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Because our previous brain slice studies have shown that chemically induced epileptiform activity can lead to elevated astrocytic Ca<jats:sup>2+<\/jats:sup>signaling and because these signals are able to induce the release of the excitotoxic transmitter glutamate from these glia, we asked whether astrocytes are activated during status epilepticus and whether they contribute to delayed neuronal death<jats:italic>in vivo<\/jats:italic>. Using two-photon microscopy<jats:italic>in vivo<\/jats:italic>, we show that status epilepticus enhances astrocytic Ca<jats:sup>2+<\/jats:sup>signals for 3 d and that the period of elevated glial Ca<jats:sup>2+<\/jats:sup>signaling is correlated with the period of delayed neuronal death. To ask whether astrocytes contribute to delayed neuronal death, we first administered antagonists which inhibit gliotransmission: MPEP [2-methyl-6-(phenylethynyl)pyridine], a metabotropic glutamate receptor 5 antagonist that blocks astrocytic Ca<jats:sup>2+<\/jats:sup>signals<jats:italic>in vivo<\/jats:italic>, and ifenprodil, an NMDA receptor antagonist that reduces the actions of glial-derived glutamate. Administration of these antagonists after SE provided significant neuronal protection raising the potential for a glial contribution to neuronal death. To test this glial hypothesis directly, we loaded Ca<jats:sup>2+<\/jats:sup>chelators selectively into astrocytes after status epilepticus. We demonstrate that the selective attenuation of glial Ca<jats:sup>2+<\/jats:sup>signals leads to neuronal protection. These observations support neurotoxic roles for astrocytic gliotransmission in pathological conditions and identify this process as a novel therapeutic target.<\/jats:p>","DOI":"10.1523\/jneurosci.2001-07.2007","type":"journal-article","created":{"date-parts":[[2007,10,3]],"date-time":"2007-10-03T16:28:07Z","timestamp":1191428887000},"page":"10674-10684","source":"Crossref","is-referenced-by-count":246,"title":["Enhanced Astrocytic Ca<sup>2+<\/sup>Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus"],"prefix":"10.1523","volume":"27","author":[{"given":"Shinghua","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Fellin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves P.","family":"Auberson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Meaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Coulter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Carmignoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip G.","family":"Haydon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2007,10,3]]},"reference":[{"key":"2023041303275196000_27.40.10674.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0473-04.2004"},{"key":"2023041303275196000_27.40.10674.2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00221.x"},{"key":"2023041303275196000_27.40.10674.3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.795"},{"key":"2023041303275196000_27.40.10674.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(02)00074-4"},{"key":"2023041303275196000_27.40.10674.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1984.tb03484.x"},{"key":"2023041303275196000_27.40.10674.6","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(91)90380-7"},{"key":"2023041303275196000_27.40.10674.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00086-4"},{"key":"2023041303275196000_27.40.10674.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2660-04.2004"},{"key":"2023041303275196000_27.40.10674.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609408104"},{"key":"2023041303275196000_27.40.10674.10","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90234-5"},{"key":"2023041303275196000_27.40.10674.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.10.011"},{"key":"2023041303275196000_27.40.10674.12","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-8119(02)00025-3"},{"key":"2023041303275196000_27.40.10674.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.08.011"},{"key":"2023041303275196000_27.40.10674.14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2836-06.2006"},{"key":"2023041303275196000_27.40.10674.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)03289-9"},{"key":"2023041303275196000_27.40.10674.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.10.011"},{"key":"2023041303275196000_27.40.10674.17","doi-asserted-by":"crossref","unstructured":"Garzillo CL Mello LE (2002) Characterization of reactive astrocytes in the chronic phase of the pilocarpine model of epilepsy. 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