Neuroprotective Effect of Lacosamide on Hypoxic-Ischemic Brain Injury in Neonatal Rats

Overview

Journal J Clin Neurol

Specialty Neurology

Date 2017 Mar 9

PMID 28271640

Citations 4

Authors

Gun Ha Kim

Jung Hye Byeon

Baik Lin Eun

Affiliations

Soon will be listed here.

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 traumatic 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 conditions including heart surgery.

Citing Articles

BDNF/Cyclin D1 Signaling System and Cognitive Performance After Perampanel and Lacosamide Treatment Singly or in Combination in an Experimental Model of Temporal Lobe Epilepsy.

Shishmanova-Doseva M, Barbutska D Curr Issues Mol Biol. 2024; 46(12):14010-14032.

PMID: 39727966 PMC: 11727337. DOI: 10.3390/cimb46120838.

Cardiac Dysfunction Associated with Lacosamide in a Premature Infant with Hypoxic Ischemic Encephalopathy: A Case Report.

Chatmethakul T, Stanford A, Rios D, Bischoff A, Czech T, McNamara P AJP Rep. 2024; 14(4):e270-e273.

PMID: 39600378 PMC: 11597592. DOI: 10.1055/a-2447-8662.

Novel nasal niosomes loaded with lacosamide and coated with chitosan: A possible pathway to target the brain to control partial-onset seizures.

Tulbah A, Elkomy M, Zaki R, Eid H, Eissa E, Ali A Int J Pharm X. 2023; 6:100206.

PMID: 37637477 PMC: 10458293. DOI: 10.1016/j.ijpx.2023.100206.

Novel Therapeutics for Neonatal Seizures.

Ziobro J, Eschbach K, Shellhaas R Neurotherapeutics. 2021; 18(3):1564-1581.

PMID: 34386906 PMC: 8608938. DOI: 10.1007/s13311-021-01085-8.

Status Epilepticus in the Neonate: Updates in Treatment Strategies.

Ahrens S, Ream M, Slaughter L Curr Treat Options Neurol. 2019; 21(2):8.

PMID: 30773607 DOI: 10.1007/s11940-019-0546-5.

References

Licko T, Seeger N, Zellinger C, Russmann V, Matagne A, Potschka H . Lacosamide treatment following status epilepticus attenuates neuronal cell loss and alterations in hippocampal neurogenesis in a rat electrical status epilepticus model. Epilepsia. 2013; 54(7):1176-85. DOI: 10.1111/epi.12196. View

Halford J, Lapointe M . Clinical perspectives on lacosamide. Epilepsy Curr. 2009; 9(1):1-9. PMC: 2668106. DOI: 10.1111/j.1535-7511.2008.01273.x. View

Errington A, Stohr T, Heers C, Lees G . The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Mol Pharmacol. 2007; 73(1):157-69. DOI: 10.1124/mol.107.039867. View

Schubert S, Brandl U, Brodhun M, Ulrich C, Spaltmann J, Fiedler N . Neuroprotective effects of topiramate after hypoxia-ischemia in newborn piglets. Brain Res. 2005; 1058(1-2):129-36. DOI: 10.1016/j.brainres.2005.07.061. View

Hensley K, Venkova K, Christov A, Gunning W, Park J . Collapsin response mediator protein-2: an emerging pathologic feature and therapeutic target for neurodisease indications. Mol Neurobiol. 2011; 43(3):180-91. DOI: 10.1007/s12035-011-8166-4. View

Vartanian M, Cordon J, Kupina N, Schielke G, Posner A, Raser K . Phenytoin pretreatment prevents hypoxic-ischemic brain damage in neonatal rats. Brain Res Dev Brain Res. 1996; 95(2):169-75. DOI: 10.1016/0165-3806(96)00073-9. View

Meldrum B . Update on the mechanism of action of antiepileptic drugs. Epilepsia. 1996; 37 Suppl 6:S4-11. DOI: 10.1111/j.1528-1157.1996.tb06038.x. View

Wiard R, Dickerson M, Beek O, Norton R, Cooper B . Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia. Stroke. 1995; 26(3):466-72. DOI: 10.1161/01.str.26.3.466. View

Edmonds Jr H, Jiang Y, Zhang P, Shank R . Topiramate as a neuroprotectant in a rat model of global ischemia-induced neurodegeneration. Life Sci. 2001; 69(19):2265-77. DOI: 10.1016/s0024-3205(01)01306-6. View

10.

Arundine M, Tymianski M . Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium. 2003; 34(4-5):325-37. DOI: 10.1016/s0143-4160(03)00141-6. View

11.

Noh M, Kim S, Sun W, Park S, Choi H, Lim J . Neuroprotective effect of topiramate on hypoxic ischemic brain injury in neonatal rats. Exp Neurol. 2006; 201(2):470-8. DOI: 10.1016/j.expneurol.2006.04.038. View

12.

Calabresi P, Cupini L, Centonze D, Pisani F, Bernardi G . Antiepileptic drugs as a possible neuroprotective strategy in brain ischemia. Ann Neurol. 2003; 53(6):693-702. DOI: 10.1002/ana.10603. View

13.

Patsalos P, Berry D . Pharmacotherapy of the third-generation AEDs: lacosamide, retigabine and eslicarbazepine acetate. Expert Opin Pharmacother. 2012; 13(5):699-715. DOI: 10.1517/14656566.2012.667803. View

14.

Yang Y, Shuaib A, Li Q, Siddiqui M . Neuroprotection by delayed administration of topiramate in a rat model of middle cerebral artery embolization. Brain Res. 1998; 804(2):169-76. DOI: 10.1016/s0006-8993(98)00410-7. View

15.

Xiong Z, Zhu X, Chu X, Minami M, Hey J, Wei W . Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell. 2004; 118(6):687-98. DOI: 10.1016/j.cell.2004.08.026. View

16.

Touma E, Kato S, Fukui K, Koike T . Calpain-mediated cleavage of collapsin response mediator protein(CRMP)-2 during neurite degeneration in mice. Eur J Neurosci. 2007; 26(12):3368-81. DOI: 10.1111/j.1460-9568.2007.05943.x. View

17.

Chan S, Reid K, Schurr A, Miller J, Iyer V, Tseng M . Fosphenytoin reduces hippocampal neuronal damage in rat following transient global ischemia. Acta Neurochir (Wien). 1999; 140(2):175-80. DOI: 10.1007/s007010050080. View

18.

Wilson S, Xiong W, Wang Y, Ping X, Head J, Brittain J . Prevention of posttraumatic axon sprouting by blocking collapsin response mediator protein 2-mediated neurite outgrowth and tubulin polymerization. Neuroscience. 2012; 210:451-66. PMC: 3358479. DOI: 10.1016/j.neuroscience.2012.02.038. View

19.

Beyreuther B, Freitag J, Heers C, Krebsfanger N, Scharfenecker U, Stohr T . Lacosamide: a review of preclinical properties. CNS Drug Rev. 2007; 13(1):21-42. PMC: 6494128. DOI: 10.1111/j.1527-3458.2007.00001.x. View

20.

Owen A, Ijaz S, Miyashita H, Wishart T, Howlett W, Shuaib A . Zonisamide as a neuroprotective agent in an adult gerbil model of global forebrain ischemia: a histological, in vivo microdialysis and behavioral study. Brain Res. 1998; 770(1-2):115-22. DOI: 10.1016/s0006-8993(97)00789-0. View