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Statins improve outcome in murine models of intracranial hemorrhage and traumatic brain injury: a translational approach.

Publication ,  Journal Article
Indraswari, F; Wang, H; Lei, B; James, ML; Kernagis, D; Warner, DS; Dawson, HN; Laskowitz, DT
Published in: J Neurotrauma
May 1, 2012

Traumatic brain injury (TBI) and intracerebral hemorrhage (ICH) are leading causes of neurological mortality and disability in the U.S. However, therapeutic options are limited and clinical management remains largely supportive. HMG-CoA reductase inhibitors (statins) have pleiotropic mechanisms of action in the setting of acute brain injury, and have been demonstrated to improve outcomes in preclinical models of ICH and TBI. To facilitate translation to clinical practice, we now characterize the optimal statin and dosing paradigm in murine models of ICH and TBI. In a preclinical model of TBI, mice received vehicle, simvastatin, and rosuvastatin at doses of 1 mg/kg and 5 mg/kg for 5 days after the impact. Immunohistochemistry, differential gene expression, and functional outcomes (rotarod and Morris water maze testing) were assessed to gauge treatment response. Following TBI, administration of rosuvastatin 1 mg/kg was associated with the greatest improvement in functional outcomes. Rosuvastatin treatment was associated with histological evidence of reduced neuronal degeneration at 24 h post-TBI, reduced microgliosis at day 7 post-TBI, and preserved neuronal density in the CA3 region at 35 days post-injury. Administration of rosuvastatin following TBI was also associated with downregulation of inflammatory gene expression in the brain. Following ICH, treatment with simvastatin 1 mg/kg was associated with the greatest improvement in functional outcomes, an effect that was independent of hemorrhage volume. Clinically relevant models of acute brain injury may be used to define variables such as optimal statin and dosing paradigms to facilitate the rational design of pilot clinical trials.

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Published In

J Neurotrauma

DOI

EISSN

1557-9042

Publication Date

May 1, 2012

Volume

29

Issue

7

Start / End Page

1388 / 1400

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Translational Research, Biomedical
  • Sulfonamides
  • Simvastatin
  • Rosuvastatin Calcium
  • Pyrimidines
  • Neuroprotective Agents
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Indraswari, F., Wang, H., Lei, B., James, M. L., Kernagis, D., Warner, D. S., … Laskowitz, D. T. (2012). Statins improve outcome in murine models of intracranial hemorrhage and traumatic brain injury: a translational approach. J Neurotrauma, 29(7), 1388–1400. https://doi.org/10.1089/neu.2011.2117
Indraswari, Fransisca, Haichen Wang, Beilei Lei, Michael L. James, Dawn Kernagis, David S. Warner, Hana N. Dawson, and Daniel T. Laskowitz. “Statins improve outcome in murine models of intracranial hemorrhage and traumatic brain injury: a translational approach.J Neurotrauma 29, no. 7 (May 1, 2012): 1388–1400. https://doi.org/10.1089/neu.2011.2117.
Indraswari F, Wang H, Lei B, James ML, Kernagis D, Warner DS, et al. Statins improve outcome in murine models of intracranial hemorrhage and traumatic brain injury: a translational approach. J Neurotrauma. 2012 May 1;29(7):1388–400.
Indraswari, Fransisca, et al. “Statins improve outcome in murine models of intracranial hemorrhage and traumatic brain injury: a translational approach.J Neurotrauma, vol. 29, no. 7, May 2012, pp. 1388–400. Pubmed, doi:10.1089/neu.2011.2117.
Indraswari F, Wang H, Lei B, James ML, Kernagis D, Warner DS, Dawson HN, Laskowitz DT. Statins improve outcome in murine models of intracranial hemorrhage and traumatic brain injury: a translational approach. J Neurotrauma. 2012 May 1;29(7):1388–1400.
Journal cover image

Published In

J Neurotrauma

DOI

EISSN

1557-9042

Publication Date

May 1, 2012

Volume

29

Issue

7

Start / End Page

1388 / 1400

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Translational Research, Biomedical
  • Sulfonamides
  • Simvastatin
  • Rosuvastatin Calcium
  • Pyrimidines
  • Neuroprotective Agents
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Mice