White matter injury in ischemic stroke

Abstract

Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions.

Spontaneous ischaemic stroke lesions in a dog brain: neuropathological characterisation and comparison to human ischaemic stroke

“…It would be of interest to perform further neuropathological characterisation of the reactions of neurons and neuroglia at different post stroke time points and investigations of vascular pathology seem highly relevant. Furthermore, white matter neuropathology has previously been linked to clinical deficits in humans with ischaemic stroke [65]. It would therefore also be of interest to investigate such white matter lesions in dogs.…”

Plasticity and motor recovery after stroke: Implications for physiotherapy

“…Firstly, the rodent brain is structurally quite different from the human brain with much less white matter relative to grey matter (Wang et al 2016). Secondly, in animals, a stroke is artificially induced in a specific and localised area (usually the motor cortex).…”

“…This creates a pure cortical infarct which spares adjacent cortical areas and white matter pathways (Wang et al 2016). In contrast, in humans, the majority of stroke damage is likely to be in subcortical regions (Bogousslavsky et al 1988, Corbetta et al 2015, Kang et al 2003, Wessels et al 2006, with damage not only to grey matter but also to ascending and descending white matter tracts and white matter connections between cortical and subcortical structures (Corbetta et al 2015, Wang et al 2016. This results in a disruption in the brain's ability to transmit a message not only via descending pathways to the muscles, but also between cortical regions.…”

“…White matter plasticity occurs in the white matter tracts through mechanisms which promote structural changes such as remyelination of axons and axonal sprouting (Brown et al 2007, Clarkson et al 2013, Fields 2005, McIver et al 2010, Wang et al 2016, Zheng and Schlaug 2015. These changes may contribute to recovery of transmission in the motor pathways.…”

Protecting Oligodendrocytes by Targeting Non-Glutamate Receptors as a New Therapeutic Strategy for Ischemic Stroke

“…It is becoming increasingly obvious that targeting neurons alone is not adequate for optimizing the likelihood of a good outcome following stroke. In fact, it is apparent that both grey matter and white matter (WM) are damaged in ischemic stroke [4]. Cerebral WM is comprised primarily of axonal bundles that are ensheathed with myelin, an electrically insulating phospholipid layer produced by oligodendrocytes (OLGs).…”