gms | German Medical Science

Objective: Subarachnoid hemorrhage (SAH) is a life threatening disease with a high morbidity and mortality within the first days after bleeding. Mechanisms of early brain injury are not completely understood but reduced cerebral blood flow (CBF) due to elevation of intracranial pressure (ICP), acute vasospasm and early inflammatory processes seem to play an important role. In this experimental study the effect of the anti-inflammatory drugs minocycline and methylprednisolone in the acute phase after SAH was investigated.

Method: SAH was induced by the endovascular filament model in male Sprague-Dawley rats (n=31). Methylprednisolone (16mg/kg BW) (n=10), minocycline (45mg/kg BW) (n=10) or physiologic salt solution (n=11) was administered intraperitoneal 30 min. after SAH. Sham-operated animals underwent an identical procedure without vessel perforation (n=4). CBF was measured via Laser Doppler Flow monitoring (LDF) over both hemispheres before and in the first three hours after bleeding. ICP, arterial blood pressure, cerebral perfusion pressure and body temperature were recorded continuously. Animals were sacrificed at 24 hours after SAH. Extent of SAH and clinical outcome were evaluated using modified grading systems by Sugawara et al. (2008). Immunohistochemical (Caspase 3) stainings were performed to asses hippocampal damage.

Results: CBF significantly decreased immediately after SAH to a mean level of 37% of baseline. Mean LDF and ICP values differed not significantly between the groups. The clinical outcome was better in the intervention groups with a better neurological score and a lower mortality rate (30% and 40% respectively) compared to the control group (55%). Hippocampal damage was markedly decreased in minocycline treated compared to control animals, with a significantly (p<0.05) lower rate of caspase-3 positive, apoptotic cells (4.4% vs. 9.6%). In methylprednisolone treated rats, we also found a reduction of caspase-3 positive hippocampal cells compared to the control group (5.7% vs. 9.6%), although the level of significance was not reached.

Conclusions: Our results suggest that treatment with the anti-inflammatory drug minocycline in the acute phase after SAH leads to a significant reduction of immunhistochemical hippocampal damage. This may lead to a better clinical outcome in this critical phase after SAH. Early inflammatory processes seem to play an important role in the pathophysiology of early brain injury and could potentially be addressed by early drug therapy.