Intracellular calcium dynamics and cerebral injury: modeling various insults in vitro

Kim-Lee, Myung H.; Stokes, Bradford T.; Anderson, Douglas K.

doi:10.1016/0006-8993(93)90467-2

Cited by 6 publications

(3 citation statements)

References 19 publications

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“…, 2004; Konur & Ghosh, 2005). In fact, calcium overactivation caused by massive calcium influx is harmful to cells, and calcium plays a pivotal role in the final common pathway for neuronal death in a variety of pathological conditions (Kim‐Lee et al. , 1993; Hyrc et al.…”

Section: Versatility Of Iconmentioning

confidence: 99%

In vivo confocal neuroimaging (ICON): non‐invasive, functional imaging of the mammalian CNS with cellular resolution

Prilloff

Fan

Henrich‐Noack

et al. 2010

Eur J of Neuroscience

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With in vivo confocal neuroimaging (ICON), single retinal ganglion cells (RGCs) can be visualized non-invasively, repeatedly, in real-time and under natural conditions. Here we report the use of ICON to visualize dynamic changes in RGC morphology, connectivity and functional activation using calcium markers, and to visualize nanoparticle transport across the blood-retina barrier by fluorescent dyes. To document the versatility of ICON, we studied the cellular response to optic nerve injury, and found evidence of reversible soma swelling, recovery of retrograde axonal transport and a difference in calcium activation dynamics between surviving and dying RGCs. This establishes ICON as a unique tool for studying CNS physiology and pathophysiology in real-time on a cellular level. ICON has potential applications in different research fields, such as neuroprotection/regeneration, degeneration, pharmacology, toxicity and drug delivery.

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Section: Versatility Of Iconmentioning

confidence: 99%

In vivo confocal neuroimaging (ICON): non‐invasive, functional imaging of the mammalian CNS with cellular resolution

Prilloff

Fan

Henrich‐Noack

et al. 2010

Eur J of Neuroscience

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“…following stimulation of NMDA receptors is blocked by dantrolene (Frandsen and Schousboe, 1993 ;Mody and MacDonald, 1995) . Besides its effect on [Ca 2+] ;, dantrolene has been shown to inhibit cell death from overactivation of NMDA receptors, i.e., excitotoxicity Schousboe, 1991, 1993;Lei et al ., 1992;Kim-Lee et al, 1993 ;Simpson et al, 1993Simpson et al, , 1995, as well as from metabotropic glutamate receptor overactivation (McDonald et al, 1993) and from HIV-1 coat protein gp-120 (Dawson et al, 1993) .…”

Section: Animal Studiesmentioning

confidence: 99%

Dantrolene Is Cytoprotective in Two Models of Neuronal Cell Death

Wei

Perry

1996

Journal of Neurochemistry

135

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The neuroprotective effects of dantrolene, an inhibitor of calcium release from intracellular stores, were investigated in a model of cell death induced by calcium release from endoplasmic reticulum in vitro. Thapsigargin (50 nM), a selective inhibitor of endoplasmic reticular Ca2+‐ATPase, significantly increased the cytosolic Ca2+ concentration to 230% over basal levels, induced DNA fragmentation, and reduced cell viability from 94% in control cells to 41% after a 24‐h treatment in GT1‐7 hypothalamic neurosecretory cells. Pretreatment with dantrolene for 30 min significantly inhibited elevation of cytosolic Ca2+ levels, DNA fragmentation, and GT1‐7 cell death induced by thapsigargin in a dose‐dependent manner. To determine if dantrolene would also be protective in an in vivo model of neurodegeneration, it was administered intravenously immediately following a 5‐min global cerebral ischemia in gerbils, and the number of intact hippocampal CA1 pyramidal neurons was counted 7 days later. The effects of dantrolene on brain and rectal temperature were monitored in a separate experiment. Dantrolene significantly increased the number of intact CA1 pyramidal neurons from 40% (untreated ischemic animals) to 67 (10 mg/kg), 78 (25 mg/kg), or 83% (50 mg/kg) of values in sham controls (all p < 0.001). No significant changes in brain or rectal temperature were detected for 4 h following 50 mg/kg dantrolene. These results suggest that abnormal Ca2+ release from intracellular stores can induce neuronal death and that such a mechanism may contribute to delayed hippocampal neuronal death after cerebral ischemia. Dantrolene may be a potentially useful drug for neuroprotection after cerebral ischemia.

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“…Additionally, altered calcium levels are seen in areas surrounding focal lesions in visual cortex and are likely involved in electrophysiological hypoactivation and subsequent hyperactivation during plasticity (Barmashenko et al ., 2001; Mittman & Eysel, 2001). On the other hand, calcium overactivation caused by massive calcium influx is harmful to the cell as it comprises the final common pathway for neuronal death in a variety of pathological conditions (Kim‐Lee et al ., 1993; Hyrc et al ., 1997; Hasbani et al ., 1998). Because of its central role in the molecular cascade of normal function and dysfunction (Gomez & Spitzer, 1999; Berridge et al ., 2000; Gomez & Spitzer, 2000; Spitzer et al ., 2000), further investigation of the dual role of calcium in neurotrauma is warranted.…”

Section: Introductionmentioning

confidence: 99%

Two faces of calcium activation after optic nerve trauma: life or death of retinal ganglion cells in vivo depends on calcium dynamics

Prilloff

Noblejas

Chedhomme

et al. 2007

Eur J of Neuroscience

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Calcium elevations after neurotrauma are not only implicated in cell death but may contribute to adaptive plasticity. We now wished to resolve this contradiction by following calcium dynamics after optic nerve crush in vivo. Adult rats received no injury (n = 5), unilateral mild (n = 10) or moderate optic nerve crush (n = 10) (ONC), or axotomy (n = 5). Before surgery, retinal ganglion cells (RGCs) were retrogradely labelled with Oregon Green BAPTA-dextran, a fluorescent calcium marker. Calcium-related fluorescence intensity (FI) was repeatedly measured in individual RGCs in vivo using the in vivo confocal neuroimaging (ICON) method. Four different RGC types were found. Normal RGCs without FI change were found in sham rats and also in both ONC groups. RGCs with mild damage were seen only after mild ONC, showing an initial calcium depression of 26% at day 4 followed by a 169% increase 15 days after ONC. RGCs with moderate damage were found only after moderate ONC and showed calcium hypoactivation followed by a slower return toward baseline and a delayed calcium increase of 72% above baseline. Sixty to sixty-five per cent of the RGCs in both ONC groups and all RGCs in the axotomy group died within 6 days following a fast and massive calcium increase of 316% with a concomitant 156% soma size increase. In conclusion rapid calcium elevation leads to cell death, while an initial calcium depression followed by a delayed and moderate calcium hyperactivation is associated with cell survival. We propose that immediate, massive calcium activation is maladaptive whereas delayed and moderate hyperactivation of surviving cells is adaptive. Implications for pharmacotherapy are discussed.

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Intracellular calcium dynamics and cerebral injury: modeling various insults in vitro

Cited by 6 publications

References 19 publications

In vivo confocal neuroimaging (ICON): non‐invasive, functional imaging of the mammalian CNS with cellular resolution

In vivo confocal neuroimaging (ICON): non‐invasive, functional imaging of the mammalian CNS with cellular resolution

Dantrolene Is Cytoprotective in Two Models of Neuronal Cell Death

Two faces of calcium activation after optic nerve trauma: life or death of retinal ganglion cells in vivo depends on calcium dynamics

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