Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke
Ischemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue plasminogen activator (tPA) remains the only approved treatment for acute ischemic stroke, but its use is limited to the first hours after stroke onset due to an increased risk of hemorrhagic tran...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2013-04-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2013.00032/full |
| _version_ | 1818228610921660416 |
|---|---|
| author | Shaheen E. Lakhan Shaheen E. Lakhan Annette Kirchgessner Annette Kirchgessner Deborah Tepper Aidan Leonard |
| author_facet | Shaheen E. Lakhan Shaheen E. Lakhan Annette Kirchgessner Annette Kirchgessner Deborah Tepper Aidan Leonard |
| author_sort | Shaheen E. Lakhan |
| collection | DOAJ |
| description | Ischemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue plasminogen activator (tPA) remains the only approved treatment for acute ischemic stroke, but its use is limited to the first hours after stroke onset due to an increased risk of hemorrhagic transformation over time resulting in enhanced brain injury. In this review we discuss the role of matrix metalloproteinases (MMPs) in blood-brain barrier (BBB) disruption as a consequence of ischemic stroke. MMP-9 in particular appears to play an important role in tPA-associated hemorrhagic complications. Reactive oxygen species can enhance the effects of tPA on MMP activation through the loss of caveolin-1 (cav-1), a protein encoded in the cav-1 gene that serves as a critical determinant of BBB permeability. This review provides an overview of MMPs’ role in BBB breakdown during acute ischemic stroke. The possible role of MMPs in combination treatment of acute ischemic stroke is also examined. |
| first_indexed | 2024-12-12T10:05:27Z |
| format | Article |
| id | doaj.art-778a5a4d21d645f8a1b748c212529e0c |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-12T10:05:27Z |
| publishDate | 2013-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-778a5a4d21d645f8a1b748c212529e0c2022-12-22T00:27:54ZengFrontiers Media S.A.Frontiers in Neurology1664-22952013-04-01410.3389/fneur.2013.0003242109Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic StrokeShaheen E. Lakhan0Shaheen E. Lakhan1Annette Kirchgessner2Annette Kirchgessner3Deborah Tepper4Aidan Leonard5Biosciences Department, Global Neuroscience Initiative FoundationBeverly Hills, CA, USANeurological Institute, Cleveland ClinicCleveland, OH, USABiosciences Department, Global Neuroscience Initiative FoundationBeverly Hills, CA, USASchool of Health and Medical Sciences, Seton Hall UniversitySouth Orange, NJ, USANeurological Institute, Cleveland ClinicCleveland, OH, USABiosciences Department, Global Neuroscience Initiative FoundationBeverly Hills, CA, USAIschemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue plasminogen activator (tPA) remains the only approved treatment for acute ischemic stroke, but its use is limited to the first hours after stroke onset due to an increased risk of hemorrhagic transformation over time resulting in enhanced brain injury. In this review we discuss the role of matrix metalloproteinases (MMPs) in blood-brain barrier (BBB) disruption as a consequence of ischemic stroke. MMP-9 in particular appears to play an important role in tPA-associated hemorrhagic complications. Reactive oxygen species can enhance the effects of tPA on MMP activation through the loss of caveolin-1 (cav-1), a protein encoded in the cav-1 gene that serves as a critical determinant of BBB permeability. This review provides an overview of MMPs’ role in BBB breakdown during acute ischemic stroke. The possible role of MMPs in combination treatment of acute ischemic stroke is also examined.http://journal.frontiersin.org/article/10.3389/fneur.2013.00032/fullmatrix metalloproteinasesblood-brain barrierstrokecaveolin-1reactive oxygen species |
| spellingShingle | Shaheen E. Lakhan Shaheen E. Lakhan Annette Kirchgessner Annette Kirchgessner Deborah Tepper Aidan Leonard Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke Frontiers in Neurology matrix metalloproteinases blood-brain barrier stroke caveolin-1 reactive oxygen species |
| title | Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke |
| title_full | Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke |
| title_fullStr | Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke |
| title_full_unstemmed | Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke |
| title_short | Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke |
| title_sort | matrix metalloproteinases and blood brain barrier disruption in acute ischemic stroke |
| topic | matrix metalloproteinases blood-brain barrier stroke caveolin-1 reactive oxygen species |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2013.00032/full |
| work_keys_str_mv | AT shaheenelakhan matrixmetalloproteinasesandbloodbrainbarrierdisruptioninacuteischemicstroke AT shaheenelakhan matrixmetalloproteinasesandbloodbrainbarrierdisruptioninacuteischemicstroke AT annettekirchgessner matrixmetalloproteinasesandbloodbrainbarrierdisruptioninacuteischemicstroke AT annettekirchgessner matrixmetalloproteinasesandbloodbrainbarrierdisruptioninacuteischemicstroke AT deborahtepper matrixmetalloproteinasesandbloodbrainbarrierdisruptioninacuteischemicstroke AT aidanleonard matrixmetalloproteinasesandbloodbrainbarrierdisruptioninacuteischemicstroke |