Time-Course of Blood-Brain Barrier Permeability Changes After Experimental Subarachnoid Haemorrhage

Abstract

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 microl 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.

Interleukin-1 Receptor Antagonist Penetrates Human Brain at Experimentally Therapeutic Concentrations

“…Since patients with SAH have leakage of blood (and consequently plasma proteins such as albumin) into the subarachnoid space at the time of haemorrhage, estimating BBB integrity by monitoring entry of plasma proteins is problematic. However, in our series, the albumin concentrations did not increase during the infusion period, suggesting that there was no further significant compromise of the BBB after the initial bleed, and animal studies of SAH indicate that BBB function is restored approximately by day 3 (Germano et al, 2000). Although this potentially represents a limitation in extrapolating these results to those with a normal BBB, it presents less compromise in terms of considering therapeutic potential in patients with central nervous system pathology.…”

The Effect of Blood Glutamate Scavengers Oxaloacetate and Pyruvate on Neurological Outcome in a Rat Model of Subarachnoid Hemorrhage

“…The chosen parameters for the assessment of the neurological outcome in this study were based on previous studies in which SAH was similarly induced by the injection of autologous blood into the cisterna magna [48]. Numerous parameters have been previously used to measure neurological damage after SAH in rats, including but not limited to examining mortality rats, behavioral and motor scores, neuronal count, brain edema, and BBB permeability.…”

“…An increase in the permeability of the BBB has been shown to follow SAH and correlate with a worsened neurological outcome [48]. In the current study, the timing for determining BBB disruption was chosen based on the observation of a maximal disruption of BBB 48 h after SAH [48].…”

“…In the current study, the timing for determining BBB disruption was chosen based on the observation of a maximal disruption of BBB 48 h after SAH [48]. Evans Blue 2 % in saline (4 ml/kg) was administered intravenously through the cannulated tail vein as a bloodbrain permeability tracer and was allowed to circulate for 60 minutes.…”

Highly Enhanced Permeability of Blood‐Brain Barrier Induced by Repeated Administration of Endothelin‐1 in Dogs and Rats

“…It has been generally accepted that cerebral ischaemia and inflammation modify blood-brain barrier permeability (Shigeno et al1982;Dó czi et al 1986), resulting in abnormal access to various drugs, water and serum protein, but the mechanisms responsible for this change are not understood (Gartshore et al 1997;Hurst et al 1998;Morley et al 1998;Germanò et al 2000). The contribution of endothelin-1 to produce pathological changes of cerebral arteries after subarachnoid haemorrhage has been well studied (Asano et al 1990;Suzuki et al 1990;Caner et al 1996;Lampl et al 1997;Suzuki et al 2000;Yakubu et al 2000;Zubkov et al 2000), however, the details regarding its participation remain to be clarified.…”