Kakeru Hosomoto, Tatsuya Sasaki, Takao Yasuhara, Masahiro Kameda, Susumu Sasada, Ittetsu Kin, Ken Kuwahara, Satoshi Kawauchi, Yosuke Okazaki, Satoru Yabuno, Chiaki Sugahara, Koji Kawai, Takayuki Nagase, Shun Tanimoto, Cesario V. Borlongan, and Isao Date
Brain Stimulation, Vol 16, Iss 2, Pp 594-603 (2023)
Subjects
Parkinson's disease, Vagus nerve stimulation, Afferent pathway, Locus coeruleus, Dopamine, Noradrenaline, Neurosciences. Biological psychiatry. Neuropsychiatry, and RC321-571
Abstract
Background: Vagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats. To date, the effects of vagal afferent- or efferent-selective stimulation on PD using continuous electrical stimulation remains to be determined. Objective: To investigate the effects of continuous and selective stimulation of vagal afferent or efferent fiber on Parkinsonian rats. Methods: Rats were divided into 5 group: intact VNS, afferent VNS (left VNS in the presence of left caudal vagotomy), efferent VNS (left VNS in the presence of left rostral vagotomy), sham, vagotomy. Rats underwent the implantation of cuff-electrode on left vagus nerve and 6-hydroxydopamine administration into the left striatum simultaneously. Electrical stimulation was delivered just after 6-OHDA administration and continued for 14 days. In afferent VNS and efferent VNS group, the vagus nerve was dissected at distal or proximal portion of cuff-electrode to imitate the selective stimulation of afferent or efferent vagal fiber respectively. Results: Intact VNS and afferent VNS reduced the behavioral impairments in cylinder test and methamphetamine-induced rotation test, which were accompanied by reduced inflammatory glial cells in substantia nigra with the increased density of the rate limiting enzyme in locus coeruleus. In contrast, efferent VNS did not exert any therapeutic effects. Conclusion: Continuous VNS promoted neuroprotective and anti-inflammatory effect in experimental PD, highlighting the crucial role of the afferent vagal pathway in mediating these therapeutic outcomes.
Satoru Yabuno, Takao Yasuhara, Takayuki Nagase, Satoshi Kawauchi, Chiaki Sugahara, Yosuke Okazaki, Kakeru Hosomoto, Susumu Sasada, Tatsuya Sasaki, Naoki Tajiri, Cesar V. Borlongan, and Isao Date
Stem Cell Research & Therapy, Vol 14, Iss 1, Pp 1-19 (2023)
Subjects
Cerebral ischemic infarct, Rehabilitation, Regenerative medicine, SB623, Voluntary exercise, Medicine (General), R5-920, Biochemistry, and QD415-436
Abstract
Abstract Background Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke. Methods Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 105 cells/5 μl) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups. Results SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p
neurogenesis, ischemic stroke, cell therapy, rehabilitations, Biology (General), and QH301-705.5
Abstract
The interruption of cerebral blood flow leads to ischemic cell death and results in ischemic stroke. Although ischemic stroke is one of the most important causes of long-term disability and mortality, limited treatments are available for functional recovery. Therefore, extensive research has been conducted to identify novel treatments. Neurogenesis is regarded as a fundamental mechanism of neural plasticity. Therefore, therapeutic strategies targeting neurogenesis are thought to be promising. Basic research has found that therapeutic intervention including cell therapy, rehabilitation, and pharmacotherapy increased neurogenesis and was accompanied by functional recovery after ischemic stroke. In this review, we consolidated the current knowledge of the relationship between neurogenesis and treatment for ischemic stroke. It revealed that many treatments for ischemic stroke, including clinical and preclinical ones, have enhanced brain repair and functional recovery post-stroke along with neurogenesis. However, the intricate mechanisms of neurogenesis and its impact on stroke recovery remain areas of extensive research, with numerous factors and pathways involved. Understanding neurogenesis will lead to more effective stroke treatments, benefiting not only stroke patients but also those with other neurological disorders. Further research is essential to bridge the gap between preclinical discoveries and clinical implementation.
Quoc-Viet Do, Takumitsu Kida, Masayuki Yamaguchi, Kensuke Washizu, Takayuki Nagase, and Toshio Tada
Polymers, Vol 14, Iss 24, p 5477 (2022)
Subjects
graded rubber, rubber elasticity, styrene–butadiene rubber, Organic chemistry, and QD241-441
Abstract
Mechanical responses after the uniaxial deformation of graded styrene–butadiene rubber (SBR) with a gradient in the crosslink points in the thickness direction were investigated as compared with those of homogenously vulcanized SBR samples. The elongational residual strain of a graded sample was found to depend on the part with a high crosslink density. Therefore, it showed good rubber elasticity. After stress removal, moreover, the graded sample showed a marked warpage. This suggested that shrinking stress acted on the surface with a high crosslink density, which would avoid a crack growth on the surface. The sample shape was then recovered to be flat very slowly, indicating that the shrinking stress worked for a long time. This unique rubber elasticity, i.e., slow strain recovery with an excellent strain recovery, makes graded rubber highly significant.
Satoshi Kawauchi, Takao Yasuhara, Kyohei Kin, Satoru Yabuno, Chiaki Sugahara, Takayuki Nagase, Kakeru Hosomoto, Yosuke Okazaki, Yousuke Tomita, Michiari Umakoshi, Tatsuya Sasaki, Masahiro Kameda, Cesario V. Borlongan, and Isao Date
CNS Neuroscience & Therapeutics. 28:1974-1985
Subjects
Pharmacology, Mesenchymal Stem Cells, Infarction, Middle Cerebral Artery, Bone Marrow Cells, cerebral infarction, Rats, Brain Ischemia, Stroke, neurogenesis, Psychiatry and Mental health, Bone Marrow, middle cerebral artery occlusion model, Physiology (medical), Animals, Humans, encapsulated cell transplantation, Pharmacology (medical), bone marrow stromal cells, and Ischemic Stroke
Abstract
Aims SB623 cells are human bone marrow stromal cells transfected with Notch1 intracellular domain. In this study, we examined potential regenerative mechanisms underlying stereotaxic transplantation of SB623 cells in rats with experimental acute ischemic stroke. Methods We prepared control group, empty capsule (EC) group, SB623 cell group (SB623), and encapsulated SB623 cell (eSB623) group. Transient middle cerebral artery occlusion (MCAO) was performed on day 0, and 24 h after MCAO, stroke rats received transplantation into the envisioned ischemic penumbra. Modified neurological severity score (mNSS) was evaluated, and histological evaluations were performed. Results In the mNSS, SB623 and eSB623 groups showed significant improvement compared to the other groups. Histological analysis revealed that the infarction area in SB623 and eSB623 groups was reduced. In the eSB623 group, robust cell viability and neurogenesis were detected in the subventricular zone that increased significantly compared to all other groups. Conclusion SB623 cells with or without encapsulation showed therapeutic effects on ischemic stroke. Encapsulated SB623 cells showed enhanced neurogenesis and increased viability inside the capsules. This study reveals the mechanism of secretory function of transplanted SB623 cells, but not cell-cell interaction as primarily mediating the cells' functional benefits in ischemic stroke.
Takayuki Nagase, Koji Tokunaga, Kyoichi Watanabe, Tsuyoshi Umeda, Yasuki Suruga, Yuji Takasugi, Satoshi Inoue, Hideki Kiriyama, and Kengo Matsumoto
JNET : journal of neuroendovascular therapy : official journal of the Japanese Society for Neuroendovascular Therapy, 2021, Vol. 15 No. 3, p. 164, 6 p.
Subjects
dural arteriovenous fistula, coil embolization, and jugular venous arch
JNET : journal of neuroendovascular therapy : official journal of the Japanese Society for Neuroendovascular Therapy, 2020, Vol. 14 No. 9, p. 339, 6 p.
Subjects
mechanical thrombectomy, medical informatics, mobile smartphone application, stroke team, and telemedicine