Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain.
In a range of animal species, exposure of the brain to general anaesthesia without surgery during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex but include an increase in brain cell death. In humans, attempts to link adverse cognit...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0173413&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850232478573264896 |
|---|---|
| author | Kevin D Broad Go Kawano Igor Fierens Eridan Rocha-Ferreira Mariya Hristova Mojgan Ezzati Jamshid Rostami Daniel Alonso-Alconada Badr Chaban Jane Hassell Bobbi Fleiss Pierre Gressens Robert D Sanders Nicola J Robertson |
| author_facet | Kevin D Broad Go Kawano Igor Fierens Eridan Rocha-Ferreira Mariya Hristova Mojgan Ezzati Jamshid Rostami Daniel Alonso-Alconada Badr Chaban Jane Hassell Bobbi Fleiss Pierre Gressens Robert D Sanders Nicola J Robertson |
| author_sort | Kevin D Broad |
| collection | DOAJ |
| description | In a range of animal species, exposure of the brain to general anaesthesia without surgery during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex but include an increase in brain cell death. In humans, attempts to link adverse cognitive development to infantile anaesthesia exposure have yielded ambiguous results. One caveat that may influence the interpretation of human studies is that infants are not exposed to general anaesthesia without surgery, raising the possibility that surgery itself, may contribute to adverse cognitive development. Using piglets, we investigated whether a minor surgical procedure increases cell death and disrupts neuro-developmental and cognitively salient gene transcription in the neonatal brain. We randomly assigned neonatal male piglets to a group who received 6h of 2% isoflurane anaesthesia or a group who received an identical anaesthesia plus 15 mins of surgery designed to replicate an inguinal hernia repair. Compared to anesthesia alone, surgery-induced significant increases in cell death in eight areas of the brain. Using RNAseq data derived from all 12 piglets per group we also identified significant changes in the expression of 181 gene transcripts induced by surgery in the cingulate cortex, pathway analysis of these changes suggests that surgery influences the thrombin, aldosterone, axonal guidance, B cell, ERK-5, eNOS and GABAA signalling pathways. This suggests a number of novel mechanisms by which surgery may influence neural and cognitive development independently or synergistically with the effects of anaesthesia. |
| format | Article |
| id | doaj-art-30006c7cc5bb4a509a7beb94ccf4e8cd |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-30006c7cc5bb4a509a7beb94ccf4e8cd2025-08-20T02:03:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01123e017341310.1371/journal.pone.0173413Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain.Kevin D BroadGo KawanoIgor FierensEridan Rocha-FerreiraMariya HristovaMojgan EzzatiJamshid RostamiDaniel Alonso-AlconadaBadr ChabanJane HassellBobbi FleissPierre GressensRobert D SandersNicola J RobertsonIn a range of animal species, exposure of the brain to general anaesthesia without surgery during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex but include an increase in brain cell death. In humans, attempts to link adverse cognitive development to infantile anaesthesia exposure have yielded ambiguous results. One caveat that may influence the interpretation of human studies is that infants are not exposed to general anaesthesia without surgery, raising the possibility that surgery itself, may contribute to adverse cognitive development. Using piglets, we investigated whether a minor surgical procedure increases cell death and disrupts neuro-developmental and cognitively salient gene transcription in the neonatal brain. We randomly assigned neonatal male piglets to a group who received 6h of 2% isoflurane anaesthesia or a group who received an identical anaesthesia plus 15 mins of surgery designed to replicate an inguinal hernia repair. Compared to anesthesia alone, surgery-induced significant increases in cell death in eight areas of the brain. Using RNAseq data derived from all 12 piglets per group we also identified significant changes in the expression of 181 gene transcripts induced by surgery in the cingulate cortex, pathway analysis of these changes suggests that surgery influences the thrombin, aldosterone, axonal guidance, B cell, ERK-5, eNOS and GABAA signalling pathways. This suggests a number of novel mechanisms by which surgery may influence neural and cognitive development independently or synergistically with the effects of anaesthesia.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0173413&type=printable |
| spellingShingle | Kevin D Broad Go Kawano Igor Fierens Eridan Rocha-Ferreira Mariya Hristova Mojgan Ezzati Jamshid Rostami Daniel Alonso-Alconada Badr Chaban Jane Hassell Bobbi Fleiss Pierre Gressens Robert D Sanders Nicola J Robertson Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain. PLoS ONE |
| title | Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain. |
| title_full | Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain. |
| title_fullStr | Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain. |
| title_full_unstemmed | Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain. |
| title_short | Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain. |
| title_sort | surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0173413&type=printable |
| work_keys_str_mv | AT kevindbroad surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT gokawano surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT igorfierens surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT eridanrochaferreira surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT mariyahristova surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT mojganezzati surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT jamshidrostami surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT danielalonsoalconada surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT badrchaban surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT janehassell surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT bobbifleiss surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT pierregressens surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT robertdsanders surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain AT nicolajrobertson surgeryincreasescelldeathandinduceschangesingeneexpressioncomparedwithanesthesiaaloneinthedevelopingpigletbrain |