Neuroprotective Effect of Lacosamide on Hypoxic-Ischemic Brain Injury in Neonatal Rats
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background and Purpose Lacosamide (LCM) is an antiepileptic drug that enhances the slow inactivation of sodium channels and modulates collapsin response mediator protein-2. LCM was recently demonstrated to exert a neuroprotective effect in a murine model of trau¬matic brain injury and status epilepticus. Assuming the same underlying excitotoxicity-related brain injury mechanism, we hypothesized that LCM would have a neuroprotective effect in hypoxic-ischemic brain injury. Methods We divided rats into three groups at each testing session: pre- or postfed with LCM, fed with normal saline, and sham. A hypoxic-ischemic brain injury was induced by subjecting 7-day-old rats to right carotid artery coagulation followed by 2.5 h of exposure to 8% oxygen. The animals were killed on postnatal day 12 to evaluate the severity of brain damage. Open field testing was also performed between week 2 and week 6, and the Morris water maze test was performed in week 7 after hypoxia-ischemia. Results The incidence of liquefactive cerebral infarction was lower in rats prefed with LCM at 100 mg/kg/dose, with the mortality rate being higher at higher doses (200 and 300 mg/kg/dose). The infarct areas were smaller in LCM-prefed rats in several brain regions including the hemisphere, hippocampus, cortex, and striatum. Spatial learning and memory function were better in LCM-prefed rats (p<0.05). No effect was observed in postfed rats. Conclusions This study suggests that LCM pretreatment exerts a neuroprotective effect on hypoxia-ischemia in neonatal rats. The obtained results suggest that LCM pretreatment could be used as an effective neuroprotective method for neonates under hypoxic-ischemic condi¬tions including heart surgery.
Abstract
Background and Purpose Lacosamide (LCM) is an antiepileptic drug that enhances the slow inactivation of sodium channels and modulates collapsin response mediator protein-2. LCM was recently demonstrated to exert a neuroprotective effect in a murine model of trau¬matic brain injury and status epilepticus. Assuming the same underlying excitotoxicity-related brain injury mechanism, we hypothesized that LCM would have a neuroprotective effect in hypoxic-ischemic brain injury. Methods We divided rats into three groups at each testing session: pre- or postfed with LCM, fed with normal saline, and sham. A hypoxic-ischemic brain injury was induced by subjecting 7-day-old rats to right carotid artery coagulation followed by 2.5 h of exposure to 8% oxygen. The animals were killed on postnatal day 12 to evaluate the severity of brain damage. Open field testing was also performed between week 2 and week 6, and the Morris water maze test was performed in week 7 after hypoxia-ischemia. Results The incidence of liquefactive cerebral infarction was lower in rats prefed with LCM at 100 mg/kg/dose, with the mortality rate being higher at higher doses (200 and 300 mg/kg/dose). The infarct areas were smaller in LCM-prefed rats in several brain regions including the hemisphere, hippocampus, cortex, and striatum. Spatial learning and memory function were better in LCM-prefed rats (p<0.05). No effect was observed in postfed rats. Conclusions This study suggests that LCM pretreatment exerts a neuroprotective effect on hypoxia-ischemia in neonatal rats. The obtained results suggest that LCM pretreatment could be used as an effective neuroprotective method for neonates under hypoxic-ischemic condi¬tions including heart surgery.
참고문헌 (26)
- Calabresi P, "Antiepileptic drugs as a possible neuroprotective strategy in brain ischemia", Ann Neurol, 53, pp.693~702 (2003)
- Liu Y, "Topiramate extends the therapeutic window for hypothermia-mediated neuroprotection after stroke in neonatal rats", Stroke, 35, pp.1460~1465 (2004)
- Noh MR, "Neuroprotective effect of topiramate on hypoxic ischemic brain injury in neonatal rats", Exp Neurol, 201, pp.470~478 (2006)
- Schubert S, "Neuroprotective effects of topiramate after hypoxia-ischemia in newborn piglets", Brain Res, 1058, pp.129~136 (2005)
- Licko T, "Lacosamide treatment following status epilepticus attenuates neuronal cell loss and alterations in hippocampal neurogenesis in a rat electrical status epilepticus model", Epilepsia, 54, pp.1176~1185 (2013)
- Wang B, "Lacosamide improves outcome in a murine model of traumatic brain injury", Neurocrit Care, 19, pp.125~134 (2013)
- Arundine M, "Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity", Cell Calcium, 34, pp.325~337 (2003)
- Calabresi P, "Cellular factors controlling neuronal vulnerability in the brain: a lesson from the striatum", Neurology, 55, pp.1249~1255 (2000)
- Meldrum BS, "Update on the mechanism of action of antiepileptic drugs", Epilepsia, 37(Suppl 6), pp.S4~S11 (1996)
- Xiong ZG, "Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels", Cell, 118, pp.687~698 (2004)
- Vartanian MG, "Phenytoin pretreatment prevents hypoxic-ischemic brain damage in neonatal rats", Brain Res Dev Brain Res, 95, pp.169~175 (1996)
- Chan SA, "Fosphenytoin reduces hippocampal neuronal damage in rat following transient global ischemia", Acta Neurochir, 140, pp.175~180 (1998)
- Edmonds HL Jr, "Topiramate as a neuroprotectant in a rat model of global ischemia-induced neurodegeneration", Life Sci, 69, pp.2265~2277 (2001)
- Yang Y, "Neuroprotection by delayed administration of topiramate in a rat model of middle cerebral artery embolization", Brain Res, 804, pp.169~176 (1998)
- Owen AJ, "Zonisamide as a neuroprotective agent in an adult gerbil model of global forebrain ischemia: a histological, in vivo microdialysis and behavioral study", Brain Res, 770, pp.115~122 (1997)
- Wiard RP, "Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia", Stroke, 26, pp.466~472 (1995)
- Hanon E, "Neuroprotective properties of the novel antiepileptic drug levetiracetam in the rat middle cerebral artery occlusion model of focal cerebral ischemia", Seizure, 10, pp.287~293 (2001)
- Beydoun A, "Lacosamide: pharmacology, mechanisms of action and pooled efficacy and safety data in partialonset seizures", Expert Rev Neurother, 9, pp.33~42 (2009)
- Beyreuther BK, "Lacosamide: a review of preclinical properties", CNS Drug Rev, 13, pp.21~42 (2007)
- Errington AC, "The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltagegated sodium channels", Mol Pharmacol, 73, pp.157~169 (2008)
- Halford JJ, "Clinical perspectives on lacosamide", Epilepsy Curr, 9, pp.1~9 (2009)
- Patsalos PN, "Pharmacotherapy of the third-generation AEDs: lacosamide, retigabine and eslicarbazepine acetate", Expert Opin Pharmacother, 13, pp.699~715 (2012)
- Wilson SM, "Prevention of posttraumatic axon sprouting by blocking collapsin response mediator protein 2-mediated neurite outgrowth and tubulin polymerization", Neuroscience, 210, pp.451~466 (2012)
- Hensley K, "Collapsin response mediator protein-2: an emerging pathologic feature and therapeutic target for neurodisease indications", Mol Neurobiol, 43, pp.180~191 (2011)
- Touma E, "Calpain-mediated cleavage of collapsin response mediator protein(CRMP)-2 during neurite degeneration in mice", Eur J Neurosci, 26, pp.3368~3381 (2007)
- Thomas D, "Low potential for drug-drug-interaction of lacosamide", Epilepsia, 47(Suppl 4), pp.200~ (2006)