Large Vessel Vasospasm Is Not Associated with Cerebral Cortical Hypoperfusion in a Murine Model of Subarachnoid Hemorrhage

Abstract

Clinical studies on subarachnoid hemorrhage (SAH) have shown discrepancies between large vessel vasospasm, cerebral perfusion, and clinical outcome. We set out to analyze the contribution of large vessel vasospasm to impaired cerebral perfusion and neurological impairment in a murine model of SAH. SAH was induced in C57BL/6 mice by endovascular filament perforation. Vasospasm was analyzed with microcomputed tomography, cortical perfusion by laser SPECKLE contrast imaging, and functional impairment with a quantitative neuroscore. SAH animals developed large vessel vasospasm, as shown by significantly lower vessel volumes of a 2.5-mm segment of the left middle cerebral artery (MCA) (SAH 5.6 ± 0.6 nL, sham 8.3 ± 0.5 nL, p < 0.01). Induction of SAH significantly reduced cerebral perfusion of the corresponding left MCA territory compared to values before SAH, which only recovered partly (SAH vs. sham, 15 min 35.7 ± 3.1 vs. 101.4 ± 10.2%, p < 0.01; 3 h, 85.0 ± 8.6 vs. 121.9 ± 13.4, p < 0.05; 24 h, 75.3 ± 4.6 vs. 110.6 ± 11.4%, p < 0.01; 72 h, 81.8 ± 4.8 vs. 108.5 ± 14.5%, n.s.). MCA vessel volume did not correlate significantly with MCA perfusion after 72 h (r = 0.34, p = 0.25). Perfusion correlated moderately with neuroscore (24 h: r = − 0.58, p < 0.05; 72 h: r = − 0.44, p = 0.14). There was no significant correlation between vessel volume and neuroscore after 72 h (r = − 0.21, p = 0.50). In the murine SAH model, cerebral hypoperfusion occurs independently of large vessel vasospasm. Neurological outcome is associated with cortical hypoperfusion rather than large vessel vasospasm.

Automated Grading of Cerebral Vasospasm to Standardize Computed Tomography Angiography Examinations After Subarachnoid Hemorrhage

“…We also observed cerebral hypoperfusion in the absence of severe vasospasm in some cases. These observations were consistent with previous studies, which showed that vasospasm and cerebral hypoperfusion can occur independently (30,33,34) and that DCI has a multifactorial genesis (4). Again, this highlights the need for multimodal monitoring of SAH patients.…”

“…In brief, the bone was virtually subtracted and the intracranial vascular tree was then virtually reconstructed by applying a standardized windowing procedure (23,24) shown to have high interrater agreement in results for vessel volumes (24). The vessel volume and the length of the corresponding vessel segment were calculated according to a standardized algorithm, as previously described (23,24,29,30), for the following vessel segments: the basilar artery, the posterior cerebral artery, the internal carotid artery, the M1 and M2 segments of the middle cerebral artery, and the A1 and A2 segments of the anterior cerebral artery. To account for individual differences in the length of the vessel segments, the vessel volumes were expressed in relation to the vessel length (volume/length ratio).…”

Neutrophils mediate early cerebral cortical hypoperfusion in a murine model of subarachnoid haemorrhage

“…Subarachnoid haemorrhage was induced by endovascular filament perforation under isoflurane anaesthesia (Abbvie, Wiesbaden, Germany) with continuous ICP monitoring as described previously 28–30 . Anaesthesia was induced with 4% isoflurane for 1 min and maintained with 2% isoflurane and 40% O 2 .…”

Inflammation: a Good Research Target to Improve Outcomes of Poor-Grade Subarachnoid Hemorrhage

“…Delayed cerebral ischemia may be caused by cerebral vasospasm, cortical spreading depolarization, and microcirculatory dysfunction [12], which may occur secondary to EBI [13]. Although cerebral vasospasm remains an important cause of delayed cerebral ischemia [14], microcirculatory disturbance and cortical spreading depolarization may be more important than cerebral vasospasm as to the impact on functional outcomes especially in poor-grade SAH patients [15]. Thus, many basic researchers have worked hard to overcome EBI, which is believed eventually to improve outcomes of poor-grade SAH patients.…”