Spontaneous intracellular calcium oscillations in cortical astrocytes from a patient with intractable childhood epilepsy (Rasmussen's Encephalitis)

Manning, Timothy J.; Sontheimer, Harald

doi:10.1002/(sici)1098-1136(199711)21:3<332::aid-glia8>3.0.co;2-6

Cited by 44 publications

(18 citation statements)

References 41 publications

(42 reference statements)

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“…In that study, the tissue was isolated during surgery, and then plated into primary culture, and astrocytic Ca 2ϩ signals were monitored thereafter. Initially, spontaneous Ca 2ϩ signals were present, although their frequency declined during the following weeks (Manning and Sontheimer, 1997). Although control tissue was not available to make comparison measurements, taking these observations together with those presented in our study raises the potential of a general principle of glial Ca 2ϩ signaling in which seizures enhance the Ca 2ϩ excitability of astrocytes for prolonged periods that outlast the duration of the seizure itself.…”

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confidence: 50%

Enhanced Astrocytic Ca²⁺Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Ding¹,

Fellin²,

Zhu³

et al. 2007

J. Neurosci.

244

260

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Status epilepticus (SE), an unremitting seizure, is known to cause a variety of traumatic responses including delayed neuronal death and later cognitive decline. Although excitotoxicity has been implicated in this delayed process, the cellular mechanisms are unclear. Because our previous brain slice studies have shown that chemically induced epileptiform activity can lead to elevated astrocytic Ca 2ϩ 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 in vivo. Using two-photon microscopy in vivo, we show that status epilepticus enhances astrocytic Ca 2ϩ signals for 3 d and that the period of elevated glial Ca 2ϩ 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 2ϩ signals in vivo, 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 2ϩ chelators selectively into astrocytes after status epilepticus. We demonstrate that the selective attenuation of glial Ca 2ϩ 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.

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confidence: 50%

Enhanced Astrocytic Ca²⁺Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Ding¹,

Fellin²,

Zhu³

et al. 2007

J. Neurosci.

244

260

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“…Do reactive astrocytes release larger quantities of glutamate that is sufficient to initiate an epileptic discharge? Astrocytes isolated from human epileptic foci exhibit elevated Ca 2ϩ oscillation frequency (Manning and Sontheimer, 1997). Additionally, of great interest is the observation that synaptotagmin IV, a vesicle protein essential for glutamate release from astrocytes (Zhang et al, 2004), is upregulated after seizures (Tocco et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Astrocytic Glutamate Is Not Necessary for the Generation of Epileptiform Neuronal Activity in Hippocampal Slices

Fellin

Gómez-Gonzalo²,

Gobbo³

et al. 2006

J. Neurosci.

159

150

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“…In this study, heterologous expression of the SCN1 mutation in HEK293 cells demonstrated increased persistent Na + current and channel availability compared with wild-type channels. Another study using cortical astrocytes from an RE patient demonstrated the occurrence of large spontaneous Ca 2+ oscillations [49]. Similar oscillations were not observed in normal rat cortical astrocytes.…”

Section: Discussionmentioning

confidence: 63%

In Rasmussen Encephalitis, Hemichannels Associated with Microglial Activation are linked to Cortical Pyramidal Neuron Coupling: A Possible Mechanism for Cellular Hyperexcitability

Cepeda¹,

Chang

Owens

et al. 2014

CNS Neurosci Ther

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Aims Rasmussen encephalitis (RE) is a rare but devastating condition, mainly in children, characterized by sustained brain inflammation, atrophy of one cerebral hemisphere, epilepsy and progressive cognitive deterioration. The etiology of RE-induced seizures associated with the inflammatory process remains unknown. Methods Cortical tissue samples from children undergoing surgical resections for the treatment of RE (n=16) and non-RE (n=12) were compared using electrophysiological, morphological, and immunohistochemical techniques to examine neuronal properties and the relationship with microglial activation using the specific microglia/macrophage calcium-binding protein, IBA1 in conjunction with connexins and pannexin expression. Results Compared with non-RE cases, pyramidal neurons from RE cases displayed increased cell capacitance and reduced input resistance. However, neuronal somatic areas were not increased in size. Instead, intracellular injection of biocytin led to increased dye-coupling between neurons from RE cases. By Western blot, expression of IBA1 and pannexin was increased while connexin 32 was decreased in RE cases compared with non-RE cases. IBA1 immunostaining overlapped with pannexin and connexin 36 in RE cases. Conclusions In RE, these results support the notion that a possible mechanism for cellular hyperexcitability may be related to increased intercellular coupling from pannexin linked to increased microglial activation. Such findings suggest that a possible anti-seizure treatment for RE may involve the use of gap junction blockers.

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Spontaneous intracellular calcium oscillations in cortical astrocytes from a patient with intractable childhood epilepsy (Rasmussen's Encephalitis)

Cited by 44 publications

References 41 publications

Enhanced Astrocytic Ca²⁺Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Enhanced Astrocytic Ca²⁺Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Astrocytic Glutamate Is Not Necessary for the Generation of Epileptiform Neuronal Activity in Hippocampal Slices

In Rasmussen Encephalitis, Hemichannels Associated with Microglial Activation are linked to Cortical Pyramidal Neuron Coupling: A Possible Mechanism for Cellular Hyperexcitability

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Spontaneous intracellular calcium oscillations in cortical astrocytes from a patient with intractable childhood epilepsy (Rasmussen's Encephalitis)

Cited by 44 publications

References 41 publications

Enhanced Astrocytic Ca2+Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Enhanced Astrocytic Ca2+Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Astrocytic Glutamate Is Not Necessary for the Generation of Epileptiform Neuronal Activity in Hippocampal Slices

In Rasmussen Encephalitis, Hemichannels Associated with Microglial Activation are linked to Cortical Pyramidal Neuron Coupling: A Possible Mechanism for Cellular Hyperexcitability

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Enhanced Astrocytic Ca²⁺Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Enhanced Astrocytic Ca²⁺Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus