Naslov
Molecular consequences of kainate induced excitotoxicity in neonatal rat spinal cord in vitro.

Autori
Kuzhandaivel A ; Mladinić Pejatović, Miranda ; Nistri A.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Skup
FENS 2010

Mjesto i datum
Amsterdam, Nizozemska, 03.-07.07.10

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
excitotoxicity; metabolic dysfunction; spinal cord injury.

Sažetak
Damage to the spinal cord, whether caused by injury or disease, cannot currently be repaired. The molecular mechanisms underlying the early pathophysiological stages of spinal cord injury remain largely unknown. The initial tissue damage spreads extensively (secondary damage) through excitotoxicity, metabolic dysfunction (including ischemia), free radicals and neuroinflammation. To understand molecular pathways underlying excitotoxicity (that is an important early process after spinal cord injury), in vitro neonatal rat spinal cord preparations were exposed to 1mM kainate for 1h followed by 24 h washout with Krebs. This insult induced massive nucleolytic pyknosis affecting the entire gray matter starting as early as 2h after insult and peaking after 4h. There was extensive loss of NeuN signal especially in the regions of high pyknosis strongly suggesting damage to neurons. Apoptotic markers (phospho histone H2A. X, caspase 8 or 3, cleaved PARP-1) were negative with immunohistochemistry and western blot, indicating that apoptosis was not the mechanism underlying neuronal pyknosis. However, there was increased expression of PARP-1, PAR and AIF. To know if PARP 1 was acting as a mediator of cell death, the PARP-1 inhibitor PHE (10-60 microM) was applied immediately after the excitotoxic insult. PHE was efficient in decreasing kainate induced neuronal pyknosis. Western blot results indicate a reduction in AIF translocation from the mitochondria to the nucleus after PHE. Our results suggest that excitotoxicity evoked a distinctive type of cell death termed parthanatos, dependent on PARP-1 activity, and outline a new target for neuroprotection during early spinal cord damage.

Izvorni jezik
Engleski

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