Considerations for the optimization of induced white matter injury preclinical models

White matter (WM) injury in relation to acute neurologic conditions, especially stroke, has remained obscure until recently. Current advances in imaging technologies in the field of stroke have confirmed that WM injury plays an important role in the prognosis of stroke and suggest that WM protection is essential for functional recovery and post-stroke rehabilitation. However, due to the lack of a reproducible animal model of WM injury, the pathophysiology and mechanisms of this injury are not well studied. Moreover, producing selective WM injury in animals, especially in rodents, has proven to be challenging. Problems associated with inducing selective WM ischemic injury in the rodent derive from differences in the architecture of the brain, most particularly, the ratio of WM to gray matter in rodents compared to humans, the agents used to induce the injury, and the location of the injury. Aging, gender differences, and comorbidities further add to this complexity. This review provides a brief account of the techniques commonly used to induce general WM injury in animal models (stroke and non-stroke related) and highlights relevance, optimization issues, and translational potentials associated with this particular form of injury.