Faculty Collaboration Database

Caffeine prevents acute mortality after TBI in rats without increased morbidity. Exp Neurol 2012 Mar;234(1):161-8

Date

01/10/2012

Pubmed ID

22226594

Pubmed Central ID

PMC3294054

DOI

10.1016/j.expneurol.2011.12.026

Scopus ID

2-s2.0-84857502482 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

Severe traumatic brain injury (TBI) is associated with a high incidence of acute mortality followed by chronic alteration of homeostatic network activity that includes the emergence of posttraumatic seizures. We hypothesized that acute and chronic outcome after severe TBI critically depends on disrupted bioenergetic network homeostasis, which is governed by the availability of the brain's endogenous neuroprotectant adenosine. We used a rat lateral fluid percussion injury (FPI) model of severe TBI with an acute mortality rate of 46.7%. A subset of rats was treated with 25mg/kg caffeine intraperitoneally within 1 min of the injury. We assessed neuromotor function at 24h and 4 weeks, and video-EEG activity and histology at 4 weeks following injury. We first demonstrate that acute mortality is related to prolonged apnea and that a single acute injection of the adenosine receptor antagonist caffeine can completely prevent TBI-induced mortality when given immediately following the TBI. Second, we demonstrate that neuromotor function is not affected by caffeine treatment at either 24h or 4 weeks following injury. Third, we demonstrate development of epileptiform EEG bursts as early as 4 weeks post-injury that are significantly reduced in duration in the rats that received caffeine. Our data demonstrate that acute treatment with caffeine can prevent lethal apnea following fluid percussion injury, with no negative influence on motor function or histological outcome. Further, we show epileptiform bursting is reduced after caffeine treatment, suggesting a potential role in the modulation of epilepsy development after severe injury.

Author List

Lusardi TA, Lytle NK, Szybala C, Boison D

Author

Nikki K. Lytle PhD Assistant Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Brain Injuries
Caffeine
Central Nervous System Stimulants
Disease Models, Animal
Dose-Response Relationship, Drug
Electroencephalography
Epilepsy
Evoked Potentials
Exploratory Behavior
Male
Rats
Rats, Sprague-Dawley
Time Factors