Toshiro Yukami1, Yoshiki Yagita2, Yukio Sugiyama2, Naoki Oyama2, Akihiro Watanabe2, Tsutomu Sasaki2, Manabu Sakaguchi2, Hideki Mochizuki2, Kazuo Kitagawa2. 1. From the Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan (T.Y., Y.S., N.O., A.W., T.S., M.S., H.M.); Department of Stroke Medicine, Kawasaki Medical School, Kurashiki, Japan (Y.Y.); and Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan (K.K.). yukami@neurol.med.osaka-u.ac.jp. 2. From the Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan (T.Y., Y.S., N.O., A.W., T.S., M.S., H.M.); Department of Stroke Medicine, Kawasaki Medical School, Kurashiki, Japan (Y.Y.); and Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan (K.K.).
Abstract
BACKGROUND AND PURPOSE: Leptomeningeal collateral growth is a key factor that defines the severity of ischemic stroke. Patients with stroke generally have vascular risk factors, such as diabetes mellitus; however, consensus is lacking on how diabetes mellitus affects leptomeningeal arteriogenesis. We investigate the influence of diabetes mellitus on the leptomeningeal arteriogenesis. METHODS: We measured the vessel diameter of the leptomeningeal anastomoses 14 days after the common carotid artery occlusion in db/db, db/+, and streptozotocin-induced hyperglycemic mice. In another set of these mice, we measured the infarct volume attributed to subsequent middle cerebral artery occlusion 14 days after the common carotid artery occlusion. Mac-2-positive cells on the dorsal brain surface and the mRNA expression of several macrophage-related factors in the cerebral cortex were examined. Finally, we tested whether the leptomeningeal arteriogenesis could be restored by pharmaceutical intervention in the db/db mice. RESULTS: Cerebral hypoperfusion led to significant ipsilateral leptomeningeal collateral growth in db/+ mice and streptozotocin-induced hyperglycemic mice. The collateral growth contributed to reduced infarct volume. In contrast, leptomeningeal arteriogenesis was impaired in the db/db mice. The number of Mac-2-positive cells was increased and tumor necrosis factor-α mRNA expression was induced after common carotid artery occlusion in the db/+ mice. However, these responses were not observed in the db/db mice. Administration of the tumor necrosis factor-α inhibitor etanercept before common carotid artery occlusion restored the hypoperfusion-induced leptomeningeal collateral growth in db/db mice. CONCLUSIONS: These results indicate that leptomeningeal arteriogenesis is impaired in db/db mice and that suppression of the tumor necrosis factor-α response to hypoperfusion is the major contributing factor.
BACKGROUND AND PURPOSE: Leptomeningeal collateral growth is a key factor that defines the severity of ischemic stroke. Patients with stroke generally have vascular risk factors, such as diabetes mellitus; however, consensus is lacking on how diabetes mellitus affects leptomeningeal arteriogenesis. We investigate the influence of diabetes mellitus on the leptomeningeal arteriogenesis. METHODS: We measured the vessel diameter of the leptomeningeal anastomoses 14 days after the common carotid artery occlusion in db/db, db/+, and streptozotocin-induced hyperglycemicmice. In another set of these mice, we measured the infarct volume attributed to subsequent middle cerebral artery occlusion 14 days after the common carotid artery occlusion. Mac-2-positive cells on the dorsal brain surface and the mRNA expression of several macrophage-related factors in the cerebral cortex were examined. Finally, we tested whether the leptomeningeal arteriogenesis could be restored by pharmaceutical intervention in the db/db mice. RESULTS:Cerebral hypoperfusion led to significant ipsilateral leptomeningeal collateral growth in db/+ mice and streptozotocin-induced hyperglycemicmice. The collateral growth contributed to reduced infarct volume. In contrast, leptomeningeal arteriogenesis was impaired in the db/db mice. The number of Mac-2-positive cells was increased and tumor necrosis factor-α mRNA expression was induced after common carotid artery occlusion in the db/+ mice. However, these responses were not observed in the db/db mice. Administration of the tumor necrosis factor-α inhibitor etanercept before common carotid artery occlusion restored the hypoperfusion-induced leptomeningeal collateral growth in db/db mice. CONCLUSIONS: These results indicate that leptomeningeal arteriogenesis is impaired in db/db mice and that suppression of the tumor necrosis factor-α response to hypoperfusion is the major contributing factor.
Authors: Asitha T Silva; Farzana Rouf; Oluwayemisi A Semola; Mark E Payton; Pamela C Lovern Journal: Am J Physiol Heart Circ Physiol Date: 2019-08-09 Impact factor: 4.733
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Authors: Emilia Scheidecker; Benjamin Pereira-Zimmermann; Arne Potreck; Dominik F Vollherbst; Markus A Möhlenbruch; Christoph Gumbinger; Martin Bendszus; Christian Herweh; Fatih Seker Journal: Neuroradiology Date: 2021-12-09 Impact factor: 2.995