Time-course of blood-brain barrier permeability changes after experimental subarachnoid haemorrhage

An increase in blood-brain barrier (BBB) permeability after subarachnoid haemorrhage (SAH) has been described in humans and has been correlated with delayed cerebral ischemia and poor clinical outcome. Few studies examined in the laboratory the relationship between SAH and BBB, with contrasting results due to limitations in experimental probes adopted and in timing of observation. The aim of this study was to quantify the time-course of BBB changes after experimental SAH. Groups of eight rats received injections of 400 mu l of autologous arterial blood into the cisterna magna. BBB was assessed 6, 12, 24, 36, 48, 60, and 72 hours after SAH and in sham-operated animals separately for cerebral cortex, i.e. frontal, temporal, parietal, occipital, subcortical gray matter (Caudate-Putamen-Thalamus), cerebellar cortex and nuclei, and brain stem by a spectrophotofluorimetric evaluation of Evans Blue dye extravasation. As compared to sham-operated controls, SAH determined a significant BBB permeability change beginning 36 hours after SAH, peaking at 48 hours, and normalizing on day 3. This study provides a quantitative description of the temporal progression and recovery of BBB dysfunction after SAH. These results have implications for the management of aneurysm patients and for assessing the rationale and the therapeutic window of new pharmacological approaches.