Stroke
General Overview :
The brain represents less than 2% [137] of human body weight. However, it alone receives more than 16% [5] of the body's total blood supply. It is an organ with very high metabolic activity, requiring more than 20% [138] of the entire body's energy intake.
Unfortunately, the brain has very small energy reserves (oxygen and glucose) [109]. Neurons die within a few minutes in the absence of a continuous energy supply [105]. If a neuron dies, there is a very low probability of it being replaced. For this reason, maintaining cerebral vascular supply is of paramount importance.
A stroke [4, 178] (cerebrovascular accident - CVA) is a sudden interruption of blood flow to a region of the brain, resulting in neurological deficits [179].
These disruptions, or strokes, manifest as two distinct entities, each with its own devastating mechanism: ischemic stroke, caused by the obstruction of a blood vessel (80% of all strokes), and hemorrhagic stroke, which causes bleeding within the brain (20% of strokes) [180].
Ischemic stroke :
Causes :
An ischemic stroke [69] is the consequence of the occlusion of an artery supplying the brain (cerebral artery, internal carotid, or vertebrobasilar system). This leads to a cerebral infarction (or cerebral softening [181]).
This obstruction can have several origins:
- Obstructive atheroma,
- The lodging of a clot formed locally or of cardiac origin (embolism),
- A tear in the arterial wall (dissection)
- Compression by a tumor...
Clinical Presentation :
The resulting deficit affects a well-defined cerebral territory; it is said to be systematized. The clinical manifestations [69] depend on the territory affected.
For instance, if the left posterior cerebral artery is affected, the subject will develop right homonymous hemianopia. If, on the other hand, the left middle cerebral artery is affected, the subject will develop a sensory-motor deficit of the right side of the body, most often associated with aphasia.
An ischemic event can be transient (Transient Ischemic Attack or TIA [31]), with a rapid return to normal without sequelae. The deficit can also be permanent, as in the case of an established ischemic stroke [184].
Pathophysiology :
A severe and prolonged interruption of cerebral blood flow, even in a small region of the brain, leads to tissue hypoxia [183, 185], resulting in:
- Metabolic changes (anaerobic glycolysis, lactic acid formation),
- Excessive release of glutamate, a neurotransmitter that is highly toxic to nerve cells at high concentrations [41],
- Dysfunction of the Na+/K+ pumps [86], leading to an intracellular influx of Ca++ [183] ...
Together, these disturbances trigger a cascade of enzymatic activations and an accumulation of acidic metabolites and cytotoxic free radicals [69], leading to irreversible cellular damage. This is why initial symptoms may be minor; but without early intervention, the clinical picture can rapidly deteriorate.
Membrane anomalies and capillary permeability disorders are complicated by cerebral edema observed in the ischemic zone. In addition to the direct impact of cerebral hypoperfusion on the ischemic region, these metabolic complications extend to the surrounding area, known as the penumbra zone [183].
Cerebral softening of ischemic origin may be complicated secondarily by bleeding within the lesion; this is referred to as hemorrhagic transformation [182].
Hemorrhagic stroke :
Hemorrhagic stroke [69] is caused by the rupture of a blood vessel that is often already damaged (an arteriovenous malformation or an aneurysm [38]) and subjected to excessive blood pressure. Tobacco and alcohol are factors that significantly weaken the blood vessels.
During a hemorrhagic stroke, a hematoma forms rapidly, causing sudden-onset focal neurological signs related to the brain structures destroyed or compressed.
The edema that develops around the hematoma worsens the compression of the brain within the skull and leads to or increases intracranial hypertension. As the skull is non-expandable, nerve structures under pressure may herniate under the falx cerebri or through the foramen magnum, an immediate life-threatening emergency.
Occasionally, during a hemorrhagic stroke, there is a massive release of calcium ions, which induces a sudden vasospasm [69], that can trigger further ischemic events.