Influence of isoflurane on neuronal death and outcome in a rat model of traumatic brain injury.
In the developing brain agents clinically used for the purpose of analgosedation can cause severe neurodegeneration. In patients with TBI analgosedation is a first-line treatment for intracranial hypertension. At the same time, damaged neuronal networks undergo conformational changes and use developmental mechanisms to restore brain function. Inhibition of repair mechanisms by sedatives may cause brain dysfunction and neuronal cell death during development and after traumatic brain injury. To test this hypothesis, the influence of sedation was experimentally evaluated in a controlled cortical impact injury model (CCII). One experimental group was preconditioned with regular sedation (isoflurane 1.0 MAC(50)) and the second group with deep sedation (isoflurane 1.67 MAC(50)). After controlled cortical impact injury (CCII) we tested the outcome at 4 h and 48 h using histological methods and a neurological test. Increased apoptosis was found in referenced cortical areas as early as 48 h after trauma (TUNEL-positive cells/field of view, mean ± SEM, 116.6 ± 9.3 and 45.3 ± 4.1, both n = 12). Along with histological findings neurological outcome was worst as indicated by a higher score in the experimental group with deep sedation (mean ± SEM 4 h, 13.9 ± 0.6, n = 14 and 20 ± 0.7, n = 15; 48 h, 8.1 ± 0.6, n = 14 and 13.3 ± 0.6, n = 15). Although blood pressure was lower with deep sedation, no frank hypotension occurred. In our experiments deep sedation with high doses of isoflurane caused neurodegeneration and worse outcome compared with regular sedation.
Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany. daniel.hertle@med.uni-heidelberg.de
Daniel
D
Hertle
Christopher
C
Beynon
K
K
Zweckberger
B
B
Vienenkötter
C S
CS
Jung
K
K
Kiening
Andreas
A
Unterberg
Oliver W
OW
Sakowitz
D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D007530:Isoflurane / Q000627:therapeutic use*; D009460:Neurologic Examination; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018685:Anesthetics, Inhalation; D007530:Isoflurane