The Changes of Tissue-Type Plasminogen Activator and Matrix Metalloproteinases in Neonatal Mice with Hypoxic-Ischemic Encephalopathy

Abstract:

Fetal distress and neonatal asphyxia are key factors which result in neonatal hypoxic-ischemic encephalopathy (HIE). There is growing evidence that tissue-type plasminogen activator (TPA) and matrix metalloproteinases (MMPs) may be involved in extracellular matrix (ECM) degradation in the central nervous system. In this study, the transmission electron microscope was used to observe the growth and development characteristics of the blood-brain barrier (BBB), follow by the activity of TPA and the expression of MMPs in HIE model were detected. The asphyxia in female mice within the last day of gestation was produced by a delayed cesarean section. The experiment was designed for 1 control group and 2 asphyctic groups (15min and 30min), then the activities of TPA and expression of MMPs were detected separately. The results showed that the BBB was not fully developed in newborns, their brain microvascular endothelial cells were not surrounded with intact basement membrane and only had discontinuous basement membrane-like materials of varying thickness. The activity of TPA and the expression of MMPs of brain increased after hypoxia-ischemia in vivo. Based on these findings we concluded that the basement membrane at the BBB was a weak link in the brain, TPA and MMPs could degrade components of the ECM. So these enzymes increased after hypoxia-ischemia might be able to attack the basement membrane of microvessels, then open the BBB and induce the cerebral edema.

• Periodical: Applied Mechanics and Materials (Volumes 195-196)
• Pages: 447-451
• DOI: https://doi.org/10.4028/www.scientific.net/AMM.195-196.447
• Online since: August 2012
• Authors: Jian Wen Xu, Wei Wang, Xiao Zhen Zhao, Geng Zhang, Juan Bing Wei
• Keywords: Blood-Brain Barrier, Development, Hypoxia-Ischemia, Matrix Metalloproteinases, Mouse, Tissue-Type Plasminogen Activator, Ultrastructure

References

[1] V.S. Ten, M. Bradley-Moore, A. J. Gingrich, R.I. Stark and D.J. Pinsky, Brain injury and neurofunctional deficit in neonatal mice with hypoxic-ischemic encephalopathy Behavioural, Brain Research. vol. 145, pp.209-219, (2003).

DOI: 10.1016/s0166-4328(03)00146-3

[2] M.C. Lai and S.N. Yang, Perinatal Hypoxic-Ischemic Encephalopathy, J Biomed Biotech. 2011, in press.

[3] K. Muramatsu, A. Fukuda, H. Togari, Y. Wada and H. Nishino, Vulnerability to cerebral hypoxic-ischemic insult in neonatal but not in adult rats is in parallel with disruption of the blood-brain barrier, Strok. vol. 28, pp.2281-2288, November (1997).

DOI: 10.1161/01.str.28.11.2281

[4] W. Wang. Relationship between extracellular matrix both in choroid plexus and the wall of lateral ventricles and intraventricular hemorrhage in preterm neonates, Clin Anat. vol. 13, pp.422-428, (2000).

DOI: 10.1002/1098-2353(2000)13:6<422::aid-ca5>3.0.co;2-f

[5] Q. Zhuo, E.G. Mary, A. Michael, E.R. Kandel and D. Kuhl. Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kinding and long-term potentiation, Nature. vol. 361, pp.453-460, (1993).

DOI: 10.1038/361453a0

[6] D. Lepperta, R.L. Lindbergb, L. Kapposa and S.L. Leibc, Matrix metalloproteinases: multifunctional effectors of inflammation in multiple sclerosis and bacterial meningitis, Brain Research Reviews. vol. 36, pp.249-257, (2001).

DOI: 10.1016/s0165-0173(01)00101-1

[7] K. Yagi, K.T. Kitazato, M. Uno, Y. Tada, T. Kinouchi, K. Shimada and S. Nagahiro, Edaravone, a free radical scavenger, inhibits MMP-9–related brain hemorrhage in rats treated with tissue plasminogen activator, Stroke. vol. 40, pp.626-631, (2009).

DOI: 10.1161/strokeaha.108.520262

[8] J.W. Xu，W. Wang Z.H. Kang and G. Zhang, Influences on the activities of tissue-type plasminogen activator of blood- brain barrier cells in hypoxia, Chinese Journal of Anatomy. vol. 23, p.536, December 2000. (in Chinese).

[9] B. Bjelke, K. Andersson, S.O. Ogren and P. Bolme Asphyctic lesion: Proliferation of tyrosine hydroxylase-immunoreactive nerve cell bodies in the rat substantia nigra and functional changes in dopamine neurotransmission, Brain Res, vol. 543, pp.1-9, (1991).

DOI: 10.1016/0006-8993(91)91041-x

[10] L.T. Furcht, Critical factors controlling angiogenesis: Cell products, cell matrix, and growth factors, Lab Invest. Vol. 55, pp.505-509, (1986).

[11] T.J. Herbst, J.B. McCarthy, E.C. Tsilibary and L.T. Furcht. Differential effects of laminin, intact type IV collagen, and specific domains of type IV collagen on endothelial cell adhesion and migration, J Cell Biol. vol. 106, pp.1365-1373, (1988).

DOI: 10.1083/jcb.106.4.1365

[12] M. Glas, B. Popp, B. Angele, U. Koedel, C. Chahli and W. A, A role for the urokinase-type plasminogen activator system in amyotrophic lateral sclerosis, Exp Neurol. vol. 207, pp.350-356, October (2007).

DOI: 10.1016/j.expneurol.2007.07.007

[13] V. Shahla. Characterization of 125I- tissue plasminogen activator binding to cerebellar granule neurons, J cell Bio. vol. 109, p.265, (1989).

DOI: 10.1083/jcb.109.1.265

[14] A.P. Sappino, R. Madani, Huarte J, D. Belin, J.Z. Kiss and A. Wohlwend, Extracellular Proteolysis in the adult murine brain, J Clin Invest. vol. 92, pp.679-685, (1993).

DOI: 10.1172/jci116637

[15] Nakajima K. Microglia isolated from rat brain secrete a urokinase-type plasminogen activator, Brain Res. vol. 577, pp.285-292, (1992).

DOI: 10.1016/0006-8993(92)90285-h

[16] N. Kawai, M. Kawanishi, M. Okada, Y. Matsumoto, and S. Nagao. Treatment of cold injury-induced brain edema with a nonspecific matrix metalloproteinase inhibitor MMI270 in rats, J Neurotrauma. vol. 20, pp.649-657, (2003).

DOI: 10.1089/089771503322144563

[17] W. Wang Z.H. Kang, C.P. Chen, X.Z. Zhao and J.W. Xu, Correlation between activity of tissue-type plasminogen activator and extracellular matrix in brains of neonatal rats during hypoxia-ischemia, J Fujian Medical University. vol. 34, pp.212-214.