Nimodipin reduziert Mikrovasospasmen nach experimenteller Subarachnoidalblutung

Nimodipine, a L-type calcium channel inhibitor, remains the singular established pharmacological intervention that enhances outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). Despite its demonstrated efficacy, the intricate neuroprotective mechanisms of nimodipine in SAH remain elusive. Recent investigations have brought to light the potential significance of spasms in the cerebral microcirculation, indicating their pivotal role in post-SAH reduced cerebral perfusion and overall outcome. This study assessed the effect of nimodipine on microcirculatory dysfunction with special focus on microvasospasm formation.

Male C57Bl/6 N mice (n=3–5/group) underwent SAH induction through the middle cerebral artery perforation model. Six hours post-SAH, a cranial window was surgically created, allowing for real-time assessment of cortical microvessel diameters via 2-photon microscopy before, during, and after nimodipine application.

In the analysis, 85 spastic vessel segments (average diameter: 16±7 μm; median microvasospasms: 2, IQR: 1) from the vehicle group (n=5) and 37 spastic vessel segments (average diameter: 18±7 μm; median microvasospasms: 2, IQR: 1) from the nimodipine group (n=3) were examined. Nimodipine treatment significantly reduced microvasospasms after SAH compared to the control group. Within 35 minutes of drug application, the treatment group exhibited nearly complete elimination of microvasospasms, whereas the vehicle-treated mice showed no significant changes over time (P=0.02). While all examined vessels gradually dilated (P=0.192), there was no notable difference between the nimodipine and control groups. Nimodipine exhibited a statistically significant reduction in posthemorrhagic microvasospasms, while non-spastic vessel diameters remained unaffected.

The efficacy of nimodipine in diminishing microvasospasms contributes novel insights into its neuroprotective mode of action, refining our comprehension of this decades-long SAH treatment. Furthermore, our findings suggest potential involvement of L-type Ca2+ channels in microvasospasm pathophysiology, hinting at a broader understanding of the drug´s multifaceted impact. This research not only enhances our understanding of nimodipine's neuroprotective effects but also provides a foundation for potential future therapeutic advancements in SAH management.