Vulnerability of postnatal hippocampal neurons to seizures varies regionally with their maturational stage

作者：Lopez Meraz Maria Leonor; Wasterlain Claude G; Rocha Luisa L; Allen Suni; Niquet Jerome^*

来源：Neurobiology of Disease, 2010, 37(2): 394-402.

DOI：10.1016/j.nbd.2009.10.019

• Necrosis
• Apoptosis
• Caspase
• Doublecortin
• Hippocampus
• Status epilepticus
• Pilocarpine
• Development

The mechanism of status epilepticus-induced neuronal death in the immature brain is not fully understood. In the present study, we examined the contribution of caspases in our lithium-pilocarpine model of status epilepticus in 14 days old rat pups. In CA1, upregulation of caspase-8, but not caspase-9, preceded caspase-3 activation in morphologically necrotic cells. Pretreatment with a pan-caspase inhibitor provided neuroprotection, showing that caspase activation was not an epiphenomenon but contributed to neuronal necrosis. By contrast, upregulation of active caspase-9 and caspase-3, but not caspase-8, was detected in apoptotic dentate gyrus neurons. which were immunoreactive for doublecortin and calbindin-negative, two features of immature neurons. These results suggest that, in cells which are aligned in series as parts of the same excitatory hippocampal circuit, the same seizures induce neuronal death through different mechanisms. The regional level of neuronal maturity may be a determining factor in the execution of a specific death program.

• 出版日期2010-2