Stroke is a general name used to define a set of brain illnesses caused by either thrombosis or bleeding in the brain. Stroke affects about 30 000 people in Sweden and it is one of the most common causes of disability worldwide. Today, there are about 120 000 people in Sweden who had been affected by stroke. Normally their brain function is reduced resulting in for instance loss of mobility, speech difficulties, memory loss and limited intellectual capacity. Brain function is affected as the result of massive cell death in the areas affected. The brain contains about 1 million neurons that are interconnected by a specialized network of axons and dendrites (see picture 1).
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Stroke can be hemorrhagic (a blood vessel ruptures in the brain) or embolic (blood flow is blocked by for example a blood clot or debris). When blood flow is affected the surrounding tissue undergoes damage (see picture 2). The neuronal network requires continuous supply of oxygen and glucose by the blood to keep its normal function (see picture 3).
Upon stroke one or several blood vessel are obstructed leading to a reduction of the blood flow in the brain, a process called ischemia, reducing oxygen and glucose access (Picture 4). Experimental studies show that cell death develops quickly under the first hours after stroke.
Many years of intensive stroke research had led to the development of clot-buster medications that are used today in a limited number of cases. Currently there are not drugs that can target the brain damage that occurs upon stroke neither can stimulate functional recovery of the brain. Rehabilitation is today the only resource to achieve functional recovery. One of the goals of the current research on stroke is to find new drugs that can protect the brain from damage upon stroke.
Stroke research has shown that cell damage occurs as a response to one or several mechanisms that can act in parallel or in serie (see picture 5). Upon reduced blood flow (ischemia), cell damage mechanisms are activated and are counteracted by the use of energy reserves and reparation processes. Simplifying, stroke is a time dependent process; for instance upon en Transitory Ischemic Attack, the damage to the surrounding tissue is quite limited and does not reach the threshold necessary to cause neuronal death.
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| Picture 5 |
On the other hand, if ischemia is present under a longer time, the damage cannot be repaired; there is threshold in the response and once this is passed neuronal death occurs (see picture 5). Experimental studies show that neuronal death can be hampered by the action of protective substances, like antioxidants, but only if administrated within a few hours after stroke (picture 6).
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| Picture 6 |
Lowering the temperature is an effective way to protect the brain. We and other research groups have shown experimentally that by reducing the body temperature to 33°C one can reduce the damage caused by ischemia. The protective properties of the cold are probably the result of the cold’s effect on several damaging processes that eventually keep the response under the neuronal death threshold. These experimental studies had led to the use of chilling as an established procedure for patients under cardiac arrest. Our experiments have also shown that upon stroke, chilling of the brain must be quick – quick chilling procedures are not available today.
Stroke patients recover some of their brain function under the first months after the lesion, showing the brain’s capability of self-healing and re-organization; this process is called plasticity. Upon injure the brain’s plasticity is activated allowing compensation for the lost functionality. One can say that stroke results in a “wound” that needs to be healed (see picture 7).
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Under this “wound-healing” process, the affected area is encapsulated to prevent toxic substances to leak and to negatively influence areas that survived the initial stroke. The surviving cells undergo remodelling to restore the lost neuronal communication. In this way, with the help of new axons the communication to the neurons that received their “information-flow” from the dead or damaged areas can be restored (picture 8). The neurons that survive have a tendency to build up more connections. This plasticity at cellular level leads to the establishment of new neuronal networks that can replace the original ones and bring back brain function. One of the major challenges of today’s stroke research is to find ways to stimulate the de novo building of neuronal networks. We study these mechanisms with the help of animal models – we aim to identify substances that promote plasticity, self-reparation and functional recovery of the brain. Some of these substances are currently tested in clinical trials.
Page Manager: Tadeusz Wieloch
Last modified: 2008-10-31
