PI3Kγ deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine

Lima, Isabel Vieira de Assis; Campos, Alline C.; Miranda, Aline Silva de; Vieira, Érica Leandro Marciano; Amaral-Martins, Flávia; Vago, Juliana P.; Santos, Rebeca Priscila de Melo; Sousa, Lirlândia P.; Vieira, Luciene Bruno; Teixeira, Antônio Lúcio; Fiebich, Bernd L.; Moraes, Márcio Flávio Dutra; Oliveira, Antônio Carlos Pinheiro de

doi:10.1016/j.expneurol.2015.02.021

Cited by 11 publications

(4 citation statements)

References 68 publications

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“…A red X indicates inhibition. (VonDran et al, 2014;Lima et al, 2015;Sanna et al, 2017). Thus, we evaluated the protein levels of BDNF by using a Western blot analysis to test whether an increase in neuroprotection after cerebrolysin administration is correlated with increases in BDNF.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have demonstrated that neurotrophic factors, including NGF and BDNF, are elevated after status epilepticus, which promotes the survival of neurons post-seizure ( VonDran et al, 2014 ; Lima et al, 2015 ; Sanna et al, 2017 ). Thus, we evaluated the protein levels of BDNF by using a Western blot analysis to test whether an increase in neuroprotection after cerebrolysin administration is correlated with increases in BDNF.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Cerebrolysin on Hippocampal Neuronal Death After Pilocarpine-Induced Seizure

et al. 2020

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Epilepsy is one of the most common and severe brain diseases. The exact cause of epilepsy is unclear. Epilepsy often occurs following brain damage, such as traumatic brain injury (TBI) and ischemia. Cerebrolysin is a porcine brain peptide that is a unique neurotropic and neuroprotective agent. Cerebrolysin has been reported to increase neuroprotective effects after TBI, ischemia, and other CNS diseases. However, the effects of cerebrolysin on seizures are not known. Therefore, this study aimed to investigate the effects of neuropeptide cerebrolysin on neuronal death in the hippocampus after a seizure. To confirm the effects of cerebrolysin, we used a pilocarpine-induced seizure animal model. Cerebrolysin (2.5 ml/kg, i.p., once per day for 7 days) was immediately injected after a seizure induction. After 1 week, we obtained brain tissues and performed staining to histologically evaluate the potentially protective effects of cerebrolysin on seizure-induced neuronal death in the hippocampus. We found that cerebrolysin decreased hippocampal neuronal death after a seizure. In addition, an increase in brain-derived neurotrophic factor (BDNF) was confirmed through Western blot analysis to further support our hypothesis. Therefore, the present study suggests that the administration of cerebrolysin can be a useful therapeutic tool for preventing neuronal death after a seizure.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of Cerebrolysin on Hippocampal Neuronal Death After Pilocarpine-Induced Seizure

et al. 2020

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“…Fluoro-Jade C (FJC) is an anionic fluorescein derivate used to label degenerating neurons 38 . Although the exact mechanism is not known, different studies have demonstrated that FJC is a reliable dye used to stain dying neurons 75 76 77 78 79 . The hippocampal slices were washed 3 times in PBS for 30 minutes and mounted on gelatinized slides.…”

Section: Methodsmentioning

confidence: 99%

“…After, blocking solution [BSA (4%), Triton X (0.5%) in TBS] was added to the slices for 2 h, and they were incubated overnight with anti-Iba-1 primary antibody (1:500; Wako Chemicals, Osaka, Japan). On the next day, the slices were incubated with the secondary antibody Alexa Fluor 594 anti-rabbit (1:1000; Invitrogen, Carlsbad, CA, USA) for 1 h, washed, mounted in gelatinized slides and coverslipped with Fluoromount media (Sigma-Aldrich, St. Louis, MO, USA) 77 .…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective effects of the anticancer drug NVP-BEZ235 (dactolisib) on amyloid-β 1–42 induced neurotoxicity and memory impairment

Bellozi

Lima

Doria

et al. 2016

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and the main cause of dementia. Substantial evidences indicate that there is over-activation of the PI3K/Akt/mTOR axis in AD. Therefore, the aim of the present study was to investigate the effects of NVP-BEZ235 (BEZ; dactolisib), a dual PI3K/mTOR inhibitor that is under phase I/II clinical trials for the treatment of some types of cancer, in hippocampal neuronal cultures stimulated with amyloid-β (Aβ) 1–42 and in mice injected with Aβ 1–42 in the hippocampus. In cell cultures, BEZ reduced neuronal death induced by Aβ. BEZ, but not rapamycin, a mTOR inhibitor, or LY294002, a PI3K inhibitor that also inhibits mTOR, reduced the memory impairment induced by Aβ. The effect induced by Aβ was also prevented in PI3Kγ−/− mice. Neuronal death and microgliosis induced by Aβ were reduced by BEZ. In addition, the compound increased IL-10 and TNF-α levels in the hippocampus. Finally, BEZ did not change the phosphorylation of Akt and p70s6K, suggesting that the involvement of PI3K and mTOR in the effects induced by BEZ remains controversial. Therefore, BEZ represents a potential strategy to prevent the pathological outcomes induced by Aβ and should be investigated in other models of neurodegenerative conditions.

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Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K

et al. 2022

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PI3Kγ deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine

Cited by 11 publications

References 68 publications

Effects of Cerebrolysin on Hippocampal Neuronal Death After Pilocarpine-Induced Seizure

Effects of Cerebrolysin on Hippocampal Neuronal Death After Pilocarpine-Induced Seizure

Neuroprotective effects of the anticancer drug NVP-BEZ235 (dactolisib) on amyloid-β 1–42 induced neurotoxicity and memory impairment

Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K

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