Name: an ultrasonic tool for nerve conduction block in diabetic rat models
Uploaded: 2017-10-20T13:00:00
Description: Watch this Scientific Journal Video about An Ultrasonic Tool for Nerve Conduction Block in Diabetic Rat Models at JoVE.com

The study was supported by the Ministry of Science and Technology (Project MOST 105-2221-E-400 -001) and the National Health Research Institutes (Project BN-105-PP-10), Taiwan.

The Institutional Animal Care and Use Committee of the National Health Research Institutes in Taiwan approved all animal protocols.
1. Induction of Diabetic Model in Male Adult Sprague - Dawley (SD) Rats
<ol>
	<li>Remove rat food pellets from the cage to fast male SD rats (300 - 350 g) for 6 h prior to STZ induction.</li>
	<li>Prepare sodium citrate buffer (0.1 M, pH 4.5).
	<ol>
		<li>Dissolve 1.05 g citric acid monohydrate (C6H8O7 &#183; H2O; mol....

<ol>
	<li>Abuaisha, B. B., Costanzi, J. B., Boulton, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acupuncture+for+the+treatment+of+chronic+painful+peripheral+diabetic+neuropathy:+A+long-term+study.">Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: A long-term study.</a> Diabetes Res Clin Pract. 39 (2), 115-121 (1998).</li><li>Hamza, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Percutaneous+electrical+nerve+stimulation:+A+novel+analgesic+therapy+for+diabetic+neuropathic+pain.">Percutaneous electrical nerve stimulation: A novel analgesic therapy for diabetic neuropathic pain.</a> Diabetes Care. 23 (3), 365-370 (2000).</li><li>Ballantine, H. T., Bell, E., Manlapaz, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Progress+and+problems+in+the+neurologic+applications+of+focused+ultrasound.">Progress and problems in the neurologic applications of focused ultrasound.</a> J Neurosurg. 17, 858-876 (1960).</li><li>Foley, J. L., Little, J. W., Vaezy, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Image-guided+high-intensity+focused+ultrasound+for+conduction+block+of+peripheral+nerves.">Image-guided high-intensity focused ultrasound for conduction block of peripheral nerves.</a> Ann Biomed Eng. 35 (1), 109-119 (2007).</li><li>Lee, Y. F., Lin, C. C., Cheng, J. S., Chen, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-intensity+focused+ultrasound+attenuates+neural+responses+of+sciatic+nerves+isolated+from+normal+or+neuropathic+rats.">High-intensity focused ultrasound attenuates neural responses of sciatic nerves isolated from normal or neuropathic rats.</a> Ultrasound Med Biol. 41 (1), 132-142 (2015).</li><li>Young, R. R., Henneman, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reversible+block+of+nerve+conduction+by+ultrasound.">Reversible block of nerve conduction by ultrasound.</a> Arch Neurol. 4, 83-89 (1961).</li><li>Lele, P. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+focused+ultrasonic+radiation+on+peripheral+nerve,+with+observations+on+local+heating.">Effects of focused ultrasonic radiation on peripheral nerve, with observations on local heating.</a> Exp Neurol. 8 (1), 47-83 (1963).</li><li>Hong, C. Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reversible+nerve+conduction+block+in+patients+with+poly-+neuropathy+after+ultrasound+thermotherapy+at+therapeutic+dosage.">Reversible nerve conduction block in patients with poly- neuropathy after ultrasound thermotherapy at therapeutic dosage.</a> Arch Phys Med Rehabil. 72 (2), 132-137 (1991).</li><li>Okada, A., Morita, Y., Fukunishi, H., Takeichi, K., Murakami, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-invasive+magnetic+resonance-guided+focused+ultrasound+treatment+of+uterine+fibroids+in+a+large+Japanese+population:+impact+of+the+learning+curve+on+patient+outcome.">Non-invasive magnetic resonance-guided focused ultrasound treatment of uterine fibroids in a large Japanese population: impact of the learning curve on patient outcome.</a> Ultrasound Obstet Gynecol. 34 (5), 579-583 (2009).</li><li>Huisman, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=International+consensus+on+use+of+focused+ultrasound+for+painful+bone+metastases:+current+status+and+future+directions.">International consensus on use of focused ultrasound for painful bone metastases: current status and future directions.</a> Int J Hyperthermia. 31 (3), 251-259 (2015).</li><li>Dickinson, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Medium-term+Outcomes+after+Whole-gland+High-intensity+Focused+Ultrasound+for+the+Treatment+of+Nonmetastatic+Prostate+Cancer+from+a+Multicentre+Registry+Cohort.">Medium-term Outcomes after Whole-gland High-intensity Focused Ultrasound for the Treatment of Nonmetastatic Prostate Cancer from a Multicentre Registry Cohort.</a> Eur Urol. 70 (4), 668-674 (2016).</li><li>Foley, J. L., Little, J. W., Vaezy, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+high-intensity+focused+ultrasound+on+nerve+conduction.">Effects of high-intensity focused ultrasound on nerve conduction.</a> Muscle Nerve. 37 (2), 241-250 (2008).</li><li>Lee, Y. F., Lin, C. C., Cheng, J. S., Chen, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nerve+conduction+block+in+diabetic+rats+using+high-intensity+focused+ultrasound+for+analgesic+applications.">Nerve conduction block in diabetic rats using high-intensity focused ultrasound for analgesic applications.</a> Br J Anaesth. 114 (5), 840-846 (2015).</li><li>Donoff, R. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nerve+regeneration:+basic+and+applied+aspects.">Nerve regeneration: basic and applied aspects.</a> Crit Rev Oral Biol Med. 6 (1), 18-24 (1995).</li><li>Fawcett, J. W., Keynes, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peripheral+nerve+regeneration.">Peripheral nerve regeneration.</a> Annu Rev Neurosci. 13, 43-60 (1990).</li><li>Nightingale, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neuropathic+pain+market.">The neuropathic pain market.</a> Nat Rev Drug Discov. 11 (2), 101-102 (2012).</li><li>Lipton, R. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Single-pulse+transcranial+magnetic+stimulation+for+acute+treatment+of+migraine+with+aura:+a+randomised,+double-blind,+parallel-group,+sham-controlled+trial.">Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomised, double-blind, parallel-group, sham-controlled trial.</a> Lancet Neurol. 9 (4), 373-380 (2010).</li></ol>

Partial and temporary suppression of action potentials of the neuropathic nerves from diabetic rats in vivo and instant occurrence of the blocking effect after HIFU treatment both were observed. The 28-day follow-up study on CMAPs demonstrated that a safe blockade of the nerve conduction could be carried out at an appropriate HIFU exposure. As a result, the above protocol of the HIFU treatment can provide an alternative solution for the reversible conduction block of sciatic nerves in diabetic rats.
<p class...

Oral medications, acupuncture1, and electrical nerve stimulation2 have been used for the treatment of painful diabetic polyneuropathy. However, the side effects of the oral medications, invasive operation of acupuncture, and electrical nerve stimulation hamper the therapeutic efficacy and patient&#39;s adherence. Ultrasound block of peripheral nerves in animal models has been investigated for decades3,4,5. The conduction of in vitro sciatic nerves of the large green frog was inhibited reversibly after the treatment of 10 - 20 pulses of ultrasound exposure for 0.4 - 1.0 s6. One factor to block nerve conduction is the temperature rise induced by ultrasound7. For patients with polyneuropathy, the suppression of compound muscle action potentials (CMAPs) was performed in the peroneal nerve exposed to low-intensity ultrasound for 2 min8. The full recovery time was within 5 min.
Recently, the Food and Drug Administration of the United States approved HIFU as a non-invasive treatment for uterine fibroid tumors9, pain palliations of bone metastases10, and prostate cancer11. An HIFU transducer emits acoustic beams outside the body, and the beams transmit in various tissue mediums and converge on the target tumor at the focus. The focal zone is immediately formed to generate localized effects on target tumors without damaging the surrounding tissues. HIFU has also been applied to inhibit nerve conduction or cause nerve denervation in in vivo experiments of normal Sprague-Dawley (SD) rats12. In addition, the short-term and long-term effects of HIFU on neuropathic nerves have been investigated13. Previous outcomes demonstrated that the reversible or permanent block of sensory nerve conduction could be achieved by HIFU with appropriate parameters. Besides analgesic applications, HIFU might be used as a tool to investigate the relative contribution of peripheral and central components to nerve conduction blockade for basic research of neurology and development of pain medication. Therefore, a HIFU blocking technology platform specific for peripheral nerves in animal models is needed. The purpose of this article is to demonstrate the procedures for partially or completely blocking the action potentials of peripheral nerves in diabetic neuropathic rats by HIFU. Diabetic rat models and evaluation of peripheral neuropathic symptoms were established. An HIFU platform and experimental processes specific for treating rat sciatic nerves are presented.

<table border="0" cellpadding="0" cellspacing="0" width="965">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:365px;">streptozotocin</td>
			<td style="width:315px;">Sigma</td>
			<td align="right" style="width:119px;">85882</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">citric acid monohydrate&#160;</td>
			<td style="width:315px;">Sigma</td>
			<td style="width:119px;">C1909</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">trisodium citrate dihydrate</td>
			<td style="width:315px;">Sigma</td>
			<td style="width:119px;">W302600</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">glucose meters</td>
			<td>Roche Accu-Check Active</td>
			<td>GC</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">electronic von Frey device</td>
			<td>IITC Life Science</td>
			<td>2390</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">hot plate</td>
			<td>IITC Life Science</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Biopac MP36 acquisition system</td>
			<td>Biopac Systems, Inc.</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">HIFU transducer</td>
			<td>Sonic Concepts</td>
			<td>H108</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">function generator</td>
			<td>Agilent</td>
			<td>33250A</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">power amplifier</td>
			<td>Electronics &#38; Innovation</td>
			<td>1040L</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:365px;">Rats&#160;</td>
			<td style="width:315px;">Biolasco taiwan</td>
			<td style="width:119px;">Sprague-Dawley</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:365px;">Puralube vet ointment</td>
			<td style="width:315px;">Dechra</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">isoflurane vaporizer</td>
			<td style="width:315px;">Parkland Scientific</td>
			<td style="width:119px;">V3000PS</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:365px;">Isoflurance</td>
			<td style="width:315px;">Attane</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:365px;">Restraint bag (Decapicones)</td>
			<td style="width:315px;">Braintree Scientific</td>
			<td style="width:119px;">DC 200</td>
			<td></td>
		</tr>
	</tbody>
</table>

an ultrasonic tool for nerve conduction block in diabetic rat models

Nerve conduction block with a high intensity-focused ultrasound (HIFU) transducer has been performed in normal and diabetic animal models recently. HIFU can reversibly block the conduction of peripheral nerves without damaging the nerves while using an appropriate ultrasonic parameter. Temporary and partial block of the action potentials of nerves shows that HIFU has the potential to be a useful clinical treatment for pain relief. This work demonstrates the procedures for suppressing the action potentials of neuropathic nerves in diabetic rats in vivo using an HIFU transducer. The first step is to generate adult male diabetic neuropathic rats by streptozotocin (STZ) injection. The second step is to evaluate the peripheral diabetic neuropathy in STZ-induced diabetic rats by an electronic von Frey probe and a hot plate. The final step is to record in vivo extracellular action potentials of the nerve exposed to HIFU sonication. The method showed here may benefit the study of ultrasound analgesic applications.

The in vivo study demonstrated that, with an HIFU dose of 3 s sonication at an intensity of 2,810 W/cm2, the CMAPs were suppressed by 20% of baseline, but they were completely recovered after 30 min (Figure 2A, diamonds) and were almost constant in the period of 28 days (Figure 2B, diamonds). For the 5 s HIFU exposure at the same intensity, the CMAPs decreased to 65.4% (9.5%) of baseline at 4 min and recovered...

Watch this Scientific Journal Video about An Ultrasonic Tool for Nerve Conduction Block in Diabetic Rat Models at JoVE.com

An Ultrasonic Tool for Nerve Conduction Block in Diabetic Rat Models

This work presents the methodology of applying high intensity-focused ultrasound to block the action potentials of diabetic neuropathic nerves.

Nerve conduction block with a high intensity-focused ultrasound (HIFU) transducer has been performed in normal and diabetic animal models recently. HIFU ...

Research

JoVE Journal

Bioengineering

Procedure for Decellularization of Rat Livers in an Oscillating-pressure Perfusion Device

Decellularization and recellularization of parenchymal organs may enable the generation of functional organs in vitro, and several protocols for rodent ...

Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice

Islet transplantation has been clinically proven to be effective at treating type 1 diabetes. However, the current intrahepatic transplantation strategy ...

An In Vitro Organ Culture Model of the Murine Intervertebral Disc

An In Vitro Organ Culture Model of the Murine Intervertebral Disc

Intervertebral disc (IVD) degeneration is a significant contributor to low back pain. The IVD is a fibrocartilaginous joint that serves to transmit and ...

A Performance-testing Platform for a Conduction Micropump with an FR-4 Copper-clad Electrode Plate

Here, a conduction micropump with symmetric planar electrode pairs prepared on flame-retardant glass-reinforced epoxy (FR-4) copper-clad laminate (CCL) is ...

An Efficient and Reproducible Protocol for Distraction Osteogenesis in a Rat Model Leading to a Functional Regenerated Femur

This protocol describes the use of a newly developed external fixator for distraction osteogenesis in a rat femoral model. Distraction osteogenesis (DO) ...

An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing

Sequencing technologies have undergone a paradigm shift from bulk to single-cell resolution in response to an evolving understanding of the role of ...

A Novel Surgical Technique As a Foundation for In Vivo Partial Liver Engineering in Rat

A Novel Surgical Technique As a Foundation for In Vivo Partial Liver Engineering in Rat

Organ engineering is a novel strategy to generate liver organ substitutes that can potentially be used in transplantation. Recently, in vivo liver ...

A Multilayer Microfluidic Platform for the Conduction of Prolonged Cell-Free Gene Expression

The limitations of cell-based synthetic biology are becoming increasingly apparent as researchers aim to develop larger and more complex synthetic genetic ...

Fabrication of the Composite Regenerative Peripheral Nerve Interface (C-RPNI) in the Adult Rat

Fabrication of the Composite Regenerative Peripheral Nerve Interface C-RPNI in the Adult Rat

Recent advances in neuroprosthetics have enabled those living with extremity loss to reproduce many functions native to the absent extremity, and this is ...

Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure

Due to the rapid development and implementation of a diverse array of engineered nanomaterials (ENM), exposure to ENM is inevitable and the development of ...