Citation

Sharma HS, Muresanu DF, Nozari A, Castellani RJ, Dey PK, Wiklund L, Sharma A. Int. Rev. Neurobiol. 2019; 146: 45-81.

Affiliation

International Experimental Central Nervous System Injury & Repair (IECNSIR), Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden.

Copyright

(Copyright © 2019, Elsevier Publishing)

DOI

10.1016/bs.irn.2019.06.006

PMID

31349932

Abstract

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 radioiodine. 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 (50mg/kg, i.p.), equithesin (3mL/kg, i.p.) and urethane (1g/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.

© 2019 Elsevier Inc. All rights reserved.

Language: en

Keywords

Anesthetics; Blood-brain barrier; Brain edema; Cerebral blood flow; Concussive head injury; Equithesin; Ether; Ketamine; Neuronal injury; Pentobarbital; Sensory motor function