Faculty Collaboration Database

Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage. Neurocrit Care 2006;5(1):71-8

Date

09/09/2006

Pubmed ID

16960300

DOI

10.1385/NCC:5:1:71

Scopus ID

2-s2.0-33748633136 (requires institutional sign-in at Scopus site)   104 Citations

Abstract

OBJECTIVES: Prophylactic treatment with antiepileptic drugs is common practice following subarachnoid hemorrhage (SAH) and traumatic brain injury. However, commonly used antiepileptic drugs have multiple drug interactions, require frequent monitoring of serum levels, and are associated with adverse effects that may prompt discontinuation. In the current study, we test the hypothesis that levetiracetam, an anticonvulsant with favorable interaction and adverse event profiles, is neuroprotective in clinically relevant models of SAH and closed head injury (CHI).

METHODS: A single intravenous dose of vehicle, low-dose (18 mg/kg), or high-dose (54 mg/kg) levetiracetam was administered intravenously followed CHI. Functional assessments were performed on a daily basis, and histological assessments performed at 24 hours. In a separate series of experiments, mice were randomized to receive intravenous administration of vehicle, low-dose, or high-dose levetiracetam every 12 hours for 3 days following SAH. Functional endpoints were assessed daily, followed by measurement of MCA luminal diameter on day 3.

RESULTS: A single dose of levetiracetam improved functional and histological outcomes after CHI. This effect appeared specific for levetiracetam and was not associated with fosphenytoin treatment. Treatment with levetiracetam also improved functional outcomes and reduced vasospasm following SAH.

CONCLUSION: Levetiracetam is neuroprotective in clinically relevant animal models of SAH and CHI. Levetiracetam may be a therapeutic alternative to phenytoin following acute brain injury in the clinical setting when seizure prophylaxis is indicated.

Author List

Wang H, Gao J, Lassiter TF, McDonagh DL, Sheng H, Warner DS, Lynch JR, Laskowitz DT

MESH terms used to index this publication - Major topics in bold

Animals
Disease Models, Animal
Drug Administration Schedule
Head Injuries, Closed
Injections, Intravenous
Male
Mice
Mice, Inbred C57BL
Neuroprotective Agents
Piracetam
Random Allocation
Subarachnoid Hemorrhage
Time Factors
Vasospasm, Intracranial