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Kourdougli N, Varpula S, Chazal G, et al. Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y-27632 in a pilocarpine model of temporal lobe epilepsy. Front Cell Neurosci. 2015;9:413doi: 10.3389/fncel.2015.00413.
Kourdougli, N., Varpula, S., Chazal, G., & Rivera, C. (2015). Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y-27632 in a pilocarpine model of temporal lobe epilepsy. Frontiers in cellular neuroscience, 9413. https://doi.org/10.3389/fncel.2015.00413
Kourdougli, Nazim, et al. "Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y-27632 in a pilocarpine model of temporal lobe epilepsy." Frontiers in cellular neuroscience vol. 9 (2015): 413. doi: https://doi.org/10.3389/fncel.2015.00413
Kourdougli N, Varpula S, Chazal G, Rivera C. Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y-27632 in a pilocarpine model of temporal lobe epilepsy. Front Cell Neurosci. 2015 Oct 23;9:413. doi: 10.3389/fncel.2015.00413. eCollection 2015. PMID: 26557054; PMCID: PMC4615811.
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Front Cell Neurosci. 2015 Oct 23;9:413. doi: 10.3389/fncel.2015.00413. eCollection 2015.

Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y-27632 in a pilocarpine model of temporal lobe epilepsy.

Frontiers in cellular neuroscience

Nazim Kourdougli, Saara Varpula, Genevieve Chazal, Claudio Rivera

Affiliations

  1. INSERM Unité 901, INMED Marseille, France ; Aix-Marseille Université, UMR S901 Marseille, France.
  2. INSERM Unité 901, INMED Marseille, France ; Aix-Marseille Université, UMR S901 Marseille, France ; Neuroscience Center, University of Helsinki Helsinki, Finland.

PMID: 26557054 PMCID: PMC4615811 DOI: 10.3389/fncel.2015.00413

Abstract

Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults where 20-30% of the patients are refractory to currently available anti-epileptic drugs. The RhoA/Rho-kinase signaling pathway activation has been involved in inflammatory responses, neurite outgrowth and neuronal death under pathological conditions such as epileptic insults. Acute preventive administration of ROCK inhibitor has been reported to have beneficial outcomes in Status Epilepticus (SE) epilepsy. In the present study, we evaluate the effect of chronic post SE treatment with the ROCK inhibitor Y-27632 in a rat pilocarpine model of TLE. We used chronic i.p. injections of Y-27632 for 5 days in 6 week old control rats or rats subjected to pilocarpine treatment as a model of TLE. Surprisingly, our findings demonstrate that a systemic administration of Y-27632 in pilocarpine-treated rats increases neuronal death in the CA3 region and ectopic recurrent mossy fiber sprouting (rMFS) in the dentate gyrus of the hippocampal formation. Interestingly, we found that chronic treatment with Y-27632 exacerbates the down-regulation and pathological distribution of the K(+)-Cl(-) cotransporter KCC2, thus providing a putative mechanism for post SE induced neuronal death. The involvement of astrogliosis in this mechanism appears to be intricate as ROCK inhibition reduces reactive astrogliosis in pilocarpine rats. Conversely, in control rats, chronic Y-27632 treatment increases astrogliosis. Together, our findings suggest that Y-27632 has a detrimental effect when chronically used post SE in a rat pilocarpine model of TLE.

Keywords: KCC2; ROCK inhibitor; astrogliosis; epileptogenesis; mossy fiber sprouting; temporal lobe epilepsy

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