Ischemic stroke pathophysiology: Difference between revisions

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==Overview==
==Overview==
[[Stroke|The]] pathophysiology of ischemic [[stroke]] may depend on the underlying cause of ischemia. Ischemic infarct may be categorized into two types depending on the area of the brain involved as focal ischemic stroke or global ischemic stroke. Hemodynamic changes in ischemic stroke results from cerebral auto regulation dysfunction as brain tissue is highly sensitive to mild changes in oxygen levels. Several minutes of [[hypoxia]] leads to irreversible injury. <ref name="pmid22712739">{{cite journal| author=Xing C, Arai K, Lo EH, Hommel M| title=Pathophysiologic cascades in ischemic stroke. | journal=Int J Stroke | year= 2012 | volume= 7 | issue= 5 | pages= 378-85 | pmid=22712739 | doi=10.1111/j.1747-4949.2012.00839.x | pmc=3985770 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22712739  }} </ref><ref name="pmid10812160">{{cite journal| author=del Zoppo GJ, Hallenbeck JM| title=Advances in the vascular pathophysiology of ischemic stroke. | journal=Thromb Res | year= 2000 | volume= 98 | issue= 3 | pages= 73-81 | pmid=10812160 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10812160  }} </ref>. Cerebral auto regulation maintains the perfusion pressure in the brain between the pressure range of 60-150 mm Hg via [[vasoconstriction]] and [[vasodilatation]].<ref name="pmid10812160">{{cite journal| author=del Zoppo GJ, Hallenbeck JM| title=Advances in the vascular pathophysiology of ischemic stroke. | journal=Thromb Res | year= 2000 | volume= 98 | issue= 3 | pages= 73-81 | pmid=10812160 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10812160  }} </ref> Prolonged ischemia decreases oxygen delivery to the cells causing anaerobic glycolysis and increased production of free oxygen and nitrate radicals which in turn causes [[cell membrane]], [[DNA]] damage and cell death.<ref name="pmid23469845">{{cite journal| author=Rodrigo R, Fernández-Gajardo R, Gutiérrez R, Matamala JM, Carrasco R, Miranda-Merchak A et al.| title=Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities. | journal=CNS Neurol Disord Drug Targets | year= 2013 | volume= 12 | issue= 5 | pages= 698-714 | pmid=23469845 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23469845  }} </ref><ref name="pmid21266064">{{cite journal| author=Woodruff TM, Thundyil J, Tang SC, Sobey CG, Taylor SM, Arumugam TV| title=Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. | journal=Mol Neurodegener | year= 2011 | volume= 6 | issue= 1 | pages= 11 | pmid=21266064 | doi=10.1186/1750-1326-6-11 | pmc=3037909 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21266064  }} </ref><ref name="pmid1346887">{{cite journal| author=Pulsinelli W| title=Pathophysiology of acute ischaemic stroke. | journal=Lancet | year= 1992 | volume= 339 | issue= 8792 | pages= 533-6 | pmid=1346887 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1346887  }} </ref><ref name="pmid18037922">{{cite journal| author=Moustafa RR, Baron JC| title=Pathophysiology of ischaemic stroke: insights from imaging, and implications for therapy and drug discovery. | journal=Br J Pharmacol | year= 2008 | volume= 153 Suppl 1 | issue=  | pages= S44-54 | pmid=18037922 | doi=10.1038/sj.bjp.0707530 | pmc=2268043 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18037922  }} </ref><ref name="pmid10441299">{{cite journal| author=Dirnagl U, Iadecola C, Moskowitz MA| title=Pathobiology of ischaemic stroke: an integrated view. | journal=Trends Neurosci | year= 1999 | volume= 22 | issue= 9 | pages= 391-7 | pmid=10441299 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10441299  }} </ref><ref name="pmid22712739">{{cite journal| author=Xing C, Arai K, Lo EH, Hommel M| title=Pathophysiologic cascades in ischemic stroke. | journal=Int J Stroke | year= 2012 | volume= 7 | issue= 5 | pages= 378-85 | pmid=22712739 | doi=10.1111/j.1747-4949.2012.00839.x | pmc=3985770 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22712739  }} </ref><ref name="pmid20074922">{{cite journal| author=Deb P, Sharma S, Hassan KM| title=Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis. | journal=Pathophysiology | year= 2010 | volume= 17 | issue= 3 | pages= 197-218 | pmid=20074922 | doi=10.1016/j.pathophys.2009.12.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20074922  }} </ref><ref name="pmid10812160">{{cite journal| author=del Zoppo GJ, Hallenbeck JM| title=Advances in the vascular pathophysiology of ischemic stroke. | journal=Thromb Res | year= 2000 | volume= 98 | issue= 3 | pages= 73-81 | pmid=10812160 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10812160  }} </ref><ref name="pmid9547024">{{cite journal| author=Futrell N| title=Pathophysiology of acute ischemic stroke: new concepts in cerebral embolism. | journal=Cerebrovasc Dis | year= 1998 | volume= 8 Suppl 1 | issue=  | pages= 2-5 | pmid=9547024 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9547024  }} </ref><ref name="pmid19075733">{{cite journal| author=Taoufik E, Probert L| title=Ischemic neuronal damage. | journal=Curr Pharm Des | year= 2008 | volume= 14 | issue= 33 | pages= 3565-73 | pmid=19075733 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19075733  }} </ref><ref name="pmid25970836">{{cite journal| author=Mangubat E, Sani S| title=Acute global ischemic stroke after cranioplasty: case report and review of the literature. | journal=Neurologist | year= 2015 | volume= 19 | issue= 5 | pages= 135-9 | pmid=25970836 | doi=10.1097/NRL.0000000000000024 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25970836  }} </ref><ref name="pmid8594224">{{cite journal| author=Siesjö BK, Katsura K, Zhao Q, Folbergrová J, Pahlmark K, Siesjö P et al.| title=Mechanisms of secondary brain damage in global and focal ischemia: a speculative synthesis. | journal=J Neurotrauma | year= 1995 | volume= 12 | issue= 5 | pages= 943-56 | pmid=8594224 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8594224  }} </ref><ref name="pmid: 19690757">{{cite journal| author=Mărgăritescu O, Mogoantă L, Pirici I, Pirici D, Cernea D, Mărgăritescu C| title=Histopathological changes in acute ischemic stroke. | journal=Rom J Morphol Embryol | year= 2009 | volume= 50 | issue= 3 | pages= 327-39 | pmid=: 19690757 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19690757  }} </ref><ref name="pmid27166383">{{cite journal| author=Brinjikji W, Duffy S, Burrows A, Hacke W, Liebeskind D, Majoie CB et al.| title=Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome: a systematic review. | journal=J Neurointerv Surg | year= 2016 | volume=  | issue=  | pages=  | pmid=27166383 | doi=10.1136/neurintsurg-2016-012391 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27166383  }} </ref><ref name="pmid24372222">{{cite journal| author=Sierra C| title=Essential hypertension, cerebral white matter pathology and ischemic stroke. | journal=Curr Med Chem | year= 2014 | volume= 21 | issue= 19 | pages= 2156-64 | pmid=24372222 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24372222  }} </ref><ref name="pmid15155970">{{cite journal| author=Price CJ, Menon DK, Peters AM, Ballinger JR, Barber RW, Balan KK et al.| title=Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study. | journal=Stroke | year= 2004 | volume= 35 | issue= 7 | pages= 1659-64 | pmid=15155970 | doi=10.1161/01.STR.0000130592.71028.92 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15155970  }} </ref>
==Pathophysiology==
==Pathophysiology==
[[Stroke|The]] pathophysiology of ischemic [[stroke]] may depend on the underlying cause of ischemia. Ischemic infarct may be categorized into two types depending on the area of the brain involved:<ref name="pmid23469845">{{cite journal| author=Rodrigo R, Fernández-Gajardo R, Gutiérrez R, Matamala JM, Carrasco R, Miranda-Merchak A et al.| title=Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities. | journal=CNS Neurol Disord Drug Targets | year= 2013 | volume= 12 | issue= 5 | pages= 698-714 | pmid=23469845 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23469845  }} </ref><ref name="pmid21266064">{{cite journal| author=Woodruff TM, Thundyil J, Tang SC, Sobey CG, Taylor SM, Arumugam TV| title=Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. | journal=Mol Neurodegener | year= 2011 | volume= 6 | issue= 1 | pages= 11 | pmid=21266064 | doi=10.1186/1750-1326-6-11 | pmc=3037909 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21266064  }} </ref><ref name="pmid1346887">{{cite journal| author=Pulsinelli W| title=Pathophysiology of acute ischaemic stroke. | journal=Lancet | year= 1992 | volume= 339 | issue= 8792 | pages= 533-6 | pmid=1346887 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1346887  }} </ref><ref name="pmid18037922">{{cite journal| author=Moustafa RR, Baron JC| title=Pathophysiology of ischaemic stroke: insights from imaging, and implications for therapy and drug discovery. | journal=Br J Pharmacol | year= 2008 | volume= 153 Suppl 1 | issue=  | pages= S44-54 | pmid=18037922 | doi=10.1038/sj.bjp.0707530 | pmc=2268043 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18037922  }} </ref><ref name="pmid10441299">{{cite journal| author=Dirnagl U, Iadecola C, Moskowitz MA| title=Pathobiology of ischaemic stroke: an integrated view. | journal=Trends Neurosci | year= 1999 | volume= 22 | issue= 9 | pages= 391-7 | pmid=10441299 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10441299  }} </ref><ref name="pmid22712739">{{cite journal| author=Xing C, Arai K, Lo EH, Hommel M| title=Pathophysiologic cascades in ischemic stroke. | journal=Int J Stroke | year= 2012 | volume= 7 | issue= 5 | pages= 378-85 | pmid=22712739 | doi=10.1111/j.1747-4949.2012.00839.x | pmc=3985770 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22712739  }} </ref><ref name="pmid20074922">{{cite journal| author=Deb P, Sharma S, Hassan KM| title=Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis. | journal=Pathophysiology | year= 2010 | volume= 17 | issue= 3 | pages= 197-218 | pmid=20074922 | doi=10.1016/j.pathophys.2009.12.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20074922  }} </ref><ref name="pmid10812160">{{cite journal| author=del Zoppo GJ, Hallenbeck JM| title=Advances in the vascular pathophysiology of ischemic stroke. | journal=Thromb Res | year= 2000 | volume= 98 | issue= 3 | pages= 73-81 | pmid=10812160 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10812160  }} </ref><ref name="pmid9547024">{{cite journal| author=Futrell N| title=Pathophysiology of acute ischemic stroke: new concepts in cerebral embolism. | journal=Cerebrovasc Dis | year= 1998 | volume= 8 Suppl 1 | issue=  | pages= 2-5 | pmid=9547024 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9547024  }} </ref><ref name="pmid19075733">{{cite journal| author=Taoufik E, Probert L| title=Ischemic neuronal damage. | journal=Curr Pharm Des | year= 2008 | volume= 14 | issue= 33 | pages= 3565-73 | pmid=19075733 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19075733  }} </ref><ref name="pmid25970836">{{cite journal| author=Mangubat E, Sani S| title=Acute global ischemic stroke after cranioplasty: case report and review of the literature. | journal=Neurologist | year= 2015 | volume= 19 | issue= 5 | pages= 135-9 | pmid=25970836 | doi=10.1097/NRL.0000000000000024 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25970836  }} </ref><ref name="pmid8594224">{{cite journal| author=Siesjö BK, Katsura K, Zhao Q, Folbergrová J, Pahlmark K, Siesjö P et al.| title=Mechanisms of secondary brain damage in global and focal ischemia: a speculative synthesis. | journal=J Neurotrauma | year= 1995 | volume= 12 | issue= 5 | pages= 943-56 | pmid=8594224 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8594224  }} </ref><ref name="pmid: 19690757">{{cite journal| author=Mărgăritescu O, Mogoantă L, Pirici I, Pirici D, Cernea D, Mărgăritescu C| title=Histopathological changes in acute ischemic stroke. | journal=Rom J Morphol Embryol | year= 2009 | volume= 50 | issue= 3 | pages= 327-39 | pmid=: 19690757 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19690757  }} </ref><ref name="pmid27166383">{{cite journal| author=Brinjikji W, Duffy S, Burrows A, Hacke W, Liebeskind D, Majoie CB et al.| title=Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome: a systematic review. | journal=J Neurointerv Surg | year= 2016 | volume=  | issue=  | pages=  | pmid=27166383 | doi=10.1136/neurintsurg-2016-012391 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27166383  }} </ref><ref name="pmid24372222">{{cite journal| author=Sierra C| title=Essential hypertension, cerebral white matter pathology and ischemic stroke. | journal=Curr Med Chem | year= 2014 | volume= 21 | issue= 19 | pages= 2156-64 | pmid=24372222 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24372222  }} </ref><ref name="pmid15155970">{{cite journal| author=Price CJ, Menon DK, Peters AM, Ballinger JR, Barber RW, Balan KK et al.| title=Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study. | journal=Stroke | year= 2004 | volume= 35 | issue= 7 | pages= 1659-64 | pmid=15155970 | doi=10.1161/01.STR.0000130592.71028.92 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15155970  }} </ref>
[[Stroke|The]] pathophysiology of ischemic [[stroke]] may depend on the underlying cause of ischemia. Ischemic infarct may be categorized into two types depending on the area of the brain involved:<ref name="pmid23469845">{{cite journal| author=Rodrigo R, Fernández-Gajardo R, Gutiérrez R, Matamala JM, Carrasco R, Miranda-Merchak A et al.| title=Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities. | journal=CNS Neurol Disord Drug Targets | year= 2013 | volume= 12 | issue= 5 | pages= 698-714 | pmid=23469845 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23469845  }} </ref><ref name="pmid21266064">{{cite journal| author=Woodruff TM, Thundyil J, Tang SC, Sobey CG, Taylor SM, Arumugam TV| title=Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. | journal=Mol Neurodegener | year= 2011 | volume= 6 | issue= 1 | pages= 11 | pmid=21266064 | doi=10.1186/1750-1326-6-11 | pmc=3037909 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21266064  }} </ref><ref name="pmid1346887">{{cite journal| author=Pulsinelli W| title=Pathophysiology of acute ischaemic stroke. | journal=Lancet | year= 1992 | volume= 339 | issue= 8792 | pages= 533-6 | pmid=1346887 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1346887  }} </ref><ref name="pmid18037922">{{cite journal| author=Moustafa RR, Baron JC| title=Pathophysiology of ischaemic stroke: insights from imaging, and implications for therapy and drug discovery. | journal=Br J Pharmacol | year= 2008 | volume= 153 Suppl 1 | issue=  | pages= S44-54 | pmid=18037922 | doi=10.1038/sj.bjp.0707530 | pmc=2268043 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18037922  }} </ref><ref name="pmid10441299">{{cite journal| author=Dirnagl U, Iadecola C, Moskowitz MA| title=Pathobiology of ischaemic stroke: an integrated view. | journal=Trends Neurosci | year= 1999 | volume= 22 | issue= 9 | pages= 391-7 | pmid=10441299 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10441299  }} </ref><ref name="pmid22712739">{{cite journal| author=Xing C, Arai K, Lo EH, Hommel M| title=Pathophysiologic cascades in ischemic stroke. | journal=Int J Stroke | year= 2012 | volume= 7 | issue= 5 | pages= 378-85 | pmid=22712739 | doi=10.1111/j.1747-4949.2012.00839.x | pmc=3985770 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22712739  }} </ref><ref name="pmid20074922">{{cite journal| author=Deb P, Sharma S, Hassan KM| title=Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis. | journal=Pathophysiology | year= 2010 | volume= 17 | issue= 3 | pages= 197-218 | pmid=20074922 | doi=10.1016/j.pathophys.2009.12.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20074922  }} </ref><ref name="pmid10812160">{{cite journal| author=del Zoppo GJ, Hallenbeck JM| title=Advances in the vascular pathophysiology of ischemic stroke. | journal=Thromb Res | year= 2000 | volume= 98 | issue= 3 | pages= 73-81 | pmid=10812160 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10812160  }} </ref><ref name="pmid9547024">{{cite journal| author=Futrell N| title=Pathophysiology of acute ischemic stroke: new concepts in cerebral embolism. | journal=Cerebrovasc Dis | year= 1998 | volume= 8 Suppl 1 | issue=  | pages= 2-5 | pmid=9547024 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9547024  }} </ref><ref name="pmid19075733">{{cite journal| author=Taoufik E, Probert L| title=Ischemic neuronal damage. | journal=Curr Pharm Des | year= 2008 | volume= 14 | issue= 33 | pages= 3565-73 | pmid=19075733 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19075733  }} </ref><ref name="pmid25970836">{{cite journal| author=Mangubat E, Sani S| title=Acute global ischemic stroke after cranioplasty: case report and review of the literature. | journal=Neurologist | year= 2015 | volume= 19 | issue= 5 | pages= 135-9 | pmid=25970836 | doi=10.1097/NRL.0000000000000024 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25970836  }} </ref><ref name="pmid8594224">{{cite journal| author=Siesjö BK, Katsura K, Zhao Q, Folbergrová J, Pahlmark K, Siesjö P et al.| title=Mechanisms of secondary brain damage in global and focal ischemia: a speculative synthesis. | journal=J Neurotrauma | year= 1995 | volume= 12 | issue= 5 | pages= 943-56 | pmid=8594224 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8594224  }} </ref><ref name="pmid: 19690757">{{cite journal| author=Mărgăritescu O, Mogoantă L, Pirici I, Pirici D, Cernea D, Mărgăritescu C| title=Histopathological changes in acute ischemic stroke. | journal=Rom J Morphol Embryol | year= 2009 | volume= 50 | issue= 3 | pages= 327-39 | pmid=: 19690757 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19690757  }} </ref><ref name="pmid27166383">{{cite journal| author=Brinjikji W, Duffy S, Burrows A, Hacke W, Liebeskind D, Majoie CB et al.| title=Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome: a systematic review. | journal=J Neurointerv Surg | year= 2016 | volume=  | issue=  | pages=  | pmid=27166383 | doi=10.1136/neurintsurg-2016-012391 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27166383  }} </ref><ref name="pmid24372222">{{cite journal| author=Sierra C| title=Essential hypertension, cerebral white matter pathology and ischemic stroke. | journal=Curr Med Chem | year= 2014 | volume= 21 | issue= 19 | pages= 2156-64 | pmid=24372222 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24372222  }} </ref><ref name="pmid15155970">{{cite journal| author=Price CJ, Menon DK, Peters AM, Ballinger JR, Barber RW, Balan KK et al.| title=Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study. | journal=Stroke | year= 2004 | volume= 35 | issue= 7 | pages= 1659-64 | pmid=15155970 | doi=10.1161/01.STR.0000130592.71028.92 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15155970  }} </ref>

Revision as of 19:43, 21 November 2016

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]

Overview

The pathophysiology of ischemic stroke may depend on the underlying cause of ischemia. Ischemic infarct may be categorized into two types depending on the area of the brain involved as focal ischemic stroke or global ischemic stroke. Hemodynamic changes in ischemic stroke results from cerebral auto regulation dysfunction as brain tissue is highly sensitive to mild changes in oxygen levels. Several minutes of hypoxia leads to irreversible injury. [1][2]. Cerebral auto regulation maintains the perfusion pressure in the brain between the pressure range of 60-150 mm Hg via vasoconstriction and vasodilatation.[2] Prolonged ischemia decreases oxygen delivery to the cells causing anaerobic glycolysis and increased production of free oxygen and nitrate radicals which in turn causes cell membrane, DNA damage and cell death.[3][4][5][6][7][1][8][2][9][10][11][12][13][14][15][16]

Pathophysiology

The pathophysiology of ischemic stroke may depend on the underlying cause of ischemia. Ischemic infarct may be categorized into two types depending on the area of the brain involved:[3][4][5][6][7][1][8][2][9][10][11][12][13][14][15][16]

Type of ischemia Pathogenesis
Underlying cause Part of the brain involved Time of initiation of cell death Type of cell death
Focal[12]

Thrombosis
Embolism

Focal area supplied by the occluded vessel

Acute onset (3-4 hrs)
Cell death (12 hrs)

Necrosis-central area
Apoptosis- Peripheral area

Global[12]

Systemic hypoperfusion

Water shed area
Hippocampal pyramidal cells, cerebellar purkinjee cells, cortical laminar cells

Delayed onset (12 hrs)
Cell death (days to weeks)

Apoptosis

Hemodynamic changes in ischemic stroke

  • Hemodynamic changes in ischemic stroke results from cerebral auto regulation dysfunction as brain tissue is highly sensitive to mild changes in oxygen levels
  • Several minutes of hypoxia leads to irreversible injury[1][2]
  • Cerebral auto regulation maintains the perfusion pressure in the brain between the pressure range of 60-150 mm Hg via vasoconstriction and vasodilatation.[2]
  • Pressure changes below 60 mm Hg and more than 150 mm Hg disrupts the normal auto regulation.
  • Below 60 mm Hg, initially there is extensive vasodilatation of the affected vessels to increase blood flow to the affected area. This is mediated by increase in endothelial nitric oxide production.
  • Extensive increase in nitric oxide production due to sustained hypoxia results in massive vasodialation and formation of large amounts of nitric oxide free radicals causing damage to cellular structures.
  • Drop in blood flow rates below 30ml/100gm results in inhibition of protein synthesis and increase in anaerobic glycolysis
  • Blood flow rates below 20ml/100gm results in extensive membrane damage causing cell death.

Molecular pathophysiology in ischemic stroke

The sequence of molecular changes that may result due to ischemia include:[4][1]

  • Prolonged ischemia- decrease in oxygen delivery to the cells
  • Anaerobic glycolysis with decline in ATP production
  • Increased lactic acid production
  • Increased free oxygen and nitrate radicals-cell membrane and DNA damage[3]
  • Excitatory neurotransmitter -glutamate is increased in neuronal synapses leading to NMDA receptor activation[7][1]
  • NMDA receptor activation causes opening of ion channels in the cell membrane causing K+ efflux and Na+, Ca2+ and water influx
  • Increased Ca2+ influx activates apoptotic cell death pathways
  • ATP required for final steps of apoptosis, hence massive decline in ATP results in necrosis of cells

Cellular changes in Ischemic stroke

The sequence of cellular changes during ischemic stroke results in loss of structural integrity of brain causing disruption of blood brain barrier and cerebral edema.

Genetics

The following gene loci may increase the risk for stroke:

Gross pathology

  • Central necrotic tissue is called umbra
  • Peripheral tissue which surrounds area of necrosis and can be salvaged with increased blood flow is called pneumbra[6]

Microscopic pathology

  • Within 1-6 min of ischemia, red neurons and vacoulation results [13]
  • If ischemia lasts > 6 min, karryorhexis and cell death occurs

Gross and microscopic changes that may occur due to ischemia with the passage of time is tabulated below: [13]

Duration Gross pathology Microscopic pathology[13]
Immediate

<24 hrs

No change Cellular edema
Acute

<1 week

Edema

Loss of grey and white matter junction

Red neurons

Necrosis

Neutrophilia[16]

Subacute

1-4 weeks

Soft friable tissue

Cyst formation

Macrophages

Liquifactive necrosis

Chronic

>4 weeks

Fibrosis

Fluid filled cysts with dark grey margin

Gliosis

Necrotic tissue cleared by macrophages

Autopsy of brain showing middle cerebral artery territory
Same image; infarct area (blue shading) and midline shift


[17]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Xing C, Arai K, Lo EH, Hommel M (2012). "Pathophysiologic cascades in ischemic stroke". Int J Stroke. 7 (5): 378–85. doi:10.1111/j.1747-4949.2012.00839.x. PMC 3985770. PMID 22712739.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 del Zoppo GJ, Hallenbeck JM (2000). "Advances in the vascular pathophysiology of ischemic stroke". Thromb Res. 98 (3): 73–81. PMID 10812160.
  3. ↑ 3.0 3.1 3.2 3.3 Rodrigo R, Fernández-Gajardo R, Gutiérrez R, Matamala JM, Carrasco R, Miranda-Merchak A; et al. (2013). "Oxidative stress and pathophysiology of ischemic stroke: novel therapeutic opportunities". CNS Neurol Disord Drug Targets. 12 (5): 698–714. PMID 23469845.
  4. ↑ 4.0 4.1 4.2 4.3 Woodruff TM, Thundyil J, Tang SC, Sobey CG, Taylor SM, Arumugam TV (2011). "Pathophysiology, treatment, and animal and cellular models of human ischemic stroke". Mol Neurodegener. 6 (1): 11. doi:10.1186/1750-1326-6-11. PMC 3037909. PMID 21266064.
  5. ↑ 5.0 5.1 Pulsinelli W (1992). "Pathophysiology of acute ischaemic stroke". Lancet. 339 (8792): 533–6. PMID 1346887.
  6. ↑ 6.0 6.1 6.2 Moustafa RR, Baron JC (2008). "Pathophysiology of ischaemic stroke: insights from imaging, and implications for therapy and drug discovery". Br J Pharmacol. 153 Suppl 1: S44–54. doi:10.1038/sj.bjp.0707530. PMC 2268043. PMID 18037922.
  7. ↑ 7.0 7.1 7.2 Dirnagl U, Iadecola C, Moskowitz MA (1999). "Pathobiology of ischaemic stroke: an integrated view". Trends Neurosci. 22 (9): 391–7. PMID 10441299.
  8. ↑ 8.0 8.1 Deb P, Sharma S, Hassan KM (2010). "Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis". Pathophysiology. 17 (3): 197–218. doi:10.1016/j.pathophys.2009.12.001. PMID 20074922.
  9. ↑ 9.0 9.1 Futrell N (1998). "Pathophysiology of acute ischemic stroke: new concepts in cerebral embolism". Cerebrovasc Dis. 8 Suppl 1: 2–5. PMID 9547024.
  10. ↑ 10.0 10.1 Taoufik E, Probert L (2008). "Ischemic neuronal damage". Curr Pharm Des. 14 (33): 3565–73. PMID 19075733.
  11. ↑ 11.0 11.1 Mangubat E, Sani S (2015). "Acute global ischemic stroke after cranioplasty: case report and review of the literature". Neurologist. 19 (5): 135–9. doi:10.1097/NRL.0000000000000024. PMID 25970836.
  12. ↑ 12.0 12.1 12.2 12.3 Siesjö BK, Katsura K, Zhao Q, Folbergrová J, Pahlmark K, Siesjö P; et al. (1995). "Mechanisms of secondary brain damage in global and focal ischemia: a speculative synthesis". J Neurotrauma. 12 (5): 943–56. PMID 8594224.
  13. ↑ 13.0 13.1 13.2 13.3 13.4 Mărgăritescu O, Mogoantă L, Pirici I, Pirici D, Cernea D, Mărgăritescu C (2009). "Histopathological changes in acute ischemic stroke". Rom J Morphol Embryol. 50 (3): 327–39. PMID 19690757 : 19690757 Check |pmid= value (help).
  14. ↑ 14.0 14.1 Brinjikji W, Duffy S, Burrows A, Hacke W, Liebeskind D, Majoie CB; et al. (2016). "Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome: a systematic review". J Neurointerv Surg. doi:10.1136/neurintsurg-2016-012391. PMID 27166383.
  15. ↑ 15.0 15.1 Sierra C (2014). "Essential hypertension, cerebral white matter pathology and ischemic stroke". Curr Med Chem. 21 (19): 2156–64. PMID 24372222.
  16. ↑ 16.0 16.1 16.2 Price CJ, Menon DK, Peters AM, Ballinger JR, Barber RW, Balan KK; et al. (2004). "Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study". Stroke. 35 (7): 1659–64. doi:10.1161/01.STR.0000130592.71028.92. PMID 15155970.
  17. ↑ Caplan LR (1992). "Intracerebral hemorrhage". Lancet. 339 (8794): 656–8. PMID 1347346.


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