The objective was to retrospectively characterise the efficacy of memantine as preventive therapy in a series of patients with frequent migraine. Patients in a university headache clinic completed a survey regarding their experience with memantine, and medical records were reviewed. All patients who received memantine as preventive therapy for migraine over a 15-month period were mailed surveys and consent forms for record review. Patients were treated with memantine beginning at a dose of 5 mg/day, increasing if needed by 5 mg/week up to 10 mg twice a day. The majority of patients (36 out of 54) treated with memantine for at least 2 months reported a significant reduction in estimated headache frequency, and improved function. Side effects were uncommon and generally mild. This limited retrospective case review suggests that memantine may be an effective preventive therapy for patients with frequent migraine. A prospective trial is warranted.

Abstract Background Purinergic receptor-mediated signaling plays an important role in the function of glial cells, including glial tumor cells. Bradykinin is also an important paracrine mediator which is highly expressed in brain tumors and may correlate with their pathological grade. Interaction between bradykinin and purinergic signaling may therefore be involved in the regulation of glial tumor cells. Results We examined the effect of bradykinin on glial purinergic signaling in an immortalized glioma cell line. Confocal calcium imaging revealed that ATP evokes an increase in [Ca2+]i in the U87 human astrocytoma cell line. This response was reduced with repetitive application of ATP, likely due to receptor desensitization. However exposure to bradykinin increased the Ca2+ response to a second application of ATP, consistent with increased resensitization. The bradykinin effect on resensitization was similar in the absence of extracellular Ca2+ or in the presence of the PKC activator PMA, but was inhibited by the protein phosphatase inhibitor okadaic acid and the PI3K inhibitor LY294002. Conclusions Modulation of protein phosphatases and the PI3K pathway may represent a mechanism by which bradykinin potentiates purinergic signaling in glial cells.

Background and purpose

Stroke treatment is constrained by limited treatment windows and the clinical inefficacy of agents that showed preclinical promise. Yet animal and clinical data suggest considerable poststroke plasticity, which could allow treatment with recovery-modulating agents. Memantine is a well-tolerated N-methyl-D-aspartate glutamate receptor antagonist in common use for Alzheimer disease.

Methods

Memantine, 30 mg/kg per day, or vehicle, was delivered chronically in drinking water beginning >2 hours after photothrombotic stroke.

Results

Although there was no difference in infarct size, behavior, or optical intrinsic signal maps in the first 7 days after stroke, mice treated chronically with memantine showed significant improvements in motor control, measured by cylinder test and grid-walking performance, compared with vehicle-treated animals. Optical intrinsic signal revealed an increased area of forepaw sensory maps at 28 days after stroke. There was decreased reactive astrogliosis and increased vascular density around the infarcted cortex. Peri-infarct Western blots revealed increased brain-derived neurotrophic factor and phosphorylated-tropomyosin-related kinase-B receptor expression.

Conclusions

Our results suggest that memantine improves stroke outcomes in an apparently non-neuroprotective manner involving increased brain-derived neurotrophic factor signaling, reduced reactive astrogliosis, and improved vascularization, associated with improved recovery of sensory and motor cortical function. The clinical availability and tolerability of memantine make it an attractive candidate for clinical translation.