¿Son los anestésicos tóxicos para el cerebro?
Are anaesthetics toxic to the brain?
Hudson AE, Hemmings HC Jr.
Department of Anesthesiology, Weill Cornell Medical College, New York, NY 10065, USA.
Br J Anaesth. 2011 Jul;107(1):30-7. doi: 10.1093/bja/aer122. Epub 2011 May 26.
Abstract
It has been assumed that anaesthetics have minimal or no persistent effects after emergence from anaesthesia. However, general anaesthetics act on multiple ion channels, receptors, and cell signalling systems in the central nervous system to produce anaesthesia, so it should come as no surprise that they also have non-anaesthetic actions that range from beneficial to detrimental. Accumulating evidence is forcing the anaesthesiacommunity to question the safety of general anaesthesia at the extremes of age. Preclinical data suggest that inhaled anaesthetics can have profound and long-lasting effects during key neurodevelopmental periods in neonatal animals by increasing neuronal cell death (apoptosis) and reducing neurogenesis. Clinical data remain conflicting on the significance of these laboratory data to the paediatric population. At the opposite extreme in age, elderly patients are recognized to be at an increased risk of postoperative cognitive dysfunction (POCD) with a well-recognized decline in cognitive function after surgery. The underlying mechanisms and the contribution of anaesthesia in particular to POCD remain unclear. Laboratory models suggest anaesthetic interactions with neurodegenerative mechanisms, such as those linked to the onset and progression ofAlzheimer's disease, but their clinical relevance remains inconclusive. Prospective randomized clinical trials are underway to address the clinical significance of these findings, but there are major challenges in designing, executing, and interpreting such trials. It is unlikely that definitive clinical studies absolving general anaesthetics of neurotoxicity will become available in the near future, requiring clinicians to use careful judgement when using these profound neurodepressants in vulnerable patients.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159425/pdf/aer122.pdf
Los anestésicos interfieren con la polarización de las neuronas corticales en desarrollo.
Anesthetics interfere with the polarization of developing cortical neurons.
Mintz CD, Smith SC, Barrett KM, Benson DL.
Department of Anesthesiology, Columbia University, New York, NY 10032, USA. cdm2134@columbia.edu
J Neurosurg Anesthesiol. 2012 Oct;24(4):368-75. doi: 10.1097/ANA.0b013e31826a03a6.
Abstract
Numerous studies from the clinical and preclinical literature indicate that general anesthetic agents have toxic effects on the developing brain, but the mechanism of this toxicity is still unknown. Previous studies have focused on the effects of anesthetics on cell survival, dendrite elaboration, and synapse formation, but little attention has been paid to possible effects of anesthetics on the developing axon. Using dissociated mouse cortical neurons in culture, we found that isoflurane delays the acquisition of neuronal polarity by interfering with axon specification. The magnitude of this effect is dependent on isoflurane concentration and exposure time over clinically relevant ranges, and it is neither a precursor to nor the result of neuronal cell death. Propofol also seems to interfere with the acquisition of neuronal polarity, but the mechanism does not require activity at GABAA receptors. Rather, the delay in axon specification likely results from a slowing of the extension of prepolarized neurites. The effect is not unique to isoflurane as propofol also seems to interfere with the acquisition of neuronal polarity. These findings demonstrate that anesthetics may interfere withbrain development through effects on axon growth and specification, thus introducing a new potential target in the search for mechanisms of pediatric anesthetic neurotoxicity.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479440/pdf/nihms401666.pdf
Atentamente
Dr. Juan C. Flores-Carrillo
Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
Are anaesthetics toxic to the brain?
Hudson AE, Hemmings HC Jr.
Department of Anesthesiology, Weill Cornell Medical College, New York, NY 10065, USA.
Br J Anaesth. 2011 Jul;107(1):30-7. doi: 10.1093/bja/aer122. Epub 2011 May 26.
Abstract
It has been assumed that anaesthetics have minimal or no persistent effects after emergence from anaesthesia. However, general anaesthetics act on multiple ion channels, receptors, and cell signalling systems in the central nervous system to produce anaesthesia, so it should come as no surprise that they also have non-anaesthetic actions that range from beneficial to detrimental. Accumulating evidence is forcing the anaesthesiacommunity to question the safety of general anaesthesia at the extremes of age. Preclinical data suggest that inhaled anaesthetics can have profound and long-lasting effects during key neurodevelopmental periods in neonatal animals by increasing neuronal cell death (apoptosis) and reducing neurogenesis. Clinical data remain conflicting on the significance of these laboratory data to the paediatric population. At the opposite extreme in age, elderly patients are recognized to be at an increased risk of postoperative cognitive dysfunction (POCD) with a well-recognized decline in cognitive function after surgery. The underlying mechanisms and the contribution of anaesthesia in particular to POCD remain unclear. Laboratory models suggest anaesthetic interactions with neurodegenerative mechanisms, such as those linked to the onset and progression ofAlzheimer's disease, but their clinical relevance remains inconclusive. Prospective randomized clinical trials are underway to address the clinical significance of these findings, but there are major challenges in designing, executing, and interpreting such trials. It is unlikely that definitive clinical studies absolving general anaesthetics of neurotoxicity will become available in the near future, requiring clinicians to use careful judgement when using these profound neurodepressants in vulnerable patients.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159425/pdf/aer122.pdf
Los anestésicos interfieren con la polarización de las neuronas corticales en desarrollo.
Anesthetics interfere with the polarization of developing cortical neurons.
Mintz CD, Smith SC, Barrett KM, Benson DL.
Department of Anesthesiology, Columbia University, New York, NY 10032, USA. cdm2134@columbia.edu
J Neurosurg Anesthesiol. 2012 Oct;24(4):368-75. doi: 10.1097/ANA.0b013e31826a03a6.
Abstract
Numerous studies from the clinical and preclinical literature indicate that general anesthetic agents have toxic effects on the developing brain, but the mechanism of this toxicity is still unknown. Previous studies have focused on the effects of anesthetics on cell survival, dendrite elaboration, and synapse formation, but little attention has been paid to possible effects of anesthetics on the developing axon. Using dissociated mouse cortical neurons in culture, we found that isoflurane delays the acquisition of neuronal polarity by interfering with axon specification. The magnitude of this effect is dependent on isoflurane concentration and exposure time over clinically relevant ranges, and it is neither a precursor to nor the result of neuronal cell death. Propofol also seems to interfere with the acquisition of neuronal polarity, but the mechanism does not require activity at GABAA receptors. Rather, the delay in axon specification likely results from a slowing of the extension of prepolarized neurites. The effect is not unique to isoflurane as propofol also seems to interfere with the acquisition of neuronal polarity. These findings demonstrate that anesthetics may interfere withbrain development through effects on axon growth and specification, thus introducing a new potential target in the search for mechanisms of pediatric anesthetic neurotoxicity.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479440/pdf/nihms401666.pdf
Atentamente
Dr. Juan C. Flores-Carrillo
Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
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