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Anesthetics influence concussive head injury induced blood-brain barrier breakdown, brain edema formation, cerebral blood flow, serotonin levels, brain pathology and functional outcome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Univ Med & Pharm, Dept Clin Neurosci, Cluj Napoca, Romania;RoNeuro Inst Neurol Res & Diagnost, Cluj Napoca, Romania.
Massachusetts Gen Hosp, Anesthesia & Crit Care, Boston, MA 02114 USA.
Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA.
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2019 (English)In: New Therapeutic Strategies for Brain Edema and Cell Injury / [ed] Sharma, HS Sharma, A, Elsevier, 2019, p. 45-81Chapter in book (Refereed)
Abstract [en]

Several lines of evidences show that anesthetics influence neurotoxicity and neuroprotection. The possibility that different anesthetic agents potentially influence the pathophysiological and functional outcome following neurotrauma was examined in a rat model of concussive head injury (CHI). The CHI was produced by an impact of 0.224N on the right parietal bone by dropping a weight of 114.6g from a 20cm height under different anesthetic agents, e.g., inhaled ether anesthesia or intraperitoneally administered ketamine, pentobarbital, equithesin or urethane anesthesia. Five hour CHI resulted in profound volume swelling and brain edema formation in both hemispheres showing disruption of the blood-brain barrier (BBB) to Evans blue and radio-iodine. A marked decrease in the cortical CBF and a profound increase in plasma or brain serotonin levels were seen at this time. Neuronal damages were present in several parts of the brain. These pathological changes were most marked in CHI under ether anesthesia followed by ketamine (35mg/kg, i.p.), pentobarbital (50 mg/kg, i.p.), equithesin (3 mL/kg, i.p.) and urethane (1 g/kg, i.p.). The functional outcome on Rota Rod performances or grid walking tests was also most adversely affected after CHI under ether anesthesia followed by pentobarbital, equithesin and ketamine. Interestingly, the plasma and brain serotonin levels strongly correlated with the development of brain edema in head injured animals in relation to different anesthetic agents used. These observations suggest that anesthetic agents are detrimental to functional and pathological outcomes in CHI probably through influencing the circulating plasma and brain serotonin levels, not reported earlier. Whether anesthetics could also affect the efficacy of different neuroprotective agents in CNS injuries is a new subject that is currently being examined in our laboratory.

Place, publisher, year, edition, pages
Elsevier, 2019. p. 45-81
Series
International Review of Neurobiology, ISSN 0074-7742 ; 146
National Category
Anesthesiology and Intensive Care Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-401923DOI: 10.1016/bs.irn.2019.06.006ISI: 000501592100003PubMedID: 31349932ISBN: 978-0-12-816754-0 (print)OAI: oai:DiVA.org:uu-401923DiVA, id: diva2:1384796
Funder
Swedish Research Council, 2710Göran Gustafsson Foundation for Research in Natural Sciences and MedicineAstraZenecaNIH (National Institute of Health), R01 AG028679Available from: 2020-01-10 Created: 2020-01-10 Last updated: 2020-01-10Bibliographically approved

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Sharma, Hari ShankerWiklund, LarsSharma, Aruna

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