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

Research output: Contribution to journalArticle

78 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalNeurocritical Care
Volume5
Issue number1
DOIs
StatePublished - Aug 1 2006

Fingerprint

etiracetam
Closed Head Injuries
Subarachnoid Hemorrhage
Anticonvulsants
Phenytoin
Therapeutics
Drug Interactions

Keywords

  • Levetiracetam
  • Neuroprotection
  • Posttraumatic epilepsy
  • Subarachnoid hemorrhage
  • Traumatic brain injury
  • Vasospasm

ASJC Scopus subject areas

  • Clinical Neurology
  • Critical Care and Intensive Care Medicine

Cite this

Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage. / Wang, Haichen; Gao, Junling; Lassiter, Timothy F.; McDonagh, David L.; Sheng, Huaxin; Warner, David S.; Lynch, John R.; Laskowitz, Daniel T.

In: Neurocritical Care, Vol. 5, No. 1, 01.08.2006, p. 71-78.

Research output: Contribution to journalArticle

Wang, H, Gao, J, Lassiter, TF, McDonagh, DL, Sheng, H, Warner, DS, Lynch, JR & Laskowitz, DT 2006, 'Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage', Neurocritical Care, vol. 5, no. 1, pp. 71-78. https://doi.org/10.1385/NCC:5:1:71
Wang, Haichen ; Gao, Junling ; Lassiter, Timothy F. ; McDonagh, David L. ; Sheng, Huaxin ; Warner, David S. ; Lynch, John R. ; Laskowitz, Daniel T. / Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage. In: Neurocritical Care. 2006 ; Vol. 5, No. 1. pp. 71-78.
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