Faculty Profiles - BABA Hiroshsi

Papers - BABA Hiroshsi

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The NR3B subunit does not alter the anesthetic sensitivities of recombinant N-methyl-D-aspartate receptors Reviewed

T Yamakura, AR Askalany, AB Petrenko, T Kohno, H Baba, K Sakimura

ANESTHESIA AND ANALGESIA 100 ( 6 ) 1687 - 1692 2005.6

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

The N-methyl-D-aspartate (NMDA) receptor NR3B subunit co-assembles with NR1 and NR2 subunits to form a receptor complex with distinct channel properties. In the present study, we investigated the effects of co-expression of the NR3B subunit on the anesthetic sensitivities of NMDA receptors for NR1/NR2 channels expressed in Xenopus oocytes. Although the NR3B subunit prominently reduced the current amplitude of NR1/NR2A-B channels, the sensitivities of NR1/ NR2A-B channels to Mg2+, ketamine, isoflurane, nitrous oxide, and ethanol were not altered by coexpression of the NR3B subunit. These results suggest that the anesthetic sensitivities of NMDA receptors do not depend on the presence or absence of the NR3 subunit. Mutations of two amino acid residues in the NR3B subunit at positions homologous to the N and N + 1 sites in the NR1 and NR2 subunits, which constitute the blocking sites for Mg2+ and ketamine, did not affect the sensitivities of NR1/NR2B/NR3B channels to Mg2+, ketamine and isoflurane. Thus, the amino acid residues at the N and N + 1 sites in NR3 subunits are unlikely to be involved in the formation of channel blocking sites in NR1/NR2/NR3 channels.

File： Yamakura(A&A2005).pdf

DOI： 10.1213/01.ANE.0000152324.30272.49

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Action of isoflurane on the substantia Gelatinosa neurons of the adult rat spinal cord Reviewed

A Wakai, T Kohno, T Yamakura, M Okamoto, T Ataka, H Baba

ANESTHESIOLOGY 102 ( 2 ) 379 - 386 2005.2

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Background Although isoflurane, a volatile anesthetic, can block the motor response to noxious stimulation (immunobility and analgesia) and suppress autonomic responsiveness, how it exerts these effects at the neuronal level in the spinal cord is not fully understood.
Methods: The effects of a clinically relevant concentration (1 rat minimum alveolar concentration [MAC]) of isoflurane on electrically evoked and spontaneous excitatory/inhibitory transmission and on the response to exogenous administration of the gamma-aminobutyric acid type A receptor agonist muscimol were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. The effect of isoflurane on the action potential-generating membrane property was also examined.
Results: Bath-applied isoflurane (1.5%, 1 rat MAC) diminished dorsal root-evoked polysynaptic but not monosynaptic excitatory postsynaptic currents. Glutamatergic miniature excitatory postsynaptic currents were also unaffected by isoflurane. In contrast, isoflurane prolonged the decay phase of evoked and miniature gamma-aminobutyric acid type A receptor-mediated inhibitory postsynaptic currents and increased the amplitude of the muscimol-induced current. Isoflurane had little effect on action potential discharge activity.
Conclusions: Isoflurane augments gamma-aminobutyric acid-mediated inhibitory transmission, leading to a decrease in the excitability of spinal dorsal horn neurons. This may be a possible mechanism for the antinociceptive effect of isoflurane in the spinal cord.

File： Wakai(Anesthesiology,2005).pdf

DOI： 10.1097/00000542-200502000-00021

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A patient with medication-overuse headache (MOH) following triptan overuse Reviewed

SHIMOHATA Keiko, SHIMOHATA Takayoshi, MOTEGI Ryoichiro, MIYASHITA Kou, BABA Hiroshi

The Journal of the Japan Society of Pain Clinicians 12 ( 1 ) 10 - 13 2005

硬膜外腔に７％炭酸水素ナトリウムを誤投与した1小児例 Reviewed

杉本祥子, 山倉智宏, 馬場洋

臨床麻酔 29 ( 2 ) 255 - 256 2005

Reduced sensitivity to ketamine and pentobarbital in mice lacking the N-methyl-D-aspartate receptor GluR epsilon 1 subunit Reviewed

AB Petrenko, T Yamakura, N Fujiwara, AR Askalany, H Baba, K Sakimura

ANESTHESIA AND ANALGESIA 99 ( 4 ) 1136 - 1140 2004.10

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Ketamine is an IV anesthetic with N-methyl-D-aspartate receptor (NMDAR)-blocking properties. However, it is still unclear whether ketamine's general anesthetic actions are mediated primarily via blockade of NMDAR. Functional NMDARs are composed by the assembly of a GluRzeta1 (NR1) subunit with GluRepsilon (GluRepsilon1-4; NR2A-D) subunits, which confer unique properties on native NMDARs. We hypothesized that animals deficient in GluRepsilon1, an abundant and ubiquitously postnatally expressed NMDAR subunit, might be resistant to the effects of ketamine. Here, we evaluated a righting reflex to determine the general anesthetic/hypnotic potency of ketamine administered intraperitoneally to GluRepsilon1 knockout mice and compared these results with those for wild-type mice. Mutant mice were more resistant to ketamine than control mice. Unexpectedly, mutant mice were also more resistant to pentobarbital, which is thought not to interact with NMDAR at clinically relevant concentrations. Although these data in no way eliminate the possibility of the involvement of the NMDAR GluRepsilon1 subunit in mediation of ketamine anesthesia/hypnosis, they suggest the difficulties with interpretation of altered anesthetic sensitivity in knockout animal models.

File： Petrenko(A&A,2004).pdf

DOI： 10.1213/01.ANE.0000131729

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術中の不適切な輸液により血糖値の異常を生じた2症例

本田博之, 山倉智宏, 馬場洋

麻酔 53 ( 8 ) 952 - 952 2004.8

Nasotracheal intubation, epistaxis and atelectasis in a patient with anhidrotic ectodermal dysplasia Reviewed

H Ishii, Watanabe, I, K Watanabe, C Kobayashi, M Maruyama, H Baba

CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE 51 ( 1 ) 96 - 97 2004.1

[Intra-spinal mechanism of inflammatory pain--special reference to PGE2]. Reviewed

Ikoma M, Baba H

Masui. The Japanese journal of anesthesiology 52 Suppl S34 - 46 2003.12

Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated excitatory transmission to the superficial spinal dorsal horn Reviewed

H Baba, RR Ji, T Kohno, KA Moore, T Ataka, A Wakai, M Okamoto, CJ Woolf

MOLECULAR AND CELLULAR NEUROSCIENCE 24 ( 3 ) 818 - 830 2003.11

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Primary afferent A-fiber stimulation normally evokes fast mono- or polysynaptic EPSCs of short duration. However, in the presence of the GABA(A) receptor antagonist bicuculline, repetitive, long lasting, polysynaptic EPSCs can be observed following the initial, fast response. A-fiber-induced ERK activation is also facilitated in the presence of bicuculline. The frequency of miniature EPSCs and the amplitude of the monosynaptic A-fiber-evoked EPSCs are not affected by bicuculline or the GABA(A) receptor agonist muscimol, suggesting that GABA(A) receptors located on somatodendritic sites of excitatory interneurons are critical for this action. Bicuculline-enhanced polysynaptic EPSCs are completely eliminated by NMDA receptor antagonists APV and ketamine, as was the augmented ERK activation. This NMDA receptor-dependent phenomenon may contribute to bicuculline-induced allodynia or hyperalgesia, as well as the hypersensitivity observed in neuropathic pain patients. (C) 2003 Elsevier Inc. All rights reserved.

File： Baba & Ji(MCN,2003).pdf

DOI： 10.1016/S1044-7431(03)00236-7

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The role of N-methyl-D-aspartate (NMDA) receptors in pain: A review Reviewed

AB Petrenko, T Yamakura, H Baba, K Shimoji

ANESTHESIA AND ANALGESIA 97 ( 4 ) 1108 - 1116 2003.10

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

There is accumulating evidence to implicate the importance of N-methyl-D-aspartate (NMDA) receptors to the induction and maintenance of central sensitization during pain states. However, NMDA receptors may also mediate peripheral sensitization and visceral pain. NMDA receptors are,composed of NR1, NR2 (A, B, C, and D), and NR3 (A and B) subunits, which determine the functional properties of native NMDA receptors. Among NMDA receptor subtypes, the NR2B subunit-containing receptors appear particularly important for nociception, thus leading to the possibility that NR2B-selective antagonists may be useful in the treatment of chronic pain.

File： Petrenko(A&A,2003).pdf

DOI： 10.1213/01.ANE.0000081061.12235.55

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Diagnosis of spinal disease with ultrafine flexible fiberscopes in patients with chronic pain Reviewed

T Tobita, M Okamoto, M Tomita, T Yamakura, H Fujihara, H Baba, S Uchiyama, W Hamann, K Shimoji

SPINE 28 ( 17 ) 2006 - 2012 2003.9

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Study Design. Spinal epidural and subarachnoid spaces were observed with the newly developed fine flexible fiberscopes in 55 patients with chronic pain.
Objectives. To evaluate the fiberscopes as diagnostic tools for spinal canal disease.
Summary of Background Data. Fine flexible fiberscopes make it possible to visualize the entire length of the spinal subarachnoid space without major complications, and they may be of value for the diagnosis of certain spinal canal diseases.
Methods. The epidural and subarachnoid spaces were accessed by fine flexible fiberscopes (Purely Fine [PF] types) in the initial 45 patients and by those equipped with a tip-steering function and a working channel (Medical Science [MS] types) in the later 10 patients, respectively. The procedures were based on those of continuous epidural or subarachnoid block.
Results. Normal and abnormal subarachnoid spaces were clearly observed. When the MS types were used, the intended sites of the spinal structures could be more easily approached. In 12 patients, new diagnoses were made (chronic arachnoiditis 9, subarachnoid cyst 2, old subdural hematoma 1) that could not be found by magnetic resonance imaging or computed tomography. Additionally, chronic arachnoiditis was found in 2 patients with spinal trauma. Pathologic changes were confirmed by fiberscopic examination in 16 patients (arachnoiditis 11, spinal trauma 2, arteriovenous malformation 2, subarachnoid cyst 1). No pathologic changes could be detected in 27 patients with spinal canal stenosis, disc herniation, reflex sympathetic dystrophy, or posttraumatic pain syndrome. There were no significant differences in incidence of new diagnoses between the PF and MS types of fiberscopes. There were no major complications. There were 2 cases of light fever in the initial 10 patients and 7 cases of headache in the initial 14 patients. Only 4 cases of headache were observed in the subsequent 41 patients, in whom 20 mL of saline was injected into the epidural space.
Conclusion. These fine flexible fiberscopes may provide new diagnostic and interventional tools for spinal canal diseases, provided skilled techniques are applied.

File： Tobita(2003).pdf

DOI： 10.1097/01.BRS.0000083595.10862.98

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産婦人科手術術後に下肢の神経障害を生じた3症例

本田博之, 小川真有美, 馬場洋

日本臨床麻酔学会誌 23 ( 8 ) S348 - S348 2003.9

月経開始日の緊急開心術患者の麻酔経験

小川真有美, 本田博之, 本間隆幸, 山倉智宏, 馬場洋

日本臨床麻酔学会誌 23 ( 8 ) S370 - S370 2003.9

The effects of isoflurane on conditioned inhibition by dorsal column stimulation Reviewed

T Tobita, M Okamoto, M Shimizu, T Yamakura, H Fujihara, K Shimoji, H Baba

ANESTHESIA AND ANALGESIA 97 ( 2 ) 436 - 441 2003.8

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Spinal dorsal column stimulation (DCS) modulates sensory transmission, including pain, at the dorsal horn of the cord. However, the mechanisms of DCS modulatory actions and the effects of anesthetics on these mechanisms remain to be investigated. We studied the effects of isoflurane (1.0% and 2.0%) on conditioned inhibition, the amplitude decrease of the spinal cord potentials (SCPs) after a conditioning volley (DCS), in the ketamine-anesthetized rat by recording the sharp negative (N) and slow positive (P) waves of the SCPs evoked by conditioning dorsal column (DC) and testing segmental stimulations. The N wave is believed to be the synchronized activity of the dorsal horn neurons, and the P wave, primary afferent depolarization (PAD), reflecting presynaptic inhibition. The P potentials evoked by either DC or segmental stimulation were depressed by isoflurane, whereas the N waves remained unchanged, indicating that the pharmacological characteristics of these N and P waves are similar between DC-evoked and segmentally evoked SCPs. The conditioned inhibition of segmental N and P waves by DC stimulation was almost completely suppressed by 2.0% isoflurane. The conditioned inhibition of the segmental N wave was not changed by spinal cord transection, whereas the conditioned inhibition of the segmental P wave was decreased. The results indicate that isoflurane depresses presynaptic inhibition without affecting the synchronized activity of dorsal horn neurons and, most profoundly, depresses the conditioned inhibition by DC stimulation of the dorsal horn neurons and PAD. Further, the results indicate that conditioned inhibition by DC stimulation of PAD receives a facilitatory influence from the supraspinal structures, whereas that of the synchronized activity of the dorsal horn neurons does not.

File： Tobita(A&A,2003).pdf

DOI： 10.1216/01.ANE.0000068980.4025.4C

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Different expression patterns of Bcl-2, Bcl-xl, and Bax proteins after sublethal forebrain ischemia in C57Black/Crj6 mouse striatum Reviewed

CR Wu, H Fujihara, J Yao, SH Qi, HP Li, K Shimoji, H Baba

STROKE 34 ( 7 ) 1803 - 1808 2003.7

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Background and Purpose - Ischemic injury in neurons can be strongly reduced by a preceding sublethal ischemic episode, of which the mechanism is poorly understood. Although changes in the expression of apoptosis-related proteins (Bcl-2, Bcl-xl, and Bax) have been considered to be crucially important in ischemic injury, the roles these proteins play in ischemic preconditioning induced by sublethal forebrain ischemia have not been elucidated. Therefore, we investigated the transcription and expression of Bcl-2, Bcl-xl, and Bax in striatum of mice subjected to sublethal forebrain ischemia and lethal ischemia, with or without ischemic preconditioning.
Methods - Sublethal forebrain ischemia was induced in C57Black/Crj6 (C57BL/6) mice by 6 minutes of bilateral common carotid artery occlusion. The transcription and expression of Bcl- 2 family genes were detected by reverse transcription polymerase chain reaction, Western blot, and immunofluorescent staining.
Results - No detectable neuronal loss was induced in striatum by 6 minutes of bilateral common carotid artery occlusion. Transcription and expression of Bcl- 2 and Bcl-xl were increased after sublethal forebrain ischemia, which attenuated the DNA fragmentation induced by lethal ischemia. The transcription and expression of Bax remained unchanged.
Conclusions - Upregulation of Bcl- 2 and Bcl-xl but not Bax may have a role in protective ischemic preconditioning. This result indicates a potential strategy for further ischemic neuronal injury therapies.

File： Chaoran Wu,.pdf

DOI： 10.1161/01.STR.0000077255.15597.69

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Unaltered pain-related behavior in mice lacking NMDA receptor GluR epsilon 1 subunit Reviewed

AB Petrenko, T Yamakura, H Baba, K Sakimura

NEUROSCIENCE RESEARCH 46 ( 2 ) 199 - 204 2003.6

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI IRELAND LTD

Noxious afferent input following tissue damage and inflammation triggers a state of neuronal hyperexcitability-a phenomenon of central sensitization-which manifests behaviorally as allodynia and hyperalgesia. At the molecular level, maintenance of central sensitization is largely dependent on the N-methyl-D-aspartate receptor (NMDAR) activation. NMDARs are composed of GluRzeta1 (NR1) and one of four GluRepsilon (NR2) subunits, which determine the functional properties of native NMDARs. Although there is accumulating evidence to implicate. GluRepsilon2-containing NMDARs in pain mechanisms, the functional significance of GluRepsilon1-containing NMDARs in this setting has not been examined in detail. Here, we used hind paw injection of formalin, complete Freund's adjuvant and a nerve injury model to investigate the effects of GluRepsilon1 subunit gene deletion on pain-related behavior in mice. In all of the models tested, GluRepsilon1-deficient mice exhibited responses similar to wild-type controls. These results suggest that GluRepsilon1 disruption does not result in altered nociceptive behavior in mice. Although the contribution of other nociceptive pathways cannot be ruled out, we speculate that the preserved function of GluRepsilon2-containing NMDARs could explain unaltered nociceptive behavior in mutant mice. (C) 2003 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/S0168-0102(03)00061-0

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Peripheral nerve injury alters excitatory synaptic transmission in lamina II of the rat dorsal horn Reviewed

T. Kohno, K. A Moore, H. Baba, C. J Woolf

The Journal of Physiology 548 ( 1 ) 131 - 138 2003.4