Neuroprotective effect of topiramate on hypoxic ischemic brain injury in neonatal rats

Noh, Mi Ra; Kim, Sung Koo; Sun, Woong; Park, Soon Kwon; Choi, Hyung Chol; Lim, Ji Hyae; Kim, Il Hwan; Kim, Hyun Ju; Eun, Baik-Lin

doi:10.1016/j.expneurol.2006.04.038

Cited by 89 publications

(56 citation statements)

References 39 publications

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“…HP and CoCl 2 preconditioning were able to reduce the extent of cortical injury and only HP reduced striatal damage. Although many treatments have been tested in the HI model at short term intervals, only a few have been examined and found to yield long-term functional outcomes (3,16,26,27). Using preconditioning with hypoxia and two hypoxia-mimetic compounds, CoCl 2 and DFX, we observed long-term protective actions of these treatment strategies.…”

Section: Discussionmentioning

confidence: 90%

Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

et al. 2008

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ABSTRACT:Preconditioning with hypoxia and hypoxia-mimetic compounds cobalt chloride (CoCl 2 ) and desferrioxamine (DFX) protects against hypoxic-ischemic (HI) injury in neonatal rat brain. We examined long-term functional and protective actions of preconditioning induced by hypoxia, CoCl 2 and DFX in a neonatal rat model of HI. Postnatal day six rat pups were exposed to preconditioning with hypoxia (8% oxygen) or injections of CoCl 2 , DFX or saline vehicle and 24 h later rats underwent HI or sham surgery. Behavioral tests were performed and at the conclusion of experiments, brains removed for morphologic analyses. HI resulted in a large unilateral lesion in the ipsilateral hemisphere compared with sham control rats. All preconditioning treatments significantly reduced the total lesion volume. Behavioral deficits were observed in HI rats compared with sham controls. The reduction in forelimb grasping strength in HI rats was attenuated by preconditioning with hypoxia, CoCl 2 and DFX. HI increased the number of foot faults in a grid-walking test and resulted in forelimb asymmetry in the cylinder test. Only preconditioning with hypoxia reversed all three functional deficits after HI. These findings indicate that preconditioning, especially when induced by hypoxia, has the potential to minimize the morphologic and functional effects of neonatal HI injury. (Pediatr Res 63: 620-624, 2008)

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Section: Discussionmentioning

confidence: 90%

Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

et al. 2008

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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.…”

Section: Resultsmentioning

confidence: 98%

“…41 Long-term effects on cognitive functions of TPM administration in early life remain to be assessed. In asphyxiated animal models treated with TPM, no cognitive deficit was demonstrated, 10 and in epileptic neonate rodents, TPM appears safer than phenobarbital or benzodiazepines. 42,43 Neuronal death occurred at doses of 50 mg/kg, which are considerably higher than common therapeutic schedules.…”

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.…”

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confidence: 99%

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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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“…Oxygen-glucose deprivation (OGD) was performed as described previously (Noh et al, 2006). On DIV10, the culture medium was replaced with deoxygenated glucose-free DMEM (Gibco BRL, USA) in an anaerobic chamber maintaining 5% CO 2 , 10% H 2 , and 85% N 2 , and the cells were incubated under oxygen-glucose deprived conditions (OGD) for 60 min.…”

Section: Methodsmentioning

confidence: 99%

Differential Expression of BNIP Family Members of BH3-Only Proteins during the Development and after Axotomy in the Rat

Cho

Choi

Park

et al. 2012

Molecules and Cells

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Neuroprotective effect of topiramate on hypoxic ischemic brain injury in neonatal rats

Cited by 89 publications

References 39 publications

Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

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

Differential Expression of BNIP Family Members of BH3-Only Proteins during the Development and after Axotomy in the Rat

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