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.
journal_name
Neurocrit Carejournal_title
Neurocritical careauthors
Wang H,Gao J,Lassiter TF,McDonagh DL,Sheng H,Warner DS,Lynch JR,Laskowitz DTdoi
10.1385/NCC:5:1:71subject
Has Abstractpub_date
2006-01-01 00:00:00pages
71-8issue
1eissn
1541-6933issn
1556-0961pii
NCC:5:1:71journal_volume
5pub_type
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