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2015 ; 9
(ä): 413
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Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor
Y-27632 in a pilocarpine model of temporal lobe epilepsy
#MMPMID26557054
Kourdougli N
; Varpula S
; Chazal G
; Rivera C
Front Cell Neurosci
2015[]; 9
(ä): 413
PMID26557054
show ga
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.