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Background HMGB1 (high‐mobility group box 1) is known to worsen the functional prognosis after cerebral ischemia. Hp (haptoglobin) binds and sequesters HMGB1. Furthermore, Hp‐HMGB1 complexes are rapidly cleared by scavenger receptors on macrophages/microglia and modulate polarization of macrophages/microglia toward the M2 phenotype. Therefore, Hp may prevent aggravation by HMGB1 after cerebral ischemia and promote tissue repair by M2 macrophages/microglia. The aim of this study was to investigate the effects of Hp on ischemic brain damage induced by a high systemic HMGB1 level in mice subjected to 4 hours of middle cerebral artery occlusion (MCAO). Methods and Results One day after MCAO, Hp was administered intraperitoneally at a dose of 20 or 200 U/kg once daily for 7 days. Neurological scores, motor coordination, and plasma HMGB1 levels were measured 1, 3, and 7 days after MCAO. Expression of M1 and M2 macrophage/microglia markers, such as CD16/32 and CD206, were evaluated by immunostaining 7 days after MCAO. Treatment with Hp for 7 days improved the neurological score, motor coordination, and survival and prevented brain damage after MCAO. The systemic HMGB1 level increased 1 to 7 days after MCAO and was higher at 7 days than at day 1. Hp significantly decreased the systemic HMGB1 level and increased the M2 phenotype when compared with the M1 phenotype after MCAO. Conclusions Hp improved functional outcomes, including survival, motor function, and brain damage by binding to HMGB1 and modulating the polarization of macrophages/microglia. Hp may be an effective option in the treatment of cerebral ischemia.

Fig. 1 A: Sagittal T 1 -weighted magnetic resonance image with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) before surgery revealing a homogeneously enhanced mass with microcysts in the clivus. The sphenoid sinus, cavernous sinus, and petrosal apex were involved, with destruction of the clivus. B: Sagittal T 1 -weighted magnetic resonance image with Gd-DTPA after surgery revealing enhanced residual tumor. 751 CASE REPORT AbstractA 64-year-old male presented with an extremely unusual case of solitary clivus metastasis from gastric cancer manifesting as mild headache and diplopia 10 years after radical excision of the primary tumor. The patient underwent surgical resection using an endoscopic transsphenoidal approach. Histological examination revealed typical signet ring cell carcinoma (SRC) which was identical to that of the previous gastric cancer. Why the late recurrence occurred such a long time after the first surgery and how it spread to the clivus remain unclear. The characteristics of SRC and the process of``tumor dormancy'' may have been involved in the mechanism underlying late metastasis.