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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Quantification of infarct areas after lacosamide (LCM) pretreatment at 100 mg/kg/dose. The mean percentage of right-side damage relative to the intact left side. Pretreatment with LCM at 100 mg/kg/dose (n=16) significantly decreased the infarcted areas in several brain regions (including the hemisphere, hippocampus, cortex, and striatum) relative to the normal-saline-treated group (NS; n=10). *p<0.05.
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Figure 2: Quantification of infarct areas after lacosamide (LCM) pretreatment at 100 mg/kg/dose. The mean percentage of right-side damage relative to the intact left side. Pretreatment with LCM at 100 mg/kg/dose (n=16) significantly decreased the infarcted areas in several brain regions (including the hemisphere, hippocampus, cortex, and striatum) relative to the normal-saline-treated group (NS; n=10). *p<0.05.

Mentions: The infarction area was quantified from cross-sectional images at the level of the anterior commissure and mid-dorsal hippocampus, and the mean percentage of right-side damage was calculated. Pretreatment with LCM at 100 mg/kg/dose (n=16) significantly decreased the infarcted areas in several brain regions including the hemisphere (10.1±3.4, mean±SEM; p=0.001), hippocampus (19.6±3.3, p=0.005), cortex (15.5±3.1, p<0.001), and striatum (14.5±2.4, p<0.001) compared to the normal-saline group (n=10): 24.1±5.4, 40.5±5.1, 38.4±3.9, and 40.2±4.6, respectively (Fig. 2).


Neuroprotective Effect of Lacosamide on Hypoxic-Ischemic Brain Injury in Neonatal Rats
Quantification of infarct areas after lacosamide (LCM) pretreatment at 100 mg/kg/dose. The mean percentage of right-side damage relative to the intact left side. Pretreatment with LCM at 100 mg/kg/dose (n=16) significantly decreased the infarcted areas in several brain regions (including the hemisphere, hippocampus, cortex, and striatum) relative to the normal-saline-treated group (NS; n=10). *p<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5392455&req=5

Figure 2: Quantification of infarct areas after lacosamide (LCM) pretreatment at 100 mg/kg/dose. The mean percentage of right-side damage relative to the intact left side. Pretreatment with LCM at 100 mg/kg/dose (n=16) significantly decreased the infarcted areas in several brain regions (including the hemisphere, hippocampus, cortex, and striatum) relative to the normal-saline-treated group (NS; n=10). *p<0.05.
Mentions: The infarction area was quantified from cross-sectional images at the level of the anterior commissure and mid-dorsal hippocampus, and the mean percentage of right-side damage was calculated. Pretreatment with LCM at 100 mg/kg/dose (n=16) significantly decreased the infarcted areas in several brain regions including the hemisphere (10.1±3.4, mean±SEM; p=0.001), hippocampus (19.6±3.3, p=0.005), cortex (15.5±3.1, p<0.001), and striatum (14.5±2.4, p<0.001) compared to the normal-saline group (n=10): 24.1±5.4, 40.5±5.1, 38.4±3.9, and 40.2±4.6, respectively (Fig. 2).

View Article: PubMed Central - PubMed

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&lt;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.

No MeSH data available.


Related in: MedlinePlus