Hypoxia preconditioning attenuates brain edema associated with kainic acid-induced status epilepticus in rats

Emerson, Mitchell R.; Nelson, Stanley R.; Samson, Frederick E.; Pazdernik, Thomas L.

doi:10.1016/s0006-8993(99)01195-6

Cited by 55 publications

(36 citation statements)

References 18 publications

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“…Human studies corroborate the occurrence of hypoxia associated with seizures, showing expression of HIF-1a in the epileptogenic focus (Gualtieri et al, 2013) and reduction of oxygen saturation during seizures, especially in seizures whose focus is the temporal lobe and that spread contralaterally (Bateman et al, 2008). Despite the degenerative effects of long hypoxic events, hypoxia preconditioning reduces seizure susceptibility, seizure severity, and acute hippocampal neuron loss (Pohle and Rauca, 1994;Emerson et al, 1999;Rauca et al, 2000;Rubaj et al, 2000;Chang et al, 2005). However, the long-term effects of hypoxic preconditioning on the chronic phase neuron loss and memory are not known.…”

Section: Introductionmentioning

confidence: 77%

“…In our study, preconditioned rats that exhibited SRS had significant neuronal protection when compared to SE animals in the acute and chronic periods. In KA or pentylenetetrazole-induced SE, a mild hypoxia is known to protect hilar, CA3, and CA1 neurons in the acute period (Pohle and Rauca, 1994;Emerson et al, 1999). Other preconditioning models also showed neuroprotection in the acute, epileptogenic and chronic period post-SE (Kelly and McIntyre, 1994;Zhang et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, studies with hypoxia and seizure preconditioning provided evidence that the priming episode induces differential gene expression, with minimal overlap to the gene expression promoted by the same stimuli in injurious levels (Stenzel-Poore et al, 2003;Simon et al, 2007). Amongst the potential neuroprotective changes promoted by hypoxia priming are downregulation of ionotropic glutamate receptors and upregulation of heat-shock proteins, glial fibrillary acidic protein, superoxide dismutase, and adenosine (Emerson et al, 1999;Kirino, 2002;Stenzel-Poore et al, 2003). The time course of neuroprotection shown by different preconditioning paradigms suggests the recruitment of distinct endogenous mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre-exposed to hypoxia

et al. 2016

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Abstract-Preconditioning can induce a cascade of cellular events leading to neuroprotection against subsequent brain insults. In this study, we investigated the chronic effects of hypoxic preconditioning on spontaneous recurrent seizures (SRS), neuronal death, and spatial memory performance in rats subjected to pilocarpine (Pilo)-induced status epilepticus (SE). Rats underwent a short hypoxic episode (7% O 2 + 93% N 2 ; 30 min on two consecutive days) preceding a 4-h SE (HSE group). Control groups were rats submitted to SE only (SE), rats subjected to hypoxia only (H) or normoxia-saline (C). Animals were monitored for the occurrence of SRS, and spatial memory performance was evaluated in the radial-arm maze. Hippocampal sections were analyzed for cell death and mossy fiber sprouting at 1 or 60 days after SE. Compared to SE group, HSE had increased SE latency, reduced number of rats with SRS, reduced mossy fiber sprouting at 60 days, and reduced cell death in the hilus and the CA3 region 1 and 60 days after SE. Additionally, HSE rats had better spatial memory performance than SE rats. Our findings indicated that short hypoxic preconditioning preceding SE promotes long-lasting protective effects on neuron survival and spatial memory. Ó

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Section: Introductionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre-exposed to hypoxia

et al. 2016

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“…Edema resulting from seizures in human or experimental model can be of two types, cytotoxic edema and vasogenic edema [63][64][65][66][67][68][69]. In the cytotoxic edema, the glutamate hyperstimulation causes intracellular Ca 2+ increase and promotes cytotoxicity in neurons and glial cells [64,70]. Conversely, in the vasogenic edema, the cellular signaling triggered by SE can induce proinflammatory cytokines release and increases the production of kinins [71][72][73][74][75][76][77][78].…”

Section: Discussionmentioning

confidence: 99%

Silencing of P2X7R by RNA interference in the hippocampus can attenuate morphological and behavioral impact of pilocarpine-induced epilepsy

Amorim

Araújo

Valero

et al. 2017

Purinergic Signalling

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Cell signaling mediated by P2X7 receptors (P2X7R) has been suggested to be involved in epileptogenesis, via modulation of intracellular calcium levels, excitotoxicity, activation of inflammatory cascades, and cell death, among other mechanisms. These processes have been described to be involved in pilocarpine-induced status epilepticus (SE) and contribute to hyperexcitability, resulting in spontaneous and recurrent seizures. Here, we aimed to investigate the role of P2X7R in epileptogenesis in vivo using RNA interference (RNAi) to inhibit the expression of this receptor. Small interfering RNA (siRNA) targeting P2X7R mRNA was injected into the lateral ventricles (icv) 6 h after SE. Four groups were studied: SalineVehicle, Saline-siRNA, Pilo-Vehicle, and Pilo-siRNA. P2X7R was quantified by western blotting and neuronal death assessed by Fluoro-Jade B histochemistry. The hippocampal volume (edema) was determined 48 h following RNAi. Behavioral parameters as latency to the appearance of spontaneous seizures and the number of seizures were determined until 60 days after the SE onset. The Saline-siRNA and Pilo-siRNA groups showed a 43 and 37% reduction, respectively, in P2X7R protein levels compared to respective vehicle groups. Neuroprotection was observed in CA1 and CA3 of the PilosiRNA group compared to Pilo-Vehicle. P2X7R silencing in pilocarpine group reversed the increase in the edema detected in the hilus, suprapyramidal dentate gyrus, CA1, and CA3; reduced mortality rate following SE; increased the time to onset of spontaneous seizure; and reduced the number of seizures, when compared to the Pilo-Vehicle group. Therefore, our data highlights the potential of P2X7R as a therapeutic target for the adjunct treatment of epilepsy.

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“…Because the effects of preconditioning on the metabolic state of the brain are far from elucidated, the implication of GLUT-1 in our model of ischemic tolerance might be of interest. Furthermore, although not directly related to ischemic tolerance, it has been reported that a protein neosynthesis is implicated in the preconditioning effects of hypoxia (9% O 2 ) against kainate-induced seizures (Emerson et al, 1999). Likewise, the implication of a protein neosynthesis in this model of tolerance would be of interest.…”

Section: Bernaudin Et Al 398mentioning

confidence: 99%

Normobaric Hypoxia Induces Tolerance to Focal Permanent Cerebral Ischemia in Association with an Increased Expression of Hypoxia-Inducible Factor-1 and its Target Genes, Erythropoietin and VEGF, in the Adult Mouse Brain

Bernaudin

Nedelec

Divoux

et al. 2002

J Cereb Blood Flow Metab

327

272

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Summary:Tolerance to cerebral ischemia is achieved by preconditioning sublethal stresses, such as ischemia or hypoxia, paradigms in which the decrease of O 2 availability may constitute an early signal inducing tolerance. In accordance with this concept, this study shows that hypoxia induces tolerance against focal permanent ischemia in adult mice. Normobaric hypoxia (8% O 2 of 1-hour, 3-hour, or 6-hour duration), performed 24 hours before ischemia, reduces infarct volume by approximately 30% when compared with controls. To elucidate the mechanisms underlying this neuroprotection, the authors investigated the effects of preconditioning on cerebral expression of hypoxia-inducible factor-1␣ (HIF-1␣) and its target genes, erythropoietin and vascular endothelial growth factor (VEGF). Hypoxia, whatever its duration (1 hour, 3 hours, 6 hours), rapidly increases the nuclear content of HIF-1␣ as well as the mRNA levels of erythropoietin and VEGF. Furthermore, erythropoietin and VEGF are upregulated at the protein level 24 hours after 6 hours of hypoxia. The authors' findings show that (1) hypoxia elicits a delayed, short-lasting (<72 hours) tolerance to focal permanent ischemia in the adult mouse brain; (2) HIF-1 target genes could contribute to the establishment of tolerance; and (3) this model might be a useful paradigm to further study the mechanisms of ischemic tolerance, to identify new therapeutic targets for stroke.

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Hypoxia preconditioning attenuates brain edema associated with kainic acid-induced status epilepticus in rats

Cited by 55 publications

References 18 publications

Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre-exposed to hypoxia

Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre-exposed to hypoxia

Silencing of P2X7R by RNA interference in the hippocampus can attenuate morphological and behavioral impact of pilocarpine-induced epilepsy

Normobaric Hypoxia Induces Tolerance to Focal Permanent Cerebral Ischemia in Association with an Increased Expression of Hypoxia-Inducible Factor-1 and its Target Genes, Erythropoietin and VEGF, in the Adult Mouse Brain

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