The effects of memantine on lipid peroxidation following closed-head trauma in rats

Abstract

Memantine is an uncompetitive N-methyl-D: -aspartate (NMDA) receptor antagonist. Unlike other NMDA antagonists, it has been used clinically for years for the treatment of Parkinson's disease, spasticity, and dementia without serious side effects. We aimed to investigate the therapeutic efficacy of memantine on a closed head trauma model. A total of 132 adult male Sprague-Dawley rats were randomly divided into four groups: sham-operated, control (closed head trauma), sham-vehicle (closed head trauma + saline), treatment (closed head trauma + memantine, 10 mg/kg, i.p.). A cranial impact was delivered to the skull, just in front of the coronal suture, over the left hemisphere, from the height of 7 cm. Saline or memantine were applied 15 min after trauma. Rats were euthanased 0.5, 1, 2, 6, 24, 48 h after trauma. Brain tissue samples were taken 5 mm away from the left frontal pole and also from the corresponding point of the contralateral hemispheres. Malondialdehyde activity (MDA) was considered to reflect the degree of lipid peroxidation. The MDA levels continued to increase for the first 2 h after the injury, then started to decrease gradually. Memantine treatment significantly reduced lipid peroxidation levels in the treatment group compared with other groups (P<0.01). The findings of the present study indicate that memantine provides beneficial effects after closed head trauma in rats.

Influence of a Brief Episode of Anesthesia during the Induction of Experimental Brain Trauma on Secondary Brain Damage and Inflammation

“…The present findings are in accordance with a recent study, in which isoflurane compared to sevoflurane given for 30 minutes after trauma reduced lipid peroxidation more efficiently [15], which plays a crucial role in secondary brain damage [16]. The beneficial action of isoflurane is likely to be multifactorial and may be attributed, in part, to cerebral vasodilation and attenuation of excitotoxicity.…”

New Prognostic Biomarkers in Patients With Traumatic Brain Injury

“…From a therapeutic perspective, the administration of antioxidant agents could be used as a new approach for the treatment of TBI patients. The use of different antioxidant agents such as melatonin ( 85 , 86 ) or memantine ( 87 ) has been found to reduce MDA levels in brain tissues in animal models. In addition, in a small randomized clinical trial (36 patients), the administration of amantadine sulphate reduced MDA levels and mortality in TBI patients ( 88 ).…”

Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development

“…Donepezil a U.S. Food and Drug Administration (FDA) approved anticholinesterase for the treatment of AD has been found to be moderately beneficial in improving memory deficits in several clinical studies and in some, but not all, experimental models of TBI (Taverni et al, 1998; Whelan et al, 2000; Masanic et al, 2001; Balesteros et al, 2008; Fujiki et al, 2008; Shaw et al, 2013; Yu et al, 2015). The N-methyl-d-aspartate antagonist memantine, a further FDA-approved drug for the symptomatic treatment of AD, has similarly been shown to be neuroprotective and to possess anti-lipid peroxidation properties in several preclinical studies involving experimentally induced TBI in rodents (Rao et al, 2001; Ozsuer et al, 2005). In contrast, other animal studies have reported injury exacerbation (Ikonomidou et al, 2000), and hence proposed caution in its use.…”