TAK-242, Toll-Like Receptor 4 Antagonist, Attenuates Brain Edema in Subarachnoid Hemorrhage Mice

Background: Brain edema is a common and critical pathology following subarachnoid hemorrhage (SAH). Toll-like receptor 4 (TLR4) activation may exacerbate brain edema. The purpose of this study was to clarify if TAK-242, a TLR4 antagonist, suppresses brain edema formation and neurological impairments after SAH in mice. Methods: A total of 46 mice underwent endovascular perforation to induce SAH or sham operation and were classified as Sham+TAK-242, SAH+ phosphate-buffered saline (PBS), and SAH + TAK-242 groups. The PBS or TAK-242 was administered intracerebroventricularly to mice at 30 min from the operation. Neurobehavioral tests, SAH severity, and brain water content were evaluated at 24 h from the operation. Results: The SAH + PBS group was significantly worse in neurological tests (P < 0.001) and brain water content of the cerebral hemisphere in the bleeding side (p = 0.005) compared with the Sham+PBS group, while there were no differences between the SAH + TAK-242 and Sham+PBS groups. SAH severity in the SAH + PBS group was similar to that in the SAH + TAK-242 group. Conclusions: Intracerebroventricular administration of TAK-242 possibly prevents neurological impairments at least via suppression of brain edema.