Name: electromagnetic controlled closed-head model of mild traumatic brain injury in mice
Uploaded: 2022-09-28T15:00:00
Description: Watch this Scientific Journal Video about Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice at JoVE.com

Dette arbejde blev delvist støttet af National Institutes of Health under tildelingsnumrene R01NS120882, RF1NS119165 og R01NS103785 og Department of Defense award nummer AZ190017. Indholdet er udelukkende forfatternes ansvar og repræsenterer ikke de officielle synspunkter fra National Institutes of Health eller Department of Defense.

De udførte eksperimenter blev godkendt af Institutional Animal Care and Use Committee (IACUC) ved University of Kentucky, og både ARRIVE og vejledningen til pleje og brug af forsøgsdyr blev fulgt under undersøgelsen.
1. Kirurgisk opsætning
BEMÆRK: Mus er anbragt i grupper på 4-5/bur, luftfugtigheden i staldrummet holdes på 43%-47%, og temperaturen holdes på 22-23 °C. Mus får ad libitum adgang til mad og vand og udsættes for en 12 ...

<ol>
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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=Mouse+closed+head+injury+model+induced+by+a+weight-drop+device.">Mouse closed head injury model induced by a weight-drop device.</a> Nature Protocols. 4 (9), 1328-1337 (2009).</li><li>Yang, Z., 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=Temporal+MRI+characterization,+neurobiochemical+and+neurobehavioral+changes+in+a+mouse+repetitive+concussive+head+injury+model.">Temporal MRI characterization, neurobiochemical and neurobehavioral changes in a mouse repetitive concussive head injury model.</a> Scientific Reports. 5, 11178 (2015).</li><li>Petraglia, A. 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Flere trin er involveret i at genskabe en konsistent skadesmodel ved hjælp af den beskrevne model. For det første er det afgørende at fastgøre dyret korrekt i den stereotaxiske ramme. Dyrets hoved bør ikke kunne bevæge sig sideværts, og kraniet skal være helt fladt med bregma og lambda, der læser de samme koordinater. Korrekt placering af ørestængerne er det sværeste aspekt af denne operation, og dette kan kun læres med praksis. Hvis kraniet ikke er plant, skal hovedet justeres, før der induceres CHI. Mangl...

Traumatisk hjerneskade (TBI) er forårsaget af en ekstern kraft på hjernen, ofte forbundet med fald, sportsskader, fysisk vold eller trafikulykker. I 2014 fastslog centrene for sygdomsbekæmpelse og forebyggelse, at 2,53 millioner amerikanere besøgte akutafdelingen for at søge lægehjælp til TBI-relaterede ulykker1. Da mild TBI (mTBI) repræsenterer størstedelen af TBI-tilfælde, er der i løbet af de sidste årtier blevet vedtaget flere modeller af mTBI, som inkluderer vægttab, stempeldrevet lukket hovedskade og kontrolleret kortikal påvirkning, rotationsskade, mild væskepercussionskade og eksplosionsskademodeller 2,3. Heterogeniteten af mTBI-modellerne er nyttig til at adressere de forskellige funktioner, der er forbundet med mTBI, der ses hos mennesker, og til at hjælpe med at evaluere de cellulære og molekylære mekanismer, der er forbundet med hjerneskade.
Af de almindeligt anvendte modeller for lukket hovedskade er en af de første og mest anvendte modeller vægttabsmetoden, hvor en genstand tabes fra en bestemt højde på dyrets hoved (bedøvet eller vågen)2,4. I vægttabsmetoden afhænger skadens sværhedsgrad af flere parametre, herunder kraniotomi udført eller ej, hoved fast eller frit, og afstanden og vægten af den faldende genstand 2,4. En ulempe ved denne model er den store variation i skadens sværhedsgrad og den høje dødelighed forbundet med respirationsdepression 5,6. Et almindeligt alternativ er at levere stødet ved hjælp af en pneumatisk eller elektromagnetisk enhed, som kan gøres direkte på den udsatte dura (kontrolleret kortikal påvirkning: CCI) eller lukket kranium (lukket hovedskade: CHI). En af styrkerne ved den stempeldrevne skade er dens høje reproducerbarhed og lave dødelighed. CCI kræver imidlertid kraniotomi7,8, og en kraniotomi i sig selv inducerer betændelse9. I stedet er der i CHI-modellen ikke behov for kraniotomi. Som allerede nævnt har hver model begrænsninger. En af begrænsningerne ved CHI-modellen beskrevet i dette papir er, at operationen udføres ved hjælp af en stereotaksisk ramme, og dyrets hoved er immobiliseret. Mens fuld hovedimmobilisering sikrer reproducerbarhed, tager den ikke højde for bevægelse efter stødet, der kan bidrage til skaden forbundet med en mTBI.
Denne protokol beskriver en grundlæggende metode til at udføre en CHI-påvirkning med en kommercielt tilgængelig elektromagnetisk slaganordning10 i en mus. Denne protokol beskriver de nøjagtige parametre, der er involveret for at opnå en meget reproducerbar skade. Især har efterforskeren præcis kontrol over parametrene (dybde af skade, opholdstid og slaghastighed) for præcist at definere skadens sværhedsgrad. Som beskrevet producerer denne CHI-model en skade, der resulterer i bilateral patologi, både diffus og mikroskopisk (dvs. kronisk aktivering af glia, aksonal og vaskulær skade) og adfærdsmæssige fænotyper 11,12,13,14,15. Derudover betragtes den beskrevne model som mild, da den ikke fremkalder strukturelle hjernelæsioner baseret på MR eller grove læsioner på patologi selv 1 år efter skaden16,17.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>9 mm Autoclip Applier</td>
			<td>Braintree scientific</td>
			<td>ACS- APL</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>9 mm Autoclip Remover</td>
			<td>Braintree scientific</td>
			<td>ACS- RMV</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>9 mm Autoclip, Case of 1,000 clips</td>
			<td>Braintree scientific</td>
			<td>ACS- CS</td>
			<td>Surgery (Staples)</td>
		</tr>
		<tr>
			<td>Aperio ImageScope software&#160;</td>
			<td>Leica BioSystems</td>
			<td>NA&#160;</td>
			<td>IHC</td>
		</tr>
		<tr>
			<td>BladeFLASK Blade Remover</td>
			<td>Fisher Scientific</td>
			<td>22-444-275</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Cotton tip applicator</td>
			<td>VWR</td>
			<td>89031-270</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Digitial mouse stereotaxic frame</td>
			<td>Stoelting</td>
			<td>51730D</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Dumont #7 Forceps</td>
			<td>Roboz</td>
			<td>RS-5047</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Ear bars</td>
			<td>Stoelting</td>
			<td>51649</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>EthoVision XT 11.0&#160;</td>
			<td>Noldus Information Technology</td>
			<td>NA</td>
			<td>RAWM&#160;</td>
		</tr>
		<tr>
			<td>Fiber-Lite</td>
			<td>Dolan-Jeffer Industries</td>
			<td>UN16103-DG</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Fisherbrand Bulb for Small Pipets</td>
			<td>Fisher Scientific</td>
			<td>03-448-21</td>
			<td>Head support apparatus</td>
		</tr>
		<tr>
			<td>Gemini Avoidance System</td>
			<td>San Diego Instruments</td>
			<td>NA</td>
			<td>Active avoidance</td>
		</tr>
		<tr>
			<td>Heating Pad</td>
			<td>Sunbeam&#160;</td>
			<td>732500000U</td>
			<td>Surgery prep</td>
		</tr>
		<tr>
			<td>HRP conjugated goat anti-rabbit IgG&#160;</td>
			<td>Jackson Immuno Research laboratories</td>
			<td>111-065-144&#160;</td>
			<td>IHC</td>
		</tr>
		<tr>
			<td>Induction chamber</td>
			<td>Kent Scientific</td>
			<td>VetFlo-0530XS</td>
			<td>Surgery prep</td>
		</tr>
		<tr>
			<td>Isoflurane, USP</td>
			<td>Covetrus</td>
			<td>NDC: 11695-6777-2</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Mouse gas anesthesia head holder</td>
			<td>Stoelting</td>
			<td>51609M</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Neuropactor Stereotaxic Impactor</td>
			<td>Neuroscience Tools</td>
			<td>n/a</td>
			<td>Surgery: Formally distributed by Lecia as impact one</td>
		</tr>
		<tr>
			<td>NexGen Mouse 500</td>
			<td>Allentown&#160;</td>
			<td>n/a</td>
			<td>Post-surgery, holding cage</td>
		</tr>
		<tr>
			<td>Parafilm</td>
			<td>Bemis</td>
			<td>PM992</td>
			<td>Head support apparatus</td>
		</tr>
		<tr>
			<td>Peanut - Professional Hair Clipper</td>
			<td>Whal</td>
			<td>8655-200&#160;</td>
			<td>Surgery prep</td>
		</tr>
		<tr>
			<td>Povidone-Iodine Solution USP, 10% (w/v), 1% (w/v) available Iodine, for laboratory</td>
			<td>Ricca</td>
			<td>3955-16</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Puralube Vet Oinment,petrolatum ophthalmic ointment, Sterile ocular lubricant</td>
			<td>Dechra</td>
			<td>17033-211-38</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Rabbit anti-GFAP&#160;</td>
			<td>Dako</td>
			<td>Z0334</td>
			<td>IHC</td>
		</tr>
		<tr>
			<td>Rabbit anti-IBA1&#160;</td>
			<td>Wako</td>
			<td>019-19741</td>
			<td>IHC</td>
		</tr>
		<tr>
			<td>8-arm Radial Arm Water Maze</td>
			<td>MazeEngineers</td>
			<td>n/a</td>
			<td>RAWM&#160;</td>
		</tr>
		<tr>
			<td>Scale</td>
			<td>OHAUS CS series</td>
			<td>BAL-101</td>
			<td>Surgery prep</td>
		</tr>
		<tr>
			<td>Scalpel Handle #7 Solid 6.25&#34;&#160;</td>
			<td>Roboz</td>
			<td>RS-9847</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Sterile Alcohol Prep Pads (isopropyl alcohol 70% v/v)</td>
			<td>Fisher Brand</td>
			<td>22-363-750</td>
			<td>Surgery prep</td>
		</tr>
		<tr>
			<td>SumnoSuite low-flow anesthesia system</td>
			<td>Kent Scientific</td>
			<td>SS-01</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>10 mL syringe Luer-Lok Tip</td>
			<td>BD Bard-Parker</td>
			<td>302995</td>
			<td>Head support apparatus</td>
		</tr>
		<tr>
			<td>Timers</td>
			<td>Fisher Scientific</td>
			<td>6KED8</td>
			<td>Surgery</td>
		</tr>
		<tr>
			<td>Topical anesthetic cream</td>
			<td>L.M.X 4</td>
			<td>NDC 0496-0882-15</td>
			<td>Surgery prep</td>
		</tr>
		<tr>
			<td>Triple antibiotic ointment</td>
			<td>Major</td>
			<td>NDC 0904-0734-31</td>
			<td>Post-surgery</td>
		</tr>
		<tr>
			<td>Tubing</td>
			<td>MasterFlex</td>
			<td>96410-16</td>
			<td>Head support apparatus</td>
		</tr>
		<tr>
			<td>Vaporizer Single Channel Anesthesia System</td>
			<td>Kent Scientific</td>
			<td>VetFlo-1210S</td>
			<td>Surgery prep</td>
		</tr>
	</tbody>
</table>

electromagnetic controlled closed-head model of mild traumatic brain injury in mice

Meget reproducerbare dyremodeller af traumatisk hjerneskade (TBI) med veldefinerede patologier er nødvendige for at teste terapeutiske indgreb og forstå mekanismerne for, hvordan en TBI ændrer hjernens funktion. Tilgængeligheden af flere dyremodeller af TBI er nødvendig for at modellere de forskellige aspekter og sværhedsgrader af TBI, der ses hos mennesker. Dette manuskript beskriver brugen af en midterlinje lukket hovedskade (CHI) til at udvikle en musemodel af mild TBI. Modellen betragtes som mild, fordi den ikke producerer strukturelle hjernelæsioner baseret på neuroimaging eller groft neuronalt tab. Imidlertid skaber en enkelt påvirkning tilstrækkelig patologi til, at kognitiv svækkelse kan måles mindst 1 måned efter skaden. En trin-for-trin protokol til inducering af en CHI i mus ved hjælp af en stereotaksisk styret elektromagnetisk slaglegeme er defineret i papiret. Fordelene ved den milde midterlinje CHI model omfatter reproducerbarheden af de skade-inducerede ændringer med lav dødelighed. Modellen er tidsmæssigt karakteriseret op til 1 år efter skaden for neuroimaging, neurokemiske, neuropatologiske og adfærdsmæssige ændringer. Modellen supplerer åbne kraniemodeller med kontrolleret kortikal påvirkning ved hjælp af den samme slaganordning. Således kan laboratorier modellere både mild diffus TBI og fokal moderat til svær TBI med samme slaglegeme.

Denne stereotaxiske elektromagnetiske slaganordning er alsidig. Det bruges til både en åben kraniekontrolleret kortikal påvirkning (CCI) eller en lukket hovedskade (CHI) kirurgi. Desuden kan skadens sværhedsgrad moduleres ved at ændre skadeparametrene såsom slaghastighed, opholdstid, slagdybde, slagkraft og skademål. Heri beskrives en CHI-operation med en 5,0 mm stålspidsslaglegeme. Denne skade betragtes som mild, fordi der ikke er nogen strukturelle hjernelæsioner. Dødeligheden hos voksne mus er mindre end 0,9...

Watch this Scientific Journal Video about Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice at JoVE.com

Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice

Protokollen beskriver mild traumatisk hjerneskade i en musemodel. Især forklares en trinvis protokol til at fremkalde en mild midterlinie lukket hovedskade og karakteriseringen af dyremodellen fuldt ud.

Elektromagnetisk kontrolleret lukket hovedmodel af mild traumatisk hjerneskade hos mus

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and ...

Research

JoVE Journal

Neuroscience

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and ...

Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury

Undersøgelser om Ændringer af hippocampus Circuit funktion efter Mild traumatisk hjerneskade

Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological ...

A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila

A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila

En metode til at påføre lukket hoved traumatisk hjerneskade i<em&gt; Drosophila</em

Traumatic brain injury (TBI) affects millions of people each year, causing impairment of physical, cognitive, and behavioral functions and death. Studies ...

A Novel In Vitro Model of Blast Traumatic Brain Injury

A Novel In Vitro Model of Blast Traumatic Brain Injury

En roman In Vitro Model af Blast traumatisk hjerneskade

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the ...

Effects of Blast-induced Neurotrauma on Pressurized Rodent Middle Cerebral Arteries

Virkningerne af Blast-induceret Neurotrauma på trykisoleret gnaver midt cerebrale arterier

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral ...

Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice

Undersøgelse af ændringer i Caecum microbiota efter traumatisk hjerneskade i mus

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also ...

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury

Avanceret diffusion Imaging i hippocampus af rotter med mild traumatisk hjerneskade

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous ...

Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury

Murine model af kontrolleret kortikale virkning for induktion af traumatisk hjerneskade

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the ...

Low-intensity Blast Wave Model for Preclinical Assessment of Closed-head Mild Traumatic Brain Injury in Rodents

Lavintensitets blastbølgemodel til præklinisk vurdering af mild traumatisk hjerneskade med lukket hoved hos gnavere

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of ...

Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury

Vurdering af ændringer i synaptisk plasticitet ved hjælp af en vågen lukket hovedskademodel af mild traumatisk hjerneskade

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of ...