title: Propofol impairs neurogenesis and neurologic recovery and increases mortality rate in adult rats after traumatic brain injury.
abstract: 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.
  
  
  METHODS
  Randomized controlled animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  One hundred sixteen male Sprague Dawley rats.
  
  
  METHODS
  Mechanical brain lesion by controlled cortical impact.
  
  
  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.
authors.affiliation: 1Department of Anesthesiology, Medical Center of Johannes Gutenberg University, Mainz, Germany. 2Department of Neuropathology, Medical Center of Johannes Gutenberg University, Mainz, Germany.
authors.forename: Serge C
authors.initials: SC
authors.lastname: Thal
authors.forename: Ralph
authors.initials: R
authors.lastname: Timaru-Kast
authors.forename: Florian
authors.initials: F
authors.lastname: Wilde
authors.forename: Philipp
authors.initials: P
authors.lastname: Merk
authors.forename: Frederik
authors.initials: F
authors.lastname: Johnson
authors.forename: Katrin
authors.initials: K
authors.lastname: Frauenknecht
authors.forename: Anne
authors.initials: A
authors.lastname: Sebastiani
authors.forename: Clemens
authors.initials: C
authors.lastname: Sommer
authors.forename: Irina
authors.initials: I
authors.lastname: Staib-Lasarzik
authors.forename: Christian
authors.initials: C
authors.lastname: Werner
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelhard
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000401:mortality; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D015742:Propofol / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects
chemical_list: D006993:Hypnotics and Sedatives; D015742:Propofol