Deneysel İnme Modelleri
Özet
İnme, dünya genelinde mortalite ve uzun dönem yeti yitiminin en önemli nedenlerinden biri olmaya devam etmektedir. Klinik inmenin karmaşık ve heterojen doğası, patofizyolojisinin anlaşılmasını ve yeni tedavi stratejilerinin geliştirilmesini zorlaştırmaktadır. Bu bağlamda deneysel inme modelleri, iskemik ve hemorajik inmenin moleküler, hücresel ve sistemik mekanizmalarını aydınlatmada vazgeçilmez araçlardır. Bu bölümde, deneysel inme modellerinin sınıflandırılması, başlıca model tipleri (endovasküler filament MCAO, tromboembolik, fototrombotik, FeCl₃ ile indüklenen trombotik, endotelin-1 tabanlı vazokonstriktif, elektrokoagülasyon ve global iskemi modelleri), hemorajik inme modelleri (intraserebral ve subaraknoid kanama) ve bu modellerde kullanılan ölçütler ile değerlendirme yöntemleri (görüntüleme, nörolojik-davranışsal testler, moleküler analizler) kapsamlı bir şekilde ele alınmaktadır. Her modelin güçlü yanları, sınırlılıkları, translasyonel değeri ve spesifik araştırma sorularına uygunluğu tartışılmaktadır. Model seçiminin araştırma hedefine, teknik olanaklara ve klinik gerçekliğe uygun yapılmasının önemi vurgulanmaktadır.
Stroke continues to be one of the most important causes of mortality and long-term disability worldwide. The complex and heterogeneous nature of clinical stroke makes it difficult to understand its pathophysiology and develop new treatment strategies. In this context, experimental stroke models are indispensable tools for elucidating the molecular, cellular, and systemic mechanisms of ischemic and hemorrhagic stroke. This chapter comprehensively addresses the classification of experimental stroke models, main model types (endovascular filament MCAO, thromboembolic, photothrombotic, FeCl₃-induced thrombotic, endothelin-1-based vasoconstrictive, electrocoagulation, and global ischemia models), hemorrhagic stroke models (intracerebral and subarachnoid hemorrhage), and the criteria and evaluation methods (imaging, neurological-behavioral tests, molecular analyses) used in these models. The strengths, limitations, translational value, and suitability for specific research questions of each model are discussed. The importance of selecting a model appropriate for the research objective, technical capabilities, and clinical reality is emphasized.
Referanslar
Feigin VL, Stark BA, Johnson CO, et al. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20(10):795-820.
Howells DW, Porritt MJ, Rewell SS, et al. Different strokes for different folks: the rich diversity of animal models of focal cerebral ischemia. J Cereb Blood Flow Metab. 2010;30(8):1412-1431.
Sommer CJ. Ischemic stroke: experimental models and reality. Acta Neuropathol. 2017;133(2):245-261.
Fluri F, Schuhmann MK, Kleinschnitz C. Animal models of ischemic stroke and their application in clinical research. Drug Des Devel Ther. 2015;9:3445-3454.
Carmichael ST. Rodent models of focal stroke: size, mechanism, and purpose. NeuroRx. 2005;2(3):396-409.
Traystman RJ. Animal models of focal and global cerebral ischemia. ILAR J. 2003;44(2):85-95.
Hossmann KA. The two pathophysiologies of focal brain ischemia: implications for translational stroke research. J Cereb Blood Flow Metab. 2012;32(7):1310-1316.
Fisher M, Feuerstein G, Howells DW, et al. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke. 2009;40(6):2244-2250.
O'Collins VE, Macleod MR, Donnan GA, et al. 1,026 experimental treatments in acute stroke. Ann Neurol. 2006;59(3):467-477.
Dirnagl U. Bench to bedside: the quest for quality in experimental stroke research. J Cereb Blood Flow Metab. 2006;26(12):1465-1478
Boltze J, Forschler A, Nitzsche B, et al. Permanent Middle Cerebral Artery Occlusion in Sheep: A Novel Large Animal Model of Focal Cerebral Ischemia. J Cereb Blood Flow Metab. 2008;28(12):1951-1964.
Mergenthaler P, Meisel A. Do Stroke Models Model Stroke? Dis Model Mech. 2012;5(6):718-725.
Cook DJ, Tymianski M. Nonhuman Primate Models of Stroke for Translational Neuroprotection Research. Neurotherapeutics. 2012;9(2):371-379.
Zaremba JD, Goodson MA, Redwine JM. Modeling Stroke in Mice: Transient Middle Cerebral Artery Occlusion via the External Carotid Artery. J Vis Exp. 2020;(161).
Durukan A, Tatlisumak T. Acute ischemic stroke: overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia. Pharmacol Biochem Behav. 2007;87(1):179-197.
Kilic E, Hermann DM, Hossmann KA. A reproducible model of thromboembolic stroke in mice. Neuroreport. 1998;9(13):2967-2970.
Koizumi J, Yoshida Y, Nakazawa T, Ooneda G. Experimental studies of ischemic brain edema, I: a new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke. 1986;8:1–8.
Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84-91.
MacLellan CL, Silasi G, Poon CC, et al. Intracerebral hemorrhage models in rat: comparing collagenase to blood infusion. J Cereb Blood Flow Metab. 2008;28(3):516-525.
Rosenberg GA, Mun-Bryce S, Wesley M, Kornfeld M. Collagenase-induced intracerebral hemorrhage in rats. Stroke. 1990;21(5):801-807.
Veelken JA, Laing RJ, Jakubowski J. The Sheffield model of subarachnoid hemorrhage in rats. Stroke. 1995;26(7):1279-1283.
Pulsinelli WA, Brierley JB. A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke. 1979;10(3):267-272.
Orset C, Macrez R, Young AR, et al. Mouse model of in situ thromboembolic stroke and reperfusion. Stroke. 2007;38(10):2771-2778.
Watson BD, Dietrich WD, Busto R, et al. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol. 1985;17(5):497-504.
Kurz KD, Main BW, Sandusky GE. Rat model of arterial thrombosis induced by ferric chloride. Thromb Res. 1990;60(4):269-280.
Fuxe K, Bjelke B, Andbjer B, et al. Endothelin-1 induced lesions of the frontoparietal cortex of the rat. A possible model of focal cortical ischemia. Neuroreport. 1997;8(11):2623-2629.
Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986;17(3):472-476.
Chen J, Li Y, Wang L, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke. 2001;32(4):1005-1011.
Bouley J, Fisher M, Henninger N. Comparison between coated vs. uncoated suture middle cerebral artery occlusion in the rat as assessed by perfusion/diffusion weighted imaging. Neurosci Lett. 2006;405(3):179-183.
Ishrat T, Sayeed I, Atif F, et al. Progesterone is neuroprotective against ischemic brain injury through its effects on the phosphoinositide 3-kinase/protein kinase B signaling pathway. Neuroscience. 2012;210:442-450.
