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
Affiliations: Traumatic Brain Injury Labraty, Department of
Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA | Centocor, 145 King of Prussia Road Mail Stop R-4-1
Radnor, PA 19087, USA | Veterans Administrations Medical Center, Philadelphia,
PA 19104, USA
Note: [] Corresponding author: T.K. McIntosh, Traumatic Brain Injury
Labraty, Department of Neurosurgery, University of Pennsylvania, 105 Hayden
Hall, 3320 Smith Walk, Philadelphia, PA 19104-6316, USA. Tel.: +1 215 898 8522;
Fax: + 1 215 573 3808; E-mail: mcintosh@seas.upenn.edu
Abstract: Purpose: 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-α (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.
