Delayed application of the anesthetic propofol contrasts the neurotoxic effects of kainate on rat organotypic spinal slice cultures
| Autor: | Dzejla Bajrektarevic, Andrea Nistri |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Time Factors General anesthetic Excitotoxicity Kainate receptor Toxicology medicine.disease_cause chemistry.chemical_compound 0302 clinical medicine neurotoxicity Excitatory Amino Acid Agonists Hypnotics and Sedatives Medicine rat methoxyflurane drug determination motoneuron receptor upregulation Spinal cord injury 4 aminobutyric acid A receptor therapy delay GABAA receptor General Neuroscience drug effect Glutamate receptor Glycine Agents GABAA and glycine receptors General anesthetic Glutamate receptors Motoneuron Neuroprotection Spinal cord injury 4 aminobutyric acid A receptor bicuculline kainic acid methoxyflurane propofol strychnine anesthesia induction animal tissue Article cell loss concentration (parameters) controlled study drug determination drug effect excitotoxicity general anesthesia motoneuron neuroprotection neurotoxicity nonhuman priority journal protein function rat receptor upregulation therapy delay Glutamate receptors protein function Neuroprotection Spinal Cord priority journal GABAA and glycine receptors strychnine bicuculline excitotoxicity medicine.drug Kainic acid In Vitro Techniques Article Choline O-Acetyltransferase animal tissue 03 medical and health sciences Organ Culture Techniques Animals controlled study GABA-A Receptor Antagonists cell loss anesthesia induction nonhuman Dose-Response Relationship Drug propofol concentration (parameters) business.industry Bicuculline medicine.disease general anesthesia Rats 030104 developmental biology chemistry Phosphopyruvate Hydratase Settore BIO/14 - Farmacologia business kainic acid Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | NeuroToxicology. 54:1-10 |
| ISSN: | 0161-813X |
| DOI: | 10.1016/j.neuro.2016.03.001 |
| Popis: | Excitotoxicity due to hyperactivation of glutamate receptors is thought to underlie acute spinal injury with subsequent strong deficit in spinal network function. Devising an efficacious protocol of neuroprotection to arrest excitotoxicity might, therefore, spare a substantial number of neurons and allow later recovery. In vitro preparations of the spinal cord enable detailed measurement of spinal damage evoked by the potent glutamate analogue kainate. Any clinically-relevant neuroprotective treatment should start after the initial lesion and spare networks for at least 24h when cell damage plateaus. Using this strategy, we have observed that the gas anesthetic methoxyflurane provided strong, delayed neuroprotection. It is unclear if this beneficial effect was due to the mechanism of action by methoxyflurane, or it was the consequence of anesthetic depression. To test this hypothesis, we investigated the effect by propofol (commonly injected i.v. for general anesthesia) after kainate excitotoxicity induced on organotypic spinal slices. At 5μM concentration, propofol significantly attenuated cell death, including neuronal losses and, especially, damage to the highly vulnerable motoneurons. The action by propofol was fully prevented when co-applied with the GABAA antagonist bicuculline, indicating that neuroprotection required intact GABAA receptor function. Although bicuculline per se was not neurotoxic, it largely enhanced the lesional effects of kainate, suggesting that GABAA receptor activity could limit excitotoxicity. Our data might offer an explanation for the beneficial clinical outcome of neurosurgery performed as soon as possible after spinal lesion: we posit that general anesthesia contributes to this outcome, regardless of the type of anesthetic used. |
| Databáze: | OpenAIRE |
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