Two faces of calcium activation after optic nerve trauma: life or death of retinal ganglion cells in vivo depends on calcium dynamics.
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.
Prilloff
S
S
Institute of Medical Psychology, Otto-von-Guericke University of Magdeburg, Medical Faculty, Leipziger Str. 44, 39120 Magdeburg, Germany.
Noblejas
M I
MI
Chedhomme
V
V
Sabel
B A
BA
D000704:Analysis of Variance; D000814:Aniline Compounds / Q000493:pharmacokinetics; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002452:Cell Count; D016923:Cell Death; D005452:Fluoresceins / Q000493:pharmacokinetics; D017711:Nonlinear Dynamics; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000473:pathology*; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D000814:Aniline Compounds; D005452:Fluoresceins; C503942:Oregon green 488 BAPTA-1; D002118:Calcium