tetrodotoxin and Cerebral-Infarction

We recently indicated that the vascular endothelial growth factor (VEGF) protects neurons against hypoxic death via enhancement of tyrosine phosphorylation of Kv1.2, an isoform of the delayed-rectifier potassium channels through activation of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway. The present study investigated whether VEGF could attenuate ischemia-induced increase of the potassium currents in the hippocampal pyramidal neurons of rats after ischemic injury. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) to induce brain ischemia. The whole-cell patch-clamp technique was used to record the potassium currents of hippocampal neurons in brain slices from the ischemically injured brains of the rats 24h after MCAO. We detected that transient MCAO caused a significant increase of voltage-gated potassium currents (Kv) and outward delayed-rectifier potassium currents (IK), but not outward transient potassium currents (IA), in the ipsilateral hippocampus compared with the sham. Moreover, we found that VEGF could acutely, reversibly and voltage-dependently inhibit the ischemia-induced IK increase. This inhibitory effect of VEGF could be completely abolished by wortmannin, an inhibitor of PI3-K. Our data indicate that VEGF attenuates the ischemia-induced increase of IK via activation of the PI3-K signaling pathway.

Topics: 4-Aminopyridine; Animals; Cerebral Infarction; Disease Models, Animal; Enzyme Inhibitors; Hippocampus; In Vitro Techniques; Infarction, Middle Cerebral Artery; Kv1.2 Potassium Channel; Male; Membrane Potentials; Neurons; Phosphatidylinositol 3-Kinases; Potassium Channel Blockers; Rats; Rats, Sprague-Dawley; Signal Transduction; Sodium Channel Blockers; Tetrodotoxin; Vascular Endothelial Growth Factor A

Neurotoxic fish poisoning appears to be a recent phenomenon in the Mediterranean Sea. We report a case of deep non-reactive reversible coma after ingestion of Mediterranean fish innards.. An 80 year-old man, heavy smoker who had a previous cerebral infarct in the posterior territory, was admitted for rapid deterioration of his neurological condition. He started having perioral tingling, then dysarthria, then became quadriparetic, then developed respiratory and hemodynamic failure and within 3-4h, entered a state of deep non-reactive coma with absence of all brainstem reflexes. He started to improve after 20 h and recovered his neurological baseline within 36 h. Later on, he stated that all his symptoms started after he ingested the gonads of a toxic fish, Lagocephalus scleratus.. Tetrodotoxin blocks voltage-gated sodium channels and inhibits the production and propagation of action potentials. This toxin is highly concentrated in the liver, gonads, intestines and skin of this fish that is well-known in Japan (where it is considered as a delicacy) and South-East Asia and seems to have migrated recently to the Mediterranean Sea. There is no known antidote to tetrodotoxin but intensive supportive treatment can be life-saving.

Topics: Aged, 80 and over; Animals; Brain Stem; Cerebral Infarction; Coma; Female; Foodborne Diseases; Humans; Male; Meat; Mediterranean Sea; Neurologic Examination; Neurotoxicity Syndromes; Ovary; Quadriplegia; Smoking; Tetraodontiformes; Tetrodotoxin

We investigated the role of the Ca(v)2.3 (alpha1E) channel in ischemic neuronal injury using Ca(v)2.3 mutant mice. In focal ischemia model with a complete occlusion of the middle cerebral artery in vivo, infarct at 24 h was significantly larger in Ca(v)2.3 mutant mice compared with that in wild-type controls. In vitro Ca2+ imaging studies using hippocampal slices revealed that oxygen-glucose deprivation induced a [Ca2+]i increase in the hippocampal CA1 region more vigorously in Ca(v)2.3 mutant mice than in wild-type controls, and that tetrodotoxin or bicuculline application abolished the difference between the genotypes. These results suggest that the Ca(v)2.3 channel plays a protective role in ischemic neuronal injury by a mechanism in which GABAergic neuronal actions are involved.

Topics: Animals; Bicuculline; Brain Ischemia; Calcium; Calcium Channels; Calcium Channels, R-Type; Cation Transport Proteins; Cerebral Infarction; GABA Antagonists; Genotype; Hippocampus; In Vitro Techniques; Mice; Mice, Mutant Strains; Nervous System; Sodium Channel Blockers; Tetrodotoxin