Lipid peroxidation and oedema in experimental brain injury: comparison of treatment with methylprednisolone, tirilazad mesylate and vitamin E.

Trauma-induced lipid peroxidation (LP) is one of the most important factors that produces tissue damage in head trauma. In the present study, the protective effects of free radical suppression with methylprednisolone (MP), tirilazad mesylate (TM) and vitamin E on the development of cerebral LP and oedema resulting from head trauma have been investigated. Rats were divided randomly into four groups. Bolus injections of physiological saline, MP (initial 30 mg/kg for 1 h, continuing administration of 5.4 mg/kg per hour until 24 h), TM (10 mg/kg), or vitamin E (30 mg/kg) were given 1 h after the head trauma. The animals were killed 24 h after the weight-drop injury for removal of the brain, and the malondialdehyde (MDA) level and water content of the brain were determined. Rats treated with TM had MDA levels which decreased significantly in comparison with the control group (P<0.03), and none of the drugs had an effect on LP and water content of the brain (P>0.05) that was statistically different. These findings demonstrated the beneficial effect of TM in this model of experimental brain injury.

Comparison of the effects of conjugated estrogen treatment on blood lipid and lipoprotein levels when initiated in the first or fifth postmenopausal year.

Although estrogen replacement therapy (ERT) is known to be protective against the development of cardiovascular disease in patients with surgical menopause, the effects of ERT on blood lipids when started late after the operation is not yet clear. In this prospective study, blood lipid and lipoprotein levels were measured within a 2 year period, in Group I (n = 28 patients) and in Group II (n = 21 patients), who had total abdominal hysterectomy and bilateral salphingo-oophorectomy 10-16 or 55-65 months ago, respectively. Each patient received 0.625 mg conjugated equine estrogen once daily. Blood levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) and very low density lipoprotein (VLDL) were measured at the beginning of the study as well as 12 and 24 months after ERT, was commenced. When the levels obtained after 12 and 24 months of ERT were compared to the baseline levels, LDL levels were decreased, whereas HDL levels were increased in Group I (p < 0.05); however, only the TC levels were significantly lower in Group II (p < 0.05). In conclusion, our results show that ERT is more effective on blood lipid changes when initiated within one year of oophorectomy compared with ERT initiated 5 years after the menopause.

Effect of methylprednisolone, tirilazad mesylate and vitamin E on lipid peroxidation after experimental spinal cord injury.

Effect of methylprednisolone (MP), tirilazad mesylate (TM) and vitamin E on lipid peroxidation (LP) was evaluated in an experimental model of spinal cord compression injury in anesthetized rats. Forty rats, divided randomly into four groups, were injured by compressing on the spinal cord at Th 3 for 1 min. Bolus injections of saline solution, MP (30 mg/kg bolus and 5.4 mg/kg/h), TM (10 mg/kg four times per day), or vitamin E (30 mg/ kg four times per day) were begun 1 h after the spinal cord injury (SCI). Twenty-four hours after treatment, the rats were killed, and malondialdehyde (MDA), a LP product, was measured in the spinal cord tissues. Rats treated with MP, TM and vitamin E had significantly decreased MDA levels (P<0.01) than rats in the control group. The lowest MDA levels were found in the TM group. These results suggest that MP, TM and vitamin E may have a protective effect against SCI in rats by its antioxidant effect.

Endogenous neuropeptides in patients with acute traumatic head injury. II: Changes in the levels of cerebrospinal fluid substance P, serotonin and lipid peroxidation products in patients with head trauma.

The cerebrospinal fluid (CSF) levels of substance P (SP), serotonin (5-HT) and lipid peroxidation (LPx) products were measured in patients with traumatic head injury and then compared to the levels obtained from control subjects. CSF samples were collected from 45 patients (31 male, 14 female, aged 19.2 +/- 17.79) within 24 h of the head trauma and the control CSF samples were obtained from 25 healthy subjects (23 male, 2 female, aged 51.44 +/- 17.6 years) having minor surgical operations under spinal anaesthesia. CSF SP and 5-HT levels in patients with head trauma were significantly lower than the levels in controls (P < 0.005, P < 0.001, respectively). On the other hand, the CSF Lpx products were significantly increased in patients with head trauma (P < 0.001). No significant correlation was found between the CSF changes and the admission Glasgow Coma Scale scores of the patients. This study constitutes the second part of our work on endogenous neuropeptides in patients with traumatic head injury and it emphasizes the role of SP, 5-HT and lipid peroxidation as additional endogenous factors in traumatic head injuries.