Prostacyclin reduces early ischemic changes in central nervous system

Abstract

The authors made a study of the effect of prostacyclin [PGI(2)] on ischemic morphological changes in the brain, extracellular calcium concentration [Ca(2+)e] and the blood-brain barrier (BBB) permeability. This was combined with physiological and neurophysiological measurements. Complete cerebral ischemia (CCI) lasting 15 or 20 min wag produced by the ligation of the brachiocephalic trunk, the left subclavian and both internal thoracic arteries. The experiments with PGI(2) were carried out in two groups. In group I, the rabbits received PGI(2) 3 min before CCI, during it and for 15 min after it. In group I1 PGI(2) was infused in the last 3 min of CCI and for 40 min after it. Control animals with CCI of the same duration were not given PGI, medication. The rabbits treated with PGI(2) were found to have recovery of the bioelectric activity of the brain in half the time that its return took in the untreated cases. PGI, was noted to have a positive effect on some parameters of the peripheral blood system after CCI. Application of PGI, reduced the depth of ischemia-evoked drop of Ca(2+)e by 50 percent without accelerating recovery during recirculation; the post-ischemic increase of BBB permeability to fluorescein was also diminished. PGI(2) reduced edema and the spectrum of neuronal changes and decreased the number of pathologically changed neurons in the brain. In the group that received PGI(2) ischemic ultrastructural changes in the cytoplasm of neurons were abolished, but PGI(2) did not prevent pathological changes in the neuronal nuclei after CCI. Those changes were manifested in numerous vesicular structures and nuclear inclusions. Hence, the described data indicate that the beneficial action of PGI(2) is directed only to early changes in the neuronal cytoplasm and reflects a transient facilitation of functional recovery rather than permanent brain protection after complete cerebral ischemia.