gms | German Medical Science

Objective: Local and continuous delivery of nimodipine was shown to be a promising concept in the treatment of cerebral vasospasm after subarachnoid hemorrhage (SAH). The purpose of the current study was to investigate for the first time the effect of local applied nimodipine prolonged-release microparticles after induction of cerebral vasospasm in vivo.

Methods: 65 male Wistar rats were categorized into three groups: 1) sham operated animals (control), 2) animals with SAH only (control) and 3) treatment group. SAH was surgically induced using the double hemorrhage model. The treatment group received a concentration of 20%, 30% or 40% of nimodipine prolonged-release microparticles. Incidence of vasospasm was analyzed 5 days later using digital subtraction angiography (DSA). Morphological examination of the brain parenchyma was performed using Nissl-staining, c-Fos immunohistochemistry and TUNEL staining.

Results: DSA images were sufficient for assessment of vasospasm in 42 animals. Significant angiographic vasospasm was induced in group 2 (SAH only), as compared to the sham operated group (p < 0.001). Group 3 with the highest nimodipine microparticle concentration (40%) as well as group 1 (sham) demonstrated the largest intracranial artery diameters. However, there was no significant difference between group 2 (SAH only) and group 3, which received lower concentrations of nimodipine microparticles (20 and 30%). Further, the variation in vessel calibers did not result in changes regarding the expression of ischemic stress proteins or induction of apoptosis.

Conclusions: Local delivery of high dose nimodipine prolonged-release microparticles resulted in significant vasodilation after experimental SAH. This data underlines the necessity for the introduction of clinical trials on nimodipine prolonged-release microparticles in patients with aneurysmal SAH.