gms | German Medical Science

The double hemorrhage model in the rat is widely accepted to simulate delayed cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in humans. The time course of the development of this simulated CVS, however, was not characterized so far, but may be important for the assessment of the compatibility of the pathological changes after SAH proven in this model.

The development of CVS was assessed in a prospective experimental setting. 54 male Sprague-Dawley rats received 0.2 ml of autologous blood in the Cisterna magna on day 1 and 2 and were randomized into 5 groups each consisting of 9 animals to specify the day of the neurological and radiological examinations. These investigations were performed on the surviving animals on days 2, 3, 5, 7 and 9, respectively. For comparison a sham group was examined on day 4. Animals were neurologically graded between 0 and 3 referring to the scale of Bederson, followed by magnet resonance imaging (MRI) with 3 tesla including perfusion weighted image (PWI) and selective vertebro-basilar digital subtraction angiography (DSA). The relative cerebral blood flow (CBF) determined by PWI was set in relation to the relative perfusion of the masseter muscle of each rat, respectively. The diameter of the basilar artery (BA) was measured in mm using the catheter tip for calibration.

The mortality rate of rats with SAH was 47% compared to 0% in the sham group. The neurological condition was significantly reduced on day 2 (grade 3), 3 (grade 3), and 5 (grade 2) (medians). Surviving animals recovered until day 9. The relative CBF/muscle BF ratio was significantly reduced on day 5 (2.5±0.8 versus 9.2±1.3 (sham group) (mean ± SEM). BA diameter was 0.32+-0.01 mm in the sham group. On days 2 and 3 BA diameter was only reduced in some animals, however, a significant reduction to 0.15±0.02 (47% of sham) occurred on day 5. In animals examined on day 7 the BA diameter was 108% compared to the sham group.

Maximum of delayed CVS in the rat double hemorrhage model proven by significant angiographic and PWI findings was detected on day 5. Animals recover neurologically not before day 9 from the initial bleeding/procedure, which is probably because of the development of CVS. Therefore, day 5 seems to represent the best point of time to investigate pathophysiological changes of delayed CVS after SAH in this model. Furthermore, our data suggest that PWI is a sufficient tool for the monitoring of CVS.