Cellular Senescence as a Contributing Cause of Secondary Harms Following Stroke
Stroke is the blockage or rupture of a blood vessel in the brain, leading to significant damage to brain tissue and consequent loss of function. Beyond the immediate harm it is now well known that stroke leads to accelerated cognitive decline over time following the event. This is perhaps mediated by increased inflammation leading to degeneration of the thalamus, a central node in communication between brain regions. This accelerated brain-wide neurodegeneration caused by stroke is not as well understood as the mechanisms driving the immediate damage and aftermath of a stroke, however.
In today's open access paper, researchers consider an increased burden of cellular senescence in the brain resulting from a stroke as a possible contributing factor to further declining function over time. Senescent cells cease to replicate and secrete a pro-inflammatory mix of signals. In the short term the presence of senescent cells and their signaling helps to coordinate regeneration from injury, to the degree that the brain is capable of such regeneration. Over the long term, however, the sustained inflammatory signaling generated by senescent cells is disruptive to tissue structure and function. In this way, lingering senescent cells are a cause of degenerative aging, in the brain and elsewhere in the body.
Traumatic brain injury (TBI) and stroke pose major health challenges, impacting millions of individuals globally. Once considered solely acute events, these neurological conditions are now recognized as enduring pathological processes with long-term consequences, including an increased susceptibility to neurodegeneration. However, effective strategies to counteract their devastating consequences are still lacking.
Cellular senescence, marked by irreversible cell-cycle arrest, is emerging as a crucial factor in various neurodegenerative diseases. Recent research further reveals that cellular senescence may be a potential driver for secondary neurodegeneration following brain injury. This review offers critical insights into the role of cellular senescence in secondary neurodegeneration following TBI and stroke. A growing body of evidence underscores a strong connection between cellular senescence, inflammation, and neurodegeneration. Notably, senescent cells, a common pathological feature, are present in the brain after TBI or stroke.
Although the precise vulnerability of different cell types to senescence and their interactions remain underexplored, the targeted elimination of these cells has yielded promising preliminary results in mitigating brain injury-induced neuronal degeneration. These findings highlight a novel therapeutic target for addressing secondary neurodegeneration following brain insult. From a translational standpoint, further rigorous investigation into the safety and efficacy of senolytic agents is imperative, as it holds the potential to open new avenues for managing the long-term consequences of brain injury.