The Neuroscience Behind Stroke

Stroke is a leading cause of disability and death worldwide. It occurs when there is a sudden interruption of blood flow to the brain, resulting in the death or damage of brain cells. While strokes have long been categorized as vascular events, they share similarities with traumatic brain injuries (TBIs) in their effects on brain tissue. Specifically, a stroke is now recognized as a type of non-traumatic brain injury (nTBI), a category that is not caused by direct physical trauma to the brain. This article explores the neuroscience behind stroke, its impact on the brain and why it is classified as an nTBI.

WHAT IS A STROKE?
A stroke occurs when there is a disruption in the blood supply to a part of the brain. This disruption can be due to two main mechanisms:

Ischemic Stroke: This type of stroke is caused by a blockage or narrowing of the blood vessels that supply the brain. A clot can form either in the brain itself (thrombotic stroke) or travel from another part of the body, such as the heart (embolic stroke).

Hemorrhagic Stroke: This occurs when a blood vessel in the brain bursts, leading to bleeding within the brain. The pooling of blood puts pressure on surrounding brain tissues, causing damage.
Both types of strokes share a common outcome: a lack of oxygen and nutrients to brain tissue, leading to cell death and neurological dysfunction. The primary difference between the two types is the mechanism causing the disruption in blood flow.

Ischemia and Oxygen Deprivation
When blood flow to a part of the brain is interrupted, the affected tissue becomes deprived of oxygen and glucose. These are essential for neurons to produce energy and function normally. Within minutes of ischemia, brain cells begin to suffer damage. The immediate effect is a phenomenon called cerebral ischemia, which causes a range of toxic processes within the brain.

THE NEUROSCIENCE OF STROKE: HOW IT AFFECTS THE BRAIN
To understand why stroke is considered an nTBI, it is important to examine the physiological mechanisms that occur during a stroke. Regardless of the type of stroke, the fundamental problem is the disruption of cerebral blood flow, which triggers a cascade of cellular and molecular events in the brain. Hemorrhagic Stroke: This occurs when a blood vessel in the brain bursts, leading to bleeding within the brain. The pooling of blood puts pressure on surrounding brain tissues, causing damage.
Both types of strokes share a common outcome: a lack of oxygen and nutrients to brain tissue, leading to cell death and neurological dysfunction. The primary difference between the two types is the mechanism causing the disruption in blood flow.

At the cellular level, neurons begin to experience energy failure, primarily due to a lack of adenosine triphosphate (ATP), which is crucial for maintaining normal cellular functions. Without ATP, the cell’s ion pumps malfunction, causing an imbalance of ions across the cell membrane. This leads to a phenomenon called excitotoxicity, where an excessive release of neurotransmitters, especially glutamate, results in an influx of calcium ions into the neuron. High calcium levels activate various enzymes that break down cellular structures, leading to cell death.

Stroke leads to inflammation in the affected brain region. This inflammation, called neuroinflammation, is triggered by the damage to brain cells and blood vessels. The activation of microglia, the brain’s resident immune cells, is a key component of this inflammatory response. Initially, microglia attempt to clear up dead cells and debris, but if the inflammation is prolonged, it can contribute to further brain injury by releasing pro-inflammatory cytokines and other toxic molecules.

Neuroinflammation is not only harmful in the acute phase of stroke but also contributes to long-term brain damage and recovery. The chronic inflammation that follows stroke has been implicated in the development of neurological deficits, cognitive decline and the progression of neurodegenerative diseases.

STROKE AS A NON-TRAUMATIC BRAIN INJURY (nTBI)
Traditionally, TBIs have been associated with external physical forces such as blows to the head, falls, or accidents. These external

forces result in direct trauma to the brain, leading to tissue damage and dysfunction. However, stroke, while not caused by a direct mechanical impact, can produce similar effects on brain tissue and functions. This has led to the recognition of stroke as a non-traumatic brain injury (nTBI).
An nTBI refers to any type of brain injury that is not the result of an external physical force but still leads to structural or functional damage to the brain. Strokes, whether ischemic or hemorrhagic, fit this definition because they result in significant brain injury due to the interruption of blood flow without any direct external impact on the brain.

WHY STROKE IS CONSIDERED AN NTBI
There are several reasons why stroke is categorized as an nTBI:
Similar Pathophysiology: Like traumatic brain injuries, stroke leads to neuronal cell death, neuroinflammation and long-term changes in brain structure and function. Both conditions cause damage to neurons and glial cells, leading to neurological deficits, cognitive impairments and emotional disturbances.

No External Trauma: Unlike TBIs, which are caused by external physical forces, strokes occur due to internal processes, such as blood clots or ruptured blood vessels. There is no direct impact on the skull or brain tissue from an external object, yet the effects on brain function can be just as devastating as a TBI.

Long-Term Consequences: Both stroke and TBI often result in long-term functional impairments, including motor deficits, sensory disturbances, cognitive decline and mood disorders. The recovery process for both conditions can be slow, requiring extensive rehabilitation and often leading to permanent disability.

Overlap in Risk Factors: Many of the risk factors for stroke overlap with those of TBI. For example, age, hypertension, diabetes and cardiovascular diseases are risk factors for both strokes and TBIs. Furthermore, individuals who have suffered a TBI are at an increased risk for stroke, further emphasizing the connection between the two conditions.

Impact on Brain Networks: Both stroke and TBI can disrupt the functioning of large-scale brain networks, affecting motor, sensory and cognitive functions. These disruptions can lead to widespread changes in brain connectivity, which is often associated with neurological deficits and difficulties in recovery.

CLINICAL IMPLICATIONS AND TREATMENT OF STROKE AS AN NTBI
Recognizing stroke as an nTBI has important clinical implications. It highlights the need for timely intervention to prevent further brain damage and improve outcomes. For example, the use of thrombolytic therapy (clot-busting drugs) and mechanical thrombectomy in ischemic stroke can restore blood flow and limit the extent of brain damage, much like how early intervention in TBI can prevent secondary injury.

Additionally, the rehabilitation of stroke patients often involves similar strategies used for TBI patients, including physical therapy, occupational therapy and neuropsychological interventions. The goal is to help patients recover lost functions and adapt to any remaining disabilities.

IN CONCLUSION
Stroke is a complex neurological event that results in the disruption of blood flow to the brain, leading to cell death, inflammation, and long-term neurological impairment. While strokes are caused by vascular issues and not external trauma, they share many similarities with traumatic brain injuries in terms of
their pathophysiology, clinical outcomes and impact on brain function. For these reasons, stroke is increasingly recognized as a form of non-traumatic brain injury (nTBI), and understanding its mechanisms can help improve treatment and rehabilitation strategies for those affected. By viewing stroke through the lens of nTBI, we can better address the needs of patients, leading to improved care and recovery outcomes.