@entity2227 -mediated injury in focal XXXX : the excitotoxin hypothesis revised.

@entity2227 @entity137 @entity308 @entity2806 @entity63 @entity26 @entity519 @entity1188 @entity143 @entity528 @entity2359
@entity528 following focal @entity2806 is widely attributed to the excitotoxic effects of @entity2227 . However, critical analysis of published data on @entity2227 @entity137 in vitro and the comparison of these data with in vivo release of @entity2227 and the therapeutic effect of @entity2227 antagonists raises doubts about a @entity2359 mechanism. An alternative explanation for @entity2227 -mediated injury is @entity519 due to peri- @entity1188 spreading @entity308 -like depolarizations. These depolarizations are triggered in the core of the @entity1188 and spread at irregular intervals into the peri- @entity1188 surrounding. In ischemically uncompromised tissue, the metabolic workload associated with spreading @entity308 is coupled to an increase in blood flow and @entity26 supply, assuring maintenance of oxidative respiration. In the penumbra region of focal @entity63 , the hemodynamic constraints of collateral blood circulation prevail the adequate adjustment of @entity26 delivery, leading to transient episodes of relative tissue @entity519 . The @entity519 episodes cause a suppression of protein synthesis, a gradual deterioration of energy metabolism and a progression of irreversibly damaged tissue into the penumbra zone. The generation of peri- @entity1188 spreading @entity308 and the associated metabolic workload can be suppressed by @entity143 and non- @entity143 antagonists. As a result, the penumbral inhibition of protein synthesis and the progressing energy failure is also prevented, and the volume of @entity1188 decreases. Interventions to improve ischemic resistance should therefore aim at improving the @entity26 supply or reducing the metabolic workload in the penumbra region.
