Effect of Interferon-β on Neuroinflammation, Brain Injury and Neurological Outcome After Experimental Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) has a poor outcome, particularly attributed to progressive injury after the initial incident. Several studies suggest a critical role for inflammation in lesion progression after SAH. Our goal was to test whether treatment with anti-inflammatory interferon-beta, which has shown promise as a therapeutic agent in experimental ischaemic stroke, can protect the brain after SAH. SAH was induced in adult male Wistar rats by puncturing the intracranial bifurcation of the right internal carotid artery. Treatment effects of daily interferon-beta (n = 16) or vehicle (n = 14) injections were serially evaluated with multiparametric MRI and behavioral tests from day 0 to 7, in compliance with recent recommendations for pre-clinical drug testing. Outcome measures included neurological status, brain lesion volume, blood-brain barrier (BBB) leakage, and levels of inflammatory markers. In animals that survived up to 7 days post-SAH, we found no significant differences between vehicle- and interferon-beta-treated animals with respect to final neurological score (14.3 +/- A 1.0 vs. 13.0 +/- A 2.2), brain lesion size on T-2-weighted MR images (59 +/- A 83 vs. 124 +/- A 99 mm(3)), BBB leakage (0.26 +/- A 0.05 vs. 0.22 +/- A 0.08 contrast-induced relative MR signal change), upregulation of brain RNA for cytokines, chemokines and cell adhesion molecules, and increased neutrophil activation. In contrast to previously published findings in experimental ischemic stroke models, interferon-beta has no clear efficacy to protect the brain after SAH. In line with recent highlighting of the significance of negative findings, our data currently do not recommend clinical testing of interferon-beta to prevent neurological damage in SAH patients.