Neuroprotection by delayed administration of topiramate in a rat model of middle cerebral artery embolization

Yang, Yi; Shuaib, Ashfaq; Qiu, Li; Siddiqui, Muzaffar

doi:10.1016/s0006-8993(98)00410-7

Cited by 113 publications

(65 citation statements)

References 37 publications

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“…However, a single dose of TPM (80 mg/kg, i.p.) did provide a significant reduction in acute neuronal injury in the CA1 region of the hippocampus compared with control, an effect that supports previous findings in both status epilepticus (31,32), and ischemia (33,34). This also demonstrates a dissociation between the neuroprotective and antiepileptic effects of TPM, as neuroprotection was maximal at a dose (80 mg/kg, i.p.)…”

Section: Discussionsupporting

confidence: 89%

Synergism between Topiramate and Budipine in Refractory Status Epilepticus in the Rat

et al. 2004

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Summary:Purpose: To evaluate the antiepileptic and neuroprotective properties of topiramate (TPM) alone and with coadministration of the N-methyl-D-aspartate (NMDA)-receptor antagonist budipine in a rat model of refractory status epilepticus.Methods: Male Sprague-Dawley rats had electrodes implanted into the perforant path and dentate granule cell layer of the hippocampus under halothane anesthesia. Approximately 1 week after surgery, the perforant path of each animal was electrically stimulated for 2 h to induce self-sustaining status epilepticus. Successfully stimulated rats were given intraperitoneally vehicle (n = 6), TPM (20-320 mg/kg; n = 28), budipine (10 mg/kg; n = 5), or budipine (10 mg/kg) and TPM (80 mg/kg; n = 6) 10 min after the end of the stimulation and monitored behaviorally and electroencephalographically for a further 3 h.The animals were killed 14 days later, and histopathology was assessed.Results: Neither budipine alone nor TPM at any dose terminated status epilepticus. Despite this, TPM resulted in various degrees of neuroprotection at doses between 40 and 320 mg/kg. Coadministration of budipine with TPM terminated the status epilepticus in all rats. This combination also significantly improved the behavioral profile and prevented status-induced cell death compared with control.Conclusions: Budipine and TPM are an effective drug combination in stopping self-sustained status epilepticus, and TPM alone was neuroprotective, despite the continuation of seizure activity.

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Section: Discussionsupporting

confidence: 89%

Synergism between Topiramate and Budipine in Refractory Status Epilepticus in the Rat

et al. 2004

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“…In neuronal cultures, cell damage induced by oxygen-glucose deprivation 10 or excitotoxic concentrations of glutamate or kainate 27 were consistently attenuated by TPM. In animal models of cerebral ischemia, TPM reduced the severity of cerebral damage either alone [5][6][7][8] or with hypothermia. 9 The neuroprotective mechanisms of TPM action appear related not only to glutamate a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors inhibition, 11,[27][28][29][30] but also to inhibition of Na + channels, 31 high voltageactivated calcium currents, 4 carbonic anhydrase isoenzymes, 32 and mitochondrial permeability transition pore.…”

Section: Resultsmentioning

confidence: 99%

“…TPM has neuroprotective properties against hypoxic ischemic brain damage, both in vitro and in animal models, and was included in neuroprotective strategies for ischemic stroke [4][5][6][7][8][9][10][11] and neonatal hypoxic-ischemic cerebral injury. 12 Several studies have demonstrated the therapeutic effects of whole-body or selective head cooling to treat asphyxiated newborns.…”

mentioning

confidence: 99%

Oral Topiramate in Neonates with Hypoxic Ischemic Encephalopathy Treated with Hypothermia: A Safety Study

Filippi

Poggi

Marca

et al. 2010

The Journal of Pediatrics

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Objective To investigate whether topiramate associated with mild or deep hypothermia in asphyxiated term infants is safe in relation to the short-term outcome.Study design We report on 27 consecutive asphyxiated newborns who were treated with whole body hypothermia and 27 additional consecutive newborns with hypothermia who were co-treated with oral topiramate, once a day for 3 consecutive days, at 2 different doses.Results Newborns were divided in 6 groups according to the depth of hypothermia and the association with higher or lower topiramate dosage. A statistical comparison of the groups identified some differences in biochemical and hemodynamic variables, but no adverse effects attributable to topiramate were detected. There were no statistically significant differences in the groups in short-term outcomes, survival rate at discharge, or incidence of pathologic brain magnetic resonance imaging. ConclusionAlthough the number of newborns in this study was limited, the short-term outcome and the safety data appear to support the evaluation of topiramate in clinical trials to explore its possible additive neuroprotective action. (J Pediatr 2010;157:361-6).See editorial, p 351 and related articles, p 367 and p 499 N eonatal hypoxic-ischemic encephalopathy (HIE), caused by perinatal asphyxia, is one of the leading causes of cerebral palsy, the incidence of which has remained essentially unchanged in recent decades despite improvements in perinatal practice and neonatal care.1 Topiramate (TPM), an anticonvulsant agent widely used in adults and children, 2,3 has multiple mechanisms of action, including an inhibitory effect on glutamate receptors. TPM has neuroprotective properties against hypoxic ischemic brain damage, both in vitro and in animal models, and was included in neuroprotective strategies for ischemic stroke 4-11 and neonatal hypoxic-ischemic cerebral injury. 12Several studies have demonstrated the therapeutic effects of whole-body or selective head cooling to treat asphyxiated newborns. [13][14][15] Consequently, mild hypothermia is recommended for the treatment of moderate degrees of encephalopathy. 1 Deep hypothermia may also be safe and neuroprotective. 16 Although TPM logically would be expected to enhance the neuroprotective effects of hypothermia in HIE, no trial has tested this combination treatment.1 Hypothermia can reduce drug clearance, thereby affecting the pharmacokinetics of drugs. 17 In an earlier pilot study, we assessed the effects of mild or deep hypothermia on TPM pharmacokinetics in neonates with HIE. We observed a slow absorption and elimination of TPM. 18 We now report the safety profile of TPM in neonates treated with hypothermia in a retrospective comparison with newborns treated with hypothermia only. MethodsWe studied asphyxiated newborns admitted in 2 neonatal intensive care units

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“…29,30 In addition, Yang et al reported benefit in a rodent model of focal ischemia. 31 Despite the suggestive efficacy of these and other GABA activators for cerebral ischemia, however, this mouse model of focal ischemia failed to demonstrate neuroprotection by either vigabatrin or topiramate. A number of reasons may be postulated for this.…”

Section: Discussionmentioning

confidence: 85%

Failure of Ischemic Neuroprotection by Potentiators of Gamma-aminobutyric Acid

Madden¹,

Clark²,

Lessov³

2003

Clinical Medicine & Research

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Neuroprotection by delayed administration of topiramate in a rat model of middle cerebral artery embolization

Cited by 113 publications

References 37 publications

Synergism between Topiramate and Budipine in Refractory Status Epilepticus in the Rat

Synergism between Topiramate and Budipine in Refractory Status Epilepticus in the Rat

Oral Topiramate in Neonates with Hypoxic Ischemic Encephalopathy Treated with Hypothermia: A Safety Study

Failure of Ischemic Neuroprotection by Potentiators of Gamma-aminobutyric Acid

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