Neurocritical Care

, Volume 5, Issue 1, pp 71–78

Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage

  • Haichen Wang
  • Junling Gao
  • Timothy F. Lassiter
  • David L. McDonagh
  • Huaxin Sheng
  • David S. Warner
  • John R. Lynch
  • Daniel T. Laskowitz
Translational Research

DOI: 10.1385/NCC:5:1:71

Cite this article as:
Wang, H., Gao, J., Lassiter, T.F. et al. Neurocrit Care (2006) 5: 71. doi:10.1385/NCC:5:1:71

Abstract

Objectives

Prophylactic treatment with antiepileptic drugs is common practice following subarchnoid 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 in travenous 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.

Key Words

Subarachnoid hemorrhagetraumatic brain injuryposttraumatic epilepsylevetiracetamvasospasmneuroprotection

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  • Haichen Wang
    • 1
    • 2
  • Junling Gao
    • 1
    • 2
    • 3
    • 4
    • 5
  • Timothy F. Lassiter
    • 3
  • David L. McDonagh
    • 1
    • 2
    • 4
  • Huaxin Sheng
    • 1
    • 4
  • David S. Warner
    • 1
    • 4
  • John R. Lynch
    • 1
    • 2
  • Daniel T. Laskowitz
    • 1
    • 2
    • 4
  1. 1.Multidisciplinary Neuroprotection LaboratoriesDuke University Medical CenterDurham
  2. 2.Department of Medicine (Neurology)Duke University Medical CenterDurham
  3. 3.Department of PharmacyDuke University Medical CenterDurham
  4. 4.Department of AnesthesiologyDuke University Medical CenterDurham
  5. 5.Department of Histology and EmbryologyNorth China Coal Medical CollegeHebeiChina