Effects of the sodium channel blocker tetrodotoxin (TTX) on cellular ion homeostasis in rat brain subjected to complete ischemia

doi:10.1016/0006-8993(94)90230-5

Brain Research

Volume 652, Issue 2, 1 August 1994, Pages 216-224

https://doi.org/10.1016/0006-8993(94)90230-5 Get rights and content

Abstract

Anoxic depolarization (AD) and failure of the cellular ion homeostasis are suggested to play a key role in ischemia-induced neuronal death. Recent studies show that the blockade of Na⁺ influx significantly improved the neuronal outcome. In the present study, we investigated the effects of 10 μM tetrodotpxin (TTX) on ischemia-induced disturbances of ion homeostasis in the isolated perfused rat brain. TTX inhibited the spontaneous EEG activity, delayed the ischemia-induced tissue acidification, and significantly postponed the occurrece of AD by 65%. The [Ca²⁺]_e elevation prior to AD was attenuated from 17.8% to 6% while the increase of the [Na⁺]_e in this period was enhanced (from 2.9% to 7.3%). These findings implied that the ischemia-induced early cellular sodium load and the corresponding shrinkage of the extracellular space was counteracted by TTX. Our results suggest that the Na⁺ influx via voltage-dependent channels preceding complete breakdown of ion homeostasis is one major factor leading to cell depolarization. The massive Na⁺ influx coinciding with AD, however, may be mainly via non-selective cation channels or/and receptor-operated channels. Persistent Na⁺ influx deteriorates neuronal tissue integrity by favouring Ca²⁺ influx and edema formation. Blockade of ischemia-induced excessive Na⁺ influx is, therefore, a promising pharmacological approach for stroke treatment.

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Effects of the sodium channel blocker tetrodotoxin (TTX) on cellular ion homeostasis in rat brain subjected to complete ischemia

Abstract

Brain Res.

Brain Res.

Brain Res.

Neuroscience

Neuroscience

Brain Res.

Biochim. Biophys. Acta

Brain Res.

J. Pharmacol. Methods

Exp. Neurol.

Exp. Neurol.

Biochem. Biophys. Res. Commun.

Trends Neurosci.

Neurosci. Lett.

Paroxysmal firing in hippocampal slices during the early phase of hypoxia

Soc. Neurosci. Abstr.

Effects of calcium entry blocker emopamil on postischemic energy metabolism of the isolated perfused rat brain

J. Cerebr. Blood Flow Metab.

Vascular and direct effects on cerebral energy metabolism of emopamil

Lactate and postischemic recovery of energy metabolites and electrical activity in the isolated perfused rat brain

J. Neorosurg. Anesthesiol.

Die anoxische Terminaldepolarisation als Indikator der Vulnerabilita¨t der Groβhirnrinde bei Anoxie und Ischa¨mie

Pflu¨gers Arch.

Ionic dependence of glutamate neurotocixity

J. Neurosci.

Human neocortical excitability is decreased during anoxia via sodium channel modulation

J. Clin. Invest.

Studies on the linkage of energy metabolism and neuronal activity in the isolated perfused rat brain

J. Neurochem.