Causes
Pathophysiology of Stroke
Ischemic stroke occurs because of a loss of blood supply to the brain, initiating the ischemic cascade. Brain tissue stops its function if lack of oxygen for more than 60 to 90 seconds and after several hours will endure irreversible damage possibly leading to death of the tissue, i.e., infarction. Atherosclerosis may interfere the blood supply by causing the shaping of blood clots in the vessel, or narrowing the lumen of blood vessels, or releasing showers of small emboli through the disintegration of atherosclerotic plaques. Embolic infarction takes place when emboli formed anywhere else in the circulatory system, especially in the heart as a result of atrial fibrillation, or in the carotid arteries. These break-offs, get into the cerebral circulation, then lodge in and block brain blood vessels.
Due to collateral circulation, there is a spectrum of severity within the region of brain tissue affected by ischemia. Therefore, part of the tissue may die in a short time while other parts may only be damaged and could potentially recover. The ischemic area where tissue might get recovery is called the “ischemic penumbra”.
As glucose or oxygen becomes exhausted in ischemic brain tissue, the production of high energy phosphate compounds such as ATP fails, resulting in the failure of energy-dependent process necessary for tissue cell survival. This sets off a set of co-related events that bring about cellular injury and death. A main cause of neuronal injury is the release of excitatory neurotransmitter glutamate. The concentration of glutamate outside the cells of nervous system is normally in a low amount as a result of so-called uptake carriers. However, stroke cuts off the supply of glucose and oxygen. Therefore the transmembrane ion gradients run down, and glutamate transporters reverse direction, releasing glutamate into the extracellular area. Glutamate works on receptors in nerve cells, producing an influx of calcium which activates enzymes that digest the proteins, lipids and nuclear material of the cells. Calcium influx can cause the failure of mitochondria as well, which may lead further to energy depletion and can trigger cell death out of apoptosis.
Ischemia may also induce production of oxygen-free radicals and other reactive oxygen species. These react with and injure a quantity of cellular and extracellular elements. Damage to the blood vessel endothelium or lining is of importance. Actually, many antioxidant neuroprotectants such as NXY-059 and uric acid, work at the level of the endothelium instead of in the brain per se. As well free radicals initiate elements of the apoptosis cascade in a direct way by ways of redox signaling.
These processes are the same for each type of ischemic tissue and are known as the ischemic cascade. But the brain tissue is vulnerable to ischemia for it has little respiratory reserve, and unlike most other organs, it is totally dependent on aerobic metabolism.
If one or more of these processes is inhibited, the survival brain tissue can be improved to some degree. Drugs that inhibit apoptosis, clear reactive oxygen species, or inhibit excitotoxic neurotransmitters, for example, have been shown to reduce tissue injury due to ischemia in experiment. Agents which work in this way are known as being neuroprotective. Until recently, with the probable exception of deep barbiturate coma, human clinical trials with neuroprotective agents have failed. Even though, more recently NXY-059 is reported to be neuroprotective in stroke. This agent seems to work at the level of the blood vessel endothelium or lining. Unfortunately, after producing positive results in a large-scale clinical trial, a second trial failed to show positive results.
In addition to injurious effects of brain cells, ischemia and infarction can lead to loss of structural integrity of brain tissue and blood vessels, partly through the release of matrix metalloproteases, which are zinc- and calcium-dependent enzymes that may break down hyaluronic acid, collagen, and other elements of connective tissue. Other proteases contribute to this process as well. The loss of vascular structural integrity leads to a breakdown of the protective blood brain barrier which contributes to cerebral edema, which may cause secondary progression of the brain injury.
As is the case with any kind of brain injury, the immune system is activated by cerebral infarction and may under some circumstances exacerbate the injury caused by the infarction. Inhibition of the inflammatory response has been shown to reduce tissue injury due to cerebral infarction in the experiment, but this has not been testified in clinical studies.
Hemorrhagic strokes lead to tissue injury by causing compression of tissue from an expanding hematomas or hematoma. This can distort and injure tissue. What is more, the pressure may cause a loss of blood supply to affected tissue with infarction, and the blood released by brain hemorrhage appears to have direct toxic effects on vasculature and brain tissue.
Arcticle Source : http://bodycountry.com/stroke/2009/pathophysiology-of-stroke.html