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Translational Stroke Research
Published in: Translational Stroke Research 3/2017

Open Access 01-06-2017 | Original Article

Evolutional Characterization of Photochemically Induced Stroke in Rats: a Multimodality Imaging and Molecular Biological Study

Authors: Nai-Wei Liu, Chien-Chih Ke, Yonghua Zhao, Yi-An Chen, Kim-Chuan Chan, David Tat-Wei Tan, Jhih-Shian Lee, You-Yin Chen, Tun-Wei Hsu, Ya-Ju Hsieh, Chi-Wei Chang, Bang-Hung Yang, Wen-Sheng Huang, Ren-Shyan Liu

Published in: Translational Stroke Research | Issue 3/2017

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Abstract

Photochemically induced cerebral ischemia is an easy-manipulated, reproducible, relatively noninvasive, and lesion controllable model for translational study of ischemic stroke. In order to longitudinally investigate the characterization of the model, magnetic resonance imaging, 18F-2-deoxy-glucose positron emission tomography, fluorescence, and bioluminescence imaging system were performed in correlation with triphenyl tetrazolium chloride (TTC), hematoxylin-eosin staining, and immunohistochemistry examinations of glial fibrillary acidic protein, CD68, NeuN, von willebrand factor, and α-smooth muscle actin in the infarct zone. The results suggested that the number of inflammatory cells, astrocytes, and neovascularization significantly elevated in peri-infarct region from day 7 and a belt of macrophage/microglial and astrocytes was formed surrounding infarct lesion at day 14. Both vasogenic and cytotoxic edema, as well as blood brain-barrier leakage, occurred since day 1 after stroke induction and gradually attenuated with time. Numerous cells other than neuronal cells infiltrated into infarct lesion, which resulted in no visible TTC negative regional existence at day 14. Furthermore, recovery of cerebral blood flow and glucose utilization in peri-infarct zone were noted and more remarkably than that in infarct core following the stroke progression. In conclusion, these characterizations may be highly beneficial to the development of therapeutic strategies for ischemic stroke.
Literature
1.
2.
Barber PA, Demchuk AM, Hirt L, Buchan AM. Biochemistry of ischemic stroke. Adv Neurol. 2003;92:151–64.PubMed
3.
4.
Bacigaluppi M, Comi G, Hermann DM. Animal models of ischemic stroke. Part two: modeling cerebral ischemia. Open Neurol J. 2010;4:34–8.PubMedPubMedCentral
5.
Watson BD, Dietrich WD. Animal models in stroke. Stroke. 1990;21:1376–7.PubMed
6.
Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol. 1985;17:497–504.CrossRefPubMed
7.
Dietrich WD, Watson BD, Busto R, Ginsberg MD, Bethea JR. Photochemically induced cerebral infarction. I. Early microvascular alterations. Acta Neuropathol. 1987;72:315–25.CrossRefPubMed
8.
Dietrich WD, Busto R, Watson BD, Scheinberg P, Ginsberg MD. Photochemically induced cerebral infarction. II. Edema and blood-brain barrier disruption. Acta Neuropathol. 1987;72:326–34.CrossRefPubMed
9.
Fluri F, Schuhmann MK, Kleinschnitz C. Animal models of ischemic stroke and their application in clinical research. Drug Des Devel Ther. 2015;9:3445–54.PubMedPubMedCentral
10.
Popa-Wagner A, Buga AM, Doeppner TR, Hermann DM. Stem cell therapies in preclinical models of stroke associated with aging. Front Cell Neurosci. 2014;8:347.CrossRefPubMedPubMedCentral
11.
Wang T, Cui W, Xie Y, Zhang W, Ding S. Controlling the volume of the focal cerebral ischemic lesion through photothrombosis. Am J Biomed Sci. 2010;2:33–42.CrossRef
12.
Schroeter M, Jander S, Stoll G. Non-invasive induction of focal cerebral ischemia in mice by photothrombosis of cortical microvessels: characterization of inflammatory responses. J Neurosci Methods. 2002;117:43–9.CrossRefPubMed
13.
Eichenbaum JW, Pevsner PH, Pivawer G, Kleinman GM, Chiriboga L, Stern A, Rosenbach A, Iannuzzi K, Miller DC. A murine photochemical stroke model with histologic correlates of apoptotic and nonapoptotic mechanisms. J Pharmacol Toxicol Methods. 2002;47:67–71.CrossRefPubMed
14.
Braeuninger S, Kleinschnitz C. Rodent models of focal cerebral ischemia: procedural pitfalls and translational problems. Exp Transl Stroke Med. 2009;1:8.CrossRefPubMedPubMedCentral
15.
Murphy TH, Li P, Betts K, Liu R. Two-photon imaging of stroke onset in vivo reveals that NMDA-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines. J Neurosci. 2008;28:1756–72.CrossRefPubMed
16.
17.
Kwiatkowski TG, Libman RB, Frankel M, Tilley BC, Morgenstern LB, Lu M, Broderick JP, Lewandowski CA, Marler JR, Levine SR, Brott T. Effects of tissue plasminogen activator for acute ischemic stroke at one year. National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator stroke study group. N Engl J Med. 1999;340:1781–7.CrossRefPubMed
18.
Jiang M, Lv L, Ji H, Yang X, Zhu W, Cai L, Gu X, Chai C, Huang S, Sun J, Dong Q. Induction of pluripotent stem cells transplantation therapy for ischemic stroke. Mol Cell Biochem. 2011;354:67–75.CrossRefPubMed
19.
Cai W, Guzman R, Hsu AR, Wang H, Chen K, Sun G, Gera A, Choi R, Bliss T, He L, Li ZB, Maag AL, Hori N, Zhao H, Moseley M, Steinberg GK, Chen X. Positron emission tomography imaging of poststroke angiogenesis. Stroke. 2009;40:270–7.CrossRefPubMed
20.
Canazza A, Minati L, Boffano C, Parati E, Binks S. Experimental models of brain ischemia: a review of techniques, magnetic resonance imaging, and investigational cell-based therapies. Front Neurol. 2014;5:19.CrossRefPubMedPubMedCentral
21.
Dijkhuizen RM, Nicolay K. Magnetic resonance imaging in experimental models of brain disorders. J Cereb Blood Flow Metab. 2003;23:1383–402.CrossRefPubMed
22.
Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 2003;17:545–80.CrossRefPubMed
23.
Chen F, Suzuki Y, Nagai N, Jin L, Yu J, Wang H, Marchal G, Ni Y. Rodent stroke induced by photochemical occlusion of proximal middle cerebral artery: evolution monitored with MR imaging and histopathology. Eur J Radiol. 2007;63:68–75.CrossRefPubMed
24.
Dietrich WD, Ginsberg MD, Busto R, Watson BD. Photochemically induced cortical infarction in the rat. 2. Acute and subacute alterations in local glucose utilization. J Cereb Blood Flow Metab. 1986;6:195–202.CrossRefPubMed
25.
Ginsberg MD, Reivich M, Giandomenico A, Greenberg JH. Local glucose utilization in acute focal cerebral ischemia: local dysmetabolism and diaschisis. Neurology. 1977;27:1042–8.CrossRefPubMed
26.
Walberer M, Backes H, Rueger MA, Neumaier B, Endepols H, Hoehn M, Fink GR, Schroeter M, Graf R. Potential of early [(18)F]-2-fluoro-2-deoxy-D-glucose positron emission tomography for identifying hypoperfusion and predicting fate of tissue in a rat embolic stroke model. Stroke. 2012;43:193–8.CrossRefPubMed
27.
Sobrado M, Delgado M, Fernández-Valle E, García-García L, Torres M, Sánchez-Prieto J, Vivancos J, Manzanares R, Moro MA, Pozo MA, Lizasoain I. Longitudinal studies of ischemic penumbra by using 18F-FDG PET and MRI techniques in permanent and transient focal cerebral ischemia in rats. NeuroImage. 2011;57:45–54.CrossRefPubMed
28.
Dunn AK, Bolay H, Moskowitz MA, Boas DA. Dynamic imaging of cerebral blood flow using laser speckle. J Cereb Blood Flow Metab. 2001;21:195–201.CrossRefPubMed
29.
Kim SG. Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique: application to functional mapping. Magn Reson Med. 1995;34:293–301.CrossRefPubMed
30.
Vandeputte C, Thomas D, Dresselaers T, Crabbe A, Verfaillie C, Baekelandt V, Van Laere K, Himmelreich U. Characterization of the inflammatory response in a photothrombotic stroke model by MRI: implications for stem cell transplantation. Mol Imaging Biol. 2011;13:663–71.CrossRefPubMed
31.
Ayata C, Dunn AK, Gursoy-OZdemir Y, Huang Z, Boas DA, Moskowitz MA. Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex. J Cereb Blood Flow Metab. 2004;24:744–55.CrossRefPubMed
32.
Macrez R, Ali C, Toutirais O, Le Mauff B, Defer G, Dirnagl U, Vivien D. Stroke and the immune system: from pathophysiology to new therapeutic strategies. Lancet Neurol. 2011;10:471–80.CrossRefPubMed
33.
Burda JE, Sofroniew MV. Reactive gliosis and the multicellular response to CNS damage and disease. Neuron. 2014;22(81):229–48.CrossRef
34.
Dheen ST, Kaur C, Ling EA. Microglial activation and its implications in the brain diseases. Curr Med Chem. 2007;14:1189–97.CrossRefPubMed
35.
36.
37.
van Bruggen N, Cullen BM, King MD, Doran M, Williams SR, Gadian DG, Cremer JE. T2- and diffusion-weighted magnetic resonance imaging of a focal ischemic lesion in rat brain. Stroke. 1992;23:576–82.CrossRefPubMed
38.
Schroeter M, Franke C, Stoll G, Hoehn M. Dynamic changes of magnetic resonance imaging abnormalities in relation to inflammation and glial responses after photothrombotic cerebral infarction in the rat brain. Acta Neuropathol. 2001;101:114–22.PubMed
39.
Lee VM, Burdett NG, Carpenter A, Hall LD, Pambakian PS, Patel S, Wood NI, James MF. Evolution of photochemically induced focal cerebral ischemia in the rat. Magnetic resonance imaging and histology. Stroke. 1996;27:2110–8.CrossRefPubMed
40.
41.
Fukumoto D, Hosoya T, Nishiyama S, Harada N, Iwata H, Yamamoto S, Tsukada H. Multiparametric assessment of acute and subacute ischemic neuronal damage: a small animal positron emission tomography study with rat photochemically induced thrombosis model. Synapse. 2011;65:207–14.CrossRefPubMed
42.
Hilger T, Blunk JA, Hoehn M, Mies G, Wester P. Characterization of a novel chronic photothrombotic ring stroke model in rats by magnetic resonance imaging, biochemical imaging, and histology. J Cereb Blood Flow Metab. 2004;24:789–97.CrossRefPubMed
43.
Armstead WM, Ganguly K, Riley J, Zaitsev S, Cines DB, Higazi AA, Muzykantov VR. RBC-coupled tPA prevents whereas tPA aggravates JNK MAPK-mediated impairment of ATP- and Ca-sensitive K Channel-mediated Cerebrovasodilation after cerebral photothrombosis. Transl Stroke Res. 2012;3(1):114–21.CrossRefPubMedPubMedCentral
44.
Kuluz JW, Prado R, He D, Zhao W, Dietrich WD, Watson B. New pediatric model of ischemic stroke in infant piglets by photothrombosis: acute changes in cerebral blood flow, microvasculature, and early histopathology. Stroke. 2007;38(6):1932–7.CrossRefPubMed
45.
Kawano KI, Fujishima K, Ikeda Y, Kondo K, Umemura K. ME3277, a GPIIb/IIIa antagonist reduces cerebral infarction without enhancing intracranial hemorrhage in photothrombotic occlusion of rabbit middle cerebral artery. J Cereb Blood Flow Metab. 2000;20(6):988–97.CrossRefPubMed
46.
Zhao BQ, Suzuki Y, Kondo K, Kawano K, Ikeda Y, Umemura K. Cerebral hemorrhage due to heparin limits its neuroprotective effects: studies in a rabbit model of photothrombotic middle cerebral artery occlusion. Brain Res. 2001;902(1):30–9.CrossRefPubMed
Metadata
Title
Evolutional Characterization of Photochemically Induced Stroke in Rats: a Multimodality Imaging and Molecular Biological Study
Authors
Nai-Wei Liu
Chien-Chih Ke
Yonghua Zhao
Yi-An Chen
Kim-Chuan Chan
David Tat-Wei Tan
Jhih-Shian Lee
You-Yin Chen
Tun-Wei Hsu
Ya-Ju Hsieh
Chi-Wei Chang
Bang-Hung Yang
Wen-Sheng Huang
Ren-Shyan Liu
Publication date
01-06-2017
Publisher
Springer US
Published in
Translational Stroke Research / Issue 3/2017
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-016-0512-4

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