ABSTRACT
BACKGROUND AND PURPOSE: N-methyl-D-aspartate (NMDA)-mediated neurotoxicity and oxidative stress have been implicated in the etiology of amyotrophic lateral sclerosis (ALS). Memantine is a low-affinity, noncompetitive NMDA receptor antagonist that may protect against motor neuron degeneration. METHODS: Thirty transgenic mice expressing the G93A SOD1 mutation were randomly divided into control, low-dose memantine (30 mg/kg/day), and high-dose memantine (90 mg/kg/day) groups, with memantine supplied daily with drinking water beginning at 75 days of age. Body weight, survival, and behavioral performances including a rotarod test, paw grip endurance, and hindlimb extension reflex were assessed in the control and memantine-diet groups. RESULTS: Clinical symptoms were evident in the G93A transgenic mice by 11 weeks of age. Memantine was tolerated well. Compared to control, mice treated with memantine performed better in the rotarod test and hindlimb extension reflex. Moreover, low-dose memantine treatment significantly prolonged the survival of the transgenic mice relative to control mice (141 vs 134 days, p<0.05). CONCLUSIONS: These findings suggest that memantine, even when administered at the time of symptom onset, has beneficial effects on patients with ALS.
Subject(s)
Animals , Humans , Mice , Administration, Oral , Amyotrophic Lateral Sclerosis , Body Weight , Drinking Water , Hand Strength , Hindlimb , Memantine , Mice, Transgenic , Motor Neurons , N-Methylaspartate , Oxidative Stress , Reflex , Rotarod Performance TestABSTRACT
Objective To investigate the effect of ketamine on c-fos gene expression in the glutamate induced injury of neuronal PC12 cells line. Methods The differentiated PC12 cells were seeded in 6-well plates(2?10~6/well) and incubated for 18 h,and then were randomly allocated to receive fresh medium(group C)or(10 mmol/L) glutamate(group G) or 0.1 mmol/L ketamine plus 10 mmol/L glutamate(group K1) or 0.5 mmol/L ketamine plus 10 mmol/L glutamate(group K2) or 1.0 mmol/L ketamine plus 10 mmol/L glutamate(group K3).At 5,15,30,60,120,240 and 360 min after administration of these drugs,the cells were collected respectively.(Total) cellular RNA was extracted.Reverse transcriptase-polymerase chain reaction was applied to determine cDNA amplification products with GAPDH mRNA as an internal control.Densities of DNA bands were quantified using the image analysis system.(Results)c-fos mRNA increased at 15 min,peaked at 30 min and 60 min,decreased at 120 min,reco-(vered) to the base level at 360 min among group G,K1 and K2.The c-fos mRNA levels were markedly elevated in group G as compared with the control levels(P
ABSTRACT
Clinical observations and recent experimental studies have suggested that the longer status epilepticus (SE) persists, the more difficult it is to control SE pharmacologically. These findings imply that there are fundamental pathophysiologic processes, which make more resistant to intervene in the refractory SE. Recently, it has been recognized that ketamine, N-methyl-D-aspartate receptor antagonists, are effective agents in the treatment of the late stages of SE in the animal model. However, only one clinical experience has been reported. Here, we report two cases with refractory SE, responsive to ketamine.