title: Optimization of a Clinically Relevant Model of White Matter Stroke in Mice: Histological and Functional Evidences.
abstract: OBJECTIVE
  White matter (WM) injury during stroke increases the risk of disability and gloomy prognosis of post-stroke rehabilitation. However, modeling of WM loss in rodents has proven to be challenging.
  
  
  METHODS
  We report improved WM injury models in male C57BL/6 mice. Mice were given either endothelin-1 (ET-1) or L-N5-(1-iminoethyl)ornitine (L-NIO) into the periventricular white matter (PVWM), in the corpus callosum (CC), or in the posterior limb of internal capsule (PLIC). Anatomical and functional outcomes were quantified on day 7 post injection.
  
  
  RESULTS
  Injection of ET-1 or L-NIO caused a small focal lesion in the injection site in the PVWM. No significant motor function deficits were observed in the PVWM lesion model. We next targeted the PLIC by using single or double injections of L-NIO and found that this strategy induced small focal infarction. Interestingly, injection of L-NIO in the PLIC also resulted in gliosis, and significant motor function deficits.
  
  
  CONCLUSIONS
  By employing different agents, doses, and locations, this study shows the feasibility of inducing brain WM injury accompanied with functional deficits in mice. Selective targeting of the injury location, behavioral testing, and the agents chosen to induce WM injury are all keys to successfully develop a mouse model and subsequent testing of therapeutic interventions against WM injury.
authors: Department of Anesthesiology and Center for Translational Research in Neurodegenerative Disease, University of Florida, FL, USA.
authors: Abdullah S
authors: AS
authors: Ahmad
authors: Department of Anesthesiology and Center for Translational Research in Neurodegenerative Disease, University of Florida, FL, USA.
authors: Irawan
authors: I
authors: Satriotomo
authors: Department of Anesthesiology and Center for Translational Research in Neurodegenerative Disease, University of Florida, FL, USA.
authors: Jawad A
authors: JA
authors: Fazal
authors: Research Service and the Brain Rehabilitation Research Center, Malcom Randall Veterans Affairs Medical Center, FL, USA; Department of Neurology, University of Florida College of Medicine, Gainesville, FL, USA.
authors: Stephen E
authors: SE
authors: Nadeau
authors: Department of Anesthesiology and Center for Translational Research in Neurodegenerative Disease, University of Florida, FL, USA; Departments of Neuroscience, Neurology, and Psychiatry, University of Florida, Gainesville, FL, USA.
authors: Sylvain
authors: S
authors: Doré
keywords: Corpus callosum; Demyelination; Ischemia; Lysophosphatidylcholine; Motor functions; NOS inhibitor; Posterior limb internal capsule; Vasoconstriction 