Article
Matrix metalloproteinase (MMP)-9 mediates brain edema development after subarachnoid hemorrhage in mice
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Published: | May 20, 2009 |
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Objective: Matrix metalloproteinase (MMP)-9 is known to degrade microvascular basal lamina proteins and, in a previous investigation, bilateral cortical expression has been demonstrated after experimental subarachnoid hemorrhage (SAH). The current study was conducted to clarify the role of the MMP-9 for the development of vasogenic cerebral edema after SAH.
Methods: 6 week old FVB/N (controls, n=18) and MMP-9 knock-out (-/-) mice (n=19) were anesthetized, intubated and mechanically ventilated after random allocation. 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 30 minutes after SAH. Mortality, neurological function and postoperative weight gain were quantified over a period of 3 days after SAH. Subsequently, ICP measurement was repeated and animals were sacrificed to quantify bilateral brain water content by the wet-dry method. All experimental steps and the data analysis were carried out by a blinded investigator.
Results: ICP and CBF did not differ between groups in the first 30 minutes after SAH. Mortality was 42% in the control group and 14% in the MMP-9 -/- group, respectively (p=0.093). The neurological function was significantly better in MMP-9 -/- mice (p<0.05) compared to control mice on postoperative day 2. 72 hours after SAH, ICP (p<0.001) and ipsilateral brain water content (p<0.05) were significantly reduced in MMP-9 knock-out mice compared to control mice.
Conclusions: Basal lamina protein degrading MMP-9 is involved in the development of vasogenic cerebral edema after experimental SAH. Thus, pharmacological inhibition of MMP-9 might be a future candidate for the treatment of post-hemorrhagic cerebral edema.