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August 7, 2014Cell Death and DiseaseOpen Access

PARP1 activation/expression modulates regional-specific neuronal and glial responses to seizure in a hemodynamic-independent manner

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Key result

PARP1 inhibitors attenuated status epilepticus-induced neuronal death in CA1 and CA3 regions but aggravated astroglial death in the dentate gyrus and CA3 stratum lucidum.

Population

Male Sprague-Dawley rats, 9-11 weeks old, subjected to pilocarpine-induced status epilepticus in vivo…

Comparison

PARP1 inhibitors administered via… vs Vehicle infusion prior to pilocarpine-induced…

Design

Preclinical

Follow-up

Up to 4 weeks after status epilepticus

Authors

JKJe Hyeong KimKorea Advanced Institute of Science and TechnologyYKYJ KimNexen (Canada)JKJ Y Kim

Discussion

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Implication

Suggests cell-specific PARP1 targeting may optimize neuroprotection in SE models; leaves open clinical translation pending human studies.

Structured PICO

P
Population
135 male Sprague-Dawley rats subjected to pilocarpine-induced status epilepticus to evaluate the role of PARP1 in regional-specific neuronal and glial responses.
I
Intervention
PARP1 inhibitors (PJ-34 3 mM or DPQ 5 mM) administered via intracerebroventricular infusion (0.5 ml/h) for 1 week prior to pilocarpine-induced status epilepticus.
C
Comparator
Vehicle (saline) infusion prior to pilocarpine-induced status epilepticus, and non-SE controls.
O
Outcome
Regional-specific neuronal damage, astroglial death, and reactive gliosis in the hippocampus and piriform cortex.surrogate

Main Result

p-value: p=<0.05

Cellular-specific PARP1 activation and degradation distinctly modulate regional-specific neuronal damage and astroglial death following status epilepticus independently of hemodynamics.

Limitations

  • The mechanism of SE-induced astroglial death in the piriform cortex remains unclear and requires further study.

Cite This Study

Kim et al. (2014) studied Status epilepticus (n=135). PARP1 inhibitors (PJ-34 and DPQ) vs. Vehicle (saline) was evaluated on Neuronal death in CA1 and CA3 regions (FJB-positive degenerative neurons/mm3) (p=<0.05). PARP1 inhibitors attenuated status epilepticus-induced neuronal death in CA1 and CA3 regions but aggravated astroglial death in the dentate gyrus and CA3 stratum lucidum.

synapsesocial.com/papers/6a930e4790d586981c41a719https://doi.org/10.1038/cddis.2014.331
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Also Consider

Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1NAD(P)H Fluorescence Transients after Synaptic Activity in Brain Slices: Predominant Role of Mitochondrial Function2006 · 99 citations
  2. 2Epidemiology of Status Epilepticus1995 · 369 citations
  3. 3Epileptogenic roles of astroglial death and regeneration in the dentate gyrus of experimental temporal lobe epilepsy2006 · 143 citations