A stroke is caused by rupture or blockage of a blood vessel in the brain. Rupture of blood vessels in the brain can occur due to the combination of (a) mechanisms that weaken blood vessel walls and (b) raised blood pressure, both of which are commonplace in older individuals. Blockage arises due to the breakup of an unstable atherosclerotic plaque, sending debris downstream. This is by far the most common cause of stroke, and one of the leading forms of human mortality. Since plaque rupture can also causes heart attack and fatal embolism elsewhere in the body, we should perhaps all pay more attention to atherosclerosis and the development of means to reverse its progression.
In an environment in which atherosclerosis cannot be reversed reliably or to any great degree, as is presently the case, a great deal of attention goes instead to coping with the aftermath of blocked blood vessels. Researchers try to find ways to repair some of the damage done to survivors, or as in today's open access paper, better understand how it is that a stroke occurring in a small part of the brain can produce lasting dysfunction throughout the brain. The answer appears to be that stroke provokes degeneration of the thalamus, a part of the brain thought to act as a form of relay, central to the flow of information between many different areas of the brain. Why this degeneration occurs following a stroke is an open question: one might suspect the usual culprit of excessive inflammatory signaling, disruptive to function in so very many ways.
Study uncovers promising new target for stroke treatment
Strokes leave behind an area where brain cells have died, called a lesion. However, this cannot explain the widespread consequences of stroke, limiting scientists' and clinicians' ability to treat them. A new study reveals that degeneration of the thalamus - an area of the brain distinct from the stroke lesion - is a significant contributor to post-stroke symptoms. "This is both good and bad news. The bad news is the impact to the brain caused by stroke is not limited to the lesion seen on a brain scan. The good news is the area that shows abnormal electrical activity outside the lesion might be treatable with innovative new therapies."
Damage to brain tissue near the stroke lesion was not the primary cause of abnormal brain electrical activity. Instead, these abnormalities were related to the thalamus, a structure located deep in the brain's centre that acts like a hub connecting numerous brain areas and activities. More than the lesion alone, the amount of degeneration in the thalamus predicted the amount of abnormal brain electrical activity measured using magnetoencephalography (MEG), and the individual's language and cognitive deficits.
Secondary thalamic dysfunction underlies abnormal large-scale neural dynamics in chronic stroke
Stroke causes pronounced and widespread slowing of neural activity. Despite decades of work exploring these abnormal neural dynamics and their associated functional impairments, their causes remain largely unclear. To close this gap in understanding, we applied a neurophysiological corticothalamic circuit model to simulate magnetoencephalography (MEG) power spectra recorded from chronic stroke patients. Comparing model-estimated physiological parameters to those of controls, patients demonstrated significantly lower intrathalamic inhibition in the lesioned hemisphere, despite the absence of direct damage to the thalamus itself. We hypothesized that this disinhibition could instead be related to secondary degeneration of the thalamus, for which growing evidence exists in the literature.
Further analyses confirmed that spectral slowing correlated significantly with overall secondary degeneration of the ipsilesional thalamus, encompassing decreased thalamic volume, altered tissue microstructure, and decreased blood flow. Crucially, this relationship was mediated by model-estimated thalamic disinhibition, suggesting a causal link between secondary thalamic degeneration and abnormal brain dynamics via thalamic disinhibition. Finally, thalamic degeneration was correlated significantly with poorer cognitive and language outcomes, but not lesion volume, reinforcing that thalamus damage may account for additional individual variability in poststroke disability. Overall, our findings indicate that the frequently observed poststroke slowing reflects a disruption of corticothalamic circuit dynamics due to secondary thalamic dysfunction, and highlights the thalamus as an important target for understanding and potentially treating poststroke brain dysfunction.
View the full article at FightAging
