Characterization of electroconvulsive seizure-induced TIMP-1 and MMP-9 in hippocampal vasculature

Matthew J. Girgenti, Emily Collier, Monica Sathyanesan, Xiaowei W. Su, Samuel S. Newton

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Degradation of the vascular basement membrane stimulates angiogenesis and is tightly controlled by balancing the actions of metalloproteases and their inhibitors. Previous work demonstrated that electroconvulsive seizure (ECS) elevates angiogenic factors and endothelial proliferation in the hippocampus. The robust induction of tissue inhibitor of matrix metalloprotease 1 (TIMP-1) in the stratum lacunosum moleculare (SLM) corresponds to sites of increased vascular density. This led us to examine the spatial and cellular expression of TIMP-1 and its substrate, matrix metalloprotease 9 (MMP-9). Chronic ECS increased TIMP-1 by 12-fold and MMP-9 by 3-fold in discrete SLM cells. We then characterized the expression of TIMP-1 mRNA in relation to vasculature in the SLM and glial-limiting membrane (GLM). Employing laser microdissection we identified the cell types associated with SLM vasculature and also phenotyped the cells expressing TIMP-1 and MMP-9. We concluded that TIMP-1 is produced by perivascular cells positive for alpha smooth actin and that MMP-9 is expressed by GFAP-positive astrocytes. These studies suggest that ECS-induced remodelling occurs at the vascular basement membrane and facilitates neovascularization.

Original languageEnglish (US)
Pages (from-to)535-544
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Issue number4
StatePublished - May 2011

All Science Journal Classification (ASJC) codes

  • General Medicine


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