Expression time course and spatial distribution of activated caspase-3 after experimental status epilepticus: contribution of delayed neuronal cell death to seizure-induced neuronal injury.
Pilocarpine-induced status epilepticus (PCSE) is a widely used model to study neurodegeneration in limbic structures after prolonged epileptic seizures. However, mechanisms mediating neuronal cell death in this model require further characterization. Examining the expression time course and spatial distribution of activated caspase-3, we sought to determine the role of apoptosis in PCSE-mediated neuronal cell death. Expression of activated caspase-3, predominantly located in neurons, was detected 24 h (amygdala; piriform and temporal cortex) and 7 days (hippocampus; amygdala; piriform, temporal and parietal cortex; thalamus) after PCSE with strongest induction being observed in the amygdala, the piriform cortex, and the hippocampus. Further analysis revealed TUNEL positivity (24 h and 7 days after SE) and a significant, progressive neuronal cell loss in all brain regions displaying caspase-3 activation. Corresponding to high levels of activated caspase-3 expression, neuronal cell loss was most pronounced in the amygdala, piriform cortex, and dorsal CA-1 hippocampus. These results demonstrate that apoptosis contributes significantly to PCSE-induced neuronal cell death.
Weise
Jens
J
Department of Neurology University of Goettingen Medical School, Robert-Koch-Str. 40, 37075 Goettingen, Germany. jweise@gwdg.de
Engelhorn
Tobias
T
Dörfler
Arnd
A
Aker
Stefanie
S
Bähr
Mathias
M
Hufnagel
Andreas
A
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis* / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D004789:Enzyme Activation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000201:enzymology*; D013226:Status Epilepticus / Q000201:enzymology*; D013997:Time Factors
C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases