Time course in the development of cerebral vasospasm after experimental subarachnoid hemorrhage: Clinical and neuroradiological assessment of the rat double hemorrhage model

OBJECTIVE: The "double hemorrhage" model in the rat is frequently used to simulate delayed cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in humans. However, an exact neurological and angiographic characterization of the CVS is not available for this model so far and is provided in the present investigation. Additionally, perfusion weighted imaging (PWI) at 3 tesla magnetic resonance (MR) tomography was implemented to assess the reduction in cerebral blood flow (CBF). METHODS: In a prospective, randomized setting CVS was induced by injection of 0.2 ml autologous blood twice in the cisterna magna of 45 male Sprague-Dawley rats. The surviving animals were examined on Days 2, 3, 5, 7 and 9 and compared to a sham Operated control group (n = 9). Rats were neurologically graded between 0 and 3, followed by MRI and selective digital subtraction angiography (DSA). The relative CBF was set in relation to the perfusion of the masseter muscle. RESULTS: The neurological state was significantly worsened on Day 2 (Grade 3), 3 (Grade 3), and 5 (Grade 2) (medians). The relative CBF/muscle BF ratio (2.5 +/- 0.8 (SAH) versus 9.2 +/- 1.3 (sham) (mean +/- SEM) and the basilar artery (BA) diameter (0.15 +/- 0.02 mm (SAH) versus 0.32 +/- 0.01 mm (sham) were significantly decreased on Day 5. Correlation between relative CBF/muscle BF ratio and BA diameter was 0.70. CONCLUSION: A valid and reproducible CVS simulation was proven by neurological score, DSA, and PWI on Day 5. Furthermore, our data demonstrate the practicability and validity of MR PWI for the monitoring of CVS in a rat SAH model.