Protection from Glutamate-Induced Excitotoxicity by Memantine

Abstract

This study investigates whether the uncompetitive NMDA receptor antagonist, memantine, is able to protect dissociated cortical neurons from glutamate-induced excitotoxicity (GIE). Treatment with glutamate resulted in a significant loss of synchronization of neuronal activity as well as a significant increase in the duration of synchronized bursting events (SBEs). By administering memantine at the same time as glutamate, we were able to completely prevent these changes to the neuronal activity. Pretreatment with memantine was somewhat effective in preventing changes to the culture synchronization but was unable to fully protect the synchronization of electrical activity between neurons that showed high levels of synchronization prior to injury. Additionally, memantine pretreatment was unable to prevent the increase in the duration of SBEs caused by GIE. Thus, the timing of memantine treatment is important for conferring neuroprotection against glutamate-induced neurotoxicity. Finally, we found that GIE leads to a significant increase in the burst duration. Our data suggest that this may be due to an alteration in the inhibitory function of the neurons.

Effects of the drug combination memantine and melatonin on impaired memory and brain neuronal deficits in an amyloid-predominant mouse model of Alzheimer's disease

“…Memantine is a non‐competitive antagonist of glutamate receptors sensitive to NMDA that was introduced into clinical practice in Europe in 2002 for the symptomatic treatment of moderately severe to severe AD. In animal models, memantine improves cognitive function and protects nerve cells from the toxic action of the neurotransmitter glutamate, excessive levels of which are found in brain in disparate diseases including AD, Parkinson's disease, epilepsy and cerebral ischaemia …”

“…In animal models, memantine improves cognitive function [14] and protects nerve cells from the toxic action of the neurotransmitter glutamate, excessive levels of which are found in brain in disparate diseases including AD, Parkinson's disease, epilepsy and cerebral ischaemia. [15,16] Melatonin, a hormone derived from the amino acid tryptophan, possesses a wide range of biological activity including control of circadian rhythm and regulation of the immune system, and it also acts as an endogenous antioxidant. [17] The antioxidative and anti-inflammatory actions of melatonin are well documented, [18][19][20] and it is used in the clinic in AD patients with the aim of improving sleep quality, as many of these patients suffer from circadian rhythm disturbances and insomnia.…”

Neuroprotective Effect of Resveratrol Against Glutamate-Induced Excitotoxicity

“…Therefore, current efforts to develop an effective therapy for hypoxic-ischemic neuronal injury are appropriately focused on NMDA antagonists and Ca2+ blockers [7]. The uncompetitive NMDA receptor antagonist memantine, is able to protect dissociated cortical neurons from Glu-induced excitotoxicity [26]. Res attenuates oxygen-glucose deprivationinduced neuron impairment and death in acute rat hippocampal slices by enhancing the activation of the large-conductance potassium channel and reducing the enhanced AMPA/NMDA receptor-mediated neuronal excitatory postsynaptic currents caused by oxygen-glucose deprivation [27].…”

Pathophysiology of Acute Coma and Disorders of Consciousness: Considerations for Diagnosis and Management

“…192 Memantine is also neuroprotective against glutamate-induced excitotoxicity. 193 Methylphenidate is a stimulant that activates noradrenergic and dopaminergic systems within the prefrontal cortex. 194 Studies of methylphenidate have focused on the treatment of attention problems after TBI in patients who are awake and aware.…”