topiramate and Ischemia

Spinal segmental myoclonus rarely occurs in peripheral neurological disorders. There are no data about the efficacy of topiramate (TPM) on spinal myoclonus. We describe a patient whose segmental myoclonus in amputation stump was ameliorated markedly by TPM.

Topics: Aged; Amputation Stumps; Amputation, Surgical; Anticonvulsants; Diagnosis, Differential; Fructose; Humans; Ischemia; Leg; Male; Myoclonus; Postoperative Complications; Spinal Cord; Topiramate

The effects of topiramate, a drug used clinically as an anti-epileptic, were investigated in excitotoxin-induced neurotoxicity models involving two different retinal primary cultures and in a rat model of retinal ischemic injury. For the in vitro studies, we used retinal-neuron cultures from rat embryos and purified retinal ganglion cells (RGCs) from newborn rats. In the retinal-neuron cultures, neurotoxicity was induced by a 10-min exposure to 1 mM glutamate or (+/-)-a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). In RGCs, neurotoxicity was induced by incubation for 3 days in a culture medium containing 25 microM glutamate. For the in vivo study, retinal ischemia was induced by elevating intraocular pressure to 130 mmHg for 45 min, and topiramate was administered intraperitoneally before and after the ischemia. Retinal damage was evaluated by measuring the number of cells in the ganglion cell layer (GCL) and the thickness of the inner plexiform layer (IPL), and by examining the a- and b-waves of the electroretinogram (ERG). Topiramate (> or =1 microM) markedly reduced the neuronal cell death induced by each of the excitotoxins in rat retinal-neuron cultures and in RGCs. Ischemia caused a decrease in GCL cells and in IPL thickness, and a diminution of the ERG waves. Histopathologic and functional analyses indicated that systemic treatment with topiramate prevented ischemia-induced damage in a dose-dependent manner. In conclusion, topiramate was protective against excitotoxic and ischemic retinal-neuron damage in vitro and in vivo, respectively. Therefore, it may be useful for treatment of the retina-related diseases such as central retinal artery occlusion, diabetic retinopathy, and glaucoma.

Topics: Animals; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Fructose; Ischemia; Male; Rats; Rats, Sprague-Dawley; Rats, Wistar; Retina; Topiramate

The neuroprotective properties of topiramate were evaluated in a rat model of stroke in which neurodegeneration was induced by temporary global ischemia. In this model, the ischemia resulted from 11 min of cardiac arrest during atraumatic chest compression. Resuscitated rats exhibit a characteristic neurological syndrome characterized by sound-induced convulsions, specific motor and behavioral deficits, and death of hippocampal CA1 pyramidal neurons. Topiramate, when administered i.v. 30 min after resuscitation, reduced the degree of motor impairment (P< 0.05 vs control at doses of 10 and 20 mg/kg) and seizure severity (P< 0.05 vs control at a dose of 10 mg/kg on the fifth recovery day). The highest dose of topiramate (20 mg/kg i.v.) eliminated nearly all histologic signs of hippocampal ischemic neuronal injury (P< 0.001). Phenytoin at 20 mg/kg i.v. exhibited neuroprotectant effects similar to those observed for topiramate at 20 mg/kg i.v.. In normal rats, neither topiramate nor phenytoin at 20 mg/kg i.v. induced any apparent neurological impairment; however, at 40 and 60 mg/kg i.v. both induced a mild impairment typical of most anticonvulsants. The results of this study support the concept that topiramate possesses neuroprotective properties.

Topics: Animals; Disease Models, Animal; Fructose; Ischemia; Male; Neurodegenerative Diseases; Neuroprotective Agents; Rats; Rats, Long-Evans; Topiramate