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Propofol Impairs Neurogenesis and Neurologic Recovery and Increases Mortality Rate in Adult Rats After Traumatic Brain Injury*

Thal, Serge C. MD1; Timaru-Kast, Ralph MD1; Wilde, Florian MD1; Merk, Philipp MD1; Johnson, Frederik MD1; Frauenknecht, Katrin MD2; Sebastiani, Anne MD1; Sommer, Clemens MD2; Staib-Lasarzik, Irina MD1; Werner, Christian MD, PhD1; Engelhard, Kristin MD, PhD1

doi: 10.1097/CCM.0b013e3182a639fd
Neurologic Critical Care

Objective: Limited data are available on the influence of sedation for critical care therapy with the widely used anesthetic propofol on recovery from acute traumatic brain injury. To establish the influence of propofol on endogenous neurogenesis and functional recovery after traumatic brain injury, rats were sedated with propofol either during or 2 hours after experimental traumatic brain injury.

Design: Randomized controlled animal study.

Setting: University research laboratory.

Subjects: One hundred sixteen male Sprague Dawley rats.

Interventions: Mechanical brain lesion by controlled cortical impact.

Measurements and Main Results: This study investigated the dose-dependent influence of propofol (36 or 72 mg/kg/hr) either during controlled cortical impact induction or in a delayed application protocol 2 hours after experimental traumatic brain injury. Infusion of propofol resulted in 1) aggravation of neurologic dysfunction, 2) increased 28-day mortality rate, and 3) impaired posttraumatic neurogenesis (5-bromo-2-deoxyuridine + NeuN-positive cells). Application of propofol during trauma induction afforded a significant stronger effect in the high-dose group compared with low-dose propofol. In the posttrauma protocol, animals were sedated with sevoflurane during the controlled cortical impact injury, and propofol was given after an awake phase. In these animals, propofol increased mortality rate and impaired neurologic function and neurogenesis compared with animals without delayed propofol anesthesia.

Conclusions: The results show that propofol may prevent or limit reparative processes in the early-phase postinjury. The results therefore indicate that anesthetics may be potentially harmful not only in very young mammalians but also in adult animals following acute cerebral injuries. The results provide first evidence for an altered sensitivity for anesthesia-related negative effects on neurogenesis, functional outcome, and survival in adult rats with brain lesions.

1Department of Anesthesiology, Medical Center of Johannes Gutenberg University, Mainz, Germany.

2Department of Neuropathology, Medical Center of Johannes Gutenberg University, Mainz, Germany.

* See also p. 211.

Drs. Thal and Timaru-Kast contributed equally to this study.

Presented, in part, as doctoral theses by Drs. Wilde, Merk, and Johnson to the Medical Faculty of the Johannes Gutenberg University, Mainz, Germany.

Dr. Thal received a grant from Else Kröner Fresenius Stiftung (Germany; P19/07//A07/07) and the Focus Program Translational Neurosciences of the Johannes Gutenberg University. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: thal@uni-mainz.de

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins