title: Administration of monoclonal antibodies neutralizing the inflammatory mediators tumor necrosis factor alpha and interleukin -6 does not attenuate acute behavioral deficits following experimental traumatic brain injury in the rat.
abstract: OBJECTIVE
  Although many previous studies have indicated that the acute inflammatory response following traumatic brain injury (TBI) is detrimental, inflammation may also positively influence outcome in the more chronic post-injury recovery period. We evaluated the effects of monoclonal antibodies (mAB), neutralizing either IL-6 (IL-6 mAB) or TNF-alpha (TNF mAB), administered intracerebroventricularly (i.c.v) on acute neurobehavioral outcome following TBI.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 173) were anesthetized (sodium pentobarbital, 60 mg/kg) and subjected to lateral fluid percussion (FP) brain injury of moderate severity (n = 123) or sham injury (n = 50). Beginning 1 h post-injury, TNF mAB (n = 41, of which 25 were brain-injured) or IL-6 mAB (n = 42, of which 25 were brain-injured) at a concentration of 2 mg/mL was infused i.c.v ipsilateral to the injury for 48 hours. Vehicle-treated animals (control IgG; n = 43, of which 26 were brain-injured) served as controls. In Study 1, cognitive function was evaluated in the Morris Water Maze (MWM) followed by evaluation of regional cerebral edema at 48 h post-injury. In Study 2, animals were evaluated for neurological motor function and post-injury learning in the MWM at one week post-injury.
  
  
  RESULTS
  FP brain injury caused significant cognitive (p < 0.05) and neurological motor (p < 0.05) deficits and increased regional brain water content in the injured hemisphere. Treatment with either TNF- or IL-6-mAB had no effect on neurological motor, cognitive function or brain edema during the first post-injury week.
  
  
  CONCLUSIONS
  Evaluation of anti-inflammatory mABs on more chronic behavioral deficits appears warranted.
authors.affiliation: Traumatic Brain Injury Labraty, Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Niklas
authors.initials: N
authors.lastname: Marklund
authors.forename: Carrie
authors.initials: C
authors.lastname: Keck
authors.forename: Rachel
authors.initials: R
authors.lastname: Hoover
authors.forename: Kristie
authors.initials: K
authors.lastname: Soltesz
authors.forename: Marie
authors.initials: M
authors.lastname: Millard
authors.forename: David
authors.initials: D
authors.lastname: LeBold
authors.forename: Zachary
authors.initials: Z
authors.lastname: Spangler
authors.forename: Adrian
authors.initials: A
authors.lastname: Banning
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Benson
authors.forename: Tracy K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D001929:Brain Edema / Q000188:drug therapy / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors