Keywords
MAP-2
Penumbra isquémica
Fisiopatología
GFAP
HMC Experimental focal ischemia
MAP-2
Ischemic penumbra
Pathophysiology
GFAP
HMC
How to Cite
Abstract
Introduction: Acute obstruction of the Middle Cerebral Artery results in decreased blood flow to the corresponding irrigated territory and triggers a process of cell death and stress that gives rise to an ischemic focus and penumbra, respectively. Changes in the neuronal cytoskeleton, glial and immunophenotype changes of the microglia are sensitive markers for cell distress. Up to now, the evolution of the various cell compartments has not been evaluated in a comprehensive model that enables the cyto-architectural evolution of infarction. Objectives: To assess in an experimental ischemic injury model any changes in the cell compartments of the brain tissue and suggest a structural model for the evolution of the lesion. Methodology: 22 male Wistar rats with average weight of 280 grams. The intraluminal obstruction technique of the middle cerebral artery, with perfusion times of 3, 12, 24 and 72 hours was used. Histological sections were processed for basic and immunohistochemical staining for MAP-2 (neuronal cytoskeleton), GFAP (glial cytoskeleton), HMC (microglia), and Caspase-3 (proteolytic activity). Results: A topographic and sequential model of the neuronal and glial compartment response and of the reaction of the macroglia in the ischemic cerebral cortex was established. Four zones with defined pathophysiological characteristics were defined. Conclusions: A joint appreciation of the reaction of the various brain cells to the ischemic injury was generated and allowed for setting the background to evaluate substances with neuroprotective potential. This helps to understand the pathophysiology of ischemic cerebral injuries.
References
White B, Sullivan J, DeGracia D, Oneil B, Neumar R, Grossman L, et al. Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. Journal of neurological sciences 2000;179:1-33. https://doi.org/10.1016/S0022-510X(00)00386-5
Kumar V, Abbas A, Fausto N, Mitchell R. ROBBINS Patología Humana. 8va ed. Barcelona, España: Elsevier Saunders; 2008.
Back T. Pathophisiology of the ischemic penumbra - Revision of a concept. Cellular and Molecular Neurobiology. 1998;18:621-38. https://doi.org/10.1023/A:1020265701407
Cardona-Gomez GP, Arango-Davila CA, Gallego-Gomez JC, Barrera-Ocampo A, Pimienta H, Garcia-Segura LM. Estrogen dissociates Tau and alpha-amino-3 -hydroxy-5-methylisoxazole-4-propionic acid receptor subunit in postischemic hippocampus. Neuroreport. 2006;17(12): 1337-41. https://doi.org/10.1097/01.wnr.0000230508.78467.96
Garcia-Galloway E, Arango-Davila CA, Pons S, Torres-Aleman I. Glutamate excitotoxicity attenuates insulin-like growth factor-I prosurvival signaling Molecular and Cellular Neuroscience. 2003;24(4):1027-37. https://doi.org/10.1016/j.mcn.2003.08.005
Ginsberg MD. Current Status of Neuroprotection for Cerebral Ischemia. Synoptic Overview. Stroke. 2009;40(suppl 1):S111 - S4. https://doi.org/10.1161/STROKEAHA.108.528877
Drewes G, Ebneth A, Mandelkow E. MAPs, MARKs and microtubule dynamics. Trends Biochem Sci. 1998;23:307-11. https://doi.org/10.1016/S0968-0004(98)01245-6
Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998;279:509-14. https://doi.org/10.1126/science.279.5350.509
Small J, Rottner K, Kaverina I. Functional design in the actin cytoskeleton. Curr Opin Cell Biol. 1999;11:54-60. https://doi.org/10.1016/S0955-0674(99)80007-6
Etienne-Manneville S. From signaling pathways to microtubule dynamics: the key players. Current Opinion in Cell Biology. 2010;22:104-11. https://doi.org/10.1016/j.ceb.2009.11.008
Lipton P. Ischemic Cell Death in Brain Neurons. Physiological Reviews. 1999;79(4):1431-568. https://doi.org/10.1152/physrev.1999.79.4.1431
Hawkins T, Mirigian M, Yasar MS, Ross JL. Mechanics of microtubules. Journal of Biomechanics. 2010;43:23-30. https://doi.org/10.1016/j.jbiomech.2009.09.005
Wiche G, Oberkanins C, Himmler A. Molecular structure and function of microtubule-associated proteins. Int Rev Cytol. 1991;124:217-73. https://doi.org/10.1016/S0074-7696(08)61528-4
Mandelkow E, Mandelkow E. Microtubules and microtubule-associated proteins. Curr Opin Cell Biol 1995;7:72-81. https://doi.org/10.1016/0955-0674(95)80047-6
Sánchez C, Díaz-Nido J, Avila J. Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function. Progress in Neurobiology. 2000;61:133-68. https://doi.org/10.1016/S0301-0082(99)00046-5
Sim A. The regulation and function of protein phosphatases in the brain. Mol Neurobiol. 1992;5:229-46. https://doi.org/10.1007/BF02935548
Goldberg Y. Protein phosphatase 2A: who shall regulate the regulator? Biochem Pharmacol 1999(57):321-8. https://doi.org/10.1016/S0006-2952(98)00245-7
Finsen B, Jorgensen M, Diemer N, Zimmer J. Microglial MHC antigen expresión after ischemic and kainik acid lesion of the adult rat hippocampus. Glia. 1993;7:41-9. https://doi.org/10.1002/glia.440070109
Banasiak K, Xia Y, Haddad G. Mechanisms underlying hypoxia-induced neuronal apoptosis. Progress in Neurobiology. 2000;62(3):215-49. https://doi.org/10.1016/S0301-0082(00)00011-3
Rami A, Agarwal R, Botez G, Winckler J. µ-Calpain activation, DNA fragmentation, and synergistic effects of caspase and calpain inhibitors in protecting hippocampal neurons from ischemic damage. Brain Research. 2000;866(1-2):299-312. https://doi.org/10.1016/S0006-8993(00)02301-5
Tetsumori Y. Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates. Progress in Neurobiology. 2000;62(3):273-95. https://doi.org/10.1016/S0301-0082(00)00006-X
Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible Middle Cerebral Artery Occlusion Without Craniectomy in Rats. Stroke. 1989;20:84-91. https://doi.org/10.1161/01.STR.20.1.84
Belayeb L, Zhao W, Ginsberg D. Transient middle cerebral artery occlusion by intraluminal suture: I. three dimentional autoradiographyc imageanalysis of local cerebral glucose metabolism-blood flow interrelationships during ischemia and early recirculatin. J Cereb Blood Flow Metab. 1997;17:1266-80. https://doi.org/10.1097/00004647-199712000-00002
Belayeb L, Zhao W, Ginsberg D. Transient middle cerebral artery occlusion by intraluminal suture: II: Neurological deficit, pixel-based correlation of histopathology with local blood flow and glucose utilization. J Cereb Blood Flow Metab. 1997;17:1281-90. https://doi.org/10.1097/00004647-199712000-00003
Arango CA, Escobar M, Pimienta H. Evaluation of a Model of Cerebral Ischemia in Rats. Salud UIS. 2002;34(3):195-201.
Leach M, Swam J, Eisenthal D, Dopson M, Nobbs M. BW619C89 a glutamate release inhibitor, protects against focal cerebral ischemic damage. Stroke. 1993;24:1063-7. https://doi.org/10.1161/01.STR.24.7.1063
Osborne K, Shigeno T, Balarsky A, Ford I, McCulloch J, Teasdale G, et al. Quantitative assessment of early brain damage in a rat model of cerebral ischaemia. J of Neurol Neuropshy and Psychiatry. 1987;50:402-10. https://doi.org/10.1136/jnnp.50.4.402
Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD. Middle Cerebral Artery Occlusion in the Rat by Intraluminal Suture. Neurological and Pathological Evaluation of an Improved Model Stroke. 1996;27:1616-23. https://doi.org/10.1161/01.STR.27.9.1616
Kuge Y, Minematsu K, Yamaguchi T, Miyake Y. Nylon monofilament for intraluminal middle cerebral artery occlusion in rat. Stroke. 1995;26:1655-8. https://doi.org/10.1161/01.STR.26.9.1655
Dereski M, Chopp M, Knight R, Rodolosi R, Gracia J. The heterogeneus temporal evolution af focal ischemic neuronl damage in the rat. Acta neuropathologica. 1993;85:327-33. https://doi.org/10.1007/BF00227730
Postmantur R, Kampel B, Liu S, Heck K, Taft W, Cifton G, et al. Cytoskeletal derangements of cortical neuronal processes three hours after traumatic brain injury in rats: an immunofluorescence study. J Neuropathol and exp neurol. 1996;55:68-80. https://doi.org/10.1097/00005072-199601000-00007
Saito N, Kawai K, Nowak T. Reexpression of developmentally regulates MAP2c mRNA after ischemia: colocalization with hsp72 mRNA in vulnerable neurons. J Cereb Blood Flow and Metab. 1995;15:205-15. https://doi.org/10.1038/jcbfm.1995.26
Toyama Y, Sako K, Yonemasu Y. Protein kinase C in focal ischemic rat brain : dual autoradiographic analysis of [14C]iodontipyrine (IAP) and [3H] phorbol-12,13-dibutyrate (PDBu). Brain Res. 1997;750:155-60. https://doi.org/10.1016/S0006-8993(96)01342-X
Kitagawa K, Matsumoto M, Niinobe M, Micoshiba K, Hata R, Ueda H, et al. Microtubule-associated protein 2 a sensitive marker for cerebral ischemic damage, immunohistochemical investigation of dendritic damage. Neuroscience. 1989;31:401-11. https://doi.org/10.1016/0306-4522(89)90383-7
Miyazawa T, Bonnekoh P, Hossmann K. Temperature effect of immunostaining of Microtubule-associated protein 2 and synaptophysin after 30 minutes of forebrain ischemia in rat. Acta Neuropathol. 1991;85:526-32. https://doi.org/10.1007/BF00230493
Yamashima T. Implication of cisteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates. Progress in Neurobiology 2000;62:273-95. https://doi.org/10.1016/S0301-0082(00)00006-X
Minger S, Geddes J, Holtz M, Craddock S, Sidney W, Whiteheart S, et al. Glutamate receptor antagonists inhibit calpain-mediated cytoeskeletal proteolysis in focal cerebral ischemia. Brain Research. 1998;810:181-99. https://doi.org/10.1016/S0006-8993(98)00921-4
Pettigres L, Holtz M, Craddock S, Minger S, Hall N, Geddes J. Microtubular preoteolisis in focal cerebral ischemia. J cereb Blood Flow and Metabolism. 2000;16:61189-202.
Li G, Farooque M, Lennmyr F, Holtz A, Olsson Y. MAP2 and neurogranin as markers for dendritic lesion in CNS injury. APMIS. 2000;108:298-06. https://doi.org/10.1034/j.1600-0463.2000.d01-32.x
Dewar D, Dawson D. Changes of cytoskeletal proein inmunoestaining in mielinating fiber tracts after focal cerebral ischemia un rats. Acta Neuropathol. 1997;93:171-7. https://doi.org/10.1007/s004010050584
Popa-Wagner A, Schröder E, Schmoll H, Walker LC, Kessler C. Upregulation of MAP1B and MAP2 in the Rat Brain After Middle Cerebral Artery Occlusion: Effect of Age. J Cereb Blood Flow Metab. 1999;19:425-34. https://doi.org/10.1097/00004647-199904000-00008
Schmidt-Kastner R, Freund TF. Selective vulnerability of the hippocampus in brain ischemia. Neuroscience. 2000;40:599-636. https://doi.org/10.1016/0306-4522(91)90001-5
Li Y, Jiang N, Power C, Chopp M. Neuronal damage and plasticity identified by microtubule associate protein 2, growth-associated protein 43and cyclin immunoreactivity after focal cerebral ischemia in rats. Stroke. 1998;29(91972-91980). https://doi.org/10.1161/01.STR.29.9.1972
Heiss W, Graff R. The ischemic penumbra. Curr Opin Neurobiol. 1994;7:11-9. https://doi.org/10.1097/00019052-199402000-00004
Ramírez-Expósito M, Martínez-Martos J. Estructura y funciones de la macroglía en el sistema nervioso central. Respuesta a procesos degenerativos. Rev Neurol. 1998;26:600-11. https://doi.org/10.33588/rn.26152.98012
Hatten M, Liem R, Shelanski M, Mason C. Astroglia in CNS injury. Glia. 1991;4:233-9 https://doi.org/10.1002/glia.440040215
Schiffer D, Giordana M, Migheli A, Giaccone G, Pezzotta S, Mauro A. Glial fibrilary acidic protein and vimentin in experimental glial reaction of the rat brain. Brain Res. 1986;374:110-8. https://doi.org/10.1016/0006-8993(86)90399-9
Witte O, Stoll G. Delayed and remote effects of focal cortical infarctions: secondary damage and reactive plasticity. Adv Neurol. 1997;73:207-27.
Jabbs R, Bekar L, Walz W. Reactive astrogliosis in the injured and postischemic brain. In: Totowa NJ, editor. Cerebral Ischemia: molecular and cellular pathophisiology: Humana Press Inc; 1999. p. 233-49. https://doi.org/10.1007/978-1-59259-479-5_9
Kondo Y. Activated and fagocytic microglía. In: Walz W, editor. Cerebral ischemia: molecular and cellular pathophysiology. Totowa NJ: Humana Press; 1999. p. 251-69." https://doi.org/10.1007/978-1-59259-479-5_10