Whole Body Metabolic Responses to Brain Trauma in the Rat

Abstract

Increases in metabolic rate reported in head-injured patients can contribute to increases in respiratory demand, raised body temperature, and host body wasting (cachexia). The objective of the present study was to quantify the metabolic responses to brain trauma in the rat and investigate the underlying mechanisms. Lateral fluid-percussion (FP) injury (applied cortical pressure 1.6–1.8 atm) in the rat resulted in consistent and reproducible cortical brain lesions (44 ± 6 mm³). Body weight and food intake were reduced significantly 24 h after brain trauma compared to sham-operated (7 and 49%,p < 0.01) and control animals (14 and 65%,p < 0.001), respectively. Resting oxygen consumption (V̇o₂, measured at 24°C) was increased significantly, by 9–16% above sham-operated, and 14–26% above control animals for 2–7 h after brain trauma (p < 0.05), but V̇o₂ was not raised thereafter (24–72 h) and colonic temperature was not changed. Raising the ambient temperature from 24°C to 28°C significantly reduced the hypermetabolism of brain-injured rats compared to sham-operated controls. Injection of the β-adrenoceptor antagonist propranolol (10 mg/kg, i.p.) completely abolished the rise in metabolic rate of brain-injured rats, and reduced significantly the rise in metabolic rate of the sham-operated animals (26%,p < 0.01 and 11%,p < 0.05; respectively). Systemic injection of the cyclo-oxygenase inhibitor indomethacin (1 mg/kg, i.p.) significantly attenuated (by 11%,p < 0.01), but did not completely abolish the hypermetabolism of brain-injured animals. Lateral FP injury in the rat causes a significant cachexia. Weight loss is due to hypophagia, and an increase in energy expenditure, which is mediated by sympathetic activation of thermogenesis and in part by prostaglandins.