CN104623803B - Migraine animal model modeling instrument under a kind of waking state - Google Patents
Migraine animal model modeling instrument under a kind of waking state Download PDFInfo
- Publication number
- CN104623803B CN104623803B CN201510073599.6A CN201510073599A CN104623803B CN 104623803 B CN104623803 B CN 104623803B CN 201510073599 A CN201510073599 A CN 201510073599A CN 104623803 B CN104623803 B CN 104623803B
- Authority
- CN
- China
- Prior art keywords
- copper wire
- copper
- modeling instrument
- screw
- electrode
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Electrotherapy Devices (AREA)
Abstract
The invention discloses migraine animal model modeling instrument under a kind of waking state, method of the modeling instrument using the double screw rivet fixed electrodes of built-in copper core, electrode is fixed on animal skull surface directly, and be connected with stimulator, increase the fastness of electrode and the feasibility of animal model Reusability, operation simplifies earlier above, and the reliability that electrode is contacted with cerebral dura mater is improved.
Description
Technical field
The present invention relates to a kind of instrument, can be used for migraine animal model modeling under waking state.
Background technology
Migraine is a kind of primary headache, and pathogenesis fail to understand that main theory has angiogenic theory, nervi trigeminus blood
Pipe theory and cortex Spreading depression theory.Migrainous animal model mainly includes at present：Angiogenic Mechanism Model, with from
Body and be object of study in the intracranial vessel of body, the research such as main pharmacokineticss with migraine remedy；Cortex expands cloth suppression
Simulation, pays close attention to the electrical activity of cortical neuron, relevant with migraine aura；Gene-correlation model, inquires in terms of hereditism
The migrainous pathogenesis of familial；Trigemino-vascular reflection model, with spinal nucleus of trigeminal nerve neuronal activation as modeling
Successfully indicate, being divided into trigeminal ganglion according to modeling mode stimulates model, nitroglycerin model and cerebral dura mater neurogenic scorching
Disease model.
The arteriovenous system of intracranial is arranged by nervi trigeminus and its branch, therefore referred to as trigemino-vascular reflection.Firmly
Meninges and neighbouring big venous sinuss are the main nociception tissues of intracranial, are arranged by ophthalmic branch of trigeminal nerve, migrainous
Play an important role in morbidity.In migraine attack, due to meningovascular expand and meninges around inflammatory stimulus cerebral dura mater and
Circumvascular Pain receptor, information by trigeminal ganglion is incoming and excited spinal nucleus of trigeminal nerve in neuron.Information
Cortex is passed up to along head pain pathway, headache is produced, while blood is discharged around the circumvascular nervi trigeminus art tip
Pipe source property bioactive peptide such as Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2, calcitonin-gene-related peptide and neuropeptide etc. promote the generation of inflammation around meninges, further emerging
The neuron that puts forth energy in spinal nucleus of trigeminal nerve, the neuron in the spinal nucleus of trigeminal nerve of activation can discharge vasoactive again
Material, forms activation loop, causes aseptic inflammation and the vasodilation of meninges, increases the time lengthening of headache, intensity.Cause
This, what cerebral dura mater neurogenic inflammation model was relatively reasonable simulates the pathophysiological process that trigemino-vascular radiates theory,
And a kind of migraine attack theory that is most approved by academia at present.
Conventional cerebral dura mater neurogenic inflammation model can be divided into chemical stimulation model and electricity irritation model again at present.Electricity
Stimulate superior sagittal sinus and its neighbouring cerebral dura mater activate can trigemino-vascular reflex system, cause trigeminal neuralgia domination region
Blood flow most increase, cause the neuronal activation of the pain such as hypothalamuses, periaqueductal gray correlation core group, simulate inclined head
The incoming process of pain sensation during pain acute attack.But, the modeling method is higher to the requirement that performs the operation, and adopt in the world at present
This kind of modeling model is built under narcotism, does not meet the situation of clinical practice migraine.Have a headache as one
Pain is planted, is the compound of the different polyesthesia of property, intensity and degree, anti-with autonomic nervous system, psychology and emotion
Weave in is answered, is a kind of complicated neural activity of mechanism.Animal is under narcotism, it is difficult to the sick Pathophysiology is described
Overall picture.Based on this kind of consideration, previously there is research once to attempt the headache model that sets up under waking state, capsaicin is noted if any scholar
Enter Conscious Rat cerebellomedullary cistern, observe corresponding headache behavior expression (excessively reason hair, escape and palikinesia, but Fructus Capsici
Element can destroy blood brain barrier, directly activate central nervous system.There is scholar to give Conscious Rat subcutaneous injection nitroglycerin, pass through
The vasodilative effect of nitroglycerin sets up Nerve in Migraine Model under waking state, but due to nitroglycerin cannot specificity be directed to intracranial
Blood vessel works, and systemic effect is larger, and therefore the activation to trigemino-vascular reflex system is limited.
Content of the invention
According to above-mentioned theory and practical experience, combined with copper wire with a kind of dual pathways plastic casing, fixed using dental cement,
Establish migraine animal model under rat waking state.The model belongs to the electricity irritation mould of cerebral dura mater neurogenic inflammation model
Type.But in practice, the Reusability model finds there is problems with：1. it is gently to be attached to powered electrode firmly that electrode is fixed
Fixed with dental cement behind meninges surface, after Reusability, dental cement easily integrally comes off, electrode and hard brain that blind makes
Film contact cannot ensure；2. the dental cement amount that fixed electrode needs is big, is covered in rat head, affects seam skin and skin to heal
Close；3. the connecting line that electrode is connected with stimulator is the outer plastic flexible pipe of copper wire, and Reusability easily snaps off, comes off.
For this purpose, we have designed and produced the double screw rivet electricity irritation modeling instrument of built-in copper core again, the modeling instrument be
Under rat waking state, the method that replaces the past dental cement fixed electrode by the double screw rivet of built-in copper core, directly by electricity
Pole is fixed on animal skull surface, and is connected with stimulator, increase electrode fastness and animal model Reusability feasible
Property, operating and simplify earlier above, the reliability that electrode is contacted with cerebral dura mater is improved.
The model that is set up using this modeling instrument belongs to the electricity irritation model of cerebral dura mater neurogenic inflammation model.In previously fiber crops
Liquor-saturated electricity irritation superior sagittal sinus and nearby dural on the basis of, by the double screw rivetings of the built-in copper core of the tack for limiting front end length
While nail is anchored on the contact surface on Rat calvarial surface, increase electrode and skull, the length that electrode gos deep in skull is limited
Degree, screw thread grappling fix more reliable and more stable, effectively simulation clinically morbidity under migraineur's waking state, fall ill repeatedly
Clinical course, model stability, favorable repeatability efficiently solve that conventional animal model access times are limited, and electrode easily comes off
The problems such as.
Description of the drawings
Fig. 1：The electrode used by embodiment one
Fig. 2：The built-in copper core screw rivet used by embodiment two
Specific embodiment
Migraine animal model is the migrainous important tool of research, can carry out the research that cannot be carried out in human body, take off
Show that migraine occurs and the important mechanisms in maintenance process, but on condition that animal model will effectively simulate the shape of disease as far as possible
State.The following describe set up two kind animal model, and the electricity irritation modeling instrument for adopting.
Embodiment one：
After laboratory animal (the application adopts rat) is with 10% chloral hydrate (0.4ml/100g) intraperitoneal injection anesthesia, cut
Turn around positive middle part hair, is fixed on stereotaxic instrument.Sterilization is simultaneously successively cut skin, fascia and periosteum to expose skull.?
Before choosing cranium center line coronal suture intersection point on skull, 4mm is prezone, and behind cross point, 6mm is rear boundary, bores brill with table dental and opens two
The circular hole of diameter about 1mm, is reduced the temperature in brill and hole, prevents dura mater of burning using 4 DEG C of normal saline during drilling；Swear in exposure
The monopolar electrode connected with line line interface is positioned over after shape hole cerebral dura mater in the stimulation hole being drilled, gentle contact dura mater, but
Note not scratching dura mater and superior sagittal sinus；It is about around electrode paving basal diameter with gear division powder after skull bone face is completely dried
The cone of 2mm, is first fixed with 502 glue, adds artificial tooth base resin to fix with gear division powder again whole after gear division powder is completely dried
Individual electrode sutures scalp skin in bone face after which is completely dried, and only stays outside line line structure and skin；At once with injection penicillium sp
Plain sodium is dissolved in normal saline lumbar injection (40,000 IU/100g) prevention infection, and all of above operation is aseptically carried out.
Hereafter every rat single cage is raised, ad lib is intake, and is dissolved in physiology salt with benzylpenicillin sodium for injection daily within postoperative three days
Line line interface is connected with the line line interface of electrostimulator, carries out electricity irritation by water lumbar injection (40,000 IU/100g) on the 4th day.Attached
Fig. 1 is the electrode adopted by the present embodiment.
But, the animal model set up by above-described embodiment one finds there is problems with：1. it is by the electricity that is powered that electrode is fixed
Fixed with dental cement after being extremely gently attached to dural surface, after Reusability, dental cement easily integrally comes off, blind makes
Electrode contact with cerebral dura mater and cannot ensure；2. the dental cement amount that fixed electrode needs is big, is covered in rat head, affects
Seam skin and skin healing；3. the connecting line that electrode is connected with stimulator is the outer plastic flexible pipe of copper wire, and Reusability is easily snapped off, taken off
Fall.Therefore, on the basis of embodiment one, the animal model of embodiment two further investigated, by the double spiral shells of built-in copper core
Silk rivet replace dental cement fixed electrode method, increase electrode firm qualitative and animal model Reusability feasible
Property, operating and simplify earlier above, the reliability that electrode is contacted with cerebral dura mater is improved.
Embodiment two
After laboratory animal (the application adopts rat) is with 10% chloral hydrate (0.4ml/100g) intraperitoneal injection anesthesia, cut
Turn around positive middle part hair, is fixed on stereotaxic instrument.Sterilization is simultaneously successively cut skin, fascia and periosteum to expose skull.?
Before choosing cranium center line coronal suture intersection point on skull, 4mm is prezone, and behind cross point, 6mm is rear boundary, exposes superior sagittal sinus cerebral dura mater.Will
Insulating outer layer is removed in the copper wire sand papering that built-in copper core screw rivet afterbody used in this application exposes, and rotation is fixed on
Skull surface, rotates depth about 1-1.5mm so that dural surface pressed close to by copper wire, as screw rivet afterbody is plane, will not
Cerebral dura mater is damaged, so as to reach the effect for stimulating meninges.Two screw rivets are all fixed on skull surface using said method
Afterwards, with skin suture after around 75% alcohol disinfecting otch and skin, rat is placed in former environment and is rested, period gives antibiosis
Plain feeding, keeps quite in environment, and room temperature is at 25 DEG C or so.After about 4-5 days, the skin healing of rat, but screw rivet
The copper wire of over top will be exposed to skin surface, give electricity irritation by the copper wire to experimental group rat.
When electricity irritation is carried out, two conductive clamps of stimulator are first clipped in be exposed to rat skin surface two respectively
The insulating outer layer on copper wire with conductive clamp contact area before folder, is removed () on copper wire, separator is connected with stimulator, application of stimulus
Device and separator row electricity irritation.The stimulator (SEN-7103) produced using Nihon Kohden Corporation and separator (SS-
Square wave current stimulation 102J) is given, and frequency is 20HZ (Duration=50 μ s, Interval=250 μ s).
After giving electricity irritation, rat model occurs excessively managing hair, gets rid of head and corelation behaviour performance of having a headache of turning one's head three kinds, thorn
Swashing the dural blood flow in local increases, and immunohistochemical staining prompting spinal nucleus of trigeminal nerve dorsal horn shallow-layer neuron swashs
Living, trident god of the migraine treatment medicine triptan class to the typical behaviour, increased cerebral dura mater blood flow and activation of pain
There is inhibitory action through nucleus of spinal tract dorsal horn shallow-layer neuron, meet (the nervi trigeminus ridge of standard in the industry of migraine animal model preparation
Beam core dorsal horn shallow-layer neuronal activation) and clinical patients performance (vasodilation, vascular pulsation sample pain), the reaction to medicine
(triptan treatment is most effective).
Accompanying drawing 2 is built-in copper core screw rivet used in this application, and the screw rivet is a plus screw, in screw
The cross central bore at top, the Kong Zhiding are passed down through whole screw, and then passing through the copper wire for covering insulating outer layer should
Hole, so that form built-in copper core screw rivet used in this application.
In addition, the electricity irritation modeling instrument of the application also has a controller, the frequency stimulated for control electric current and strong
Degree, on the one hand, experimenter can manually adjust the frequency and intensity of galvanism, and on the other hand, controller can also be monitored
The physiological status data of laboratory animal, according to the physiological status data, and the regulation rule for pre-setting, automatically adjust electricity
The frequency and intensity that stream stimulates.
The animal model that is set up using the electricity irritation modeling instrument of embodiment two belongs to cerebral dura mater neurogenic inflammation model
Electricity irritation model.The past anesthesia electricity irritation superior sagittal sinus and near dural on the basis of, by what front end length was limited
While the double screw rivets of the built-in copper core of tack are anchored on the contact surface on Rat calvarial surface, increase electrode and skull, limit
The length that electrode gos deep in skull, with fixed more reliable and more stable, effectively clinically migraineur regains consciousness for simulation for screw thread grappling
Morbidity, the clinical course that falls ill repeatedly, model stability, favorable repeatability under state, efficiently solve conventional animal model and use
Number of times is limited, the problems such as electrode easily comes off.
The model actually used during, it has been found that due to electrode generate heat and electrode material itself stimulation
The simulation effect of animal model will be affected, therefore in order to obtain more stable and effective simulation effect, needs further to carry out
Improve.
First, in order to reduce heating to dural impact, the thickness of copper wire itself should be heterogeneous.Preferably,
The dural one end of copper wire contact is most thick, and the other end is most thin, and from most butt end to most taper end, the fineness of copper wire assumes linear change
Change.
Further, we are had found in the simulation process of animal model, and brain affects to be very quick for extraneous temperature
Sense, temperature high a little and lower all can be to simulating effect generation large effect, therefore in order to obtain optimum efficiency, copper wire
Linear variation coefficient should select with caution.Assume that copper wire certain point is X apart from the length of its most butt end, horizontal stroke of the copper wire in the point
Sectional area is A, and the cross-sectional area of copper wire most butt end is S, and whole copper wire total length L, whole copper wire meet following formula A=(L-nX/
M) S/L, wherein n and m are natural numbers, and n ＜ m, n/m are the linear variation coefficients of copper wire.We have chosen 10 rats, in n and m
In the case of different values, these rats are done with controlled trial, observed the stability that rat simulates effect, by nearly thousand times
Controlled trial, it has been found that work as n=3, during m=7, the simulation effect of rat is highly stable, the migraine performance base of 10 rats
Originally reach unanimity, meet the standard in the industry (spinal nucleus of trigeminal nerve dorsal horn shallow-layer neuronal activation) of migraine animal model preparation
With the performance (vasodilation, vascular pulsation sample pain) of clinical patients, and the reaction to medicine.That is, in preferably side
Under case, copper wire should meet formula A=(L-3X/7) S/L.
In order to prevent electrode material to dural stimulus effects, the material of screw rivet should use copper alloy.Fine copper
Intensity is not high, it is difficult to meets the requirement of structural member, it is necessary to carries out the alloying of copper.In general, Cr, Fe, P, Si, Zr, Ti etc.
Element is easily caused the conductivity of copper alloy and declines substantially, is not suitable for the present invention and uses as electrode material.Alloying element Ag
Reduction impact on copper alloy conductivity is little, is noble metal electrode material most cheap at present, and its too high levels can cause into
This rising, the present invention select to introduce 2% silver in copper alloy.The machinery using raising copper alloy electrode material of Sn elements is strong
Degree and hardness, corrosion resistance are preferable.The present invention selects used in copper alloy 10% Sn.Finally, Ni is also use of the present invention
One of main alloy element, Ni elements can significantly improve intensity, corrosion resistance, conduction and the heat conductivity of copper.In addition, being worth mentioning
, in the copper alloy of the present invention, do not contain any lead composition, safety and environmental protection, environmental sound.The present invention copper alloy purity compared with
Height, without impurity such as S, P, Si.
For the above reasons, screw rivet preferred component of the present invention be copper, stannum, the alloy of four kinds of elements of silver and nickel, copper conjunction
In gold, the element ratio of alloying element stannum, silver and nickel is up to 20%.The copper alloy according to percentage by weight is：80% copper,
10% stannum, 2% silver, 8% nickel.And do not contain S, P, Si, Pb, Cr, Fe, Si, Zr, Ti impurity.
Claims (8)
1. migraine animal model modeling instrument under a kind of waking state, the modeling instrument include two built-in copper core screw rivets, thorns
Sharp device and separator；Wherein
The screw rivet is plus screw, and in the cross central bore of the screw head, the Kong Zhiding is passed down through whole spiral shell
Nail, then will cover the copper wire of insulating outer layer through the hole, forms built-in copper core screw rivet, and screw rivet afterbody exposes
Insulating outer layer is removed in copper wire sand papering so that the copper wire that afterbody exposes can be contacted with the cerebral dura mater of laboratory animal；
There are the stimulator two conductive clamps, each described conductive clamp to be clipped in the copper wire exposed at the top of a screw rivet respectively
On, the insulating outer layer on copper wire with conductive clamp contact area is removed before folder；The separator is connected with stimulator, applies the thorn
Sharp device and separator give square wave current stimulation；
The thickness of wherein copper wire itself is heterogeneous, and the dural one end of copper wire contact is most thick, and the other end is most thin, from most butt end
Most taper end is arrived, the fineness of copper wire assumes linear change, it is assumed that copper wire certain point is X apart from the length of its most butt end, copper wire
It is A in the cross-sectional area of the point, the cross-sectional area of copper wire most butt end is S, and whole copper wire total length is L, then the copper wire meets public
Formula A=(L-3X/7) S/L.
2. modeling instrument as claimed in claim 1, the wherein frequency of galvanism are 20HZ.
3. modeling instrument as claimed in claim 1, wherein the modeling instrument also have a controller, stimulate for control electric current
Frequency and intensity.
4. modeling instrument as claimed in claim 3, wherein described controller can with the physiological status data of monitoring experiment animal,
According to the physiological status data, and the regulation rule for pre-setting, automatically adjust the frequency and intensity of galvanism.
5. the modeling instrument as described in claim 1-4 any one, the material of wherein described screw rivet is copper alloy.
6. modeling instrument as claimed in claim 5, the composition of wherein described screw rivet include copper, stannum, silver and nickel.
7. modeling instrument as claimed in claim 6, wherein described copper alloy according to percentage by weight is：80% copper, 10%
Stannum, 2% silver, 8% nickel.
8. modeling instrument as claimed in claim 7, wherein copper alloy do not contain S, P, Si, Pb, Cr, Fe, Si, Zr, Ti impurity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510073599.6A CN104623803B (en) | 2015-02-12 | 2015-02-12 | Migraine animal model modeling instrument under a kind of waking state |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510073599.6A CN104623803B (en) | 2015-02-12 | 2015-02-12 | Migraine animal model modeling instrument under a kind of waking state |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104623803A CN104623803A (en) | 2015-05-20 |
| CN104623803B true CN104623803B (en) | 2017-03-15 |
Family
ID=53203337
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510073599.6A Expired - Fee Related CN104623803B (en) | 2015-02-12 | 2015-02-12 | Migraine animal model modeling instrument under a kind of waking state |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104623803B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107198826A (en) * | 2017-05-16 | 2017-09-26 | 于生元 | Rat sinus sagittalis superior electro photoluminescence model and method for building up |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104324446A (en) * | 2014-11-28 | 2015-02-04 | 王麟鹏 | Rat cerebral electrical stimulation device and electrode fixing bases thereof |
-
2015
- 2015-02-12 CN CN201510073599.6A patent/CN104623803B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN104623803A (en) | 2015-05-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kasten et al. | Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury | |
| Normann et al. | Clinical applications of penetrating neural interfaces and Utah Electrode Array technologies | |
| JP5108787B2 (en) | A method for routing current to body tissue through embedded passive conductors | |
| US10426967B2 (en) | Apparatus and method for electromagnetic treatment of neurological injury or condition caused by a stroke | |
| Mitchell et al. | Effects of chronic high-rate electrical stimulation on the cochlea and eighth nerve in the deafened guinea pig | |
| US9415233B2 (en) | Apparatus and method for electromagnetic treatment of neurological pain | |
| CA2776696C (en) | Extracranial implantable devices, systems and methods for the treatment of neurological disorders | |
| US20140221726A1 (en) | Apparatus and method for electromagnetic treatment of neurodegenerative conditions | |
| CN108882885A (en) | The control of vagal stimulation | |
| US20050177192A1 (en) | Neurostimulation for affecting sleep disorders | |
| JP2001507951A (en) | Drug-device combination for controlling muscle contractility | |
| US20070049988A1 (en) | Optimal electrode contact polarity configurations for implantable stimulation systems | |
| Piallat et al. | Monophasic but not biphasic pulses induce brain tissue damage during monopolar high-frequency deep brain stimulation | |
| JP2008512197A5 (en) | ||
| JP2012506262A (en) | System and method for facial nerve stimulation | |
| KR20140037803A (en) | Device, system and methods for the treatment of medical disorders | |
| EA014361B1 (en) | Electrode array | |
| Sun et al. | Corticofugal control of central auditory sensitivity in the big brown bat, Eptesicus fuscus | |
| US9358393B1 (en) | Stimulation methods and systems for treating an auditory dysfunction | |
| Agnew et al. | MK-801 protects against neuronal injury induced by electrical stimulation | |
| CN102793592B (en) | Optic nerve implantable neural interface device with fan-shaped attaching function | |
| CN104623803B (en) | Migraine animal model modeling instrument under a kind of waking state | |
| Villalobos et al. | Cortical activation following chronic passive implantation of a wide-field suprachoroidal retinal prosthesis | |
| Macia et al. | Neuronal activity in the monkey motor thalamus during bicuculline‐induced dystonia | |
| WO2011109080A2 (en) | A device for intranasal and extranasal neuromodulation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170315 Termination date: 20180212 |