Name: microelectrode guided implantation of electrodes into the subthalamic nucleus of rats for long-term deep brain stimulation
Uploaded: 2015-10-02T15:00:00
Description: Watch this Scientific Journal Video about Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation at JoVE.com

We wish to thank Mr Wabbel for preparing the wires and Mr Tietsch for constructing the plugs and cages according to our plans. This work was supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 688). Felix Fluri holds a fellowship of the Interdisziplin&#228;re Zentrum f&#252;r Klinische Forschung (IZKF), University Clinics W&#252;rzburg, Germany.

Animal experiments were approved by the University of W&#252;rzburg and the legal state authorities (Lower Franconia, approval number: 54-2531.01-102/13) and performed according to the recommendations for research in experimental stroke studies17 and the current Animal Research: Reporting of In Vivo Experiments Guidelines (http://www.nc3rs.org.uk/arrive-guidelines).
1. Anesthesia
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	<li>Check the anesthetic system to ensure adequate amounts of supply gas (oxygen) and i...

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This study presents a step-by-step set of instructions for implanting a monopolar chronic electrode into the STN of rats. Although tungsten electrodes with low impedance are often used for DBS18,19, a monopolar electrode made of platinum/iridium (Pt/Ir) was employed that had an impedance of about 1 M&#937;. Pt/Ir electrodes are also used in patients with Parkinson&#8217;s disease because of their favorable properties: they demonstrate minimal erosion20 and do not produce relevant tissue damage2...

Deep brain stimulation (DBS) is a treatment based on the delivery of electrical impulses via implanted electrodes to specific cerebral structures, such as the internal globus pallidus1, the subthalamic nucleus (STN)2&#8211;4 or the ventral intermediate thalamus5. In the last two decades, this treatment has been established as a powerful therapeutic tool for Parkinson&#39;s disease1&#8211;4, dystonia6 and tremor7, and is also used to modulate chronic pain7, psychiatric disorders (i.e., obsessive&#8211;compulsive disorder8, major depression9) or intractable epilepsy10,11. Furthermore, DBS might, in the future, become a treatment option for refractory arterial hypertension12 or orthostatic hypotension13.
The physiological mechanisms underlying the effects of DBS remain poorly understood. Studies in anesthetized rodents have provided insight into neural responses to high-frequency stimulation that mimic clinically applied DBS14. However, these studies not only lack behavioral corroboration of the DBS effect but also result in considerable variability depending on the stimulation parameters applied14.
To investigate more concisely the behavioral effects and underlying mechanisms of DBS in conscious rodents, a stimulation set-up is needed that fulfills specific requirements. DBS is mostly used as a long-term therapy (e.g., Parkinson&#39;s disease, chronic pain). Thus, the stimulation set-up in rodents should be designed so that the unit consists of an electrode with a plug, as well as a wire from the plug to an external stimulator; and this unit should be lightweight but unbreakable when fixed onto the skull. Furthermore, freedom of movement is indispensable for rats during stimulation over a prolonged period. The target structures of DBS are small; for example, the STN in rats has a length of 1.2 mm and a volume of 0.8 mm3,15. Therefore, electrodes must be designed such that the nucleus is not lesioned during insertion and targeting needs to be precise. As most DBS studies conducted in rodents have used landmark based stereotactic insertion of the electrode to the target structure, the error rate can be relatively high, even when using the coordinates according to Paxinos and Watson16. This results in a larger number of animals needed to reach a statistically meaningful result.
In the present study an electrode implantation technique is introduced, that targets the STN with high accuracy by using a microrecording system while advancing the electrode. In addition, a stimulation system is presented that does not only allow a high degree of mobility for the stimulated animal but also guarantees continuous stimulation via secure fixation of the stimulation wire (which is protected by a stainless-steel spring) onto the head of the rat.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Pt/Ir electrode</td>
			<td>FHC Inc.</td>
			<td>UE</td>
			<td>Custom-made: Specification: UEPSEGSECN1M</td>
		</tr>
		<tr>
			<td>Plugs</td>
			<td>GT Labortechnik (Arnstein/Germany)</td>
			<td></td>
			<td>Custom-made</td>
		</tr>
		<tr>
			<td>Pin header</td>
			<td>DISTRELEC</td>
			<td>143-95-324</td>
			<td>single-row, 90&#176; 1x3 datamate, Type M80-8420342</td>
		</tr>
		<tr>
			<td>Socket</td>
			<td>DISTRELEC</td>
			<td>143-95-621</td>
			<td>single-row,straight 2 mm pole no.1x3 datamate, Type M80-8400342</td>
		</tr>
		<tr>
			<td>Stainless steel spring</td>
			<td>Plastics ONE</td>
			<td>SS0102</td>
			<td>Part-#: .120 X .156 Spring ID (mm): 3.0&#160; Spring OD (mm): 4.0</td>
		</tr>
		<tr>
			<td>Dental cement/Paladur</td>
			<td>Heraeus Kulzer</td>
			<td>64707938</td>
			<td>Liquid, 500 ml</td>
		</tr>
		<tr>
			<td>Dental cement/Paladur</td>
			<td>Heraeus Kulzer</td>
			<td>64707954</td>
			<td>Powder, rose, 500g</td>
		</tr>
		<tr>
			<td>Head screw</td>
			<td>Hummer &#38; Reiss</td>
			<td>V2ADIN84 M1.6x3</td>
			<td></td>
		</tr>
		<tr>
			<td>Jodosept PVP</td>
			<td>Vetoquinol</td>
			<td></td>
			<td>435678/E04</td>
		</tr>
		<tr>
			<td>Mepivacain 1%</td>
			<td>AstraZeneca</td>
			<td></td>
			<td>PZN03338515</td>
		</tr>
		<tr>
			<td>Epinephrine</td>
			<td>Sanofi-Aventis</td>
			<td></td>
			<td>PZN00176118</td>
		</tr>
		<tr>
			<td>Tramadolhydrochloride</td>
			<td>Rotexmedica</td>
			<td></td>
			<td>38449.00.00</td>
		</tr>
	</tbody>
</table>

microelectrode guided implantation of electrodes into the subthalamic nucleus of rats for long-term deep brain stimulation

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, dystonia or tremor. DBS is based on the delivery of electrical stimuli to specific deep anatomic structures of the central nervous system. However, the mechanisms underlying the effect of DBS remain enigmatic. This has led to an interest in investigating the impact of DBS in animal models, especially in rats. As DBS is a long-term therapy, research should be focused on molecular-genetic changes of neural circuits that occur several weeks after DBS. Long-term DBS in rats is challenging because the rats move around in their cage, which causes problems in keeping in place the wire leading from the head of the animal to the stimulator. Furthermore, target structures for stimulation in the rat brain are small and therefore electrodes cannot easily be placed at the required position. Thus, a set-up for long-lasting stimulation of rats using platinum/iridium electrodes with an impedance of about 1 M&#937; was developed for this study. An electrode with these specifications allows for not only adequate stimulation but also recording of deep brain structures to identify the target area for DBS. In our set-up, an electrode with a plug for the wire was embedded in dental cement with four anchoring screws secured onto the skull. The wire from the plug to the stimulator was protected by a stainless-steel spring. A swivel was connected to the circuit to prevent the wire from becoming tangled. Overall, this stimulation set-up offers a high degree of free mobility for the rat and enables the head plug, as well as the wire connection between the plug and the stimulator, to retain long-lasting strength.

Implanting an electrode into the STN of a rat using a recording system &#8211; as presented here &#8211; is an effective and accurate procedure for DBS that takes approximately 1 hr per animal. This model is a fairly minor procedure: out of 10 rats subjected to surgery, all survived the intervention. Twenty-four hr after intervention, the state of each rat was monitored and no animal achieved more than 1 of 3 points according to the severity code. During the period of continuous stimulation (14 days, 24 hr a day), no wir...

Watch this Scientific Journal Video about Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation at JoVE.com

Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation

A method for implanting electrodes into the subthalamic nucleus (STN) of rats is described. Better localization of the STN was achieved by using a microrecording system. Furthermore, a stimulation set-up is presented that is characterized by long-lasting connections between the head of the animal and the stimulator.

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, ...

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