Oral Administration of Memantine Prolongs Survival in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

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.

Cerebrovascular Reactivity According to Migraine Subtypes: with or without Aura

BACKGROUND: In migraine studies, the cerebrovascular reactivity (CVR) using a transcranial Doppler (TCD) has been investigated to elucidate the nature and role of the vascular response. However, past studies have not comprised the posterior circulation including functionally important brainstem structures. The purpose of this study was to compare the simultaneous CVRs between the middle cerebral artery (MCA) and basilar artery (BA) in migraine patients with and without aura, by means of a power motion mode Doppler (PMD) with an anterior-posterior probes fixating device. METHODS: Thirty-six consecutive patients with migranes [15 migraine patients with aura (MA) and 21 migraine patients without aura (MWA)] were compared with 29 healthy volunteers. CVR [(Vmax-Vbase)x100/Vbase] was evaluated by the re-breathing technique. TCD was performed as two steps. First, the velocities and spectra of the MCAs through both temporal windows were simultaneously monitored. Second, those were simultaneously monitored between MCA and BA. RESULT: There were no significant differences in age, sex, baseline hemodynamic values (blood pressure, heart rate), and those of the baseline mean flow velocity and CVR of TCD between the migraine patients and the controls. However, the CVR of the BA significantly differed between the MA and the MWA (39.4+/-13.7 vs 64.6+/-25.4%; p=0.001), among MA, MWA, and controls (39.4+/-13.7, 64.6+/-25.4, 45.6+/-14.9%; p<0.001). CONCLUSIONS: CVR of BA was entirely different according to migraine subtypes: with or without aura. Our study suggests that MWA and MWOA seem to be distinct disorders in terms of different vascular responses of the BA during the interictal period.