Considerations for the optimization of induced white matter injury preclinical models

It should be a simple matter to calculate how much white matter was damaged during your stroke.
1. Locate the epicenter
2. calculate the radius of gray matter damage from the regular scans, after the neuronal cascade of death is finished.
3. extrapolate that radius into the white matter.
This is not rocket science, Considering the large radius of my infarct, my white matter damage must be massive. Yet, there is absolutely no intervention or protocol for recovering from such damage. What should be occurring is using interventions that;
1. accelerate dendritic branching and
2.  axon pathfinding.
If I remember correctly I've written 17 posts on dendritic branching and 15 posts on axon pathfinding.
Your doctor, if any good at all, should know of all of these and have created stroke protocols for them.
http://journal.frontiersin.org/article/10.3389/fneur.2015.00172/full?utm_source=newsletter&utm_medium=email&utm_campaign=Neurology-w35-2015

Abdullah Shafique Ahmad^1†, Irawan Satriotomo^1†, Jawad Fazal¹, Stephen E. Nadeau^2,3 and Sylvain Doré^{1,2,3,4,5,6,7,8}*

• ¹Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA
• ²Research Service, Brain Rehabilitation Research Center, Malcom Randall Veterans Affairs Medical Center, Gainesville, FL, USA
• ³Department of Neurology, University of Florida, Gainesville, FL, USA
• ⁴Department of Neuroscience, University of Florida, Gainesville, FL, USA
• ⁵Department of Neurology, University of Florida, Gainesville, FL, USA
• ⁶Department of Pharmaceutics, University of Florida, Gainesville, FL, USA
• ⁷Department of Psychology, University of Florida, Gainesville, FL, USA
• ⁸Department of Psychiatry, University of Florida, Gainesville, FL, USA

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.

Introduction

The human brain comprises both gray matter and white matter (WM), with the latter constituting roughly 60% of the total volume. Gray matter consists of neuronal cell bodies, their dendrites and axons, glial cells, and blood vessels (1). On the other hand, WM consists of myelinated and unmyelinated axons that connect various gray matter areas of the brain and support communication between neurons, as well as convey information among the network of efferent and afferent axonal fibers. Disruption of these conduction pathways may cause motor and sensory dysfunction, neurobehavioral syndromes, and cognitive impairment (2–4). In clinical settings, WM injury can occur at any time in the life span, such as with the development of periventricular leukomalacia due to hypoxic ischemic injury in infants, cardiac arrest and stroke in adults, and vascular dementia in the elderly (5–8). WM injury is the major cause of paresis in all types of stroke (9). Most obviously this is true for lacunar infarcts, which comprise about 25% of all strokes, and for lower extremity paresis in large vessel distribution strokes (except in the rare circumstance that the anterior cerebral artery territory is involved). However, because anterior circulation large vessel strokes are almost always due to clots embolizing or propagating to the carotid T-junction or the proximal middle cerebral artery, and because infarcts in both locations cause ischemia in the posterior periventricular WM, through which corticospinal and corticobulbar pathways pass, ischemic WM injury also accounts for most upper extremity paresis in large vessel distribution strokes. Furthermore, the site of periventricular WM lesions that cause paresis is also the site of crossing callosal fibers. Damage to these may contribute to apraxia after left brain stroke and may interfere with language recovery after stroke.

Thus, the extent to which WM injuries contribute to neurological impairment after stroke and the frequency with which WM damage contributes to other neurologic disorders highlights the need for therapeutic intervention strategies aimed at ameliorating WM damage or promoting WM recovery, as well as the need to dissect the molecular mechanisms involved in the pathophysiology of this injury. This review focuses essentially on techniques reported to induce WM injury. For other topics such as WM injury induced by traumatic brain injury, the pathophysiology of WM injury, WM hypersensitivity, and genetics variants leading to stroke and WM injury, which are beyond the scope of this paper, see reviews (10–17) and original research articles (18–20).

Lots more to read.