gms | German Medical Science

Objective: The kallikrein-kinin system is involved in inflammatory signaling after traumatic brain injury and cerebral ischemia via bradykinin B2 receptors. The current study was conducted to clarify the role of both bradykinin receptor subtypes (B1 and B2) for the development of secondary brain damage after experimental subarachnoid hemorrhage (SAH).

Methods: 6–8 week old C57/Bl6 mice (controls) and bradykinin B₁- and B₂-receptor knock-out (-/-) mice were anesthetized, intubated and mechanically ventilated. The SAH was induced by endovascular puncture. Intracranial pressure (ICP, parenchymal probe) and cerebral blood flow (CBF, Laser-Doppler flowmetry) were continuously measured from 15 minutes before until 15 minutes after SAH. 24 hours after SAH ICP measurement was repeated and animals were subsequently sacrificed to quantify the brain water content. Mortality, neurological function and postoperative weight gain was quantified over a period of 7 days after SAH.

Results: ICP and CBF did not differ between groups in the first 15 minutes after SAH. 24 hours after SAH, however, ICP (p<0.05) and brain water content (p<0.05 B₂ ^-/-) was reduced in bradykinin receptor knock-out animals. 7-day mortality was 43%, 71% (p<0.05 vs. controls), and 14% (p<0.05 vs. controls) in control, B₁ ^-/-, and B₂ ^-/- mice, respectively. The neurological function was significantly better in B₂ ^-/- mice (p<0.05) compared to control and B₁ ^-/- mice on the first postoperative day. B₂ ^-/- animals also exhibited a better weight gain on postoperative day 4 whereas the B₁ ^-/- group showed a lesser weight gain from postoperative 3 through 7 compared to control animals (p<0.05).

Conclusions: An inflammatory response mediated by bradykinin B₂ receptors plays a role for the development of secondary brain damage after SAH. Thus, pharmacological inhibition of B₂ receptors might be a future candidate for the treatment of post-hemorrhagic cerebral edema.