The involvement of Na+, K+-ATPase activity and free radical generation in the susceptibility to pentylenetetrazol-induced seizures after experimental traumatic brain injury

Silva, Luiz Fernando Almeida; Hoffmann, Maurício Scopel; Rambo, Leonardo Magno; Ribeiro, Leandro Rodrigo; Lima, Frederico Diniz; Furian, Ana Flávia; Oliveira, Mauro Schneider; Fighera, Michele Rechia; Royes, Luiz Fernando Freire

doi:10.1016/j.jns.2011.06.030

Cited by 53 publications

(38 citation statements)

References 62 publications

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“…Evidence in the literature has demonstrated a decrease in both the activity and the expression of Na + ,K + -ATPase and Ca 2+ -ATPase in the development of neurodegenerative diseases, as well as in MS, due to axonal degeneration and a reduction in the synaptic terminals [15][16][17]. Moreover, the marked reduction of these ions pumps can occur due to the oxidation of the SH groups present in its structure, as well as the oxidation of the lipid membranes that lead to a destabilization of the optimal conformation and ion transport [102,56,[103][104][105][106]. Additionally, we found a correlation between the decreases in Na + ,K + -ATPase and Ca 2+ -ATPase activity and the increase in markers of oxidative stress (Fig.…”

Section: Discussionmentioning

confidence: 99%

Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination

Carvalho

Gutierres

Bohnert

et al. 2015

The Journal of Nutritional Biochemistry

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Section: Discussionmentioning

confidence: 99%

Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination

Carvalho

Gutierres

Bohnert

et al. 2015

The Journal of Nutritional Biochemistry

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“…There is limited information on antioxidant drug effects in models of epilepsy induced by acute injuries other than SE. One notable study reported that chronic NAC treatment (100 mg/kg/d by intragastric gavage for 5 weeks postinjury), starting immediately after FPI in rats, normalized the FPI‐induced reduction of seizure threshold to systemic PTZ (latency to myoclonus and time spent in tonic‐clonic seizures) measured 5 weeks after the acute brain injury …”

Section: N‐acetylcysteinementioning

confidence: 99%

Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?

et al. 2020

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Prevention of epilepsy is a great unmet need. Acute central nervous system (CNS) insults such as traumatic brain injury (TBI), cerebrovascular accidents (CVA), and CNS infections account for 15%‐20% of all epilepsy. Following TBI and CVA, there is a latency of days to years before epilepsy develops. This allows treatment to prevent or modify postinjury epilepsy. No such treatment exists. In animal models of acquired epilepsy, a number of medications in clinical use for diverse indications have been shown to have antiepileptogenic or disease‐modifying effects, including medications with excellent side effect profiles. These include atorvastatin, ceftriaxone, losartan, isoflurane, N‐acetylcysteine, and the antiseizure medications levetiracetam, brivaracetam, topiramate, gabapentin, pregabalin, vigabatrin, and eslicarbazepine acetate. In addition, there are preclinical antiepileptogenic data for anakinra, rapamycin, fingolimod, and erythropoietin, although these medications have potential for more serious side effects. However, except for vigabatrin, there have been almost no translation studies to prevent or modify epilepsy using these potentially “repurposable” medications. We may be missing an opportunity to develop preventive treatment for epilepsy by not evaluating these medications clinically. One reason for the lack of translation studies is that the preclinical data for most of these medications are disparate in terms of types of injury, models within different injury type, dosing, injury–treatment initiation latencies, treatment duration, and epilepsy outcome evaluation mode and duration. This makes it difficult to compare the relative strength of antiepileptogenic evidence across the molecules, and difficult to determine which drug(s) would be the best to evaluate clinically. Furthermore, most preclinical antiepileptogenic studies lack information needed for translation, such as dose–blood level relationship, brain target engagement, and dose‐response, and many use treatment parameters that cannot be applied clinically, for example, treatment initiation before or at the time of injury and dosing higher than tolerated human equivalent dosing. Here, we review animal and human antiepileptogenic evidence for these medications. We highlight the gaps in our knowledge for each molecule that need to be filled in order to consider clinical translation, and we suggest a platform of preclinical antiepileptogenesis evaluation of potentially repurposable molecules or their combinations going forward.

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“…Previous studies in rats using the fluid percussion injury (FPI) model have demonstrated an increase in seizure susceptibility, as measured by a second-hit chemoconvulsant challenge, as well as the development of spontaneous epileptiform discharges, the hallmark of epilepsy (Silva et al, 2011; Kharatishvili et al, 2006). One of the main benefits of this model in rats is the high reproducibility.…”

Section: Introductionmentioning

confidence: 99%

Increased Seizure Susceptibility in Mice 30 Days after Fluid Percussion Injury

Mukherjee¹,

Zeitouni²,

Cavarsan³

et al. 2013

Front. Neurol.

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Traumatic brain injury (TBI) has been reported to increase seizure susceptibility and also contribute to the development of epilepsy. However, the mechanistic basis of the development of increased seizure susceptibility and epilepsy is not clear. Though there is substantial work done using rats, data are lacking regarding the use of mice in the fluid percussion injury (FPI) model. It is unclear if mice, like rats, will experience increased seizure susceptibility following FPI. The availability of a mouse model of increased seizure susceptibility after FPI would provide a basis for the use of genetically modified mice to study mechanism(s) of the development of post-traumatic epilepsy. Therefore, this study was designed to test the hypothesis that, mice subjected to a FPI develop increased seizure susceptibility to a subconvulsive dose of the chemoconvulsant, pentylenetetrazole (PTZ). Three groups of mice were used: FPI, sham, and naïve controls. On day 30 after FPI, mice from the three groups were injected with PTZ. The results showed that FPI mice exhibited an increased severity, frequency, and duration of seizures in response to PTZ injection compared with the sham and naïve control groups. Histopathological assessment was used to characterize the injury at 1, 3, 7, and 30 days after FPI. The results show that mice subjected to the FPI had a pronounced lesion and glial response that was centered at the FPI focus and peaked at 3 days. By 30 days, only minimal evidence of a lesion is observed, although there is evidence of a chronic glial response. These data are the first to demonstrate an early increase in seizure susceptibility following FPI in mice. Therefore, future studies can incorporate transgenic mice into this model to further elucidate mechanisms of TBI-induced increases in seizure susceptibility.

show abstract

The involvement of Na+, K+-ATPase activity and free radical generation in the susceptibility to pentylenetetrazol-induced seizures after experimental traumatic brain injury

Cited by 53 publications

References 62 publications

Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination

Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination

Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?

Increased Seizure Susceptibility in Mice 30 Days after Fluid Percussion Injury

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