gms | German Medical Science

Objective: Inflammatory mechanisms have become an interesting target for analysis of early and delayed brain injury after subarachnoid hemorrhage (SAH). Our group could demonstrate a microglia activation in the central nervous system (CNS) after SAH, which peaks 7-14 days after the bleeding. To evaluate a relationship of microglia activation with neuronal injury, a microglia-depletion mouse model was applied.

Method: Mice harbouring a Herpes simplex virus thymidine kinase (HSVTK) underwent intraventricular implantation of an osmotic minipump filled with ganciclovir (GCV) for microglia depletion in the CNS. Experimental SAH was induced through endovascular perforation. Wildtype mice and sham operated animals (with and without GCV pump) served as controls. Neuronal injury was evaluated in frozen brain sections using a NeuN/TUNEL Kit co-staining and counting of apoptoses in serial sections.

Results: A marked increase of neuronal apoptosis was documented on day 7 and 14 after SAH in wildtype animals compared to sham animals (without GCV pump) (day7: 212 ± 125 vs. 98 ± 19; day14: 273 ± 127 vs. 63 ± 21 (counts per brain slice)). In HSVTK-/- mice (with GCV pump) 219 ± 52 apoptoses were counted on day 7, while in HSTTK+/+ mice (with GCV pump), only 61 ± 15 apoptoses were seen (p < .01)

Conclusions: The activation of brain residential microglia cells parallels neuronal apoptosis after subarachnoid hemorrhage. The depletion of microglia leads to a significant reduction of neuronal apoptosis. These results show, that inflammatory microglia activation within the CNS parenchyma contributes to secondary brain injury after SAH.