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Matrix Metalloproteinases and Tissue Plasminogen Activator Reperfusion Therapy for Stroke

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Reperfusion therapy with intravenous tissue plasminogen activator (t‐PA) is the only FDA‐approved Medical therapy for acute ischemic stroke. Properly titrated use of t‐PA improves clinical outcomes. However, the near tenfold‐associated risk of intracerebral hemorrhage after t‐PA may keep this therapy from many acute stroke patients. Emerging data now suggest that some of the potentially neurotoxic side effects of t‐PA may be due to its signaling actions in the neurovascular unit. Besides its intended role in clot lysis, t‐PA is also an extracellular protease and signaling molecule in the brain. t‐PA mediates matrix remodeling during brain development and plasticity. By interacting with the NMDA‐type glutamate receptor, t‐PA may amplify potentially excitotoxic calcium currents. At selected concentrations, t‐PA may be vasoactive. Finally, by augmenting matrix metalloproteinase (MMP) dysregulation after stroke, t‐PA may degrade extracellular matrix integrity and increase risks of neurovascular cell death, blood–brain barrier leakage, edema, and hemorrhage. Understanding these pleiotropic actions of t‐PA may reveal new therapeutic opportunities for increasing the safety and efficacy of reperfusion strategies for stroke therapy.

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Abbreviations

MMP:

Matrix metalloproteinase

BBB:

blood brain barrier

t‐PA:

tissue plasminogen activator

rt‐PA:

recombinant tissue plasminogen activator

NINDS:

National Institute of Neurological Disorders and Stroke

ICH:

intracerebral haemorrhage

HT:

Hemorrhagic transformation

NVU:

neurovascular unit

ECM:

extracellular matrix

i.v.:

intravenous

CNS:

central nervous system

LTP:

long‐term potentiation

LRP:

lipoprotein receptor‐related protein

PKA:

protein kinase A

MCAO:

middle cerebral artery occlusion

NO:

nitric oxide

NOS:

nitric oxide synthase

TBI:

traumatic brain injury

PMNL:

polymorphonuclear leukocytes

MAP kinase:

mitogen‐activated protein kinase

SOD:

superoxide dismutase

MBP:

myelin basic protein

ROS:

Reactive oxygen species

References

  • 1993. Protocol for the multicenter acute stroke trial—thrombolysis study. Clin Trials Metaanal 28 (6): 329–344.

    Google Scholar 

  • Abilleira S, Montaner J, Molina CA, Monasterio J, Castillo J, et al. 2003. Matrix metalloproteinase‐9 concentration after spontaneous intracerebral hemorrhage. J Neurosurg 99 (1): 65–70.

    Article  CAS  PubMed  Google Scholar 

  • Akassoglou K, Kombrinck KW, Degen JL, Strickland S. 2000. Tissue plasminogen activator‐mediated fibrinolysis protects against axonal degeneration and demyelination after sciatic nerve injury. J Cell Biol 149 (5): 1157–1166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Albers GW, Clark WM, Madden KP, Hamilton SA. 2002. ATLANTIS trial: results for patients treated within 3 hours of stroke onset. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. Stroke 33 (2): 493–495.

    Article  PubMed  Google Scholar 

  • American Heart Association. Heart Disease and Stroke Statistics—2006 Update. Dallas, Texas: American Heart Association; 2006.

    Google Scholar 

  • Andersen M, Overgaard K, Meden P, Boysen G, Choi SC. 1999. Effects of citicoline combined with thrombolytic therapy in a rat embolic stroke model. Stroke 30 (7): 1464–1471.

    Article  CAS  PubMed  Google Scholar 

  • Aoki T, Sumii T, Mori T, Wang X, Lo EH. 2002. Blood‐brain barrier disruption and matrix metalloproteinase‐9 expression during reperfusion injury: mechanical versus embolic focal ischemia in spontaneously hypertensive rats. Stroke 33 (11): 2711–2717.

    Article  PubMed  Google Scholar 

  • Asahi M, Wang X, Mori T, Sumii T, Jung JC, et al. 2001. Effects of matrix metalloproteinase‐9 gene knock‐out on the proteolysis of blood‐brain barrier and white matter components after cerebral ischemia. J Neurosci 21 (19): 7724–7732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Backstrom JR, Lim GP, Cullen MJ, Tokes ZA. 1996. Matrix metalloproteinase‐9 (MMP‐9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid‐beta peptide (1–40). J Neurosci 16 (24): 7910–7919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baranes D, Lederfein D, Huang YY, Chen M, Bailey CH, et al. 1998. Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway. Neuron 21 (4): 813–825.

    Article  CAS  PubMed  Google Scholar 

  • Beck KF, Eberhardt W, Frank S, Huwiler A, Messmer UK, et al. 1999. Inducible NO synthase: role in cellular signalling. J Exp Biol 202 (Pt. 6): 645–653.

    Article  CAS  PubMed  Google Scholar 

  • Bignami A, Cella G, Chi NH. 1982. Plasminogen activators in rat neural tissues during development and in Wallerian degeneration. Acta Neuropathol (Berl) 58 (3): 224–228.

    Article  CAS  Google Scholar 

  • Buchan AM, Warren DT. (2002). tPA toxicity in experimental cerebral ischemia: mechamnisms and clinical implications. In: Phamacology of cerebral ischemia (Krieglstein J, Klumpp S, eds), 193–199.

    Google Scholar 

  • Bugge TH, Flick MJ, Daugherty CC, Degen JL. 1995. Plasminogen deficiency causes severe thrombosis but is compatible with development and reproduction. Genes Dev 9 (7): 794–807.

    Article  CAS  PubMed  Google Scholar 

  • Calabresi P, Napolitano M, Centonze D, Marfia GA, Gubellini P, et al. 2000. Tissue plasminogen activator controls multiple forms of synaptic plasticity and memory. Eur J Neurosci 12 (3): 1002–1012.

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P, Schoonjans L, Kieckens L, Ream B, Degen J, et al. 1994. Physiological consequences of loss of plasminogen activator gene function in mice. Nature 368 (6470): 419–424.

    Article  CAS  PubMed  Google Scholar 

  • Carroll PM, Tsirka SE, Richards WG, Frohman MA, Strickland S. 1994. The mouse tissue plasminogen activator gene 5'′ flanking region directs appropriate expression in development and a seizure‐enhanced response in the CNS. Development 120 (11): 3173–3183.

    Article  CAS  PubMed  Google Scholar 

  • Carter LP, Guthkelch AN, Orozco J, Temeltas O. 1992. Influence of tissue plasminogen activator and heparin on cerebral ischemia in a rabbit model. Stroke 23 (6): 883–888.

    Article  CAS  PubMed  Google Scholar 

  • Castellanos M, Leira R, Serena J, Pumar JM, Lizasoain I, et al. 2003. Plasma metalloproteinase‐9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke 34 (1): 40–46.

    Article  CAS  PubMed  Google Scholar 

  • Chan PH. 1996. Role of oxidants in ischemic brain damage. Stroke 27 (6): 1124–1129.

    Article  CAS  PubMed  Google Scholar 

  • Chan PH. 2001. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21 (1): 2–14.

    Article  CAS  PubMed  Google Scholar 

  • Chen ZL, Strickland S. 1997. Neuronal death in the hippocampus is promoted by plasmin‐catalyzed degradation of laminin. Cell 91 (7): 917–925.

    Article  CAS  PubMed  Google Scholar 

  • Chen ZL, Yoshida S, Kato K, Momota Y, Suzuki J, et al. 1995. Expression and activity‐dependent changes of a novel limbic‐serine protease gene in the hippocampus. J Neurosci 15 (7 Pt. 2): 5088–5097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, et al. 1999. Recombinant tissue‐type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 282 (21): 2019–2026.

    Article  CAS  PubMed  Google Scholar 

  • Davies BJ, Pickard BS, Steel M, Morris RG, Lathe R. 1998. Serine proteases in rodent hippocampus. J Biol Chem 273 (36): 23004–23011.

    Article  CAS  PubMed  Google Scholar 

  • Donnan GA, Hommel M, Davis SM, McNeil JJ. 1995. Streptokinase in acute ischaemic stroke. Steering Committees of the ASK and MAST‐E trials. Australian Streptokinase Trial. Lancet 346 (8966): 56.

    Article  CAS  PubMed  Google Scholar 

  • Eberhardt W, Beck KF, Pfeilschifter J. 2002. Cytokine‐induced expression of tPA is differentially modulated by NO and ROS in rat mesangial cells. Kidney Int 61 (1): 20–30.

    Article  CAS  PubMed  Google Scholar 

  • Egeblad M, Werb Z. 2002. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2 (3): 161–174.

    Article  CAS  PubMed  Google Scholar 

  • Fagan SC, Morgenstern LB, Petitta A, Ward RE, Tilley BC, et al. 1998. Cost‐effectiveness of tissue plasminogen activator for acute ischemic stroke. NINDS rt‐PA Stroke Study Group. Neurology 50 (4): 883–890.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez‐Monreal M, Lopez‐Atalaya JP, Benchenane K, Leveille F, Cacquevel M, et al. 2004. Is tissue‐type plasminogen activator a neuromodulator? Mol Cell Neurosci 25 (4): 594–601.

    Article  PubMed  CAS  Google Scholar 

  • Frey U, Muller M, Kuhl D. 1996. A different form of long‐lasting potentiation revealed in tissue plasminogen activator mutant mice. J Neurosci 16 (6): 2057–2063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friedman GC, Seeds NW. 1995. Tissue plasminogen activator mRNA expression in granule neurons coincides with their migration in the developing cerebellum. J Comp Neurol 360 (4): 658–670.

    Article  CAS  PubMed  Google Scholar 

  • Frisch SM, Francis H. 1994. Disruption of epithelial cell‐matrix interactions induces apoptosis. J Cell Biol. 124: 619–626.

    Article  CAS  PubMed  Google Scholar 

  • Gasche Y, Copin JC, Sugawara T, Fujimura M, Chan PH. 2001. Matrix metalloproteinase inhibition prevents oxidative stress‐associated blood‐brain barrier disruption after transient focal cerebral ischemia. J Cereb Blood Flow Metab 21 (12): 1393–1400.

    Article  CAS  PubMed  Google Scholar 

  • Gautier S, Petrault O, Gele P, Laprais M, Bastide M, et al. 2003. Involvement of thrombolysis in recombinant tissue plasminogen activator‐induced cerebral hemorrhages and effect on infarct volume and postischemic endothelial function. Stroke 34 (12): 2975–2979.

    Article  CAS  PubMed  Google Scholar 

  • Gingrich MB, Junge CE, Lyuboslavsky P, Traynelis SF. 2000. Potentiation of NMDA receptor function by the serine protease thrombin. J Neurosci 20 (12): 4582–4595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • The National Institute of Neurological Disorders and Stroke rt‐PA Stroke Study. 1995. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333 (24): 1581–1587.

    Google Scholar 

  • The NINDS Stroke Program Review. 2000. Report of the Stroke Progress Review Group, NINDS. 1–116.

    Google Scholar 

  • Gschwend TP, Krueger SR, Kozlov SV, Wolfer DP, Sonderegger P. 1997. Neurotrypsin, a novel multidomain serine protease expressed in the nervous system. Mol Cell Neurosci 9 (3): 207–219.

    Article  CAS  PubMed  Google Scholar 

  • Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, et al. 2002. S‐nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 297 (5584): 1186–1190.

    Article  CAS  PubMed  Google Scholar 

  • Gualandris A, Jones TE, Strickland S, Tsirka SE. 1996. Membrane depolarization induces calcium‐dependent secretion of tissue plasminogen activator. J Neurosci 16 (7): 2220–2225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hacke W, Bluhmki E, Steiner T, Tatlisumak T, Mahagne MH, et al. 1998a. Dichotomized efficacy end points and global end‐point analysis applied to the ECASS intention‐to‐treat data set: post hoc analysis of ECASS I. Stroke 29 (10): 2073–2075.

    Article  CAS  PubMed  Google Scholar 

  • Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, et al. 1998b. Randomised double‐blind placebo‐controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European‐Australasian Acute Stroke Study Investigators. Lancet 352 (9136): 1245–1251.

    Article  CAS  PubMed  Google Scholar 

  • Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, et al. 2004. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt‐PA stroke trials. Lancet 363 (9411): 768–774.

    Article  PubMed  Google Scholar 

  • Hamann GF, Okada Y, del Zoppo GJ. 1996. Hemorrhagic transformation and microvascular integrity during focal cerebral ischemia/reperfusion. J Cereb Blood Flow Metab 16 (6): 1373–1378.

    Article  CAS  PubMed  Google Scholar 

  • Hamann GF, Okada Y, Fitridge R, del Zoppo GJ. 1995. Microvascular basal lamina antigens disappear during cerebral ischemia and reperfusion. Stroke 26 (11): 2120–2126.

    Article  CAS  PubMed  Google Scholar 

  • Hill MD, Buchan AM. 2001. Methodology for the Canadian Activase for Stroke Effectiveness Study (CASES). CASES Investigators. Can J Neurol Sci 28 (3): 232–238.

    Article  CAS  PubMed  Google Scholar 

  • Hoffman KB, Larson J, Bahr BA, Lynch G. 1998. Activation of NMDA receptors stimulates extracellular proteolysis of cell adhesion molecules in hippocampus. Brain Res 811 (1–2): 152–155.

    Article  CAS  PubMed  Google Scholar 

  • Hommel M, Boissel JP, Cornu C, Boutitie F, Lees KR, et al. 1995. Termination of trial of streptokinase in severe acute ischaemic stroke. MAST Study Group. Lancet 345 (8941): 57.

    Article  CAS  PubMed  Google Scholar 

  • Huang YY, Bach ME, Lipp HP, Zhuo M, Wolfer DP, et al. 1996. Mice lacking the gene encoding tissue‐type plasminogen activator show a selective interference with late‐phase long‐term potentiation in both Schaffer collateral and mossy fiber pathways. Proc Natl Acad Sci USA 93 (16): 8699–8704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Z, Huang PL, Panahian N, Dalkara T, Fishman MC, et al. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 265 (5180): 1883–1885.

    Google Scholar 

  • Justicia C, Panes J, Sole S, Cervera A, Deulofeu R, et al. 2003. Neutrophil infiltration increases matrix metalloproteinase‐9 in the ischemic brain after occlusion/reperfusion of the middle cerebral artery in rats. J Cereb Blood Flow Metab 23 (12): 1430–1440.

    Article  CAS  PubMed  Google Scholar 

  • Kano T, Katayama Y, Tejima E, Lo EH. 2000. Hemorrhagic transformation after fibrinolytic therapy with tissue plasminogen activator in a rat thromboembolic model of stroke. Brain Res 854 (1–2): 245–248.

    Article  CAS  PubMed  Google Scholar 

  • Katzan IL, Furlan AJ, Lloyd LE, Frank JI, Harper DL, et al. 2000. Use of tissue‐type plasminogen activator for acute ischemic stroke: the Cleveland area experience. JAMA 283 (9): 1151–1158.

    Article  CAS  PubMed  Google Scholar 

  • Kaur J, Zhao Z, Klein GM, Lo EH, Buchan AM. 2004. The neurotoxicity of tissue plasminogen activator? J Cereb Blood Flow Metab 24 (9): 945–963.

    Article  CAS  PubMed  Google Scholar 

  • Kilic E, Bahr M, Hermann DM. 2001. Effects of recombinant tissue plasminogen activator after intraluminal thread occlusion in mice: role of hemodynamic alterations. Stroke 32 (11): 2641–2647.

    Article  CAS  PubMed  Google Scholar 

  • Klein GM, Li H, Sun P, Buchan AM. 1999. Tissue plasminogen activator does not increase neuronal damage in rat models of global and focal ischemia. Neurology 52 (7): 1381–1384.

    Article  CAS  PubMed  Google Scholar 

  • Krystosek A, Seeds NW. 1981. Plasminogen activator release at the neuronal growth cone. Science 213 (4515): 1532–1534.

    Article  CAS  PubMed  Google Scholar 

  • Krystosek A, Seeds NW. 1984. Peripheral neurons and Schwann cells secrete plasminogen activator. J Cell Biol 98 (2): 773–776.

    Article  CAS  PubMed  Google Scholar 

  • Lapchak PA, Chapman DF, Zivin JA. 2000. Metalloproteinase inhibition reduces thrombolytic (tissue plasminogen activator)‐induced hemorrhage after thromboembolic stroke. Stroke 31 (12): 3034–3040.

    Article  CAS  PubMed  Google Scholar 

  • Lee SR, Lo EH. 2004. Induction of caspase‐mediated cell death by matrix metalloproteinases in cerebral endothelial cells after hypoxia‐reoxygenation. J Cereb Blood Flow Metab 24 (7): 720–727.

    Article  CAS  PubMed  Google Scholar 

  • Lijnen HR. 2001. Plasmin and matrix metalloproteinases in vascular remodeling. Thromb Haemost 86 (1): 324–333.

    CAS  PubMed  Google Scholar 

  • Lo EH, Broderick JP, Moskowitz MA. 2004. tPA and proteolysis in the neurovascular unit. Stroke 35 (2): 354–356.

    Article  PubMed  Google Scholar 

  • Lo EH, Dalkara T, Moskowitz MA. 2003. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4 (5): 399–415.

    Article  CAS  PubMed  Google Scholar 

  • Lo EH, Wang X, Cuzner ML. 2002. Extracellular proteolysis in brain injury and inflammation: role for plasminogen activators and matrix metalloproteinases. J Neurosci Res 69 (1): 1–9.

    Article  CAS  PubMed  Google Scholar 

  • Lu W, Tsirka SE. 2002. Partial rescue of neural apoptosis in the Lurcher mutant mouse through elimination of tissue plasminogen activator. Development 129 (8): 2043–2050.

    Article  CAS  PubMed  Google Scholar 

  • Madani R, Hulo S, Toni N, Madani H, Steimer T, et al. 1999. Enhanced hippocampal long‐term potentiation and learning by increased neuronal expression of tissue‐type plasminogen activator in transgenic mice. EMBO J 18 (11): 3007–3012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maier CM, Ahern K, Cheng ML, Lee JE, Yenari MA, et al. 1998. Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia: effects on neurologic outcome, infarct size, apoptosis, and inflammation. Stroke 29 (10): 2171–2180.

    Article  CAS  PubMed  Google Scholar 

  • Maier CM, Hsieh L, Yu F, Bracci P, Chan PH. 2004. Matrix metalloproteinase‐9 and myeloperoxidase expression: quantitative analysis by antigen immunohistochemistry in a model of transient focal cerebral ischemia. Stroke 35 (5): 1169–1174.

    Article  CAS  PubMed  Google Scholar 

  • Mecenas PE, Tsirka SE, Salles F, Strickland S. 1997. Removal of tissue plasminogen activator does not protect against neuronal degeneration in the cerebellum of the weaver mouse. Brain Res 772 (1–2): 233–238.

    Article  CAS  PubMed  Google Scholar 

  • Meng W, Wang X, Asahi M, Kano T, Asahi K, et al. 1999. Effects of tissue type plasminogen activator in embolic versus mechanical models of focal cerebral ischemia in rats. J Cereb Blood Flow Metab 19 (12): 1316–1321.

    Article  CAS  PubMed  Google Scholar 

  • Montaner J, Alvarez‐Sabin J, Molina C, Angles A, Abilleira S, et al. 2001. Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke 32 (8): 1759–1766.

    Article  CAS  PubMed  Google Scholar 

  • Montaner J, Molina CA, Arenillas JF, Ribó M, Huertas R, et al. 2004. Proteolytic modifications on the metalloproteinase system (MMP‐9‐Laminin‐TIMP‐1) induced by t‐PA treatment for acute cerebral ischemia in humans. Stroke 35: 339.

    Google Scholar 

  • Montaner J, Molina CA, Monasterio J, Abilleira S, Arenillas JF, et al. 2003. Matrix metalloproteinase‐9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke. Circulation 107 (4): 598–603.

    Article  CAS  PubMed  Google Scholar 

  • Mori T, Wang X, Aoki T, Lo EH. 2002. Downregulation of matrix metalloproteinase‐9 and attenuation of edema via inhibition of ERK mitogen activated protein kinase in traumatic brain injury. J Neurotrauma 19 (11): 1411–1419.

    Article  PubMed  Google Scholar 

  • Mori T, Wang X, Kline AE, Siao CJ, Dixon CE, et al. 2001. Reduced cortical injury and edema in tissue plasminogen activator knockout mice after brain trauma. Neuroreport 12 (18): 4117–4120.

    Article  CAS  PubMed  Google Scholar 

  • Morita‐Fujimura Y, Fujimura M, Gasche Y, Copin JC, Chan PH. 2000. Overexpression of copper and zinc superoxide dismutase in transgenic mice prevents the induction and activation of matrix metalloproteinases after cold injury‐induced brain trauma. J Cereb Blood Flow Metab 20 (1): 130–138.

    Article  PubMed  Google Scholar 

  • Mun‐Bryce S, Rosenberg GA. 1998. Matrix metalloproteinases in cerebrovascular disease. J Cereb Blood Flow Metab 18 (11): 1163–1172.

    Article  PubMed  Google Scholar 

  • Murphy G, Atkinson S, Ward R, Gavrilovic J, Reynolds JJ. 1992. The role of plasminogen activators in the regulation of connective tissue metalloproteinases. Ann N Y Acad Sci 667: 1–12.

    Article  CAS  PubMed  Google Scholar 

  • Nagai N, De Mol M, Lijnen HR, Carmeliet P, Collen D. 1999a. Role of plasminogen system components in focal cerebral ischemic infarction: a gene targeting and gene transfer study in mice. Circulation 99 (18): 2440–2444.

    Article  CAS  PubMed  Google Scholar 

  • Nagai N, Vanlinthout I, Collen D. 1999b. Comparative effects of tissue plasminogen activator, streptokinase, and staphylokinase on cerebral ischemic infarction and pulmonary clot lysis in hamster models. Circulation 100 (25): 2541–2546.

    Article  CAS  PubMed  Google Scholar 

  • Nagai N, Zhao BQ, Suzuki Y, Ihara H, Urano T, et al. 2002. Tissue‐type plasminogen activator has paradoxical roles in focal cerebral ischemic injury by thrombotic middle cerebral artery occlusion with mild or severe photochemical damage in mice. J Cereb Blood Flow Metab 22 (6): 648–651.

    Article  CAS  PubMed  Google Scholar 

  • Nagase H, Visse R, Murphy G. 2006. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res Feb 15; 69(3): 562–73.

    Google Scholar 

  • Neuhoff H, Roeper J, Schweizer M. 1999. Activity‐dependent formation of perforated synapses in cultured hippocampal neurons. Eur J Neurosci 11 (12): 4241–4250.

    Article  CAS  PubMed  Google Scholar 

  • Nicole O, Docagne F, Ali C, Margaill I, Carmeliet P, et al. 2001. The proteolytic activity of tissue‐plasminogen activator enhances NMDA receptor‐mediated signaling. Nat Med 7 (1): 59–64.

    Article  CAS  PubMed  Google Scholar 

  • Ning MM, Lo EH, Furie KL, Koroshetz WJ, Sleeper L, et al. 2004. T‐PA‐mediated increase in matrix metalloproteinase‐9 in acute ischemic stroke is independent of inflammatory response. Stroke 35 (1): 298.

    Google Scholar 

  • Ning MM, Furie KL, Koroshetz WJ, Lee H, Barron M, Lederer M, Wang XY, Zhu MW, Sorensen AG, Lo EH, Kelly PJ. 2006. Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke. Neurology (66): 1550–1555 .

    Article  CAS  PubMed  Google Scholar 

  • Nishibori M, Ohtsuka A, Kawabata M, Nakaya N, Murakami T, et al. 1995. A novel serpin‐like protein, B‐43, exists in both neurons and astrocytes: an immunohistochemical study in the parietal region of the bovine brain. Neurosci Lett 200 (2): 125–128.

    Article  CAS  PubMed  Google Scholar 

  • Opdenakker G, Van den Steen PE, Dubois B, Nelissen I, Van Coillie E, et al. 2001. Gelatinase B functions as regulator and effector in leukocyte biology. J Leukoc Biol 69 (6): 851–859.

    CAS  PubMed  Google Scholar 

  • Parmer RJ, Mahata M, Mahata S, Sebald MT, O'Connor DT, et al. 1997. Tissue plasminogen activator (t‐PA) is targeted to the regulated secretory pathway. Catecholamine storage vesicles as a reservoir for the rapid release of t‐PA. J Biol Chem 272 (3): 1976–1982.

    Article  CAS  PubMed  Google Scholar 

  • Pawlak R, Strickland S. 2002. Tissue plasminogen activator and seizures: a clot‐buster's secret life. J Clin Invest 109 (12): 1529–1531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petty MA, Lo EH. 2002. Junctional complexes of the blood‐brain barrier: permeability changes in neuroinflammation. Prog Neurobiol 68 (5): 311–323.

    Article  CAS  PubMed  Google Scholar 

  • Pfefferkorn T, Rosenberg GA. 2003. Closure of the blood‐brain barrier by matrix metalloproteinase inhibition reduces rtPA‐mediated mortality in cerebral ischemia with delayed reperfusion. Stroke 34 (8): 2025–2030.

    Article  PubMed  Google Scholar 

  • Qian Z, Gilbert ME, Colicos MA, Kandel ER, Kuhl D. 1993. Tissue‐plasminogen activator is induced as an immediate‐early gene during seizure, kindling and long‐term potentiation. Nature 361 (6411): 453–457.

    Article  CAS  PubMed  Google Scholar 

  • Rogove AD, Siao C, Keyt B, Strickland S, Tsirka SE. 1999. Activation of microglia reveals a non‐proteolytic cytokine function for tissue plasminogen activator in the central nervous system. J Cell Sci 112 (Pt. 22): 4007–4016.

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg GA. 1995. Matrix metalloproteinases in brain injury. J Neurotrauma 12 (5): 833–842.

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg GA. 2002. Matrix metalloproteinases in neuroinflammation. Glia 39 (3): 279–291.

    Article  PubMed  Google Scholar 

  • Rosenberg GA, Estrada EY, Dencoff JE. 1998. Matrix metalloproteinases and TIMPs are associated with blood‐brain barrier opening after reperfusion in rat brain. Stroke 29 (10): 2189–2195.

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg GA, Kornfeld M, Estrada E, Kelley RO, Liotta LA, et al. 1992. TIMP‐2 reduces proteolytic opening of blood‐brain barrier by type IV collagenase. Brain Res 576 (2): 203–207.

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg GA, Navratil M, Barone F, Feuerstein G. 1996. Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Flow Metab 16 (3): 360–366.

    Article  CAS  PubMed  Google Scholar 

  • Salles FJ, Strickland S. 2002. Localization and regulation of the tissue plasminogen activator‐plasmin system in the hippocampus. J Neurosci 22 (6): 2125–2134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sappino AP, Madani R, Huarte J, Belin D, Kiss JZ, et al. 1993. Extracellular proteolysis in the adult murine brain. J Clin Invest 92 (2): 679–685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scarisbrick IA, Isackson PJ, Ciric B, Windebank AJ, Rodriguez M. 2001. MSP, a trypsin‐like serine protease, is abundantly expressed in the human nervous system. J Comp Neurol 431 (3): 347–361.

    Article  CAS  PubMed  Google Scholar 

  • Siao CJ, Tsirka SE. 2002. Extracellular proteases and neuronal cell death. Cell Mol Biol (Noisy‐le‐grand) 48 (2): 151–161.

    CAS  Google Scholar 

  • Siao CJ, Fernandez SR, Tsirka SE. 2003. Cell type‐specific roles for tissue plasminogen activator released by neurons or microglia after excitotoxic injury. J Neurosci 23 (8): 3234–3242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siconolfi LB, Seeds NW. 2001. Mice lacking tPA, uPA, or plasminogen genes showed delayed functional recovery after sciatic nerve crush. J Neurosci 21 (12): 4348–4355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steiner T, Bluhmki E, Kaste M, Toni D, Trouillas P, et al. 1998. The ECASS 3‐hour cohort. Secondary analysis of ECASS data by time stratification. ECASS Study Group. European Cooperative Acute Stroke Study. Cerebrovasc Dis 8 (4): 198–203.

    Article  CAS  PubMed  Google Scholar 

  • Sumii T, Lo EH. 2002. Involvement of matrix metalloproteinase in thrombolysis‐associated hemorrhagic transformation after embolic focal ischemia in rats. Stroke 33 (3): 831–836.

    Article  CAS  PubMed  Google Scholar 

  • Tabrizi P, Wang L, Seeds N, McComb JG, Yamada S, et al. 1999. Tissue plasminogen activator (tPA) deficiency exacerbates cerebrovascular fibrin deposition and brain injury in a murine stroke model: studies in tPA‐deficient mice and wild‐type mice on a matched genetic background. Arterioscler Thromb Vasc Biol 19 (11): 2801–2806.

    Article  CAS  PubMed  Google Scholar 

  • Tanne D, Bates VE, Verro P, Kasner SE, Binder JR, et al. 1999. Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke: a multicenter survey. The t‐PA Stroke Survey Group. Neurology 53 (2): 424–427.

    Article  CAS  PubMed  Google Scholar 

  • Tsirka SE, Gualandris A, Amaral DG, Strickland S. 1995. Excitotoxin‐induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature 377 (6547): 340–344.

    Article  CAS  PubMed  Google Scholar 

  • Tsirka SE, Rogove AD, Bugge TH, Degen JL, Strickland S. 1997. An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J Neurosci 17 (2): 543–552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsirka SE, Rogove AD, Strickland S. 1996. Neuronal cell death and tPA. Nature 384 (6605): 123–124.

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Lo EH. 2003. Triggers and mediators of hemorrhagic transformation in cerebral ischemia. Mol Neurobiol 28 (3): 229–244.

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Jung J, Asahi M, Chwang W, Russo L, et al. 2000. Effects of matrix metalloproteinase‐9 gene knock‐out on morphological and motor outcomes after traumatic brain injury. J Neurosci 20 (18): 7037–7042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Lee SR, Arai K, Tsuji K, Rebeck GW, et al. 2003. Lipoprotein receptor‐mediated induction of matrix metalloproteinase by tissue plasminogen activator. Nat Med 9 (10): 1313–1317.

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Mori T, Jung JC, Fini ME, Lo EH. 2002. Secretion of matrix metalloproteinase‐2 and ‐9 after mechanical trauma injury in rat cortical cultures and involvement of MAP kinase. J Neurotrauma 19 (5): 615–625.

    Article  PubMed  Google Scholar 

  • Wang X, Tsuji K, Lee SR, Ning M, Furie KL, et al. 2004. Mechanisms of Hemorrhagic Transformation After Tissue Plasminogen Activator Reperfusion Therapy for Ischemic Stroke. Stroke.

    Google Scholar 

  • Wang YF, Tsirka SE, Strickland S, Stieg PE, Soriano SG, et al. 1998. Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild‐type and tPA‐deficient mice. Nat Med 4 (2): 228–231.

    Article  CAS  PubMed  Google Scholar 

  • Warren DT, Klein G, Eliasziw M, Buchan AM. 2003. Neurotoxic Effects of t‐PA in a rat model of permanent focal ischemia. Nuerology 60 (Suppl. 1): A65.

    Google Scholar 

  • Wu YP, Siao CJ, Lu W, Sung TC, Frohman MA, et al. 2000. The tissue plasminogen activator (tPA)/plasmin extracellular proteolytic system regulates seizure‐induced hippocampal mossy fiber outgrowth through a proteoglycan substrate. J Cell Biol 148 (6): 1295–1304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Li Q, Yang T, Hussain M, Shuaib A. 2003. Reduced brain infarct volume and improved neurological outcome by inhibition of the NR2B subunit of NMDA receptors by using CP101,606–627 alone and in combination with rt‐PA in a thromboembolic stroke model in rats. J Neurosurg 98 (2): 397–403.

    Article  CAS  PubMed  Google Scholar 

  • Yenari MA, Palmer JT, Bracci PM, Steinberg GK. 1995. Thrombolysis with tissue plasminogen activator (tPA) is temperature dependent. Thromb Res 77 (5): 475–481.

    Article  CAS  PubMed  Google Scholar 

  • Yepes M, Sandkvist M, Coleman TA, Moore E, Wu JY, et al. 2002. Regulation of seizure spreading by neuroserpin and tissue‐type plasminogen activator is plasminogen‐independent. J Clin Invest 109 (12): 1571–1578.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yong VW, Power C, Forsyth P, Edwards DR. 2001. Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci 2 (7): 502–511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang RL, Zhang L, Jiang Q, Zhang ZG, Goussev A, et al. 2000. Postischemic intracarotid treatment with TNK‐tPA reduces infarct volume and improves neurological deficits in embolic stroke in the unanesthetized rat. Brain Res 878 (1–2): 64–71.

    Article  CAS  PubMed  Google Scholar 

  • Zhao BQ, Ikeda Y, Ihara H, Urano T, Fan W, et al. 2004. Essential role of endogenous tissue plasminogen activator through matrix metalloproteinase 9 induction and expression on heparin‐produced cerebral hemorrhage after cerebral ischemia in mice. Blood 103 (7): 2610–2616.

    Article  CAS  PubMed  Google Scholar 

  • Zhuo M, Holtzman DM, Li Y, Osaka H, De Maro J, et al. 2000. Role of tissue plasminogen activator receptor LRP in hippocampal long‐term potentiation. J Neurosci 20 (2): 542–549.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgment

We thank Dr Pei-Chen Ning, Dr Su Yu Xu, and Dr David McMullin for their insightful review and critique of this manuscript.

Authors
  1. M. M. Ning
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  2. J. Montaner
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  3. X. Wang
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  4. S.‐R. Lee
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  5. K. Tsuji
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  6. E. Tejima
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  7. A. M. Buchan
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  8. E. H. Lo
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, Newyork, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, California, 94305-5487, USA

    Pak H. Chan (Director Neurosurgical Labouratories) (Director Neurosurgical Labouratories)

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Ning, M.M. et al. (2007). Matrix Metalloproteinases and Tissue Plasminogen Activator Reperfusion Therapy for Stroke. In: Lajtha, A., Chan, P.H. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30383-3_15

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