Hiroshi Kagusa, Yamaguchi Izumi, Shono Kenji, Mizobuchi Yoshifumi, Shikata Eiji, Taku Matsuda, Takeshi Miyamoto, Keijiro Hara, Kitazato T Keiko, Yoshihiro Uto, Kanematsu Yasuhisa and Yasushi Takagi : Differences in amyloid-β and tau/p-tau deposition in blood-injected mouse brains using micro-syringe to mimic traumatic brain microhemorrhages, Journal of Chemical Neuroanatomy, Vol.130, 102258, 2023.
(要約)
Cerebral microbleeds (CMBs) due to traumatic brain injuries (TBI) have been shown to lead to cognitive decline and impairment. CMBs caused by TBI may be associated with pathophysiological mechanisms involving inflammation and the accumulation of amyloid-β (Aβ), tau, and phosphorylated tau (p-tau), contributing to cognitive abnormalities. However, their relationships remain unclear. To test our hypothesis that Aβ, tau, and p-tau are accumulated and regulated separately in mice with injuries imitating CMBs from TBI, we studied. Seven-week-old C57BL/6 male mice were injected with 15 μL of heparinized autologous blood or saline by micro-syringe into the front lobe. Expression profiles and regulation of Aβ, tau, and p-tau were assessed immunohistochemically over time. On day 7 after blood injection, Iba-1 and S100B cells in damaged cortex adjacent to the injection site were higher than saline injection group and non-injected sham. On days 3-14, Aβ deposition were gradually increased but normalized by day 28. In contrast, tau/p-tau deposition gradually increased during days 14-28 and dispersed along the corticomedullary junction adjacent to hem deposits, indicating different expression profiles from Aβ. Deposits of Aβ, but not tau/p-tau, were phagocytosed by CD163 macrophages increased by Gc-protein macrophage-activating factor during days 7-28, suggesting different mechanisms of deposition and regulation between Aβ and tau/p-tau. Deposition and regulation differ between Aβ and tau/p-tau in mice with injuries mimicking CMBs from TBI. Further clarification of relationships between the pathologies of cognitive impairment and their neurodegenerative consequences is needed.
Yoshitaka Kurashiki, Hiroshi Kagusa, Kenji Yagi, Tomoya Kinouchi, Manabu Sumiyoshi, Takeshi Miyamoto, Kenji Shimada, Keiko T Kitazato, Yoshihiro Uto and Yasushi Takagi : Role of post-ischemic phase-dependent modulation of anti-inflammatory M2-type macrophages against rat brain damage, Journal of Cerebral Blood Flow and Metabolism, 2022.
(要約)
Cerebral ischemia triggers inflammatory changes, and early complications and unfavorable outcomes of endovascular thrombectomy for brain occlusion promote the recruitment of various cell types to the ischemic area. Although anti-inflammatory M2-type macrophages are thought to exert protective effects against cerebral ischemia, little has been clarified regarding the significance of post-ischemic phase-dependent modulation of M2-type macrophages. To test our hypothesis that post-ischemic phase-dependent modulation of macrophages represents a potential therapy against ischemic brain damage, the effects on rats of an M2-type macrophage-specific activator, Gc-protein macrophage-activating factor (GcMAF), were compared with vehicle-treated control rats in the acute (day 0-6) or subacute (day 7-13) phase after ischemia induction. Acute-phase GcMAF treatment augmented both anti-inflammatory CD163 M2-type- and pro-inflammatory CD16 M1-type macrophages, resulting in no beneficial effects. Conversely, subacute-phase GcMAF injection increased only CD163 M2-type macrophages accompanied by elevated mRNA levels of arginase-1 and interleukin-4. M2-type macrophages co-localized with CD36 phagocytic cells led to clearance of the infarct area, which were abrogated by clodronate-liposomes. Expression of survival-related molecules on day 28 at the infarct border was augmented by GcMAF. These data provide new and important insights into the significance of M2-type macrophage-specific activation as post-ischemic phase-dependent therapy.
Yoshifumi Mizobuchi, Aki Shimada, Kohhei Nakajima, Hiroshi Kagusa and Yasushi Takagi : Reversible Hearing Impairment Due to Inferior Colliculi Compression by a Pineal Glial Cyst, NMC Case Report Journal, Vol.8, No.1, 79-84, 2021.
Kenji Shono, Izumi Yamaguchi, Yoshifumi Mizobuchi, Hiroshi Kagusa, Akiko Sumi, Toshitaka Fujihara, Kohhei Nakajima, T Keiko Kitazato, Kazuhito Matsuzaki, Hideyuki Saya and Yasushi Takagi : Downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes contributes to antitumor effects in a mouse model of malignant glioma., Scientific Reports, Vol.10, No.1, 2020.
(要約)
Glioblastoma multiforme involves glioma stem cells (GSCs) that are resistant to various therapeutic approaches. Here, we studied the importance of paracrine signaling in the glioma microenvironment by focusing on the celecoxib-mediated role of chemokines C-C motif ligand 2 (CCL2), C-X-C ligand 10 (CXCL10), and their receptors, CCR2 and CXCR3, in GSCs and a GSC-bearing malignant glioma model. C57BL/6 mice were injected with orthotopic GSCs intracranially and divided into groups administered either 10 or 30 mg/kg celecoxib, or saline to examine the antitumor effects associated with chemokine expression. In GSCs, we analyzed cell viability and expression of chemokines and their receptors in the presence/absence of celecoxib. In the malignant glioma model, celecoxib exhibited antitumor effects in a dose dependent manner and decreased protein and mRNA levels of Ccl2 and CxcL10 and Cxcr3 but not of Ccr2. CCL2 and CXCL10 co-localized with Nestin
Koji Bando, Toshiyuki Okazaki, Hideo Mure, Masaaki Korai and Hiroshi Kagusa : A Juvenile Case of Bow Hunter's Syndrome Caused by Atlantoaxial Dislocation with Vertebral Artery Dissecting Aneurysm., World Neurosurgery, Vol.137, 393-397, 2020.
(要約)
Bow hunter's syndrome (BHS) is caused by posterior circulation insufficiency that results from the occlusion or compression of the vertebral artery (VA) during neck rotation. Owing to its rarity, there is no guideline to support the decision of selecting a conservative or a surgical approach. Management of BHS is dependent on each patient. A 13-year-old girl presented with transient visual disturbance, hypoesthesia, and paralysis of the left side of the body. Magnetic resonance imaging revealed an acute cerebral infarction in the right thalamus, and magnetic resonance angiography demonstrated occlusion of the right posterior cerebral artery and dilation of V3 of the left VA. Digital subtraction angiography revealed a left VA dissecting aneurysm at V3 and left VA occlusion at the level of C1-C2 during neck rotation to the right. A dynamic x-ray suggested atlantoaxial joint instability, and three-dimensional computed tomography revealed aplasia of C1 lamina and atlantoaxial rotatory dislocation. BHS with left VA dissecting aneurysm caused by atlantoaxial rotatory dislocation was diagnosed. We performed C1-C2 posterior fusion by the Goel-Harms technique. Stroke did not recur, and computed tomography angiography obtained 8 months postoperatively demonstrated a decrease in the dissecting aneurysm. To our knowledge, this is the first case of BHS with VA dissecting aneurysm and aplasia of C1 lamina. Based on this case, we suggest that C1-C2 posterior fusion is effective for BHS with VA dissecting aneurysm.
Hiroshi Kagusa, Yoshifumi Mizobuchi, Kohhei Nakajima, Toshitaka Fujihara, Yoshimi Bando and Yasushi Takagi : Metastatic tumor to the orbital cavity from a primary carcinoma of the uterine cervix : a case report., The Journal of Medical Investigation : JMI, Vol.66, No.3,4, 355-357, 2019.
(要約)
Metastatic tumors to the orbit of the eye, especially from primary carcinomas of the uterine cervix are very rare. A 64-year-old woman with a history of carcinoma of the uterine cervix presented with right eye pain and blepharoptosis for 2 weeks. Magnetic resonance imaging revealed a mass at the right orbital apex. Surgical extirpation was performed due to severe pain. Postoperative pathology demonstrated a poorly differentiated squamous cell carcinoma. The origin was ultimately considered to be the carcinoma of the uterine cervix. In conclusion, this report describes a rare case of a metastatic tumor at the orbital apex derived from the cervix of the uterus. J. Med. Invest. 66 : 355-357, August, 2019.