Abstract
Tissue plasminogen activator (tPA) has been used to treat acute thrombotic lesions. Roles other than the activation of fibrinolytic pathways have been suggested for tPA in the mature brain. We used the in situ hybridization technique to investigate the changes in tPA mRNA expression within the brain after cortical ablation. We found that expression of tPA mRNA started to increase diffusely in the cortex ipsilateral to the injury 6 h after ablation. This increase had become prominent 24 h after ablation. On d 5, the expression of tPA mRNA had returned to that of the control animals except for the area near the injury. We also found that administration of MK-801 before injury suppressed the increase of tPA mRNA in the ipsilateral cortex. These results suggest that the increase in tPA mRNA is likely to be mediated via activation of NMDA receptors.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Gualandris A., Jones T. E., Strickland S., and Tsirka S.E. (1996) Membrane depolarization induces calcium-dependent secretion of tissue plasminogen activator. J. Neurosci. 16, 2220–2225.
Hekman C. M. and Loskutoff D. J. (1988) Kinetic analysis of the interactions between plasminogen activator inhibitor 1 and both urokinase and tissue plasminogen activator. Arch. Biochem. Biophys. 262, 199–210.
Kalderon N. (1984) Schwann cell proliferation and localized proteolysis: expression of plasminogen-activator activity predominates in the proliferating cell populations. Proc. Natl. Acad. Sci. USA 81, 7216–7220.
Kaliko K., Harris V. A., Ranger Y., Duvall M. E., and Welsh F. A. (1998) Effect of cortical spreading depression on the level of mRNA coding for putative neuroprotective proteins in rat brain. J. Cereb. Blood Flow Metab. 18, 1308–1315.
Kohmura E., Yuguchi T., Yamada K., Sakaguchi T., Wanaka A., and Hayakawa T. (1995) Expression of c-fos mRNA after cortical ablation in rat brain is modulated by basic fibroblast growth factor (bFGF) and the NMDA receptor is induced in c-fos expression. Mol. Brain Res. 28, 117–121.
Krystosek A. and Seeds N. W. (1981) Plasminogen activator release at the neuronal growth cone. Science 213, 1532–1534.
McGuire P. G. and Seeds N. W. (1990) Degradation of underlying extracellular matrix by sensory neurons during neurite outgrowth. Neuron 4, 633–642.
Moonen G., Grau-Wagemans M.-P., and Selak I. (1982) Plasminogen activator-plasmin system and neuronal migration. Nature 298, 753–755.
Moonen G., Grau-Wagemans M.-P., Selak I., Lefebvre P. P., Rogister B., Vassalli J. D., and Belin D. (1985) Plasminogen activator is a mitogen for astrocytes in developing cerebellum. Dev. Brain Res. 20, 41–48.
Pennica D., Holmes W. E., Kohr W. J., Harkins R. N., Vehar G. A., Ward C. A., et al. (1983) Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 301, 214–221.
Qian Z., Gilbert M. E., Colicos M. A., Kandel E. R., and Kuhl D. (1993) Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation. Nature 361, 453–457.
Reddington M., Hass C., and Kreutzberg G. W. (1994). The plasminogen activator system in neurons and glia during motoneuron regeneration. Neuropathol. Appl. Neurobiol. 20, 188–190.
Rickles R. J., Darrow A. L., and Strickland S. (1988) Molecular cloning of complementary DNA to mouse tissue plasminogen activator mRNA and its expression during F9 teratocarcinoma cell differentiation. J. Biol. Chem. 263, 1563–1569.
Scarisbrick I. A., Towner M. D., and Isackson P. J. (1997) Nervous system-specific expression of a novel serine protease: regulation in the adult rat spinal cord by excitotoxic injury. J. Neurosci. 17, 8156–8168.
Seeds N. W., Williams B. L., and Bickford P. C. (1995) Tissue plasminogen activator induction in Purkinje neurons after cerebellar motor learning. Science 270, 1992–1994.
Sharp J. W., Sagar S. M., Hisanaga K., Jasper P., and Sharp F. R. (1990) The NMDA receptor mediates cortical induction of fos and fos related antigens following cortical injury. Exp. Neurol. 109, 323–332.
Tsirka S. E., Gualandris A., Amaral D. G., and Strickland S. (1995) Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature 377, 340–344.
Tsirka S. E. (1997a) Clinical implications of the involvement of tPA in neuronal call death. J. Mol. Med. 75, 341–347.
Tsirka S. E., Rogove A. D., Bugge T. H., Degen J. L., and Strickland S. (1997b) An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J. Neurosci. 15, 543–552.
Wang Y. F., Tsirka S. E., Strickland S., Stieg P. E., Soriano S. G., and Lipton S. A. (1998) Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nature Med. 4, 228–231.
Ware J. H., Dibenedetto A. J., and Pittman R. N. (1995) Localization of tissue plasminogen activator mRNA in adult rat brain. Brain Res. Bull. 3, 275–281.
Yuguchi T., Kohmura E., Yamada K., Wanaka A., Otsuki H., Sakaguchi T., et al. (1994) Messenger RNA and protein expression of basic fibroblast growth factor receptor after cortical ablation. Mol. Brain. Res. 25, 50–56.
Yuguchi T., Kohmura E., Yamada K., Otsuki H., Sakaki T., Yamashita T., et al. (1997) Expression of tPA mRNA in the facial nerve transection in the rat. Neuroreport 8, 419–422.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kohmura, E., Yuguchi, T., Sakaki, T. et al. Changes in tissue-plasminogen activator mRNA expression following cortical ablation in the rat brain. J Mol Neurosci 14, 53–59 (2000). https://doi.org/10.1385/JMN:14:1-2:053
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/JMN:14:1-2:053