CN110025394A - A kind of non-human primates cerebral apoplexy Model R & D method - Google Patents
A kind of non-human primates cerebral apoplexy Model R & D method Download PDFInfo
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- CN110025394A CN110025394A CN201810032244.6A CN201810032244A CN110025394A CN 110025394 A CN110025394 A CN 110025394A CN 201810032244 A CN201810032244 A CN 201810032244A CN 110025394 A CN110025394 A CN 110025394A
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- A61D1/00—Surgical instruments for veterinary use
Abstract
The present invention relates to clinical science studying technological domains, and disclose preparing experiment material: the compatible ventilator of syringe needle, 5F arterial cannula, 4F angiography catheter, 0.25mm angiography micro-wire, digital subtraction angiography (DSA) system, MRI system, nuclear magnetic resonance of 18gage, the compatible bio-signal acquisition system of nuclear magnetic resonance.The non-human primates cerebral apoplexy Model R & D method, stable machin cerebral ischemia re-pouring animal model is precisely prepared for by intravascular Coil embolization method, experimental animal infarct size is moderate and does not occur infarcted region hemorrhagic conversion after Reperfu- sion, animal energy long-term surviving, with corresponding neurologic impairment symptom and pass through the stability of the evaluation certificate of long-term iconography and behavior model, position and the degree of stroke can be accurately controlled using this method, and experimental animal is able to maintain stable clinical symptoms, therefore, this model is appropriate for safety and the efficiency assessment of cerebral apoplexy new treatment and novel drugs.
Description
Technical field
The present invention relates to clinical science studying technological domains, specially a kind of non-human primates cerebral apoplexy Model R & D side
Method.
Background technique
Cerebral apoplexy has become the common cause of the death of the world's second largest, caused by death and disabled to be that the whole world is brought heavy
Financial burden, according to global stroke general pictures in 2014, analysis shows that, stroke incidence occupied first place in the world, and the death rate occupies the world the
Two, there are about 3/4 apoplexy patient can there are the 60.3-80.5% that different degrees of sequelae, cerebral arterial thrombosis account for about stroke.
Non-human primate is due to anatomical structure, development and functionally similar to human nervous system's height, benefit
Carry out Treatment of Stroke research with monkey stroke model, is to realize to answer from more mature rodent models to unknown Human clinical
With a step essential in conversion, but still lack standard, widely accepted primate cerebral apoplexy model both at home and abroad at present,
The generally existing experimental animal survival rate of the primate model reported both at home and abroad is low, and the animal of energy long-term surviving is often without phase
The neurologic impairment symptom answered can not carry out subsequent assessment, this is because currently used modeling method such as thromboembolism
Method, balloon embolization method, line brush, desmurgia, photochemical method etc. are poor to the controllability of infarct size, the excessive animal of infarct size
Ischemic reaction weight, the death rate is high, and infarct size is small, though energy long-term surviving symptom is slight or does not have manifest symptom, or part is built
Mould method differs larger with the pathophysiological change of disease itself, and current research due to animal survival rate it is low, almost do not have
It is included in iconography and ethological long-term evaluation, especially ethological assessment.
Summary of the invention
(1) the technical issues of solving
In view of the deficiencies of the prior art, the present invention provides a kind of non-human primates cerebral apoplexy Model R & D methods, solve
The problem of situation carry out long-term assessment can not be improved to function.
(2) technical solution
In order to achieve the above object, the present invention is achieved by the following technical programs: a kind of non-human primates cerebral apoplexy mould
Type researches and develops method, comprising the following steps:
A1. preparing experiment material: syringe needle, 5F arterial cannula, 4F angiography catheter, the 0.25mm angiography of 18gage
The compatible ventilator of micro-wire, digital subtraction angiography (DSA) system, MRI system, nuclear magnetic resonance, the compatible physiology of nuclear magnetic resonance
Signal detection system.
A2. preparing experiment animal: five between twenty and fifty machins, male, the age 6-8 year old, weight 5-6kg, five old eat
Crab monkey, male, age are greater than 10 years old, and weight is greater than 10kg.
A3. the preoperative health of preparing experiment animal and Baseline detection and inspection (baseline profiling check),
Test metabolizing parameters, hepatic and renal function, CBC.
The additional whole part serum sample of acquisition simultaneously saves, for the biomarker analysis in later period.
Neurology baseline estimate (Baseline neurological assessment).
A4. the method for building up of limitation cerebral ischemic model: machin similar in 6-9 years old weight of selection, experimental animal preserved skin
Disinfection after Intravenous Anesthesia, takes a side position, and outer urethral catheterization gives electrocardio blood pressure monitoring, when necessary mask oxygen inhalation, using improvement
Seldinger ' s method punctures right common femoral artery, is placed in 4F arterial sheath, is inserted into 4F conduit to right carotid, row right side through sheath
Arteria carotis communis positive side position radiography is inserted into microtubular and seal wire to right side middle cerebral artery M 1 segment China and foreign countries 1/3 along 4F conduit later, makes
Shadow confirms that position is accurately placed in 2 hours backed off after random spring rings of spring ring (2X6mm) Dense embolization afterwards and carries out in particular point in time
Iconography, behaviouristics, blood biochemistry checking assessment.
A5. postoperative care
Operated cohort anus temperature is monitored after surgery, and 48 hours of blood pressure and heart rate, animal respiratory will maintain unobstructed shape
State is waken up completely until animal.
Intervening equipment will take out after surgery, press point of puncture 30 minutes, then carry out pressure dressing with disinfection bandage.
Analgesic: injection terbutaline 0.01-0.03mg/ml.
Antibiotic: due to lasting exposed wound surgical procedure, in the preoperative with it is postoperative require according to the guidance of animal doctor into
Row administration, medicament selection need to effectively antagonize the common pathogen that can cause wound infection, such as: cephalosporin, preoperative half
Hour, postoperative 5-7 days, in this case: cefoperazone sodium 100mg/kg, bid.
Liquid supply: carrying out liquid supply to animal in the guidance of animal doctor, and animal recovery process needs to carry out in recovery room,
IV conduit can retain during this period, be, if water shortage symptom occurs in animal, to need to give animal each vein drop for liquid supply
100ml salting liquid is infused, the animal injury degree shown according to MRI, dehydration therapy is to reduce intracranial pressure.
If the spasm of epilepsy pattern occurs in animal, animal antiepileptic is given.
Diet: animal will receive fluid replacement therapy, until restoring normal diet.
A6. postoperative follow-up
The assessment of neurology:
Before T2- imaging, postoperative in MCAO, every animal can all comment according to common non-human primate neurology
Quantization table is assessed, can be there are two independent each self-appraisal of observer experienced in terms of neurological deficit assessment
Point, this table focuses on motion function, and can also consider Behavioral change (state of mind) and vision and cranial nerve damage
Wound, score is lower to represent bad function output.
A7.MRI is checked
Magnetic resonance angiography inspection can be in cerebral ischaemia the latter hour, latter two hour of Reperfu- sion and MCAO
Restore and magnetic resonance disperse with the overturning of T2 attenuating liquid 24 hours after Reperfu- sion operation, is carried out after one hour of Reperfu- sion
Amount imaging is to observe local ischemic damage and reperfusion injury, because embolism amount is measured by T2/Flair image, T2/
Flair image and histological evaluation have high correlation, and the assessment of infarct damage is based entirely on T2 image.
(3) beneficial effect
Compared with prior art, the present invention provides a kind of non-human primates cerebral apoplexy Model R & D method, have following
The utility model has the advantages that
It is precisely prepared for stable machin cerebral ischemia re-pouring animal model by intravascular Coil embolization method, tests
Animal infarct size is moderate and does not occur infarcted region hemorrhagic conversion after Reperfu- sion, animal energy long-term surviving, has corresponding neural function
Can defective symptom and by the stability of the evaluation certificate of long-term iconography and behavior model, can accurately be controlled using this method
The position of stroke processed and degree, and experimental animal is able to maintain stable clinical symptoms, therefore, this model is appropriate for brain soldier
The safety of middle new treatment and novel drugs and efficiency assessment.
Detailed description of the invention
Fig. 1 is latter two hour schematic diagram of MCAO art of the present invention；
Fig. 2 is the postoperative one week schematic diagram of MCAO of the present invention.
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical solution in the embodiment of the present invention is clearly and completely retouched
It states, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Based on the present invention
In embodiment, every other implementation obtained by those of ordinary skill in the art without making creative efforts
Example, shall fall within the protection scope of the present invention.
A kind of non-human primates cerebral apoplexy Model R & D method, comprising the following steps:
A1. preparing experiment material: syringe needle, 5F arterial cannula, 4F angiography catheter, the 0.25mm angiography of 18gage
The compatible ventilator of micro-wire, digital subtraction angiography (DSA) system, MRI system, nuclear magnetic resonance, the compatible physiology of nuclear magnetic resonance
Signal detection system.
A2. preparing experiment animal: five between twenty and fifty machins, male, the age 6-8 year old, weight 5-6kg, five old eat
Crab monkey, male, age are greater than 10 years old, and weight is greater than 10kg.
A3. the preoperative health of preparing experiment animal and Baseline detection and inspection (baseline profiling check),
Test metabolizing parameters, hepatic and renal function, CBC.
The additional whole part serum sample of acquisition simultaneously saves, for the biomarker analysis in later period.
Neurology baseline estimate (Baseline neurological assessment).
A4. the method for building up of limitation cerebral ischemic model: machin similar in 6-9 years old weight of selection, experimental animal preserved skin
Disinfection after Intravenous Anesthesia, takes a side position, and outer urethral catheterization gives electrocardio blood pressure monitoring, when necessary mask oxygen inhalation, using improvement
Seldinger ' s method punctures right common femoral artery, is placed in 4F arterial sheath, is inserted into 4F conduit to right carotid, row right side through sheath
Arteria carotis communis positive side position radiography is inserted into microtubular and seal wire to right side middle cerebral artery M 1 segment China and foreign countries 1/3 along 4F conduit later, makes
Shadow confirms that position is accurately placed in 2 hours backed off after random spring rings of spring ring (2X6mm) Dense embolization afterwards and carries out in particular point in time
Iconography, behaviouristics, blood biochemistry checking assessment.
A5. postoperative care
Operated cohort anus temperature is monitored after surgery, and 48 hours of blood pressure and heart rate, animal respiratory will maintain unobstructed shape
State is waken up completely until animal.
Intervening equipment will take out after surgery, press point of puncture 30 minutes, then carry out pressure dressing with disinfection bandage.
Analgesic: injection terbutaline 0.01-0.03mg/ml.
Antibiotic: due to lasting exposed wound surgical procedure, in the preoperative with it is postoperative require according to the guidance of animal doctor into
Row administration, medicament selection need to effectively antagonize the common pathogen that can cause wound infection, such as: cephalosporin, preoperative half
Hour, postoperative 5-7 days, in this case: cefoperazone sodium 100mg/kg, bid.
Liquid supply: carrying out liquid supply to animal in the guidance of animal doctor, and animal recovery process needs to carry out in recovery room,
IV conduit can retain during this period, be, if water shortage symptom occurs in animal, to need to give animal each vein drop for liquid supply
100ml salting liquid is infused, the animal injury degree shown according to MRI, dehydration therapy is to reduce intracranial pressure.
If the spasm of epilepsy pattern occurs in animal, animal antiepileptic is given.
Diet: animal will receive fluid replacement therapy, until restoring normal diet.
A6. postoperative follow-up
The assessment of neurology:
Before T2- imaging, postoperative in MCAO, every animal can all comment according to common non-human primate neurology
Quantization table is assessed.It can be there are two independent each self-appraisal of observer experienced in terms of neurological deficit assessment
Point, this table focuses on motion function, and can also consider Behavioral change (state of mind) and vision and cranial nerve damage
Wound, score is lower to represent bad function output.
A7.MRI is checked
Magnetic resonance angiography inspection can be in cerebral ischaemia the latter hour, latter two hour of Reperfu- sion and MCAO
Restore and magnetic resonance disperse with the overturning of T2 attenuating liquid 24 hours after Reperfu- sion operation, is carried out after one hour of Reperfu- sion
Amount imaging is to observe local ischemic damage and reperfusion injury, because embolism amount is measured by T2/Flair image, T2/
Flair image and histological evaluation have high correlation, and the assessment of infarct damage is based entirely on T2 image.
The beneficial effects of the present invention are: being precisely prepared for stable machin cerebral ischemia by intravascular Coil embolization method
Reperfu- sion animal model, experimental animal infarct size is moderate and does not occur infarcted region hemorrhagic conversion after Reperfu- sion, and animal can be long-term
Survival, has corresponding neurologic impairment symptom and by the stability of the evaluation certificate of long-term iconography and behavior model,
Position and the degree of stroke can be accurately controlled using this method, and experimental animal is able to maintain stable clinical symptoms, because
This, this model is appropriate for safety and the efficiency assessment of cerebral apoplexy new treatment and novel drugs.
It although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, can be with
A variety of variations, modification, replacement can be carried out to these embodiments without departing from the principles and spirit of the present invention by understanding
And modification, the scope of the present invention is defined by the appended.
Claims (1)
1. a kind of non-human primates cerebral apoplexy Model R & D method, which comprises the following steps:
A1. preparing experiment material: the syringe needle of 18gage, 5F arterial cannula, 4F angiography catheter, 0.25mm angiography is micro- leads
Silk, the compatible ventilator of digital subtraction angiography (DSA) system, MRI system, nuclear magnetic resonance, the compatible physiological signal of nuclear magnetic resonance
Detection system；
A2. preparing experiment animal: five between twenty and fifty machins, male, the age 6-8 year old, weight 5-6kg, five old age machins,
Male, age are greater than 10 years old, and weight is greater than 10kg；
A3. the preoperative health of preparing experiment animal and Baseline detection and inspection (baseline profiling check),
Test metabolizing parameters, hepatic and renal function, CBC；
The additional whole part serum sample of acquisition simultaneously saves, for the biomarker analysis in later period；
Neurology baseline estimate (Baseline neurological assessment)；
A4. the method for building up of limitation cerebral ischemic model: machin similar in 6-9 year old weight of selection, experimental animal preserved skin sterilize,
After Intravenous Anesthesia, a side position is taken, outer urethral catheterization gives electrocardio blood pressure monitoring, when necessary mask oxygen inhalation, using improvement
Seldinger ' s method punctures right common femoral artery, is placed in 4F arterial sheath, is inserted into 4F conduit to right carotid, row right side through sheath
Arteria carotis communis positive side position radiography is inserted into microtubular and seal wire to right side middle cerebral artery M 1 segment China and foreign countries 1/3 along 4F conduit later, makes
Shadow confirms that position is accurately placed in 2 hours backed off after random spring rings of spring ring (2X6mm) Dense embolization afterwards and carries out in particular point in time
Iconography, behaviouristics, blood biochemistry checking assessment；
A5. postoperative care
Operated cohort anus temperature is monitored after surgery, and 48 hours of blood pressure and heart rate, the state that animal respiratory will remain unobstructed is straight
It wakes up completely to animal；
Intervening equipment will take out after surgery, press point of puncture 30 minutes, then carry out pressure dressing with disinfection bandage；
Analgesic: injection terbutaline 0.01-0.03mg/ml；
Antibiotic: due to lasting exposed wound surgical procedure, in the preoperative with it is postoperative require to be carried out according to the guidance of animal doctor to
Medicine, medicament selection need to effectively antagonize the common pathogen that can cause wound infection, such as: cephalosporin, preoperative half an hour,
Postoperative 5-7 days, in this case: cefoperazone sodium 100mg/kg, bid；
Liquid supply: liquid supply is carried out to animal in the guidance of animal doctor, animal recovery process needs to carry out in recovery room, herein
Period IV conduit can retain, and be, if water shortage symptom occurs in animal, to need to give animal each intravenous drip for liquid supply
100ml salting liquid, the animal injury degree shown according to MRI, dehydration therapy is to reduce intracranial pressure；
If the spasm of epilepsy pattern occurs in animal, animal antiepileptic is given；
Diet: animal will receive fluid replacement therapy, until restoring normal diet；
A6. postoperative follow-up
The assessment of neurology:
Before T2- imaging, postoperative in MCAO, every animal all can be according to common non-human primate neurological score amount
Change table to be assessed, can respectively score there are two independent observer experienced in terms of neurological deficit assessment, this
A table focuses on motion function, and can also consider Behavioral change (state of mind) and vision and cranial nerve damage, obtains
Divide the lower function output for representing bad luck；
A7.MRI is checked
Magnetic resonance angiography inspection can in cerebral ischaemia the latter hour, latter two hour of Reperfu- sion and MCAO and again
24 hours after perfusion operation, T2 attenuating liquid overturning recovery and diffusion tensor imaging are carried out after one hour of Reperfu- sion
Local ischemic damage and reperfusion injury are observed, because embolism amount is measured by T2/Flair image, T2/Flair
Image and histological evaluation have high correlation, and the assessment of infarct damage is based entirely on T2 image.
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| CN201810032244.6A CN110025394A (en) | 2018-01-12 | 2018-01-12 | A kind of non-human primates cerebral apoplexy Model R & D method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110569968A (en) * | 2019-10-18 | 2019-12-13 | 上海大学 | Method and system for evaluating entrepreneurship failure resilience based on electrophysiological signals |
| CN116525121A (en) * | 2023-07-05 | 2023-08-01 | 昆明同心医联科技有限公司 | Method for establishing primary spring coil recommendation model of embolic aneurysm and application of primary spring coil recommendation model |
-
2018
- 2018-01-12 CN CN201810032244.6A patent/CN110025394A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110569968A (en) * | 2019-10-18 | 2019-12-13 | 上海大学 | Method and system for evaluating entrepreneurship failure resilience based on electrophysiological signals |
| CN116525121A (en) * | 2023-07-05 | 2023-08-01 | 昆明同心医联科技有限公司 | Method for establishing primary spring coil recommendation model of embolic aneurysm and application of primary spring coil recommendation model |
| CN116525121B (en) * | 2023-07-05 | 2023-09-26 | 昆明同心医联科技有限公司 | Method for establishing primary spring coil recommendation model of embolic aneurysm and application of primary spring coil recommendation model |
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Application publication date: 20190719 |
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