Systems NeuroscienceResearch PaperVascular changes in epilepsy: functional consequences and association with network plasticity in pilocarpine-induced experimental epilepsy
Section snippets
Animals
Adult male Sprague–Dawley rats (Harlan, AD, Horst, Netherland) weighing 300–350 g were used. The rats were housed in a controlled environment (temperature 22±1 °C; humidity 50%–60%; lights on 0700–1900) with free access to food and water. Animal procedures were approved by the Animal Care and Use Committee of the University of Kuopio, Finland, and conducted in accordance with the guidelines set by the European Community Council Directives 86/609/EEC.
Induction of status epilepticus
Rats were injected s.c. with scopolamine (1
Distribution and density of EBA positive blood vessels in the hippocampus after SE
EBA is located in the endothelial cells on the luminal side of blood vessels (Ghabriel et al., 2002). Several studies have demonstrated that EBA is very unstable in injured brain with vascular damage (Sternberger et al., 1989, Rosenstein et al., 1992, Lin et al., 2001). Hence, it can be used as a sensitive indicator of BBB impairment.
Discussion
Previous studies have suggested that vascular density is increased after SE, and that damage to existing or leakiness of newly formed vessels results in extravasation of plasma proteins which contributes to epileptogenesis and ictogenesis (van Vliet et al., 2007, Seiffert et al., 2004). However, there have been no study that has investigated whether endothelial cells actually proliferate after SE, and what is the time course and magnitude of angiogenesis during epileptogenesis. Also,
Conclusion
Here we demonstrate that experimental SE has multiple effects on blood vessels, including early loss of immunolabeled vessels associated with BBB leakage and formation of thrombocyte clots. Vascular injury is followed by endothelial cell proliferation and angiogenesis which restores vascular length within 2 wk post-SE and increases CBV. The magnitude of vascular injury and consequent angiogenesis are not temporally or quantitatively related to formation of epileptogenic circuitry in the dentate
Acknowledgments
This study was supported by European CommissionEC FP6, MEST-CT-2005-019217, Academy of Finland, and the Sigrid Juselius Foundation.
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