Effects of memantine and MK-801 on ischemia in an experimental model of acute subdural hematoma

Abstract

Objective: Cerebral ischemia due to secondary injuries plays an important role in the high mortality rate of acute subdural hematoma (SDH). Although promising results were obtained from experimental works with excitatory amino acid (EAA) antagonists which inhibit the excitotoxic mechanism in the development of cerebral ischemia, these agents could not be used clinically due to their psychomimetic side effects. Memantine, also an EAA antagonist, has been used for a long time in the treatment of different neurodegenerative diseases; however, it was not used in treatment of acute subdural hematoma before. This study has been designed to investigate the development of cerebral ischemia and ischemic edema under experimental acute subdural hematoma and the effect of memantine (Sigma M-9292) and MK-801 (Sigma M-107) in the treatment of ischemia.Methods: Forty-two adult female Sprague–Dawley rats were divided into two groups: Group A for investigation of ischemia related to SDH and its treatment, and Group B for investigation of cerebral edema. Both groups were further divided into five subgroups, i.e. for sham operations, formation of SDH and treatment with saline, MK-801 and memantine. Treatment of cerebral edema could not be investigated because formation of cerebral edema could not be proven statistically. For evaluation of ischemia, the ratio of ischemic area/the total brain area was calculated as percentages in coronal slices of the rats' brains.Results: In all of the evaluated slices, statistical analysis showed that treatment with MK-801 as well as memantine reduced ischemia caused by SDH.Discussion: Our study showed that memantine, which is already considered as a safe treatment alternative for other central nervous system (CNS) diseases, can be useful in the treatment of acute SDH as well.