Deneysel Serebral İskemi Modelleri
Özet
Serebral iskemi (inme), bilinçli ve bilinçaltı fizyolojik fonksiyonların sürdürülmesinde hayati önem taşıyan serebral kan akımının azalmasıyla meydana gelen bir merkezi sinir sistemi hastalığıdır. Dünyada ve ülkemizde hızla artan inme vakaları ciddi sağlık ve ekonomik sorunlara yol açtığından, hasarı önleyecek ve iyileşmeyi hızlandıracak etkin tedavi yöntemlerinin geliştirilmesi büyük önem taşımaktadır. Klinik vakaların patofizyolojisini araştırmak ve yeni terapötik ajanları keşfetmek amacıyla, kemirgenler üzerinde uygulanan deneysel hayvan modelleri sıklıkla tercih edilmektedir. Bu kapsamda global, fokal ve ön beyin iskemi modelleri yapılandırılmış olup, klinikte en sık karşılaşılan inme tipini en iyi taklit eden yöntem olan geçici orta serebral arter oklüzyonu (MCAO) cerrahi basamaklarıyla detaylandırılmıştır. İskemi sonrası kan akımının tekrar sağlanmasının, aşırı serbest radikal üretimi ve kalsiyum homeostazisinin bozulması nedeniyle dokuya iskemiden daha fazla zarar verebildiği vurgulanmıştır. İskemik hasar boyutunun ve enfarktüs hacminin kantitatif tespiti için motor davranış indeksi ve trifeniltetrazolyum klorür (TTC) boyama yöntemleri kullanılmaktadır. Sonuç olarak, inme tedavisinde asıl amacın penumbra alanını kurtarmak olduğu ve geçici serebral iskemi modellerinin bu moleküler mekanizmaları aydınlatmada kritik rol oynadığı belirtilmektedir.
Cerebral ischemia (stroke) is a central nervous system disease that occurs with the decrease of cerebral blood flow, which is vital for maintaining conscious and subconscious physiological functions. Since stroke cases are rapidly increasing worldwide and in our country, causing serious health and economic problems, developing effective treatment methods to prevent damage and accelerate recovery is of great importance. In order to investigate the pathophysiology of clinical cases and discover new therapeutic agents, experimental animal models performed on rodents are frequently preferred. Within this scope, global, focal, and forebrain ischemia models are structured, and the transient middle cerebral artery occlusion (MCAO) method, which best mimics the most common clinical type of stroke, is detailed with its surgical steps. It is emphasized that the restoration of blood flow after ischemia can cause more damage to the tissue than ischemia itself due to excessive free radical production and disruption of calcium homeostasis. For the quantitative determination of ischemic damage size and infarct volume, motor behavior index and triphenyltetrazolium chloride (TTC) staining methods are utilized. In conclusion, it is stated that the primary goal in stroke treatment is to salvage the penumbra area, and transient cerebral ischemia models play a critical role in elucidating these molecular mechanisms.
Referanslar
Akçay, G., Cerebral Ischemia Model Created by Transient Middle Cerebral Artery Occlusion. Turk Hij Den Biyol Derg, 2021. 78(2): p. 0-0.
Akcay, G. and A. Bahadır, The Therapeutic Effects of Non-Invasive Transcranial Direct Current Stimulation (tDCS) in Experimental Models of Stroke, in Research Advancements In Health Scıences, P.M. Chernopolskı, N.L. Shapekova, and B. Ak, Editors. 2021: St. Klıment Ohrıdskı Unıversıty Press. p. 28-49.
Bahadır, A. and G. Akcay, The Recovery Effects of Non-Invasive Repetitive Transcranial Magnetic Stimulation (rTMS) in Experimental Models of Stroke, in Research Advancements In Health Scıences, P.M. Chernopolskı, N.L. Shapekova, and B. Ak, Editors. 2021: St. Klıment Ohrıdskı Unıversıty Press. p. 2-27.
Akcay G., Deneysel Serebral İskemi Modeline Bağlı Öğrenme ve Hafıza Değişikliklerine Transkraniyal Doğru Akım Stimülasyonunun Etkilerinin Araştırılması, in Biyofizik. 2020, Akdeniz Üniversitesi. p. 102.
Kumral, E., Santral Sinir Sisteminin Damarsal Hastalıkları. 2011, Güneş Tıp Kitapevleri.
Kablan, Y., İnme: Epidemiyoloji ve Risk Faktörleri. 2018: Türkiye Klinikleri. p. 1-19.
Benjamin, E.J., et al., Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation, 2018. 137(12): p. e67-e492.
Krishnamurthi, R.V., et al., Stroke Prevalence, Mortality and Disability-Adjusted Life Years in Adults Aged 20-64 Years in 1990-2013: Data from the Global Burden of Disease 2013 Study. Neuroepidemiology, 2015. 45(3): p. 190-202.
Akcay G., Aslan M., and Derin N. Serebral İskemi Sonrası Motor Fonksiyonların Tedavisinde Transkraniyal Doğru Akım Stimülasyonu Etkileri. in 18. Ulusal Sinirbilim Kongresi. 6-9 Kasım 2020. Bilkent Üniversitesi, Ankara (Türkiye).
Kaya, D. and Y.G. Özdemir, Serebral Kan Akımı ve Metabolizması, in Santral Sinir Sisteminin Damarsal Hastalıkları, E. Kumral, Editor. 2011: Güneş Kitapevleri.
Astrup, J., Energy-requiring cell functions in the ischemic brain. Their critical supply and possible inhibition in protective therapy. J Neurosurg, 1982. 56(4): p. 482-97.
Siesjo, B.K. and F. Bengtsson, Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: a unifying hypothesis. J Cereb Blood Flow Metab, 1989. 9(2): p. 127-40.
Oğul, E., Klinik Nöroloji. Birinci Baskı ed. 2002, Nobrl&Güneş.
Sahan, M., et al., İskemik İnme ve Akut Faz Reaktanları. Arşiv Kaynak Tarama Dergisi, 2010. 19(2): p. 85-140.
Berg, J.M., J.L. Tymoczko, and L. Stryer, The Glycolytic Pathway Is Tightly Controlled. 5th edition ed. Biochemistry. 2002.
Sims, N.R. and H. Muyderman, Mitochondria, oxidative metabolism and cell death in stroke. Biochim Biophys Acta, 2010. 1802(1): p. 80-91.
Yager, J.Y., R.M. Brucklacher, and R.C. Vannucci, Cerebral energy metabolism during hypoxia-ischemia and early recovery in immature rats. Am J Physiol, 1992. 262(3 Pt 2): p. H672-7.
Zhang, Y., et al., Remifentanil mimics cardioprotective effect of ischemic preconditioning via protein kinase C activation in open chest of rats. Acta Pharmacol Sin, 2005. 26(5): p. 546-50.
Simard, J.M., K.V. Tarasov, and V. Gerzanich, Non-selective cation channels, transient receptor potential channels and ischemic stroke. Biochim Biophys Acta, 2007. 1772(8): p. 947-57.
Bogousslavsky, J., G. Van Melle, and F. Regli, The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke, 1988. 19(9): p. 1083-92.
Liang, D., T.M. Dawson, and V.L. Dawson, What have genetically engineered mice taught us about ischemic injury? Curr Mol Med, 2004. 4(2): p. 207-25.
Shalak, L. and J.M. Perlman, Hypoxic-ischemic brain injury in the term infant-current concepts. Early Hum Dev, 2004. 80(2): p. 125-41.
Xing, C., et al., Pathophysiologic cascades in ischemic stroke. Int J Stroke, 2012. 7(5): p. 378-85.
Chan, P.H., Role of oxidants in ischemic brain damage. Stroke, 1996. 27(6): p. 1124-9.
Simonian, N.A. and J.T. Coyle, Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol, 1996. 36: p. 83-106.
Nicotera, P. and S.A. Lipton, Excitotoxins in neuronal apoptosis and necrosis. J Cereb Blood Flow Metab, 1999. 19(6): p. 583-91.
Yamashima, T., Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates. Prog Neurobiol, 2000. 62(3): p. 273-95.
Hillered, L., et al., Dynamics of extracellular metabolites in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis. J Cereb Blood Flow Metab, 1989. 9(5): p. 607-16.
Davalos, A., A. Shuaib, and N.G. Wahlgren, Neurotransmitters and pathophysiology of stroke: evidence for the release of glutamate and other transmitters/mediators in animals and humans. J Stroke Cerebrovasc Dis, 2000. 9(6 Pt 2): p. 2-8.
Lee, J.M., et al., Brain tissue responses to ischemia. J Clin Invest, 2000. 106(6): p. 723-31.
Yamashima, T., et al., Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates. Hippocampus, 2003. 13(7): p. 791-800.
Memezawa, H., M.L. Smith, and B.K. Siesjo, Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats. Stroke, 1992. 23(4): p. 552-9.
Salford, L.G., F. Plum, and J.B. Brierley, Graded hypoxia-oligemia in rat brain. II. Neuropathological alterations and their implications. Arch Neurol, 1973. 29(4): p. 234-8.
Belov Kirdajova, D., et al., Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells. Front Cell Neurosci, 2020. 14: p. 51.
Ghosh, A., et al., Neuroprotective role of nanoencapsulated quercetin in combating ischemia-reperfusion induced neuronal damage in young and aged rats. PLoS One, 2013. 8(4): p. e57735.
Bouma, G.J., et al., Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg, 1992. 77(3): p. 360-8.
Suarez, J.I., Outcome in neurocritical care: advances in monitoring and treatment and effect of a specialized neurocritical care team. Crit Care Med, 2006. 34(9 Suppl): p. S232-8.
Yuan, H.J., 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(1): p. 176-83.
Li, M.H., et al., Calcium-permeable ion channels involved in glutamate receptor-independent ischemic brain injury. Acta Pharmacol Sin, 2011. 32(6): p. 734-40.
Valko, M., H. Morris, and M.T. Cronin, Metals, toxicity and oxidative stress. Curr Med Chem, 2005. 12(10): p. 1161-208.
Ward, J.D., et al., Failure of prophylactic barbiturate coma in the treatment of severe head injury. J Neurosurg, 1985. 62(3): p. 383-8.
Xiong, L.-z., Neuroanesthesia and neuroprotection: where are we now? Chinese Medical Journal, 2006. 119(11): p. 883-886.
Sivenius, J., et al., Continuous 15-year decrease in incidence and mortality of stroke in Finland: the FINSTROKE study. Stroke, 2004. 35(2): p. 420-5.
Gasche, Y., et al., Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction. J Cereb Blood Flow Metab, 1999. 19(9): p. 1020-8.
Granger, D.N., G. Rutili, and J.M. McCord, Superoxide radicals in feline intestinal ischemia. Gastroenterology, 1981. 81(1): p. 22-9.
Perlman, J.M., Intervention strategies for neonatal hypoxic-ischemic cerebral injury. Clin Ther, 2006. 28(9): p. 1353-65.
Behringer, W., et al., Rapid induction of mild cerebral hypothermia by cold aortic flush achieves normal recovery in a dog outcome model with 20-minute exsanguination cardiac arrest. Acad Emerg Med, 2000. 7(12): p. 1341-8.
Böttiger, B.W., et al., The cerebral 'no-reflow' phenomenon after cardiac arrest in rats--influence of low-flow reperfusion. Resuscitation, 1997. 34(1): p. 79-87.
Hossmann, K.A., Cerebral ischemia: models, methods and outcomes. Neuropharmacology, 2008. 55(3): p. 257-70.
Kofler, J., et al., Histopathological and behavioral characterization of a novel model of cardiac arrest and cardiopulmonary resuscitation in mice. J Neurosci Methods, 2004. 136(1): p. 33-44.
Makarenko, N.V., [The higher nervous activity in dogs revived following prolonged terms of clinical death from drowning or bloodletting]. Zh Vyssh Nerv Deiat Im I P Pavlova, 1972. 22(1): p. 82-8.
Pulsinelli, W.A. and J.B. Brierley, A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke, 1979. 10(3): p. 267-72.
Levine, S. and H. Payan, Effects of ischemia and other procedures on the brain and retina of the gerbil (Meriones unguiculatus). Exp Neurol, 1966. 16(3): p. 255-62.
Holloway, P.M. and F.N. Gavins, Modeling Ischemic Stroke In Vitro: Status Quo and Future Perspectives. Stroke, 2016. 47(2): p. 561-9.
Goldberg, M.P. and D.W. Choi, Combined oxygen and glucose deprivation in cortical cell culture: calcium-dependent and calcium-independent mechanisms of neuronal injury. J Neurosci, 1993. 13(8): p. 3510-24.
Matsumoto, K., et al., Role of pyruvate in ischaemia-like conditions on cultured neurons. Neurol Res, 1994. 16(6): p. 460-4.
Newell, D.W., et al., Glutamate and non-glutamate receptor mediated toxicity caused by oxygen and glucose deprivation in organotypic hippocampal cultures. J Neurosci, 1995. 15(11): p. 7702-11.
Wolf, P.A., et al., Secular trends in stroke incidence and mortality. The Framingham Study. Stroke, 1992. 23(11): p. 1551-5.
Kelly, S., J. McCulloch, and K. Horsburgh, Minimal ischaemic neuronal damage and HSP70 expression in MF1 strain mice following bilateral common carotid artery occlusion. Brain Res, 2001. 914(1-2): p. 185-95.
Herrmann, M., et al., Effect of inherent epileptic seizures on brain injury after transient cerebral ischemia in Mongolian gerbils. Exp Brain Res, 2004. 154(2): p. 176-82.
Paschen, W., et al., Biochemical changes during graded brain ischemia in gerbils. Part 2. Regional evaluation of cerebral blood flow and brain metabolites. J Neurol Sci, 1983. 58(1): p. 37-44.
Levine, S., Anoxic-ischemic encephalopathy in rats. Am J Pathol, 1960. 36(1): p. 1-17.
Overgaard, K., Thrombolytic therapy in experimental embolic stroke. Cerebrovasc Brain Metab Rev, 1994. 6(3): p. 257-86.
Tsirka, S.E., A.D. Rogove, and S. Strickland, Neuronal cell death and tPA. Nature, 1996. 384(6605): p. 123-4.
Uzdensky, A.B., Photothrombotic Stroke as a Model of Ischemic Stroke. Transl Stroke Res, 2018. 9(5): p. 437-451.
Labat-gest, V. and S. Tomasi, Photothrombotic ischemia: a minimally invasive and reproducible photochemical cortical lesion model for mouse stroke studies. J Vis Exp, 2013(76).
Klebe, D., et al., Intracerebral Hemorrhage in Mice. Methods Mol Biol, 2018. 1717: p. 83-91.
Manaenko, A., et al., Comparison of different preclinical models of intracerebral hemorrhage. Acta Neurochir Suppl, 2011. 111: p. 9-14.
Gupta, Y.K. and S. Briyal, Animal models of cerebral ischemia for evaluation of drugs. Indian J Physiol Pharmacol, 2004. 48(4): p. 379-94.
Chen, J.C., et al., Down-regulation of the glial glutamate transporter GLT-1 in rat hippocampus and striatum and its modulation by a group III metabotropic glutamate receptor antagonist following transient global forebrain ischemia. Neuropharmacology, 2005. 49(5): p. 703-14.
Liu, F. and L.D. McCullough, Middle cerebral artery occlusion model in rodents: methods and potential pitfalls. J Biomed Biotechnol, 2011. 2011: p. 464701.
Shahjouei, S., et al., Middle Cerebral Artery Occlusion Model of Stroke in Rodents: A Step-by-Step Approach. J Vasc Interv Neurol, 2016. 8(5): p. 1-8.
Longa, E.Z., et al., Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 1989. 20(1): p. 84-91.
Lee, S., et al., Comparison of surgical methods of transient middle cerebral artery occlusion between rats and mice. J Vet Med Sci, 2014. 76(12): p. 1555-61.
Wattanathorn, J., et al., Cerebroprotective Effect against Cerebral Ischemia of the Combined Extract of Oryza sativa and Anethum graveolens in Metabolic Syndrome Rats. Oxid Med Cell Longev, 2019. 2019: p. 9658267.
Lin, T.N., et al., Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke, 1993. 24(1): p. 117-21.
Schimidt, H.L., et al., Memory deficits and oxidative stress in cerebral ischemia-reperfusion: neuroprotective role of physical exercise and green tea supplementation. Neurobiol Learn Mem, 2014. 114: p. 242-50.
Sharifi, Z.N., et al., Neuroprotective Treatment With FK506 Reduces Hippocampal Damage and Prevents Learning and Memory Deficits After Transient Global Ischemia in Rat. Archives of Neuroscience, 2013. 1: p. 35-40.
Braun, R., et al., Transcranial direct current stimulation accelerates recovery of function, induces neurogenesis and recruits oligodendrocyte precursors in a rat model of stroke. Exp Neurol, 2016. 279: p. 127-136.
Pascual, J.M., et al., Glutamate, glutamine, and GABA as substrates for the neuronal and glial compartments after focal cerebral ischemia in rats. Stroke, 1998. 29(5): p. 1048-56; discussion 1056-7.
Pulsinelli, W.A., The therapeutic window in ischemic brain injury. Curr Opin Neurol, 1995. 8(1): p. 3-5.
Pulsinelli, W.A., et al., Ischemic brain injury and the therapeutic window. Ann N Y Acad Sci, 1997. 835: p. 187-93.
Krzyzanowska, W., et al., Glutamate transporters in brain ischemia: to modulate or not? Acta Pharmacol Sin, 2014. 35(4): p. 444-62.
Hu, Y., et al., Increased Susceptibility to Ischemic Brain Injury in Neuroplastin 65-Deficient Mice Likely via Glutamate Excitotoxicity. Front Cell Neurosci, 2017. 11: p. 110.
