Neurological recovery from closed head injury is impaired in diabetic rats.

Diabetes mellitus is a metabolic disorder associated with central nervous system impairments. Recent studies implicate oxidative stress mediated by reactive oxygen species (ROS) in the pathogenesis of diabetic complications. ROS have been shown to play role in the pathophysiology of brain injury. In the present study, closed head injury (CHI) was induced in diabetic rats to test the hypothesis that chronic oxidative stress exacerbates brain damage following CHI. Neurological recovery, edema, levels of low molecular weight antioxidants (LMWA), and markers of lipid peroxidation were determined at different intervals after injury. Diabetic rats (4 weeks after induction with streptozotocin) were subjected to CHI. Brain edema (percent water) and clinical status (neurological severity score) were assessed during 7 days. Brain LMWA were determined using cyclic voltammetry (CV) and HPLC-EC. In addition, conjugated dienes and thiobarbituric acid reactive substances (TBARS) were measured. Diabetic-CHI rats exhibited a lower rate of recovery and greater and more sustained edema (p < 0.01), as compared with the controls. At all times diabetic rats had higher levels of TBARS and conjugated dienes and lower concentrations of LMWA, and of vitamins C and E, suggesting chronic oxidative stress. At 5 min of CHI, the amounts of LMWA in control-CHI brains decreased (approximately 50%, p < 0.01) and returned to normal by 48 h and 7 days. In the diabetic-CHI brain only one class of LMWA slightly declined but remained low for 7 days. The present results support the hypothesis that diabetic rats are under chronic oxidative stress, and suffer greater neurological dysfunction, associated with further lipid peroxidation following CHI.