Nitric Oxide Synthase Expression in the Cerebral Cortex of Patients with Epilepsy

Abstract

The fact that NOS upregulation is more evident in patients with a long seizure history suggests that this is a consequence of seizures, acting probably as an adaptative response to the sustained release of excitatory amino acids.

Opposite caudal versus rostral brain nitric oxide synthase response to generalized seizures in a novel rodent model of reflex epilepsy

“…Our results indicate that variations in nNOS (but not in eNOS) expression could be a main factor in the changes in NOS activity changes appearing after epileptic seizures, which agrees with the above mentioned studies in patients and cell culture (González-Hernández et al, 2000;Catania et al, 2003;Kamida et al, 2007;González-Martínez et al, 2009). No differences were found between the non-stimulated GASH:Sal and control hamsters, suggesting that in our model nNOS may be more involved in the response to the epileptic seizures than in the susceptibility to suffer a crisis.…”

“…No differences were found between the non-stimulated GASH:Sal and control hamsters, suggesting that in our model nNOS may be more involved in the response to the epileptic seizures than in the susceptibility to suffer a crisis. This notion agrees with previous experimental studies indicating that NOS was produced as a consequence of convulsant administration (Masukawa et al, 1998;Kaneko et al, 2002) and also supports results of clinical studies where a higher increase in nNOS production was found in surgical patients with a prolonged history of seizures (González-Hernández et al, 2000).…”

“…To that effect, we employed animals of the GASH:Sal strain (Generalized Audiogenic Seizure Hamster, University of Salamanca, Spain), examining areas across the brain rostro-caudal axis. We studied constitutive NOS (cNOS) activity and the expression of the two cNOS isoforms (nNOS and eNOS) based on previous studies showing a more prominent role of cNOS over iNOS in epileptic crises (Murashima et al, 2000;González-Hernández et al, 2000;Tutka et al, 2007;Itoh and Watanabe, 2009;Kovács et al, 2009;Bahremand et al, 2010). The present work shows a differential activation and expression of nNOS in the caudal versus the rostral areas of the epileptic brain after 10 crises.…”

“…With specific regard to epilepsy, nNOS has been shown to be upregulated in cortical neurons of epileptic patients (González-Hernández et al, 2000;Kamida et al, 2007;González-Martínez et al, 2009) and NO has been considered to play a fundamental role in the genesis and spreading of epileptiform hyperactivity and proposed as a possible therapeutic target (Yasuda et al, 2001;Jelenković et al, 2002;Kovács et al, 2009;Bahremand et al, 2010). However, although abundant experimental research has demonstrated a functional involvement of NO in the control of epileptic phenomena, the available data are conflicting and it cannot be concluded whether this atypical messenger acts as a pro-convulsant or an anticonvulsant agent (Barbiro-Michaely et al, 2011;Hrnčić et al, 2010Hrnčić et al, , 2011Przegaliñski et al, 1996;Tutka et al, 1997;Masukawa et al, 1998;Borowicz et al, 2000;Lesani et al, 2010;Łuszczki et al, 2006, 2011Sardo et al, 2008;Itoh and Watanabe, 2009;Nieoczym et al, 2010).…”

Dysfunction of hippocampal interneurons in epilepsy

“…NO is involved in the pathophysiology of epilepsy, and the expression of nNOS in neurons is increased in epileptic patients and pilocarpine-induced animal models of epilepsy [62] . Systemic treatment with a highly selective nNOS inhibitor, L-NPA, reduces the severity and duration of seizures, the EEG power in the gamma band, and the frequency of epileptiform spikes during SE, suggesting that nNOS facilitates seizure generation and may be with the development of chronic epilepsy, especially in the early stages [63] .…”