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-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.