising treatment for acute stroke? Stroke; J Cereb Circ. 2013;44:1191–7.CrossRef
2.
go back to reference Hossmann KA. Pathophysiological basis of translational stroke research. Folia neuropathologica/Association of Polish Neuropathologists and Medical Research Centre. Pol Acad Sci. 2009;47:213–27. Hossmann KA. Pathophysiological basis of translational stroke research. Folia neuropathologica/Association of Polish Neuropathologists and Medical Research Centre. Pol Acad Sci. 2009;47:213–27.
3.
go back to reference Hossmann KA. The two pathophysiologies of focal brain ischemia: implications for translational stroke research. Journal of cerebral blood flow and metabolism. Off J Int Soc Cereb Blood Flow Metab. 2012;32:1310–6.CrossRef Hossmann KA. The two pathophysiologies of focal brain ischemia: implications for translational stroke research. Journal of cerebral blood flow and metabolism. Off J Int Soc Cereb Blood Flow Metab. 2012;32:1310–6.CrossRef
4.
go back to reference Siegel C, Turtzo C, McCullough LD. Sex differences in cerebral ischemia: possible molecular mechanisms. J Neurosci Res. 2010;88:2765–74.PubMedCrossRef Siegel C, Turtzo C, McCullough LD. Sex differences in cerebral ischemia: possible molecular mechanisms. J Neurosci Res. 2010;88:2765–74.PubMedCrossRef
6.
go back to reference McCullough LD, Zeng Z, Blizzard KK, Debchoudhury I, Hurn PD. Ischemic nitric oxide and poly (ADP-ribose) polymerase-1 in cerebral ischemia: male toxicity, female protection. Journal of cerebral blood flow and metabolism. Off J Int Soc Cereb Blood Flow Metab. 2005;25:502–12.CrossRef McCullough LD, Zeng Z, Blizzard KK, Debchoudhury I, Hurn PD. Ischemic nitric oxide and poly (ADP-ribose) polymerase-1 in cerebral ischemia: male toxicity, female protection. Journal of cerebral blood flow and metabolism. Off J Int Soc Cereb Blood Flow Metab. 2005;25:502–12.CrossRef
7.
go back to reference Albers GW, Goldstein LB, Hess DC, Wechsler LR, Furie KL, Gorelick PB, et al. Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies. Stroke; J Cereb Circ. 2011;42:2645–50.CrossRef Albers GW, Goldstein LB, Hess DC, Wechsler LR, Furie KL, Gorelick PB, et al. Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies. Stroke; J Cereb Circ. 2011;42:2645–50.CrossRef
8.
go back to reference Meng W, Wang X, Asahi M, Kano T, Asahi K, Ackerman RH, et al. Effects of tissue type plasminogen activator in embolic versus mechanical models of focal cerebral ischemia in rats. Journal of cerebral blood flow and metabolism. Off J Int Soc Cereb Blood Flow Metab. 1999;19:1316–21.CrossRef Meng W, Wang X, Asahi M, Kano T, Asahi K, Ackerman RH, et al. Effects of tissue type plasminogen activator in embolic versus mechanical models of focal cerebral ischemia in rats. Journal of cerebral blood flow and metabolism. Off J Int Soc Cereb Blood Flow Metab. 1999;19:1316–21.CrossRef
9.
go back to reference Hoda MN, Siddiqui S, Herberg S, Periyasamy-Thandavan S, Bhatia K, Hafez SS, et al. Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke. Stroke; J Cereb Circ. 2012;43:2794–9.CrossRef Hoda MN, Siddiqui S, Herberg S, Periyasamy-Thandavan S, Bhatia K, Hafez SS, et al. Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke. Stroke; J Cereb Circ. 2012;43:2794–9.CrossRef
10.
go back to reference Hoda MN, Li W, Ahmad A, Ogbi S, Zemskova MA, Johnson MH, et al. Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke. Exp Transl Stroke Med. 2011;3:16.PubMedCentralPubMedCrossRef Hoda MN, Li W, Ahmad A, Ogbi S, Zemskova MA, Johnson MH, et al. Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke. Exp Transl Stroke Med. 2011;3:16.PubMedCentralPubMedCrossRef
11.
go back to reference Li W, Prakash R, Kelly-Cobbs AI, Ogbi S, Kozak A, El-Remessy AB, et al. Adaptive cerebral neovascularization in a model of type 2 diabetes: relevance to focal cerebral ischemia. Diabetes. 2010;59:228–35.PubMedCentralPubMedCrossRef Li W, Prakash R, Kelly-Cobbs AI, Ogbi S, Kozak A, El-Remessy AB, et al. Adaptive cerebral neovascularization in a model of type 2 diabetes: relevance to focal cerebral ischemia. Diabetes. 2010;59:228–35.PubMedCentralPubMedCrossRef
12.
go back to reference Yuan HJ, Zhu XH, Luo Q, Wu YN, Kang Y, Jiao JJ, et al. Noninvasive delayed limb ischemic preconditioning in rats increases antioxidant activities in cerebral tissue during severe ischemia-reperfusion injury. J Surg Res. 2012;174:176–83.PubMedCrossRef Yuan HJ, Zhu XH, Luo Q, Wu YN, Kang Y, Jiao JJ, et al. Noninvasive delayed limb ischemic preconditioning in rats increases antioxidant activities in cerebral tissue during severe ischemia-reperfusion injury. J Surg Res. 2012;174:176–83.PubMedCrossRef
13.
go back to reference Dm R, Ve H, Ge T, Mo J, Sd K. Remote ischemic preconditioning reduces thrombus formation in the rat. JTH: Journal of thrombosis and haemostasis; 2012. Dm R, Ve H, Ge T, Mo J, Sd K. Remote ischemic preconditioning reduces thrombus formation in the rat. JTH: Journal of thrombosis and haemostasis; 2012.
14.
go back to reference Zhao BQ, Chauhan AK, Canault M, Patten IS, Yang JJ, Dockal M, et al. von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke. Blood. 2009;114:3329–34.PubMedCentralPubMedCrossRef Zhao BQ, Chauhan AK, Canault M, Patten IS, Yang JJ, Dockal M, et al. von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke. Blood. 2009;114:3329–34.PubMedCentralPubMedCrossRef
15.
go back to reference Zhao BQ, Wang S, Kim HY, Storrie H, Rosen BR, Mooney DJ, et al. Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat Med. 2006;12:441–5.PubMedCrossRef Zhao BQ, Wang S, Kim HY, Storrie H, Rosen BR, Mooney DJ, et al. Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat Med. 2006;12:441–5.PubMedCrossRef
16.
go back to reference Choudhri TF, Hoh BL, Solomon RA, Connolly Jr ES, Pinsky DJ. Use of a spectrophotometric hemoglobin assay to objectively quantify intracerebral hemorrhage in mice. Stroke; J Cereb Circ. 1997;28:2296–302.CrossRef Choudhri TF, Hoh BL, Solomon RA, Connolly Jr ES, Pinsky DJ. Use of a spectrophotometric hemoglobin assay to objectively quantify intracerebral hemorrhage in mice. Stroke; J Cereb Circ. 1997;28:2296–302.CrossRef
17.
go back to reference Hoda MN, Singh I, Singh AK, Khan M. Reduction of lipoxidative load by secretory phospholipase A2 inhibition protects against neurovascular injury following experimental stroke in rat. J Neuroinflammation. 2009;6:21.PubMedCentralPubMedCrossRef Hoda MN, Singh I, Singh AK, Khan M. Reduction of lipoxidative load by secretory phospholipase A2 inhibition protects against neurovascular injury following experimental stroke in rat. J Neuroinflammation. 2009;6:21.PubMedCentralPubMedCrossRef
18.
go back to reference Liu R, Liu Q, He S, Simpkins JW, Yang SH. Combination therapy of 17beta-estradiol and recombinant tissue plasminogen activator for experimental ischemic stroke. J Pharmacol Exp Ther. 2010;332:1006–12.PubMedCentralPubMedCrossRef Liu R, Liu Q, He S, Simpkins JW, Yang SH. Combination therapy of 17beta-estradiol and recombinant tissue plasminogen activator for experimental ischemic stroke. J Pharmacol Exp Ther. 2010;332:1006–12.PubMedCentralPubMedCrossRef
19.
go back to reference Santizo RA, Xu HL, Galea E, Muyskens S, Baughman VL, Pelligrino DA. Combined endothelial nitric oxide synthase upregulation and caveolin-1 downregulation decrease leukocyte adhesion in pial venules of ovariectomized female rats. Stroke; J Cereb Circ. 2002;33:613–6.CrossRef Santizo RA, Xu HL, Galea E, Muyskens S, Baughman VL, Pelligrino DA. Combined endothelial nitric oxide synthase upregulation and caveolin-1 downregulation decrease leukocyte adhesion in pial venules of ovariectomized female rats. Stroke; J Cereb Circ. 2002;33:613–6.CrossRef
20.
go back to reference Cipolla MJ, Godfrey JA, Wiegman MJ. The effect of ovariectomy and estrogen on penetrating brain arterioles and blood-brain barrier permeability. Microcirculation. 2009;16:685–93.PubMedCentralPubMedCrossRef Cipolla MJ, Godfrey JA, Wiegman MJ. The effect of ovariectomy and estrogen on penetrating brain arterioles and blood-brain barrier permeability. Microcirculation. 2009;16:685–93.PubMedCentralPubMedCrossRef
21.
go back to reference Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med. 2009;15:1031–7.PubMedCrossRef Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med. 2009;15:1031–7.PubMedCrossRef
22.
go back to reference De Silva DA, Fink JN, Christensen S, Ebinger M, Bladin C, Levi CR, et al. Assessing reperfusion and recanalization as markers of clinical outcomes after intravenous thrombolysis in the echoplanar imaging thrombolytic evaluation trial (EPITHET). Stroke; J Cereb Circ. 2009;40:2872–4.CrossRef De Silva DA, Fink JN, Christensen S, Ebinger M, Bladin C, Levi CR, et al. Assessing reperfusion and recanalization as markers of clinical outcomes after intravenous thrombolysis in the echoplanar imaging thrombolytic evaluation trial (EPITHET). Stroke; J Cereb Circ. 2009;40:2872–4.CrossRef
23.
go back to reference Soares BP, Tong E, Hom J, Cheng SC, Bredno J, Boussel L, et al. Reperfusion is a more accurate predictor of follow-up infarct volume than recanalization: a proof of concept using CT in acute ischemic stroke patients. Stroke; J Cereb Circ. 2010;41:e34–40.CrossRef Soares BP, Tong E, Hom J, Cheng SC, Bredno J, Boussel L, et al. Reperfusion is a more accurate predictor of follow-up infarct volume than recanalization: a proof of concept using CT in acute ischemic stroke patients. Stroke; J Cereb Circ. 2010;41:e34–40.CrossRef
24.
go back to reference Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, et al. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012;79:1853–61.PubMedCrossRef Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, et al. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012;79:1853–61.PubMedCrossRef
25.
go back to reference Liu F, Li Z, Li J, Siegel C, Yuan R, McCullough LD. Sex differences in caspase activation after stroke. Stroke; J Cereb Circ. 2009;40:1842–8.CrossRef Liu F, Li Z, Li J, Siegel C, Yuan R, McCullough LD. Sex differences in caspase activation after stroke. Stroke; J Cereb Circ. 2009;40:1842–8.CrossRef
26.
go back to reference McElroy JF, Wade GN. Short- and long-term effects of ovariectomy on food intake, body weight, carcass composition, and brown adipose tissue in rats. Physiol Behav. 1987;39:361–5.PubMedCrossRef McElroy JF, Wade GN. Short- and long-term effects of ovariectomy on food intake, body weight, carcass composition, and brown adipose tissue in rats. Physiol Behav. 1987;39:361–5.PubMedCrossRef
27.
go back to reference Rocca WA, Grossardt BR, Miller VM, Shuster LT, Brown Jr RD. Premature menopause or early menopause and risk of ischemic stroke. Menopause. 2012;19:272–7.PubMedCentralPubMedCrossRef Rocca WA, Grossardt BR, Miller VM, Shuster LT, Brown Jr RD. Premature menopause or early menopause and risk of ischemic stroke. Menopause. 2012;19:272–7.PubMedCentralPubMedCrossRef
28.
go back to reference McCarthy AM, Menke A, Ouyang P, Visvanathan K. Bilateral oophorectomy, body mass index, and mortality in U.S. women aged 40 years and older. Cancer Prev Res (Phila). 2012;5:847–54.CrossRef McCarthy AM, Menke A, Ouyang P, Visvanathan K. Bilateral oophorectomy, body mass index, and mortality in U.S. women aged 40 years and older. Cancer Prev Res (Phila). 2012;5:847–54.CrossRef
Metadata
Title
Remote Ischemic Perconditioning is Effective After Embolic Stroke in Ovariectomized Female Mice
Authors
Md Nasrul Hoda
Kanchan Bhatia
Sherif S. Hafez
Maribeth H. Johnson
Shahneela Siddiqui
Adviye Ergul
Syed Kashif Zaidi
Susan C. Fagan
David C. Hess
Publication date
01-08-2014
Publisher
Springer US
Published in
Translational Stroke Research / Issue 4/2014
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-013-0318-6

Other articles of this Issue 4/2014

Translational Stroke Research 4/2014 Go to the issue