The natural course of lesion development in brain ischemia.

Histopathologic and NMR imaging studies show that focally ischemic brain lesions tend to increase in size over time. In animal models of stroke as well as in patients presenting with hemispheric stroke, considerable lesion growth was observed. In focal cerebral ischemia, lesions predominantly enlarge early (<12 hrs postinsult) and show complete ischemic injury due to pan necrosis in the vast majority of affected tissue. In global cerebral ischemia--a condition that is present after cardiac arrest--lesions appear late (>12 hrs) in selectively vulnerable brain regions and neurons are damaged by apoptosis. The short resuscitation time of the brain explains why periods of global ischemia result in widespread and global loss of energy metabolites combined with diffuse brain edema and global damage. Mechanisms involved in lesion growth include excitotoxicity, peri-infarct depolarizations, lactacidosis, microcirculatory disturbances, and flow-metabolism uncoupling among others. Problems involved in the subject under focus are related to maturation phenomena of injury and the different imaging modalities (metabolic imaging, NMR imaging, positron emission tomography) that require a subtly differentiated interpretation of the alterations observed.

Early thrombolysis inhibits peri-infarct depolarizations in embolic MCA occlusion.

Rats submitted to middle cerebral artery (MCA) clot embolism were treated with tissue plasminogen activator (TPA) 1.5 and 3.5 h post-occlusion. Reperfusion patterns were monitored by measuring cortical laser-Doppler flow; the direct current potential was measured to detect peri-infarct depolarizations (PID), a known mechanism of ischemic injury. TPA treatment induced reperfusion in 58% of treated animals that was delayed by 41 +/- 7 min (mean +/- s.e.m.) from treatment onset. The probability of reperfusion did not differ significantly between the two treatment groups. TPA treatment led to a 3-fold reduced frequency of PID if administered early or if successful reperfusion was observed (each p < 0.001). Early thrombolysis inhibits, but does not block, PID as an important mechanism of ischemic injury in embolic stroke.