Faculty Profiles - BABA Hiroshsi

Be on the alert again for the risk of pulmonary air embolisation in paediatric patients during the insertion of a central venous catheter under general anaesthesia with spontaneous respiration Reviewed

Other Link： http://link.springer.com/article/10.1186/s40981-019-0239-9/fulltext.html

Tomohiro Yamamoto, Yusuke Mitsuma, Hiroshi Baba

Anaesthesiology Intensive Therapy 51 ( 5 ) 412 - 413 2019

Effect of remifentanil on postoperative nausea and vomiting: a randomized pilot study. Reviewed

Watanabe T, Moriya K, Tsubokawa N, Baba H

Journal of anesthesia 32 ( 5 ) 781 - 785 2018.9

Language：English Publishing type：Research paper (scientific journal)

Opioid-related postoperative nausea and vomiting should not occur following remifentanil administration because of its relatively short time to elimination. However, studies have indicated that the incidence of postoperative nausea and vomiting associated with remifentanil is similar to that with other opioids. Hence, we aimed to determine whether intraoperative remifentanil itself is associated with postoperative nausea and vomiting when postoperative pain is managed without opioid use. In this prospective pilot study, 150 patients who underwent unilateral upper limb surgery under general anesthesia with brachial plexus block were included. Patients in the remifentanil and control groups received 0.5 µg/kg/min remifentanil and saline, respectively. Postoperative pain was managed using a brachial plexus block, non-steroidal anti-inflammatory drugs, and acetaminophen. The presence of postoperative nausea and vomiting within the first 24 h after anesthesia was assessed by an evaluator blinded to patient allocation. Eight patients were excluded from the final analysis, resulting in 72 and 70 patients in the remifentanil and control groups, respectively. Postoperative nausea and vomiting within 24 h after surgery occurred in 11 and 9 patients in the remifentanil and control groups, respectively. These data suggest that remifentanil use only minimally affects the incidence of postoperative nausea and vomiting under sevoflurane anesthesia. UMIN Clinical Trials Registry identification number: UMIN000016110.

File： Watanabe T(JA,2018).pdf

DOI： 10.1007/s00540-018-2550-4

Pediatric Patients with High Pulmonary Arterial Pressure in Congenital Heart Disease Have Increased Tracheal Diameters Measured by Computed Tomography. Reviewed International journal

Ohashi N, Imai H, Seino Y, Baba H

Journal of cardiothoracic and vascular anesthesia 32 ( 4 ) 1676 - 1681 2018.8

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Determination of the appropriate tracheal tube size using formulas based on age or height often is inaccurate in pediatric patients with congenital heart disease (CHD), particularly in those with high pulmonary arterial pressure (PAP). Here, the authors compared tracheal diameters between pediatric patients with CHD with high PAP and low PAP. DESIGN: Retrospective clinical study. SETTING: Hospital. PARTICIPANTS: Pediatric patients, from birth to 6 months of age, requiring general anesthesia and tracheal intubation who underwent computed tomography were included. Patients with mean pulmonary artery pressure >25 mmHg were allocated to the high PAP group, and the remaining patients were allocated to the low PAP group. The primary outcome was the tracheal diameter at the cricoid cartilage level, and the secondary goal was to observe whether the size of the tracheal tube was appropriate compared with that obtained using predictable formulas based on age or height. MEASUREMENTS AND MAIN RESULTS: The mean tracheal diameter was significantly larger in the high PAP group than in the low PAP group (p < 0.01). Pediatric patients with high PAP required a larger tracheal tube size than predicted by formulas based on age or height (p = 0.04 for age and height). CONCLUSIONS: Pediatric patients with high PAP had larger tracheal diameters than those with low PAP and required larger tracheal tubes compared with the size predicted using formulas based on age or height.

File： Ohashi N (J Car and Vasc Anes,2018).pdf

DOI： 10.1053/j.jvca.2017.12.004

Marked attenuation of the amplitude of transcranial motor-evoked potentials after intravenous bolus administration of ketamine: a case report. Reviewed International journal

Kenta Furutani, Mari Matsuhashi, Hiroyuki Deguchi, Yusuke Mitsuma, Nobuko Ohashi, Hiroshi Baba

Journal of medical case reports 12 ( 1 ) 204 - 204 2018.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: It is believed that ketamine does not affect motor-evoked potential amplitude, whereas various anesthetic drugs attenuate the amplitude of transcranial motor-evoked potential. However, we encountered a patient with marked attenuation of motor-evoked potential amplitude after intravenous bolus administration of ketamine. CASE PRESENTATION: A 15-year-old Japanese girl with a diagnosis of adolescent idiopathic scoliosis was admitted to our hospital to undergo posterior spinal fusion at T4-L3. After induction of general anesthesia using a continuous infusion of propofol and remifentanil, we confirmed that transcranial electrical motor-evoked potentials were being recorded correctly. Ketamine 1.25 mg/kg was administered intravenously for intraoperative and postoperative analgesia. About 3 minutes later, the motor-evoked potential amplitude was markedly attenuated. No other drugs were administered except for ketamine. The patient's vital signs were stable, and the surgery had not yet started. The motor-evoked potential amplitude was recovered at about 6 minutes after administration of ketamine. The surgery was performed uneventfully, and the patient had no neurologic deficit when she emerged from general anesthesia. CONCLUSIONS: Although there is a widely held belief in the field of anesthesiology that ketamine does not affect motor-evoked potential amplitude, it has been suggested that ketamine could affect its monitoring.

File： Furutani(JM case reports,2018).pdf

DOI： 10.1186/s13256-018-1741-9

Free radical scavenger edaravone produces robust neuroprotection in a rat model of spinal cord injury. Reviewed International journal

Hideaki Ishii, Andrey B Petrenko, Mika Sasaki, Yukio Satoh, Yoshinori Kamiya, Toshiyuki Tobita, Kenta Furutani, Mari Matsuhashi, Tatsuro Kohno, Hiroshi Baba

Brain research 1682 24 - 35 2018.3

Language：English Publishing type：Research paper (scientific journal)

We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord injury (SCI). SCI was induced by extradural compression of thoracic spinal cord. In experiment 1, 30 min prior to compression, rats received a 3 mg/kg intravenous bolus of edaravone followed by a maintenance infusion of 1 (low-dose), 3 (moderate-dose), or 10 (high-dose) mg/kg/h edaravone. Although both moderate- and high-dose edaravone regimens promoted recovery of spinal motor-evoked potentials (MEPs) at 2 h post-SCI, the effect of the moderate dose was more pronounced. In experiment 2, moderate-dose edaravone was administered 30 min prior to compression, at the start of compression, or 10 min after decompression. Although both preemptive and coincident administration resulted in significantly improved spinal MEPs at 2 h post-SCI, the effect of preemptive administration was more pronounced. A moderate dose of edaravone resulted in significant attenuation of lipid peroxidation, as evidenced by lower concentrations of the free radical malonyldialdehyde in the spinal cord 3 h post-SCI. Malonyldialdehyde levels in the high-dose edaravone group were not reduced. Both moderate- and high-dose edaravone resulted in significant functional improvements, evidenced by better Basso-Beattie-Bresnahan (BBB) scores and better performance on an inclined plane during an 8 week period post-SCI. Both moderate- and high-dose edaravone significantly attenuated neuronal loss in the spinal cord at 8 weeks post-SCI, as evidenced by quantitative immunohistochemical analysis of NeuN-positive cells. In conclusion, early administration of a moderate dose of edaravone minimized the negative consequences of SCI and facilitated functional recovery.

File： Ishi (Brain Res, 2018).pdf

DOI： 10.1016/j.brainres.2017.12.035

Effective prevention of sorafenib-induced hand-foot syndrome by dried-bonito broth. Reviewed International journal

Kenya Kamimura, Yoko Shinagawa-Kobayashi, Ryo Goto, Kohei Ogawa, Takeshi Yokoo, Akira Sakamaki, Satoshi Abe, Hiroteru Kamimura, Takeshi Suda, Hiroshi Baba, Takayuki Tanaka, Yoshizu Nozawa, Naoto Koyama, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Yutaka Aoyagi, Shuji Terai

Cancer management and research 10 805 - 813 2018

Language：English Publishing type：Research paper (scientific journal)

Background: Sorafenib (SOR) is a molecular medicine that prolongs the survival of patients with hepatocellular carcinoma (HCC). Therefore, the management of side effects is essential for the longer period of continuous medication. Among the various side effects, hand-foot syndrome (HFS) is the most common, occurring in 30%-50% of patients, and often results in discontinuation of the SOR medication. However, its mechanism has not been clarified, and no effective prevention method has been reported for the symptoms. Therefore, this study aimed to analyze its mechanism and to develop an effective prevention regimen for the symptoms. Materials and methods: To assess the mechanism of SOR-induced HFS, the peripheral blood flow in the hand and foot was carefully monitored by Doppler ultrasound, thermography, and laser speckle flowgraphy in the cases treated with SOR and its contribution was assessed. Then, the effect of dried-bonito broth (DBB), which was reported to improve peripheral blood flow, on the prevention of the symptom was examined by monitoring its occurrence and the peripheral blood flow. Results: A total of 25 patients were enrolled in this study. In all, eight patients developed HFS, and all cases showed a significant decrease in the peripheral blood flow. DBB contributed to an increase in the flow (p = 0.009) and significantly decreased occurrence of HFS (p = 0.005) than control. Multivariable analysis showed that the ingestion of DBB is a significant independent contributor to HFS-free survival period (p = 0.035). Conclusion: The mechanism of SOR-induced HFS involves a decrease in the peripheral blood flow, and the ingestion of DBB effectively prevents the development of the syndrome by maintaining the flow.

File： Kamimura K(Cancer management and research,2018).pdf

DOI： 10.2147/CMAR.S159370

A case of increased systemic vascular resistance as a result of hiper acute rejection during the operation for ABO-incompatible living related kidney transplantation Reviewed

A case of interventricular septal hematoma diagnosed using intraoperative transesophageal echocardiography during congenital heart surgery Reviewed

BABA Hiroshi

Cardiovascular Anesthesia 22 133 - 137 2018

Hara F, Takamatsu M, Baba H

masui 66 ( 11 ) 1216 - 1219 2017.11

Significant decreases in blood propofol concentrations during adrenalectomy for phaeochromocytoma Reviewed

Tatsunori Watanabe, Haruhiko Hiraoka, Takuya Araki, Daisuke Nagano, Tohru Aomori, Tomonori Nakamura, Koujirou Yamamoto, Hiroshi Baba

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 83 ( 10 ) 2205 - 2213 2017.10

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

AIM
The kinetics of propofol are influenced by cardiac output. The aim of this study was to examine changes in blood propofol concentrations during phaeochromocytoma surgery using target-controlled infusion (TCI) anaesthesia with propofol.
METHODS
This is a prospective observational study. Ten patients with phaeochromocytoma who underwent unilateral adrenalectomy were included. Cardiac output was measured using an arterial pressure-based cardiac output analysis method. The target blood propofol concentrations were adjusted to maintain an approximate bispectral index (BIS) value of 40 before initiating surgery. The settings remained constant during surgery. Blood samples for propofol concentrations were collected from the radial artery at seven time points: two before tumour manipulation (T1, 2), two during tumour manipulation (T3, 4), and three after tumour vein ligation (T4-7). BIS values, the arterial pressure cardiac index (APCI) and haemodynamic parameters were measured at the same time points as the blood samples. The prop-ratio was calculated by dividing blood propofol concentrations by target concentrations of TCI.
RESULTS
APCI increased during tumour manipulation and after tumour vein ligation. The prop-ratio was reduced significantly by approximately 40% and showed a significant negative correlation with APCI. BIS values increased significantly and showed a significant negative correlation with the prop-ratio.
CONCLUSION
The increased APCI during tumour manipulation and after tumour vein ligation was associated with markedly reduced blood propofol concentrations. These results reveal that significant decreases in the anaesthetic effect may be observed in patients undergoing phaeochromocytoma surgery even if TCI anaesthesia is used with propofol.

File： Watanabe T(bjcp,2017).pdf

DOI： 10.1111/bcp.13334

Comparison of a curved forceps with a conventional straight forceps for nasogastric tube insertion under videolaryngoscopic guidance A randomized, crossover manikin study Reviewed

Kenta Furutani, Tatsunori Watanabe, Yoshinori Kamiya, Hiroshi Baba

MEDICINE 96 ( 35 ) e7983 2017.9

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

Background: Nasogastric tube (NGT) insertion is an easy procedure that can be routinely performed under general : anesthesia. However, for difficult cases, there are limited insertion techniques available in routine clinical practice, considering the flexibility of NGTs. The SUZY curved forceps are designed for the removal of pharyngolaryngeal foreign bodies under guidance of the McGRATH MAC (McG) videolaryngoscope. Because McG enables clear visualization of the esophageal inlet, we hypothesized that the SUZY forceps can facilitate easier NGT insertion compared with the conventional Magill forceps under McG guidance and designed a randomized, crossover manikin study to test this hypothesis.
Materials and Methods: Ten anesthesiologists participated in this study. Each participant was instructed to insert an NGT using either the SUZY or the Magill forceps under McG guidance. Both types of forceps were used by each participant in a computer-generated random order. The primary outcome measure was the number of "strokes" (1 stroke was defined by a specific sequence of participant actions) required to advance the NGT 30cm from the starting point. Data are expressed as medians (interquartile ranges [ranges]).
Results: The number of strokes required for NGT insertion was fewer in the SUZY group than in the Magill group {7 [7.0-12.5 (5-14)] vs 16.5 [13.5-20.3 (7-22)]; P < .05}. The time required for NGT insertion was also lesser in the SUZY group than in the Magill group {15.4 [13.7-20.0 (7.0-38.3)] seconds vs 30.3 [22.0-42.3 (12.8-47.5) seconds]; P < .05}.
Conclusions: The SUZY curved forceps facilitated NGT insertion more effectively than the Magill straight forceps under McG guidance. Our results suggest that NGT insertion using the SUZY forceps under McG guidance is a secure and easy procedure.

File： Furutani (Medicine,2018).pdf

DOI： 10.1097/MD.0000000000007983

Intraoperative Detection of Persistent Endoleak by Detecting Residual Spontaneous Echocardiographic Contrast in the Aneurysmal Sac During Thoracic Endovascular Aortic Repair Reviewed

Hidekazu Imai, Nobuko Ohashi, Takayuki Yoshida, Takeshi Okamoto, Nobutaka Kitamura, Takahiro Tanaka, Hiroshi Baba

ANESTHESIA AND ANALGESIA 125 ( 2 ) 417 - 420 2017.8

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

Persistent endoleaks may lead to adverse events after endovascular aortic repair. We prospectively examined the relationship between intraoperative residual spontaneous echocardiographic contrast (SEC) within the aneurysmal sac and the incidence of postoperative endoleaks in 60 patients undergoing thoracic endovascular aortic repair. Patients with SEC had a higher incidence of postoperative endoleaks than did patients without SEC within a few days postoperatively (60.0% vs 12.5%, respectively; P < .001) and at 6 months postoperatively (40.0% vs 2.5%, respectively; P < .001). Intraoperative confirmation of the absence of SEC may identify patients at low risk for persistent endoleaks after thoracic endovascular aortic repair.

File： Intraoperative_Detection_of_Persistent_Endolea.pdf

DOI： 10.1213/ANE.0000000000002207

Anesthetic management of abdominal radical trachelectomy for uterine cervical cancer during pregnancy Reviewed

Jun Terukina, Misako Takamatsu, Takayuki Enomoto, Hiroshi Baba

JOURNAL OF ANESTHESIA 31 ( 3 ) 467 - 471 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

Abdominal radical trachelectomy has been identified as a surgical option for fertility preservation in cervical cancer patients, particularly in pregnant women who strongly desire to continue their pregnancy. Since this procedure requires operating in the uterus, the hardness of the uterus can affect the ease of surgery. Generally, sevoflurane is used for anesthesia in non-obstetric surgery for pregnant women because uterine relaxation is advantageous for uterine blood flow maintenance. However, the use of sevoflurane during radical trachelectomy has not been thoroughly evaluated. Here, we report on anesthesia use in three cases of abdominal radical trachelectomy during pregnancy. Propofol enabled maintenance of uterine tension while not significantly affecting fetal growth. It is important to consider maintenance of uterine tension and fetal circulation in anesthesia management. During the operation, we performed an ultrasound examination every 30 min to confirm fetal well-being. Although frequent fetal heart rate monitoring of the pre-viable fetus is not recommended, if fetal bradycardia is detected, sevoflurane may then be used to improve fetal circulation. Additionally, if the fetal heartbeat stops, a radical hysterectomy would then be required. Therefore, we consider that fetal heart rate monitoring during this procedure is necessary, and propofol is suitable as an anesthetic for this surgery during pregnancy.

File： Terukina(JA, 2017).pdf

DOI： 10.1007/s00540-017-2325-3

Evaluation of the diagnostic accuracy of nonverbal signs used by medical staff to assess postoperative pain Reviewed

Tatsunori Watanabe, Reiko Okawa, Tsuyoshi Sato, Andrey B. Petrenko, Hiroshi Baba

EUROPEAN JOURNAL OF ANAESTHESIOLOGY 34 ( 5 ) 318 - 320 2017.5

A Rising Tide Lifts All Boats: Increased Ventilation May Be Involved in Accelerated Recovery from Isoflurane Anesthesia after Flumazenil Administration Reviewed

Andrey B. Petrenko, Hiroshi Baba

ANESTHESIOLOGY 126 ( 2 ) 351 - 352 2017.2

Risk factors for rescue analgesic use on the first postoperative day after upper limb surgery performed under single-injection brachial plexus block: a retrospective study of 930 cases. Reviewed International journal

Watanabe T, Moriya K, Yoda T, Tsubokawa N, Petrenko AB, Baba H

JA clinical reports 3 ( 1 ) 39 - 39 2017

Language：English Publishing type：Research paper (scientific journal)

Background: Postoperative pain management after upper limb surgery is important for preventing adverse events that can prolong hospital stay and cause readmission. This study aimed to identify the risk factors associated with rescue analgesic use on the first postoperative day after upper limb surgery performed under single-injection brachial plexus block (BPB). Findings: We retrospectively analyzed records from 930 patients who underwent upper limb surgery under a single-injection BPB. Postoperatively, patients were administered oral loxoprofen regularly and rescue analgesics when analgesia was insufficient. We assessed the association between patient, surgical information, and rescue analgesic use on the first day after surgery (from 7:00 PM on the day of surgery to 7:00 AM on the first postoperative day), using a logistic regression model. Multivariate analysis revealed a significant association between rescue analgesic use and bone surgery, in particular, osteotomy, ligament repair and reconstruction, osteosynthesis, treatment for an amputated digit, and surgical duration. Conclusion: Bone surgery (osteotomy, ligament repair and reconstruction, osteosynthesis, treatment for an amputated digit) and a longer operative time were risk factors for rescue analgesic use for treating postoperative pain after upper limb surgery performed under single-injection BPB.

File： Watanabe(JA Clinical aReport, 2017).pdf

DOI： 10.1186/s40981-017-0110-9

Effect of anesthesiologists' intervention on pain relief during high-dose-rate brachytherapy for cervical cancer : a retrospective study Reviewed

62 ( 5 ) 693 - 699 2017

Analgesic efficacy of bilateral continuous transversus abdominis plane blocks using an oblique subcostal approach in patients undergoing laparotomy for gynaecological cancer: a prospective, randomized, triple-blind, placebo-controlled study Reviewed

T. Yoshida, K. Furutani, Y. Watanabe, N. Ohashi, H. Baba

BRITISH JOURNAL OF ANAESTHESIA 117 ( 6 ) 812 - 820 2016.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

Background. The analgesic efficacy of continuous transversus abdominis plane (TAP) blocks in comparison with that of single-injection TAP blocks is not clear. This randomized, triple-blind, placebo-controlled trial investigated the benefits of adding continuous TAP blocks to single-injection TAP blocks after a laparotomy.
Methods. Eighty consecutive patients undergoing midline laparotomy for gynaecological cancer were randomized and received bilateral TAP infusions with either ropivacaine 0.1% (n=40, Rop group) or normal saline (n_40, NS group) at 10 ml h-1 per side for 50 h after surgery. After surgery, bilateral oblique subcostal TAP blocks were performed using ropivacaine 0.1%, 50 ml per side, and then catheters were threaded into the bilateral TAPs. Subsequently, continuous TAP infusions and patient-controlled ix. morphine administration were initiated. The primary outcome was cumulative morphine consumption by 24 h after TAP catheter placement. Secondary outcomes included pain scores, postoperative nausea and vomiting severity, and time to first ambulation and flatus.
Results. The cumulative morphine consumption (median [interquartile range]) 24h after TAP catheter placement was lower in the Rop group (0.25 [0.11-0.48] mg kg 1) than in the NS group (0.44 [0.24-0.73] mg kg 1; 95% confidence interval difference in medians, 0.30 to 0.03; P=0.01). No statistically significant differences were observed in the secondary outcomes, except for reduced pain scores in the Rop group obtained during coughing 1 and 24 h after TAP catheter placement.
Conclusions. Addition of continuous TAP blocks to single-injection TAP blocks reduces pain and morphine consumption after a laparotomy for gynaecological cancer. Clinical trial registration. UMIN Clinical Trials Registry identification number UMIN000013449 (http://www.umin.ac.jp/ctr/ index.htm).

File： Yoshida(2016,BJA).pdf

DOI： 10.1093/bja/aew339

Clinically relevant concentration of pregabalin has no acute inhibitory effect on excitation of dorsal horn neurons under normal or neuropathic pain conditions: An intracellular calcium-imaging study in spinal cord slices from adult rats Reviewed

Hiroshi Baba, Andrey B. Petrenko, Naoshi Fujiwara

BRAIN RESEARCH 1648 ( Pt A ) 445 - 458 2016.10

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to alpha 2 delta - 1 subunits of voltage-gated calcium (Ca2+) channels. However, the exact analgesic mechanism after its binding to alpha 2 delta - 1 subunits remains largely unknown. Whether a clinical concentration of pregabalin ( 10 uM) can cause acute inhibition of dorsal horn neurons in the spinal cord is controversial. To address this issue, we undertook intracellular Ca2+-imaging studies using spinal cord slices with an intact attached L5 dorsal root, and examined if pregabalin acutely inhibits the primary afferent stimulation-evoked excitation of dorsal horn neurons in normal rats and in rats with streptozotocin-induced painful diabetic neuropathy. Under normal conditions, stimulation of a dorsal root evoked Ca2+ signals predominantly in the superficial dorsal horn. Clinically relevant (10 mu M) and a very high concentration of pregabalin (100 pM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca2+ signals, whereas an extremely high dose of pregabalin (300 mu M) slightly but significantly attenuated Ca2+ signals in normal rats and in diabetic neuropathic (DN) rats. There was no difference between normal rats and DN rats with regard to the extent of signal attenuation at all concentrations tested. These results suggest that the activity of dorsal horn neurons in the spinal cord is not inhibited acutely by clinical doses of pregabalin under normal or DN conditions. It is very unlikely that an acute inhibitory action in the dorsal horn is the main analgesic mechanism of pregabalin in neuropathic pain states. (C) 2016 Elsevier B.V. All rights reserved.

File： Pregabalin(2016).pdf

DOI： 10.1016/j.brainres.2016.08.018

HYDROGEN PEROXIDE MODULATES NEURONAL EXCITABILITY AND MEMBRANE PROPERTIES IN VENTRAL HORN NEURONS OF THE RAT SPINAL CORD Reviewed

Masayuki Ohashi, Toru Hirano, Kei Watanabe, Hirokazu Shoji, Nobuko Ohashi, Hiroshi Baba, Naoto Endo, Tatsuro Kohno

NEUROSCIENCE 331 206 - 220 2016.9

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Hydrogen peroxide (H2O2), a reactive oxygen species, is an important signaling molecule for synaptic and neuronal activity in the central nervous system; it is produced excessively in brain ischemia and spinal cord injury. Although H2O2-mediated modulations of synaptic transmission have been reported in ventral horn (VH) neurons of the rat spinal cord, the effects of H2O2 on neuronal excitability and membrane properties remain poorly understood. Accordingly, the present study investigated such effects using a whole-cell patch-clamp technique. The bath-application of H2O2 decreased neuronal excitability accompanied by decreased input resistance, firing frequency, and action potential amplitude and by increased rheobase. These H2O2-mediated changes were induced by activation of extrasynaptic, but not synaptic, GABA(A) receptors. Indeed, GABAergic tonic currents were enhanced by H2O2. On the other hand, the amplitude of medium and slow afterhyperpolarization (mAHP and sAHP), which plays important roles in controlling neuronal excitability and is mediated by small-conductance calcium-activated potassium (SK) channels, was significantly decreased by H2O2. When extrasynaptic GABA(A) receptors were completely blocked, these decreases of mAHP and sAHP persisted, and H2O2 increased excitability, suggesting that H2O2 per se might have the potential to increase neuronal excitability via decreased SK channel conductance. These findings indicate that activating extrasynaptic GABA(A) receptors or SK channels may attenuate acute neuronal damage caused by H2O2-induced hyperexcitability and therefore represent a novel therapeutic target for the prevention and treatment of H2O2-induced motor neuron disorders. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

File： Ohashi M(Neuroscience,2016).pdf

DOI： 10.1016/j.neuroscience.2016.06.033