Following an ischemic insult, the early damage associated with the energy
defect gives rise to molecular events, which may occur even during reperfusion to
sustain a progression of the damage in the ensuing hours or days. Neuroprotection
refers to interventions that are supposed to beneficially interfere with the maturation of
the ischemic damage. The post-ischemic molecular events embrace a huge variety of
mechanisms. Each mechanism is entangled with others, to configure a pathogenic
process that has the characteristics of a near-chaotic phenomenon. To add to the
complexity, the ischemic process includes both mechanisms that fuel the pathogenic
process promoting cell death, and mechanisms reflecting the effort of the organism to
oppose the process.
Interventions aimed to oppose the maturation process activate brain repair and
epigenetic mechanisms to promote survival pathways. Examples of potential
neuroprotective approaches are: pre- and post-conditioning, hypothermia, and a number
of drugs. All the treatments, however, that were proven to be effective in animal
models, failed in clinical trials. No unique explanation accounts for the gap between
laboratory animal and clinical studies.
Keywords: Acute ischemic stroke, Clinical trials, Experimental stroke models,
Ischemic cascade, Ischemic conditioning, Mynocycline, Neuroprotection,
Therapeutic hypothermia.
