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Imran 2015 J Neurochem

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Publications in the MiPMap
Imran I, Hillert MH, Klein J (2015) Early metabolic responses to lithium/pilocarpine-induced status epilepticus in rat brain. J Neurochem 135:1007-18.

Β» PMID: 26365376

Imran I, Hillert MH, Klein J (2015) J Neurochem

Abstract: The lithium-pilocarpine model of status epilepticus is a well-known animal model of temporal lobe epilepsy. We combined this model with in vivo-microdialysis to investigate energy metabolites and acute cellular membrane damage during seizure development. Rats were implanted with dialysis probes and pretreated with lithium chloride (127 mg/kg i.p.). 24 hours later, they received pilocarpine (30 mg/kg s.c.) which initiated seizures within 30 min. In the dialysate from rat hippocampus, we observed a transient increase of glucose and a prominent, five-fold increase of lactate during seizures. Lactate release was due to neuronal activation because it was strongly reduced by infusion of tetrodotoxin, administration of atropine, or when seizures were terminated by diazepam or ketamine. In ex vivo-assays, mitochondrial function as measured by respirometry was not affected by 90 minutes of seizures. Extracellular levels of choline, however, increased twofold, and glycerol levels ten-fold, which indicates cellular phospholipid breakdown during seizures. Within 60 min of pilocarpine administration, hydroxylation of salicylate increased two-fold, and formation of isoprostanes twenty-fold, revealing significant oxidative stress in hippocampal tissue. Increases of lactate, glycerol and isoprostanes were abrogated, and increases of choline completely prevented, when hippocampal probes were perfused with calcium-free solution. Similarly, administration of pregabalin (100 mg/kg i.p.), a calcium channel ligand, 15 min prior to pilocarpine strongly attenuated parameters of membrane damage and oxidative stress. We conclude that seizure development in a rat model of status epilepticus is accompanied by increases of extracellular lactate, choline and glycerol, and by oxidative stress, while mitochondrial function remains normal for at least 90 minutes. Membrane damage depends on calcium influx and can be prevented by treatment with pregabalin. This article is protected by copyright. β€’ Keywords: Glycerol, Hippocampus, Isoprostanes, Lactate, Microdyalisis, Seizures

Labels: MiParea: Respiration, mt-Medicine  Pathology: Other 

Organism: Rat  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k