Posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury
Abstract Background The benzodiazepine midazolam is a γ-aminobutyric acid (GABA)-A receptor agonist frequently used for sedation or stress control in patients suffering from traumatic brain injury (TBI). However, experimental studies on benzodiazepines have reported divergent results, raising concer...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | BMC Anesthesiology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12871-022-01592-x |
| _version_ | 1818917996798672896 |
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| author | Anne Sebastiani Simone Bender Michael K. E. Schäfer Serge C. Thal |
| author_facet | Anne Sebastiani Simone Bender Michael K. E. Schäfer Serge C. Thal |
| author_sort | Anne Sebastiani |
| collection | DOAJ |
| description | Abstract Background The benzodiazepine midazolam is a γ-aminobutyric acid (GABA)-A receptor agonist frequently used for sedation or stress control in patients suffering from traumatic brain injury (TBI). However, experimental studies on benzodiazepines have reported divergent results, raising concerns about its widespread use in patients. Some studies indicate that benzodiazepine-mediated potentiation of GABAergic neurotransmission is detrimental in brain-injured animals. However, other experimental investigations demonstrate neuroprotective effects, especially in pretreatment paradigms. This study investigated whether single-bolus midazolam administration influences secondary brain damage post-TBI. Methods Two different midazolam dosages (0.5 and 5 mg/kg BW), a combination of midazolam and its competitive antagonist flumazenil, or vehicle solution (NaCl 0.9%) was injected intravenously to mice 24 h after experimental TBI induced by controlled cortical impact. Mice were evaluated for neurological and motor deficits using a 15-point neuroscore and the rotarod test. Histopathological brain damage and mRNA expression of inflammatory marker genes were analyzed using quantitative polymerase chain reaction three days after insult. Results Histological brain damage was not affected by posttraumatic midazolam administration. Midazolam impaired functional recovery, and this effect could not be counteracted by administering the midazolam antagonist flumazenil. An increase in IL-1β mRNA levels due to postinjury application of midazolam was reversible by flumazenil administration. However, other inflammatory parameters were not affected. Conclusions This study merely reports minor effects of a postinjury midazolam application. Further studies focusing on a time-dependent analysis of posttraumatic benzodiazepine administration are required. |
| first_indexed | 2024-12-20T00:42:57Z |
| format | Article |
| id | doaj.art-b92422003b67403ca2354345eba2c25c |
| institution | Directory Open Access Journal |
| issn | 1471-2253 |
| language | English |
| last_indexed | 2024-12-20T00:42:57Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Anesthesiology |
| spelling | doaj.art-b92422003b67403ca2354345eba2c25c2022-12-21T19:59:30ZengBMCBMC Anesthesiology1471-22532022-03-0122111010.1186/s12871-022-01592-xPosttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injuryAnne Sebastiani0Simone Bender1Michael K. E. Schäfer2Serge C. Thal3Department of Anesthesiology, HELIOS University Hospital Wuppertal, University of Witten/HerdeckeDepartment of Anesthesiology, University Medical Center of the Johannes Gutenberg UniversityDepartment of Anesthesiology, University Medical Center of the Johannes Gutenberg UniversityDepartment of Anesthesiology, HELIOS University Hospital Wuppertal, University of Witten/HerdeckeAbstract Background The benzodiazepine midazolam is a γ-aminobutyric acid (GABA)-A receptor agonist frequently used for sedation or stress control in patients suffering from traumatic brain injury (TBI). However, experimental studies on benzodiazepines have reported divergent results, raising concerns about its widespread use in patients. Some studies indicate that benzodiazepine-mediated potentiation of GABAergic neurotransmission is detrimental in brain-injured animals. However, other experimental investigations demonstrate neuroprotective effects, especially in pretreatment paradigms. This study investigated whether single-bolus midazolam administration influences secondary brain damage post-TBI. Methods Two different midazolam dosages (0.5 and 5 mg/kg BW), a combination of midazolam and its competitive antagonist flumazenil, or vehicle solution (NaCl 0.9%) was injected intravenously to mice 24 h after experimental TBI induced by controlled cortical impact. Mice were evaluated for neurological and motor deficits using a 15-point neuroscore and the rotarod test. Histopathological brain damage and mRNA expression of inflammatory marker genes were analyzed using quantitative polymerase chain reaction three days after insult. Results Histological brain damage was not affected by posttraumatic midazolam administration. Midazolam impaired functional recovery, and this effect could not be counteracted by administering the midazolam antagonist flumazenil. An increase in IL-1β mRNA levels due to postinjury application of midazolam was reversible by flumazenil administration. However, other inflammatory parameters were not affected. Conclusions This study merely reports minor effects of a postinjury midazolam application. Further studies focusing on a time-dependent analysis of posttraumatic benzodiazepine administration are required.https://doi.org/10.1186/s12871-022-01592-xMidazolamFlumazenilBenzodiazepinesγ-aminobutyric acid-A receptorNeurotoxicityTraumatic brain injury |
| spellingShingle | Anne Sebastiani Simone Bender Michael K. E. Schäfer Serge C. Thal Posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury BMC Anesthesiology Midazolam Flumazenil Benzodiazepines γ-aminobutyric acid-A receptor Neurotoxicity Traumatic brain injury |
| title | Posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury |
| title_full | Posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury |
| title_fullStr | Posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury |
| title_full_unstemmed | Posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury |
| title_short | Posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury |
| title_sort | posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury |
| topic | Midazolam Flumazenil Benzodiazepines γ-aminobutyric acid-A receptor Neurotoxicity Traumatic brain injury |
| url | https://doi.org/10.1186/s12871-022-01592-x |
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