Deneysel Travmatik Beyin Hasarı Modelleri
Özet
Travmatik beyin hasarı (TBH), dünya çapında yüksek mortalite ve morbiditeye yol açan, motor, bilişsel ve duyusal işlev kayıpları ile karakterize önemli bir sağlık sorunudur. Hasarın patofizyolojisi, travma anında mekanik güçlerle oluşan primer hasar ile bunu izleyen nöroinflamasyon, oksidatif stres ve hücresel ölüm süreçlerini içeren sekonder hasardan meydana gelir. Tedavi stratejileri, klinik öncesi aşamada geri döndürülemez primer hasarı büyüten bu sekonder hasar yolaklarını engellemeye odaklansa da henüz tam anlamıyla etkili bir nöroprotektif yöntem bulunamamıştır. Bu süreçlerin mekanizmasını anlamak ve yeni terapötik ajanlar geliştirmek amacıyla, insan TBH heterojenliğini taklit eden çeşitli kemirgen modelleri kullanılmaktadır. Deneysel araştırmalarda en sık tercih edilen modeller; doğrudan beyin deformasyonu yaratan Sıvı Perküsyon (FPI) ve Kontrollü Kortikal Etki (CCI) modelleri ile serbest düşüş prensibine dayanan Ağırlık Düşürme (Marmarou, Feeney, Shohami) ve askeri travmaları taklit eden Patlama Dalgası modelleridir. Her modelin kendine özgü hasar mekanizması, biyomekanik parametre ayarı, mortalite oranları, tekrarlanabilirlik düzeyleri gibi avantaj ve dezavantajları bulunmaktadır. Ayrıca, yaş, cinsiyet hormonları ve klinik takibi zorlaştıran komorbiditeler gibi unsurlar da modellerin klinik etkinliğe dönüştürülmesinde sınırlılıklar oluşturmaktadır. Sonuç olarak, insan TBH tablosunun tamamını tek bir modelle karşılamak mümkün olmadığından, araştırmanın amacına uygun doğru deneysel modelin seçilmesi kritik önem taşır.
Traumatic brain injury (TBI) is a major public health issue worldwide that causes high mortality and morbidity, characterized by motor, cognitive, and sensory functional losses. The pathophysiology of the injury consists of primary injury caused by mechanical forces at the moment of trauma, and subsequent secondary injury involving neuroinflammation, oxidative stress, and cellular death processes. Although treatment strategies focus on inhibiting these secondary injury pathways that exacerbate the irreversible primary damage during the preclinical stage, an fully effective neuroprotective method has not yet been discovered. To understand the mechanism of these processes and develop new therapeutic agents, various rodent models that mimic the heterogeneity of human TBI are utilized. The most frequently preferred models in experimental research include Fluid Percussion (FPI) and Controlled Cortical Impact (CCI) models, which create direct brain deformation, as well as Weight-Drop models (Marmarou, Feeney, Shohami) based on the free-fall principle, and Blast Wave models that simulate military traumas. Each model has its own advantages and disadvantages regarding injury mechanism, biomechanical parameter adjustment, mortality rates, and reproducibility levels. Furthermore, factors such as age, sex hormones, and comorbidities that complicate clinical follow-up pose limitations in translating models into clinical efficacy. Consequently, since it is not possible to cover the entire human TBI spectrum with a single model, selecting the correct experimental model appropriate for the purpose of the research is of critical importance.
Referanslar
Masel, B.E. and D.S. DeWitt, Traumatic brain injury: a disease process, not an event. J Neurotrauma, 2010. 27(8): p. 1529-40.
Michael G, et al., A Review of Traumatic Brain Injury Animal Models: Are We Lacking Adequate Models Replicating Chronic Traumatic Encephalopathy? Journal of Neurology and Neurobiology, 2015. 2(1).
Langlois, J.A., W. Rutland-Brown, and M.M. Wald, The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil, 2006. 21(5): p. 375-8.
Maas, A.I., N. Stocchetti, and R. Bullock, Moderate and severe traumatic brain injury in adults. Lancet Neurol, 2008. 7(8): p. 728-41.
Ma, X., et al., Animal Models of Traumatic Brain Injury and Assessment of Injury Severity. Mol Neurobiol, 2019. 56(8): p. 5332-5345.
Briones, T.L., Chapter 3 animal models of traumatic brain injury: is there an optimal model that parallels human brain injury? Annu Rev Nurs Res, 2015. 33: p. 31-73.
Davis, A.E., Mechanisms of traumatic brain injury: biomechanical, structural and cellular considerations. Crit Care Nurs Q, 2000. 23(3): p. 1-13.
Cernak, I., Animal models of head trauma. NeuroRx, 2005. 2(3): p. 410-22.
Gaetz, M., The neurophysiology of brain injury. Clin Neurophysiol, 2004. 115(1): p. 4-18.
Hay, J., et al., Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury. Annu Rev Pathol, 2016. 11: p. 21-45.
Xiong, Y., A. Mahmood, and M. Chopp, Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs, 2009. 14(1): p. 67-84.
Doppenberg, E.M., S.C. Choi, and R. Bullock, Clinical trials in traumatic brain injury: lessons for the future. J Neurosurg Anesthesiol, 2004. 16(1): p. 87-94.
Maas, A.I., Neuroprotective agents in traumatic brain injury. Expert Opin Investig Drugs, 2001. 10(4): p. 753-67.
Faden, A.I., Neuroprotection and traumatic brain injury: theoretical option or realistic proposition. Curr Opin Neurol, 2002. 15(6): p. 707-12.
Schouten, J.W., Neuroprotection in traumatic brain injury: a complex struggle against the biology of nature. Curr Opin Crit Care, 2007. 13(2): p. 134-42.
Irvine, K.-A. and J.D. Clark, Chronic Pain After Traumatic Brain Injury: Pathophysiology and Pain Mechanisms. Pain Medicine, 2018. 19: p. 1315–1333.
Povlishock, J.T. and C.W. Christman, The pathobiology of traumatically induced axonal injury in animals and humans: a review of current thoughts. J Neurotrauma, 1995. 12(4): p. 555-64.
Xiong, Y., A. Mahmood, and M. Chopp, Animal models of traumatic brain injury. Nat Rev Neurosci, 2013. 14(2): p. 128-42.
Raghupathi, R., Cell death mechanisms following traumatic brain injury. Brain Pathol, 2004. 14(2): p. 215-22.
Bramlett, H.M. and W.D. Dietrich, Progressive damage after brain and spinal cord injury: pathomechanisms and treatment strategies. Prog Brain Res, 2007. 161: p. 125-41.
Raghupathi, R., D.I. Graham, and T.K. McIntosh, Apoptosis after traumatic brain injury. J Neurotrauma, 2000. 17(10): p. 927-38.
Yakovlev, A.G., et al., Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during brain development and after traumatic brain injury. J Neurosci, 2001. 21(19): p. 7439-46.
Margulies, S. and R. Hicks, Combination therapies for traumatic brain injury: prospective considerations. J Neurotrauma, 2009. 26(6): p. 925-39.
Marklund, N., et al., Evaluation of pharmacological treatment strategies in traumatic brain injury. Curr Pharm Des, 2006. 12(13): p. 1645-80.
McIntosh, T.K., et al., Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience, 1989. 28(1): p. 233-44.
Chen J, Xu XM, and X. ZC, Animal Models of Acute Neurological Injuries. 2009, Berlin, Germany.
Gennarelli, T.A., Animate models of human head injury. J Neurotrauma, 1994. 11(4): p. 357-68.
Spain, A., et al., Mild fluid percussion injury in mice produces evolving selective axonal pathology and cognitive deficits relevant to human brain injury. J Neurotrauma, 2010. 27(8): p. 1429-38.
Su, Y., et al., Taurine improves functional and histological outcomes and reduces inflammation in traumatic brain injury. Neuroscience, 2014. 266: p. 56-65.
Kabadi, S.V., et al., CR8, a novel inhibitor of CDK, limits microglial activation, astrocytosis, neuronal loss, and neurologic dysfunction after experimental traumatic brain injury. J Cereb Blood Flow Metab, 2014. 34(3): p. 502-13.
Huang, E.Y., et al., Amantadine ameliorates dopamine-releasing deficits and behavioral deficits in rats after fluid percussion injury. PLoS One, 2014. 9(1): p. e86354.
Hameed, M.Q., et al., A rapid lateral fluid percussion injury rodent model of traumatic brain injury and post-traumatic epilepsy. Neuroreport, 2014. 25(7): p. 532-6.
Lifshitz, J., B.J. Kelley, and J.T. Povlishock, Perisomatic thalamic axotomy after diffuse traumatic brain injury is associated with atrophy rather than cell death. J Neuropathol Exp Neurol, 2007. 66(3): p. 218-29.
Cao, T., et al., Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat. Neuroscience, 2012. 225: p. 65-75.
Thompson, H.J., et al., Lateral fluid percussion brain injury: a 15-year review and evaluation. J Neurotrauma, 2005. 22(1): p. 42-75.
Hicks, R., et al., Temporal and spatial characterization of neuronal injury following lateral fluid-percussion brain injury in the rat. Acta Neuropathol, 1996. 91(3): p. 236-46.
Liu, Y.R., et al., Progressive metabolic and structural cerebral perturbations after traumatic brain injury: an in vivo imaging study in the rat. J Nucl Med, 2010. 51(11): p. 1788-95.
Hamm, R.J., Neurobehavioral assessment of outcome following traumatic brain injury in rats: an evaluation of selected measures. J Neurotrauma, 2001. 18(11): p. 1207-16.
Pierce, J.E., et al., Enduring cognitive, neurobehavioral and histopathological changes persist for up to one year following severe experimental brain injury in rats. Neuroscience, 1998. 87(2): p. 359-69.
Dixon, C.E., et al., A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Methods, 1991. 39(3): p. 253-62.
Chen, Y., et al., A modified controlled cortical impact technique to model mild traumatic brain injury mechanics in mice. Front Neurol, 2014. 5: p. 100.
Smith, S.L. and E.D. Hall, Mild pre- and posttraumatic hypothermia attenuates blood-brain barrier damage following controlled cortical impact injury in the rat. J Neurotrauma, 1996. 13(1): p. 1-9.
Osier, N.D. and C.E. Dixon, The Controlled Cortical Impact Model: Applications, Considerations for Researchers, and Future Directions. Front Neurol, 2016. 7: p. 134.
Washington, P.M., et al., The effect of injury severity on behavior: a phenotypic study of cognitive and emotional deficits after mild, moderate, and severe controlled cortical impact injury in mice. J Neurotrauma, 2012. 29(13): p. 2283-96.
Fox, G.B., et al., Sustained sensory/motor and cognitive deficits with neuronal apoptosis following controlled cortical impact brain injury in the mouse. J Neurotrauma, 1998. 15(8): p. 599-614.
Marklund, N. and L. Hillered, Animal modelling of traumatic brain injury in preclinical drug development: where do we go from here? Br J Pharmacol, 2011. 164(4): p. 1207-29.
Dixon, C.E., et al., Amantadine improves water maze performance without affecting motor behavior following traumatic brain injury in rats. Restor Neurol Neurosci, 1999. 14(4): p. 285-294.
Dixon, C.E., et al., One-year study of spatial memory performance, brain morphology, and cholinergic markers after moderate controlled cortical impact in rats. J Neurotrauma, 1999. 16(2): p. 109-22.
Kochanek, P.M., et al., Cerebral blood flow at one year after controlled cortical impact in rats: assessment by magnetic resonance imaging. J Neurotrauma, 2002. 19(9): p. 1029-37.
Mychasiuk, R., A. Farran, and M.J. Esser, Assessment of an experimental rodent model of pediatric mild traumatic brain injury. J Neurotrauma, 2014. 31(8): p. 749-57.
Morales, D.M., et al., Experimental models of traumatic brain injury: do we really need to build a better mousetrap? Neuroscience, 2005. 136(4): p. 971-89.
Viano, D.C., et al., Evaluation of three animal models for concussion and serious brain injury. Ann Biomed Eng, 2012. 40(1): p. 213-26.
Marmarou, A., et al., A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg, 1994. 80(2): p. 291-300.
Flierl, M.A., et al., Mouse closed head injury model induced by a weight-drop device. Nat Protoc, 2009. 4(9): p. 1328-37.
Adelson, P.D., et al., A model of diffuse traumatic brain injury in the immature rat. J Neurosurg, 1996. 85(5): p. 877-84.
Statler, K.D., et al., Isoflurane exerts neuroprotective actions at or near the time of severe traumatic brain injury. Brain Res, 2006. 1076(1): p. 216-24.
Feeney, D.M., et al., Responses to cortical injury: I. Methodology and local effects of contusions in the rat. Brain Res, 1981. 211(1): p. 67-77.
Albert-Weissenberger, C. and A.L. Sirén, Experimental traumatic brain injury. Exp Transl Stroke Med, 2010. 2(1): p. 16.
Nilsson, P., et al., Continuous measurement of changes in regional cerebral blood flow following cortical compression contusion trauma in the rat. J Neurotrauma, 1996. 13(4): p. 201-7.
Lindh, C., et al., Differences in cell death between high and low energy brain injury in adult rats. Acta Neurochir (Wien), 2008. 150(12): p. 1269-75;discussion 1275.
Shapira, Y., et al., Experimental closed head injury in rats: mechanical, pathophysiologic, and neurologic properties. Crit Care Med, 1988. 16(3): p. 258-65.
Chen, Y., et al., An experimental model of closed head injury in mice: pathophysiology, histopathology, and cognitive deficits. J Neurotrauma, 1996. 13(10): p. 557-68.
Zhu, F., et al., Biomechanical responses of a pig head under blast loading: a computational simulation. Int J Numer Method Biomed Eng, 2013. 29(3): p. 392-407.
Reneer, D.V., et al., A multi-mode shock tube for investigation of blast-induced traumatic brain injury. J Neurotrauma, 2011. 28(1): p. 95-104.
Koliatsos, V.E., et al., A mouse model of blast injury to brain: initial pathological, neuropathological, and behavioral characterization. J Neuropathol Exp Neurol, 2011. 70(5): p. 399-416.
Yi, J., et al., Chronic traumatic encephalopathy. Curr Sports Med Rep, 2013. 12(1): p. 28-32.
Geddes, J.F., et al., Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol, 1999. 98(2): p. 171-8.
Weber, J.T., Experimental models of repetitive brain injuries. Prog Brain Res, 2007. 161: p. 253-61.
Uryu, K., et al., Repetitive mild brain trauma accelerates Abeta deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosis. J Neurosci, 2002. 22(2): p. 446-54.
DeFord, S.M., et al., Repeated mild brain injuries result in cognitive impairment in B6C3F1 mice. J Neurotrauma, 2002. 19(4): p. 427-38.
Huang, L., et al., Tissue vulnerability is increased following repetitive mild traumatic brain injury in the rat. Brain Res, 2013. 1499: p. 109-20.
Luo, J., et al., Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury. Front Neurol, 2014. 5: p. 12.
Rákos, G., et al., Evans Blue fluorescence permits the rapid visualization of non-intact cells in the perilesional rim of cold-injured rat brain. Acta Neurobiol Exp (Wars), 2007. 67(2): p. 149-54.
Raslan, F., et al., Inhibition of bradykinin receptor B1 protects mice from focal brain injury by reducing blood-brain barrier leakage and inflammation. J Cereb Blood Flow Metab, 2010. 30(8): p. 1477-86.
Brotfain, E., et al., Neuroprotection by Estrogen and Progesterone in Traumatic Brain Injury and Spinal Cord Injury. Curr Neuropharmacol, 2016. 14(6): p. 641-53.
Prins, M.L. and D.A. Hovda, Developing experimental models to address traumatic brain injury in children. J Neurotrauma, 2003. 20(2): p. 123-37.
Potts, M.B., et al., Traumatic injury to the immature brain: inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets. NeuroRx, 2006. 3(2): p. 143-53.
Rabinowitz, A.R. and H.S. Levin, Cognitive sequelae of traumatic brain injury. Psychiatr Clin North Am, 2014. 37(1): p. 1-11.
Osier, N.D., et al., Chronic Histopathological and Behavioral Outcomes of Experimental Traumatic Brain Injury in Adult Male Animals. J Neurotrauma, 2015. 32(23): p. 1861-82.
Johnson, V.E., et al., Animal models of traumatic brain injury. Handb Clin Neurol, 2015. 127: p. 115-28.
