The neurotoxicity of tissue plasminogen activator?
Tissue plasminogen activator (tPA), a fibrin specific activator for the conversion of plasminogen to plasmin, stimulates thrombolysis and rescues ischemic brain by restoring blood flow. However, emerging data suggests that under some conditions, both tPA and plasmin, which are broad spectrum proteas...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1797065246611865600 |
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| author | Kaur, J Zhao, Z Klein, G Lo, E Buchan, A |
| author_facet | Kaur, J Zhao, Z Klein, G Lo, E Buchan, A |
| author_sort | Kaur, J |
| collection | OXFORD |
| description | Tissue plasminogen activator (tPA), a fibrin specific activator for the conversion of plasminogen to plasmin, stimulates thrombolysis and rescues ischemic brain by restoring blood flow. However, emerging data suggests that under some conditions, both tPA and plasmin, which are broad spectrum protease enzymes, are potentially neurotoxic if they reach the extracellular space. Animal models suggest that in severe ischemia with injury to the blood brain barrier (BBB) there is injury attributed to the protease effects of this exogenous tPA. Besides clot lysis per se, tPA may have pleiotropic actions in the brain, including direct vasoactivity, cleaveage of the N-methyl-D-aspartate (NMDA) NR1 subunit, amplification of intracellular Ca++ conductance, and activation of other extracellular proteases from the matrix metalloproteinase (MMP) family, e.g. MMP-9. These effects may increase excitotoxicity, further damage the BBB, and worsen edema and cerebral hemorrhage. If tPA is effective and reverses ischemia promptly, the BBB remains intact and exogenous tPA remains within the vascular space. If tPA is ineffective and ischemia is prolonged, there is the risk that exogenous tPA will injure both the neurovascular unit and the brain. Methods of neuroprotection, which prevent tPA toxicity or additional mechanical means to open cerebral vessels, are now needed. |
| first_indexed | 2024-03-06T21:25:55Z |
| format | Journal article |
| id | oxford-uuid:4314f986-149d-4547-a775-0ead8108a92f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:25:55Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:4314f986-149d-4547-a775-0ead8108a92f2022-03-26T14:53:20ZThe neurotoxicity of tissue plasminogen activator?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4314f986-149d-4547-a775-0ead8108a92fEnglishSymplectic Elements at Oxford2004Kaur, JZhao, ZKlein, GLo, EBuchan, ATissue plasminogen activator (tPA), a fibrin specific activator for the conversion of plasminogen to plasmin, stimulates thrombolysis and rescues ischemic brain by restoring blood flow. However, emerging data suggests that under some conditions, both tPA and plasmin, which are broad spectrum protease enzymes, are potentially neurotoxic if they reach the extracellular space. Animal models suggest that in severe ischemia with injury to the blood brain barrier (BBB) there is injury attributed to the protease effects of this exogenous tPA. Besides clot lysis per se, tPA may have pleiotropic actions in the brain, including direct vasoactivity, cleaveage of the N-methyl-D-aspartate (NMDA) NR1 subunit, amplification of intracellular Ca++ conductance, and activation of other extracellular proteases from the matrix metalloproteinase (MMP) family, e.g. MMP-9. These effects may increase excitotoxicity, further damage the BBB, and worsen edema and cerebral hemorrhage. If tPA is effective and reverses ischemia promptly, the BBB remains intact and exogenous tPA remains within the vascular space. If tPA is ineffective and ischemia is prolonged, there is the risk that exogenous tPA will injure both the neurovascular unit and the brain. Methods of neuroprotection, which prevent tPA toxicity or additional mechanical means to open cerebral vessels, are now needed. |
| spellingShingle | Kaur, J Zhao, Z Klein, G Lo, E Buchan, A The neurotoxicity of tissue plasminogen activator? |
| title | The neurotoxicity of tissue plasminogen activator? |
| title_full | The neurotoxicity of tissue plasminogen activator? |
| title_fullStr | The neurotoxicity of tissue plasminogen activator? |
| title_full_unstemmed | The neurotoxicity of tissue plasminogen activator? |
| title_short | The neurotoxicity of tissue plasminogen activator? |
| title_sort | neurotoxicity of tissue plasminogen activator |
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