Details of a Researcher - Takizawa, Tsubasa

Papers - Takizawa, Tsubasa

Division display 81 - 100 of about 102 ／ All the affair displays >>

Neurovascular coupling during optogenetic functional activation: Local and remote stimulus-response characteristics, and uncoupling by spreading depression.

Maximilian Böhm, David Y Chung, Carlos A Gómez, Tao Qin, Tsubasa Takizawa, Homa Sadeghian, Kazutaka Sugimoto, Sava Sakadžić, Mohammad A Yaseen, Cenk Ayata

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 40 ( 4 ) 808 - 822 2020.04

Neurovascular coupling is a fundamental response that links activity to perfusion. Traditional paradigms of neurovascular coupling utilize somatosensory stimulation to activate the primary sensory cortex through subcortical relays. Therefore, examination of neurovascular coupling in disease models can be confounded if the disease process affects these multisynaptic pathways. Optogenetic stimulation is an alternative to directly activate neurons, bypassing the subcortical relays. We employed minimally invasive optogenetic cortical activation through intact skull in Thy1-channelrhodopsin-2 transgenic mice, examined the blood flow changes using laser speckle imaging, and related these to evoked electrophysiological activity. Our data show that optogenetic activation of barrel cortex triggers intensity- and frequency-dependent hyperemia both locally within the barrel cortex (>50% CBF increase), and remotely within the ipsilateral motor cortex (>30% CBF increase). Intriguingly, activation of the barrel cortex causes a small (∼10%) but reproducible hypoperfusion within the contralateral barrel cortex, electrophysiologically linked to transhemispheric inhibition. Cortical spreading depression, known to cause neurovascular uncoupling, diminishes optogenetic hyperemia by more than 50% for up to an hour despite rapid recovery of evoked electrophysiological activity, recapitulating a unique feature of physiological neurovascular coupling. Altogether, these data establish a minimally invasive paradigm to investigate neurovascular coupling for longitudinal characterization of cerebrovascular pathologies.

Access to Document (DOI)

Resilience to capsaicin-induced mitochondrial damage in trigeminal ganglion neurons.

Mamoru Shibata, Yohei Kayama, Tsubasa Takizawa, Keiji Ibata, Toshihiko Shimizu, Michisuke Yuzaki, Norihiro Suzuki, Jin Nakahara

Molecular pain 16 1744806920960856 - 1744806920960856 2020

Capsaicin is an agonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). Strong TRPV1 stimulation with capsaicin causes mitochondrial damage in primary sensory neurons. However, the effect of repetitive and moderate exposure to capsaicin on the integrity of neuronal mitochondria remains largely unknown. Our electron microscopic analysis revealed that repetitive stimulation of the facial skin of mice with 10 mM capsaicin induced short-term damage to the mitochondria in small-sized trigeminal ganglion neurons. Further, capsaicin-treated mice exhibited decreased sensitivity to noxious heat stimulation, indicating TRPV1 dysfunction, in parallel with the mitochondrial damage in the trigeminal ganglion neurons. To analyze the capsaicin-induced mitochondrial damage and its relevant cellular events in detail, we performed cell-based assays using TRPV1-expressing PC12 cells. Dose-dependent capsaicin-mediated mitochondrial toxicity was observed. High doses of capsaicin caused rapid destruction of mitochondrial internal structure, while low doses induced mitochondrial swelling. Further, capsaicin induced a dose-dependent loss of mitochondria and autophagy-mediated degradation of mitochondria (mitophagy). Concomitantly, transcriptional upregulation of mitochondrial proteins, cytochrome c oxidase subunit IV, Mic60/Mitofilin, and voltage-dependent anion channel 1 was observed, which implied induction of mitochondrial biogenesis to compensate for the loss of mitochondria. Collectively, although trigeminal ganglion neurons transiently exhibit mitochondrial damage and TRPV1 dysfunction following moderate capsaicin exposure, they appear to be resilient to such a challenge. Our in vitro data show a dose-response relationship in capsaicin-mediated mitochondrial toxicity. We postulate that induction of mitophagy and mitochondrial biogenesis in response to capsaicin stimulation play important roles in repairing the damaged mitochondrial system.

Access to Document (DOI)

Therapeutic implications of cortical spreading depression models in migraine.

Tsubasa Takizawa, Cenk Ayata, Shih-Pin Chen

Progress in brain research 255 29 - 67 2020

Migraine is among the most common and disabling neurological diseases in the world. Cortical spreading depression (CSD) is a wave of near-complete depolarization of neurons and glial cells that slowly propagates along the cortex creating the perception of aura. Evidence suggests that CSD can trigger migraine headache. Experimental models of CSD have been considered highly translational as they recapitulate migraine-related phenomena and have been validated for screening migraine therapeutics. Here we outline the essential components of validated experimental models of CSD and provide a comprehensive review of potential modulators and targets against CSD. We further focus on novel interventions that have been recently shown to suppress CSD susceptibility that may lead to therapeutic targets in migraine.

Access to Document (DOI)

Effects of olcegepant and sumatriptan on locomotive activity after cortical spreading depolarization in mice

Mamoru Shibata, Chunhua Tang, Miyuki Unekawa, Satoshi Kitagawa, Tsubasa Takizawa, Yohei Kayama, Jin Nakahara

CEPHALALGIA (SAGE PUBLICATIONS LTD) 39 144 - 145 2019.09

Accepted, ISSN 0333-1024

Spreading depression as a preclinical model of migraine.

Andrea M Harriott, Tsubasa Takizawa, David Y Chung, Shih-Pin Chen

The journal of headache and pain 20 ( 1 ) 45 - 45 2019.05

Spreading depression (SD) is a slowly propagating wave of near-complete depolarization of neurons and glial cells across the cortex. SD is thought to contribute to the underlying pathophysiology of migraine aura, and possibly also an intrinsic brain activity causing migraine headache. Experimental models of SD have recapitulated multiple migraine-related phenomena and are considered highly translational. In this review, we summarize conventional and novel methods to trigger SD, with specific focus on optogenetic methods. We outline physiological triggers that might affect SD susceptibility, review a multitude of physiological, biochemical, and behavioral consequences of SD, and elaborate their relevance to migraine pathophysiology. The possibility of constructing a recurrent episodic or chronic migraine model using SD is also discussed.

Access to Document (DOI)

Noninvasive Vagus Nerve Stimulation Prevents Ruptures and Improves Outcomes in a Model of Intracranial Aneurysm in Mice.

Tomoaki Suzuki, Tsubasa Takizawa, Yoshinobu Kamio, Tao Qin, Tomoki Hashimoto, Yukihiko Fujii, Yuichi Murayama, Aman B Patel, Cenk Ayata

Stroke 50 ( 5 ) 1216 - 1223 2019.05

Background and Purpose- Inflammation is a critical determinant of aneurysmal wall destabilization, growth, and rupture risk. Targeting inflammation may suppress aneurysm rupture. Vagus nerve stimulation (VNS) has been shown to suppress inflammation both systemically and in the central nervous system. Therefore, we tested the effect of a novel noninvasive transcutaneous VNS approach on aneurysm rupture and outcome in a mouse model of intracranial aneurysm formation with wall inflammation. Methods- Aneurysms were induced by a single stereotaxic injection of elastase into the cerebrospinal fluid at the skull base, combined with systemic deoxycorticosterone-salt hypertension, without or with high-salt diet, for mild or severe outcomes, respectively. Cervical VNS (two 2-minute stimulations 5 minutes apart) was delivered once a day starting from the day after elastase injection for the duration of follow-up. Transcutaneous stimulation of the femoral nerve (FNS) served as control. Multiple aneurysms developed in the circle of Willis and its major branches, resulting in spontaneous ruptures and subarachnoid hemorrhage, neurological deficits, and mortality. Results- In the milder model, VNS significantly reduced aneurysm rupture rate compared with FNS (29% versus 80%, respectively). Subarachnoid hemorrhage grades were also lower in the VNS group. In the more severe model, both VNS and FNS arms developed very high rupture rates (77% and 85%, respectively). However, VNS significantly improved the survival rate compared with FNS after rupture (median survival 13 versus 6 days, respectively), without diminishing the subarachnoid hemorrhage grades. Chronic daily VNS reduced MMP-9 (matrix metalloproteinase-9) expression compared with FNS, providing a potential mechanism of action. As an important control, chronic daily VNS did not alter systemic arterial blood pressure compared with FNS. Conclusions- VNS can reduce aneurysm rupture rates and improve the outcome from ruptured aneurysms.

Access to Document (DOI)

Real-time non-invasive in vivo visible light detection of cortical spreading depolarizations in mice.

David Y Chung, Kazutaka Sugimoto, Paul Fischer, Maximilian Böhm, Tsubasa Takizawa, Homa Sadeghian, Andreia Morais, Andrea Harriott, Fumiaki Oka, Tao Qin, Nils Henninger, Mohammad A Yaseen, Sava Sakadžić, Cenk Ayata

Journal of neuroscience methods 309 143 - 146 2018.11

BACKGROUND: Cortical spreading depolarization (CSD) is a phenomenon classically associated with migraine aura. CSDs have also been implicated in secondary injury following ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury; however, most investigations involving these disease processes do not account for the occurrence of CSDs. A major barrier to detection of CSDs in experimental models is that currently validated methods are invasive and require specialized equipment and a high level of expertise to implement. NEW METHOD: We present a low-cost, easy-to-implement approach to the detection of CSDs in the mouse through full-thickness intact skull. Our method uses the optical intrinsic signal from white light illumination (OIS-WL) and allows for real-time in vivo detection of CSDs using readily available USB cameras. RESULTS: OIS-WL detected 100% of CSDs that were seen with simultaneous electrode recording (69 CSDs in 28 mice), laser Doppler flowmetry (82 CSDs in 10 mice), laser speckle flowmetry (68 CSDs in 25 mice), or combined electrode recording plus laser speckle flowmetry (29 CSDs in 20 mice). OIS-WL detected 1 additional CSD that was missed by laser Doppler flowmetry. COMPARISON WITH EXISTING METHODS: OIS-WL is less invasive than electrophysiological recordings and easier to implement than laser speckle flowmetry. Moreover, it provides excellent spatial and temporal resolution for dynamic imaging of CSDs in the setting of brain injury. CONCLUSIONS: Detection of CSDs with an inexpensive USB camera and white light source provides a reliable method for the in vivo and non-invasive detection of CSDs through unaltered mouse skull.

Access to Document (DOI)

Spreading depolarizations trigger caveolin-1-dependent endothelial transcytosis.

Homa Sadeghian, Baptiste Lacoste, Tao Qin, Xavier Toussay, Roberto Rosa, Fumiaki Oka, David Y Chung, Tsubasa Takizawa, Chenghua Gu, Cenk Ayata

Annals of neurology 84 ( 3 ) 409 - 423 2018.09

OBJECTIVE: Cortical spreading depolarizations (CSDs) are intense and ubiquitous depolarization waves relevant for the pathophysiology of migraine and brain injury. CSDs disrupt the blood-brain barrier (BBB), but the mechanisms are unknown. METHODS: A total of six CSDs were evoked over 1 hour by topical application of 300 mM of KCl or optogenetically with 470 nm (blue) LED over the right hemisphere in anesthetized mice (C57BL/6 J wild type, Thy1-ChR2-YFP line 18, and cav-1-/- ). BBB disruption was assessed by Evans blue (2% EB, 3 ml/kg, intra-arterial) or dextran (200 mg/kg, fluorescein, 70,000 MW, intra-arterial) extravasation in parietotemporal cortex at 3 to 24 hours after CSD. Endothelial cell ultrastructure was examined using transmission electron microscopy 0 to 24 hours after the same CSD protocol in order to assess vesicular trafficking, endothelial tight junctions, and pericyte integrity. Mice were treated with vehicle, isoform nonselective rho-associated kinase (ROCK) inhibitor fasudil (10 mg/kg, intraperitoneally 30 minutes before CSD), or ROCK-2 selective inhibitor KD025 (200 mg/kg, per oral twice-daily for 5 doses before CSD). RESULTS: We show that CSD-induced BBB opening to water and large molecules is mediated by increased endothelial transcytosis starting between 3 and 6 hours and lasting approximately 24 hours. Endothelial tight junctions, pericytes, and basement membrane remain preserved after CSDs. Moreover, we show that CSD-induced BBB disruption is exclusively caveolin-1-dependent and requires rho-kinase 2 activity. Importantly, hyperoxia failed to prevent CSD-induced BBB breakdown, suggesting that the latter is independent of tissue hypoxia. INTERPRETATION: Our data elucidate the mechanisms by which CSDs lead to transient BBB disruption, with diagnostic and therapeutic implications for migraine and brain injury.

Access to Document (DOI)

Low-signal Intensity Rims along the Cerebral Cortex and U-fibers on Susceptibility-weighted Imaging in Progressive Multifocal Leukoencephalopathy.

Yuki Arita, Hirokazu Fujiwara, Jun Kurasawa, Suketaka Momoshima, Tsubasa Takizawa, Masahiro Jinzaki

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 17 ( 2 ) 109 - 110 2018.04

Access to Document (DOI)

Functional interactions between transient receptor potential M8 and transient receptor potential V1 in the trigeminal system: Relevance to migraine pathophysiology.

Yohei Kayama, Mamoru Shibata, Tsubasa Takizawa, Keiji Ibata, Toshihiko Shimizu, Taeko Ebine, Haruki Toriumi, Michisuke Yuzaki, Norihiro Suzuki

Cephalalgia : an international journal of headache 38 ( 5 ) 833 - 845 2018.04

Background Recent genome-wide association studies have identified transient receptor potential M8 ( TRPM8) as a migraine susceptibility gene. TRPM8 is a nonselective cation channel that mediates cool perception. However, its precise role in migraine pathophysiology is elusive. Transient receptor potential V1 (TRPV1) is a nonselective cation channel activated by noxious heat. Both TRPM8 and TRPV1 are expressed in trigeminal ganglion (TG) neurons. Methods We investigated the functional roles of TRPM8 and TRPV1 in a meningeal inflammation-based migraine model by measuring the effects of facial TRPM8 activation on thermal allodynia and assessing receptor coexpression changes in TG neurons. We performed retrograde tracer labeling to identify TG neurons innervating the face and dura. Results We found that pharmacological TRPM8 activation reversed the meningeal inflammation-induced lowering of the facial heat pain threshold, an effect abolished by genetic ablation of TRPM8. No significant changes in the heat pain threshold were seen in sham-operated animals. Meningeal inflammation caused dynamic alterations in TRPM8/TRPV1 coexpression patterns in TG neurons, and colocalization was most pronounced when the ameliorating effect of TRPM8 activation on thermal allodynia was maximal. Our tracer assay disclosed the presence of dura-innervating TG neurons sending collaterals to the face. Approximately half of them were TRPV1-positive. We also demonstrated functional inhibition of TRPV1 by TRPM8 in a cell-based assay using c-Jun N-terminal kinase phosphorylation as a surrogate marker. Conclusions Our findings provide a plausible mechanism to explain how facial TRPM8 activation can relieve migraine by suppressing TRPV1 activity. Facial TRPM8 appears to be a promising therapeutic target for migraine.

Access to Document (DOI)

Serial changes of corticospinal tract hyperintensity on magnetic resonance imaging from the preclinical stage in amyotrophic lateral sclerosis

Tsubasa Takizawa, Gen Shiihashi, Junki Maehara, Koichi Oki, Mayuko Osaka, Hirokazu Fujiwara, Hidenori Ojima, Yuichi Ichinose, Mamoru Shibata, Shinichi Takahashi, Norihiro Suzuki

NEUROLOGY AND CLINICAL NEUROSCIENCE (WILEY) 6 ( 1 ) 29 - 30 2018.01

Accepted, ISSN 2049-4173

Access to Document (DOI)

Signaling Pathways Relevant to Nerve Growth Factor-induced Upregulation of Transient Receptor Potential M8 Expression.

Yohei Kayama, Mamoru Shibata, Tsubasa Takizawa, Keiji Ibata, Jin Nakahara, Toshihiko Shimizu, Haruki Toriumi, Michisuke Yuzaki, Norihiro Suzuki

Neuroscience 367 178 - 188 2017.12

Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel that primarily detects the innocuous cold. In pathological conditions, TRPM8 plays a role in the development of cold hyperalgesia/allodynia. Nerve growth factor (NGF) is an important mediator involved in various pain disorders. In the present study, the NGF-TrkA pathway increased TRPM8 expression by stabilizing TRPM8 mRNA through the actions of phosphatidylinositol 3-kinase and p38 MAP kinase. Moreover, c-Jun N-terminal kinase and Src tyrosine kinase were identified as a positive and negative regulator of TRPM8 expression, respectively, via post-transcriptional mechanisms independent of mRNA stabilization. PTEN activity was found to increase protein TRPM8 expression. Calcium imaging confirmed that NGF induced TRPM8 functional upregulation. Time-lapse fluorescence microscopic analysis and a cell fractionation assay revealed that NGF promoted the trafficking of TRPM8 to the plasma membrane. In the presence of NGF, lysosome-associated membrane protein-2 (LAMP-2) was localized to TRPM8-positive dot-like and linear structures, the latter of which were observed in the periphery of the cytoplasm. It was inferred that LAMP-2 was involved in the vesicular transport of TRPM8. Pharmacological blockade of the proteasome with MG132 led to a further increase in NGF-induced TRPM8 expression, indicating that the proteasome system played a pivotal role in the degradation of TRPM8. Our findings provide novel insight into the signaling pathways involved in NGF-mediated TRPM8 upregulation and its reversion to the normal state.

Access to Document (DOI)

New onset of myasthenia gravis after intravesical Bacillus Calmette-Guerin: A case report and literature review.

Tsubasa Takizawa, Marenori Kojima, Shigeaki Suzuki, Takashi Osada, Satoshi Kitagawa, Jin Nakahara, Shinichi Takahashi, Norihiro Suzuki

Medicine 96 ( 46 ) e8757 2017.11

RATIONALE: Recently, drug-related myasthenia gravis (MG) has received attention, because the number of reported cases involving MG associated with immune checkpoint inhibitors, a new immunotherapy, is increasing. We present a case involving the new onset of MG, in which the symptoms started shortly after intravesical Bacillus Calmette-Guerin (BCG) for bladder cancer. PATIENT CONCERNS: A 69-year-old male with bladder cancer developed ptosis and diplopia 4 days after the completion of a treatment regimen with intravesical BCG weekly for 6 weeks. DIAGNOSES: Ocular MG was confirmed by a positive serum anti-acetylcholine receptor antibody test. INTERVENTIONS: Treatment with high-dose methylprednisolone pulse therapy was given, after insufficient treatment with pyridostigmine bromide and 10 mg/d prednisolone. OUTCOMES: Symptoms resolved completely 12 days after high-dose methylprednisolone pulse therapy. LESSONS: Intravesical BCG could be listed as a novel drug that may induce a new onset of MG along with drugs such as D-penicillamine and immune checkpoint inhibitors.

Access to Document (DOI)

Possible Involvement of Hypotension in Postprandial Headache: A Case Series.

Tsubasa Takizawa, Mamoru Shibata, Takahiro Hiraide, Morinobu Seki, Shinichi Takahashi, Norihiro Suzuki

Headache 57 ( 9 ) 1443 - 1448 2017.10

BACKGROUND: It is commonly known that headaches are induced by intake of specific food, drink, and/or additive. In addition, some patients experience postprandial headache independent of ingestion of specific items. Currently, information on the pathophysiology underlying this particular type of headache is scarce. CASE REPORTS: We report two cases in which headaches were observed after each meal. Postprandial hypotension was demonstrated in both cases. Tonometry-based continuous blood pressure measurement during head-up tilt revealed sympathetic dysfunction. In one patient, meta-iodobenzylguanidine (MIBG) myocardial scintigraphy detected cardiac sympathetic denervation, and diagnosis of pure autonomic failure was made. In both cases, treatment of postprandial hypotension was effective in relieving postprandial headache. DISCUSSION: The possibility of postprandial hypotension should be explored in patients with headache that occurs after meal. To this end, tonometry-based blood pressure measurement and MIBG myocardial scintigraphy may be useful diagnostic investigations. Treating postprandial hypotension may be effective in alleviating the symptoms.

Access to Document (DOI)

Facial TRPM8 stimulation ameliorates thermal hyperalgesia in a mouse migraine model

Yohei Kayama, Mamoru Shibata, Tsubasa Takizawa, Toshihiko Shimizu, Haruki Toriumi, Taeko Ebine, Norihiro Suzuki

CEPHALALGIA (SAGE PUBLICATIONS LTD) 37 294 - 294 2017.09

Accepted, ISSN 0333-1024

High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression.

Tsubasa Takizawa, Mamoru Shibata, Yohei Kayama, Toshihiko Shimizu, Haruki Toriumi, Taeko Ebine, Miyuki Unekawa, Anri Koh, Akihiko Yoshimura, Norihiro Suzuki

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 37 ( 3 ) 890 - 901 2017.03

Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CSD inductions caused microglial hypertrophy (activation) accompanied by a greater impact on the transcription activity of the HMGB1 receptor genes, TLR2 and TLR4, while the total number of cortical microglia was not affected. Both an HMGB1-neurtalizing antibody and the HMGB1 inhibitor glycyrrhizin abrogated multiple CSD-induced microglial hypertrophy. Moreover, multiple CSD inductions failed to induce microglial hypertrophy in TLR2/4 double knockout mice. These results strongly implicate the HMGB1-TLR2/4 axis in the activation of microglia following multiple CSD inductions. Increased expression of the lysosomal acid hydrolase cathepsin D was detected in activated microglia by immunostaining, suggesting that lysosomal phagocytic activity may be enhanced in multiple CSD-activated microglia.

Access to Document (DOI)

Alterations in the threshold of the potassium concentration to evoke cortical spreading depression during the natural estrous cycle in mice.

Taeko Ebine, Haruki Toriumi, Toshihiko Shimizu, Miyuki Unekawa, Tsubasa Takizawa, Yohei Kayama, Mamoru Shibata, Norihiro Suzuki

Neuroscience research 112 57 - 62 2016.11

Cortical spreading depression (CSD) has been implicated in a variety of neurological disorders. However, the relationship between serum sex hormones and susceptibility to the development of CSD in naturally estrous cycling female animals is largely unknown. The natural estrous cycle of mice consists of four stages, namely, proestrus, estrus, metestrus and diestrus. We measured the serum concentration of estradiol and progesterone in estrus and diestrus and compared the minimum potassium concentrations necessary to evoke CSD in each stage and in males. In diestrus, the minimum potassium concentration required to evoke CSD was significantly lower compared to the other three phases and male animals. The serum level of estradiol is significantly higher and serum level of progesterone is significantly lower in diestrus compared to estrus. Furthermore, when we administered an estrogen receptor antagonist, the susceptibility to the development of CSD was decreased. Conversely, the administration of a progesterone receptor antagonist increased the susceptibility to CSD. Our results demonstrated that neuronal excitability related to CSD induction differs among the natural estrous phases in mice.

Access to Document (DOI)

Repetitive trigeminal nociceptive stimulation in rats increases their susceptibility to cortical spreading depression.

Haruki Toriumi, Toshihiko Shimizu, Taeko Ebine, Tsubasa Takizawa, Yohei Kayama, Anri Koh, Mamoru Shibata, Norihiro Suzuki

Neuroscience research 106 74 - 8 2016.05

We examined the ability of trigeminal nerve activation to induce cortical spreading depression in rats. Capsaicin was injected into the bilateral plantar or whisker pad for either 4 or 6 days in rats. The number and duration of cortical spreading depressions induced by potassium were significantly increased in animals injected with capsaicin in the bilateral whisker pad compared with animals injected in the bilateral plantar or in controls, while administration of a GABAA receptor agonist decreased these effects. Repetitive nociceptive stimulation of the trigeminal nerve lowers the threshold for the induction of cortical spreading depression by altering GABAergic neuronal activity.

Access to Document (DOI)

Adult-onset recurrent painful ophthalmoplegic neuropathy displaying atypical oculomotor nerve gadolinium-enhancement pattern in the orbit and cavernous sinus.

Tsubasa Takizawa, Mamoru Shibata, Hirokazu Fujiwara, Toshihiko Shimizu, Suketaka Momoshima, Norihiro Suzuki

Cephalalgia : an international journal of headache 36 ( 2 ) 199 - 200 2016.02

Access to Document (DOI)

Temporal profiles of high-mobility group box 1 expression levels after cortical spreading depression in mice.

Tsubasa Takizawa, Mamoru Shibata, Yohei Kayama, Haruki Toriumi, Taeko Ebine, Anri Koh, Toshihiko Shimizu, Norihiro Suzuki

Cephalalgia : an international journal of headache 36 ( 1 ) 44 - 52 2016.01

INTRODUCTION: Cortical spreading depression (CSD) has recently been shown to induce the release of the nuclear protein termed high-mobility group box 1 from neurons, causing activation of the trigeminovascular system. Here, we explored the effects of single and multiple cortical spreading depression inductions on high-mobility group box 1 (HMGB1) transcriptional activity relative to high-mobility group box 1 protein expression levels and intracellular localization in cortical neurons and astrocytes. METHODS: Single or multiple cortical spreading depression inductions were achieved by KCl application to the mouse cerebral cortex. The animals were sacrificed at 30 minutes, 3 hours and 24 hours after cortical spreading depression induction. High-mobility group box 1 expression levels were explored with in situ hybridization, Western blotting and immunostaining. RESULTS: Cortical spreading depression up-regulated high-mobility group box 1 transcriptional activity in neurons at 3 hours in a manner that was dependent on the number of cortical spreading depression inductions. At 24 hours, the high-mobility group box 1 transcriptional activity had returned to basal levels. Cortical spreading depression induced a reduction in high-mobility group box 1 protein expression at 3 hours, which was also dependent on the number of cortical spreading depression inductions. Following cortical spreading depression, the release of high-mobility group box 1 from the nucleus was observed in a small proportion of neurons, but not in astrocytes. CONCLUSION: Cortical spreading depression induced translocation of high-mobility group box 1 from neuronal nuclei, driving transcriptional up-regulation of high-mobility group box 1 to maintain protein levels.

Access to Document (DOI)

　 Previous page - Next page 　