Abstract:

This perspective shows an attempt to obtain synergy effects to fight ischemic stroke by combining agents acting on two different homeo-static mechanisms: inflammation and unfolded protein response. Different pharmacological approaches have been assayed to alleviate cerebrovascular accident (stroke), which represents one of the most devastating diseases in the elderly. There are two main types of cerebrovascular accidents: ischemic and hemorrhagic strokes. The former, reaching up to 87% of incidences, represents the most relevant form of cerebrovascular accident. The deprivation of glucose and oxygen due to ischemia results in a lack of energy in cells that leads them to activate mechanisms to recover homeostasis or to death if they cannot overcome the damage. In this regard, after the blood flow in a specific area of the brain is blocked (focal ischemia), two areas can be detected in the injured tissue: the ischemic core, where blood flow is reduced to less than 7 mL/100 g per minute and the penumbra area where some blood flow (7–17 mL/100 g per minute) remains. The ischemic core is characterized by the presence of necrosis, an immediate, irreversible and non-reg-ulated type of cell death. The penumbra surrounds the ischemic core, and presents regulated cell death subroutines such as apoptosis or necroptosis. The delayed cell death in the penumbra area provides some opportunities to prevent the neuronal demise and a consider-able effort in research has been focused on limiting the damage in this area. The global cerebral ischemia model where blood flow is blocked to the whole brain for a short time does not present an ischemic core and can be considered as a penumbra model for the whole brain. Thus, this model is very useful for comparing the responses of different areas of the brain to ischemia and in pharmacological research aimed to look for therapies that rescue the damaged cells in the penumbra area.