Name: rat model of blood-brain barrier disruption to allow targeted neurovascular therapeutics
Uploaded: 2012-11-30T12:00:00
Description: Watch this Scientific Journal Video about Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics at JoVE.com

Dette arbejde blev støttet af JB Marshall Foundation.

1. Forbered Animal og udstyr til procedure <ol><li> Før påbegyndelse af kirurgi, forberede det kirurgiske område og dyret. Gøre carotis kateteret ved at indsætte en 23-gauge stump nål i den ene ende af 12 &quot;af PE50 rør. Skær en ca 45 ° affasning i den modsatte ende af kateteret. Steriliseres udstyret forud for proceduren. Bære en hår motorhjelm, kirurgisk maske og sterile handsker. </li><li> Anbring en varmepude på overfladen, hvor operationen udføres. Aktivere den, og lad den varme. Dæk området med...

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	<li>Abbott, N. J., Patabendige, A. A. K., Dolman, D. E. M., Yusof, S. R., Begley, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Structure+and+function+of+the+blood-brain+barrier.">Structure and function of the blood-brain barrier.</a> Neurobiology of disease. 37, 13-25 (2010).</li><li>Smith, Q. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Blood-Brain+Barrier.">The Blood-Brain Barrier.</a> 89, 193-208 (2003).</li><li>Kroll, R. A., Neuwelt, E. 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A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemotherapy+administered+in+conjunction+with+osmotic+blood-brain+barrier+modification+in+patients+with+brain+metastases.">Chemotherapy administered in conjunction with osmotic blood-brain barrier modification in patients with brain metastases.</a> Journal of neuro-oncology. 4, 195-207 (1987).</li><li>Doolittle, N. D., 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=Safety+and+efficacy+of+a+multicenter+study+using+intraarterial+chemotherapy+in+conjunction+with+osmotic+opening+of+the+blood-brain+barrier+for+the+treatment+of+patients+with+malignant+brain+tumors.">Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with malignant brain tumors.</a> Cancer. 88, 637-647 (2000).</li><li>Guillaume, D. 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G., 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=The+influence+of+anesthetic+choice,+PaCO2,+and+other+factors+on+osmotic+blood-brain+barrier+disruption+in+rats+with+brain+tumor+xenografts.">The influence of anesthetic choice, PaCO2, and other factors on osmotic blood-brain barrier disruption in rats with brain tumor xenografts.</a> Anesthesia &amp; Analgesia. 88, 559-559 (1999).</li><li>Nilaver, G., 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=Delivery+of+herpesvirus+and+adenovirus+to+nude+rat+intracerebral+tumors+after+osmotic+blood-brain+barrier+disruption.">Delivery of herpesvirus and adenovirus to nude rat intracerebral tumors after osmotic blood-brain barrier disruption.</a> Proceedings of the National Academy of Sciences. 92, 9829 (1995).</li><li>Fortin, D., McCormick, C. 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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=Primary+CNS+lymphoma+treated+with+osmotic+blood-brain+barrier+disruption:+prolonged+survival+and+preservation+of+cognitive+function.">Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: prolonged survival and preservation of cognitive function.</a> Journal of clinical oncology. 9, 1580 (1991).</li><li>Remsen, L. G., Trail, P. A., Hellstr&#246;m, I., Hellstr&#246;m, K. E., Neuwelt, E. 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Der er nogle få mulighed for at maksimere effektiviteten af ​​BBBD. Det er vigtigt at minimere blødning under cut-down fase. Blodtryk og hjertefrekvens kan påvirkes af betydelige blødning og disse faktorer vides at påvirke omfanget af BBBD 13. Blødning kan reduceres ved hjælp af suturer at ligere større kar, såsom overlegen skjoldbruskkirtlen og occipital arterierne, som skal opdeles. Derudover kan elektrokirurgi bruges til at opdele fartøjer og dissekere områder, der har en rig blodforsyning. ...

<table border="1"><tbody><tr><td> Materialets navn </td><td> Firma </td><td> Katalognummer </td><td> Kommentar </td></tr><tr><td> Long Evans rotter </td><td> Harlan Laboratories </td><td></td><td> 210-250 g, mandlig </td></tr><tr><td> PE 50 slange </td><td> Beckton-Dickinson </td><td></td><td></td></tr><tr><td> 18 gauge x 2,5 &quot;IV kateter </td><td> Terumo </td><td></td><td> For ET rør </td></tr><tr><td> 30 &quot;IV udvidelse indeholder </td><td> Abbott </td><td></td><td></td></tr><tr><td> 26 gauge veterinære IV kateter </td><td> Monoject </td><td></td><td></td></tr><tr><td> Evans-blåt farvestof </td><td> Sigma </td><td> E2129 </td><td></td></tr><tr><td> Bipolar </td><td> Codman </td><td></td><td></td></tr><tr><td> Filter, 5 um </td><td> Braun </td><td></td><td></td></tr></tbody></table>

rat model of blood-brain barrier disruption to allow targeted neurovascular therapeutics

Endotelceller med tight junctions sammen med basalmembran og astrocyt ende fødder surround cerebrale blodkar til dannelse af blodhjernebarrieren 1. Barrieren selektivt udelukker molekyler fra kryds mellem blodet og hjernen baseret på deres størrelse og ladning. Denne funktion kan hindre afgivelse af terapeutika til neurologiske lidelser. Et antal kemoterapeutiske lægemidler, for eksempel, vil ikke effektivt krydser blod-hjernebarrieren for at nå tumorceller 2. Således forbedre leveringen af ​​lægemidler over blod-hjerne-barrieren er et område af interesse. De mest udbredte fremgangsmåder til forøgelse af leveringen af lægemidler til hjernen, er direkte cerebral infusion og blod-hjerne-barrieren forstyrrelser 3. Direkte intracerebral infusion garanterer, at terapier når hjernen, men denne fremgangsmåde har en begrænset evne til at dispergere medikamentet 4. Blod-hjerne barrieren forstyrrelser (BBBD) alnedture medicin at strømme direkte fra kredsløbssystemet ind i hjernen og således mere effektivt at nå dispergerede tumorceller. Tre metoder til barriere forstyrrelser omfatter osmotisk barriere forstyrrelser, farmakologiske barriere forstyrrelser, og fokuseret ultralyd med mikrobobler. Osmotisk forstyrrelser, udviklet af Neuwelt, anvender en hypertonisk opløsning af 25% mannitol, der dehydratiserer de celler i blod-hjernebarrieren får dem til at krympe og forstyrre deres tight junctions. Barriere forstyrrelser kan også opnås farmakologisk med vasoaktive stoffer, såsom histamin 5 og bradykinin 6. Denne fremgangsmåde er imidlertid selektivt primært til hjerne-tumor barrieren 7. Endvidere blev RMP-7, en analog af peptidet bradykinin, viser sig at være ringere sammenlignet hoved-mod-hoved med osmotisk BBBD med 25% mannitol 8. En anden fremgangsmåde, fokuseret ultralyd (FUS), sammenholdt med mikroboble ultralydskontrastmidler, har også vist sigtil reversibelt at åbne blod-hjerne barrieren 9. I forhold til FUS, selv om 25% mannitol har en længere historie af sikkerhed i menneskelige patienter, der gør det til et gennemprøvet værktøj til translationel forskning 10-12. For at opnå BBBD skal mannitol leveres ved en høj hastighed direkte ind i hjernens arterielle kredsløb. Hos mennesker er en endovaskulær kateter styres til hjernen, hvor hurtige, direkte strømning kan opnås. Denne protokol modeller menneskelig BBBD så tæt som muligt. Efter en cut-ned til bifurcatio af den fælles carotidarterie, indsættes et kateter retrograd i ECA og anvendes til afgivelse mannitol direkte ind i den indre carotidarterie (ICA) omsætning. Propofol og N2O anæstesi anvendes til deres evne til at maksimere effektiviteten af barrieren forstyrrelser 13. Hvis korrekt udført, denne fremgangsmåde har evnen til sikkert, effektivt, og reversibelt åbne blod-hjernebarrieren og forbedringsprojekte leveringen af lægemidler, der ikke normalt når hjernen 8,13,14.

<img alt="Figur 1" src="/files/ftp_upload/50019/50019fig1.jpg" /> Figur 1. Visualisering af blod-hjerne barrieren forstyrrelser via Evans-blåt farvestof ekstravasation. Evans-blåt farvestof er et pigment, som binder til albumin og er ikke ekstravaseret i hjernen under fysiologiske betingelser. En nedbrydning af blod-hjerne-barrieren på en side af hjernen giver Evans blue at komme ind og plette det sprængte halvkugle blå, mens den ikke-brudt halvkugle forbl...

Watch this Scientific Journal Video about Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics at JoVE.com

Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics

Blod-hjerne barrieren forstyrrelser hjælper levering af visse lægemidler til hjernen. Mannitol leveret intraarterielt krymper celler omgivende blodkar med henblik på fysisk at ødelægge barrieren.

Rottemodel af blod-hjerne barrieren Disruption at muliggøre målrettede neurovaskulær Therapeutics

Endothelial cells with tight junctions along with the basement membrane and astrocyte end feet surround cerebral blood vessels to form the blood-brain ...

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Medicine

MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model

MR-guided Forstyrrelse af blod-hjerne barrieren ved hjælp af Transcranial fokuseret ultralyd i en rottemodel

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a ...

Stretch in Brain Microvascular Endothelial Cells (cEND) as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

Stretch in Brain Microvascular Endothelial Cells cEND as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

Stræk i Brain mikrovaskulære endotelceller (cEND) som et<em&gt; In Vitro</em&gt; Traumatisk Hjerneskade Model af blod-hjerne barrieren

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying ...

Setting-up an In Vitro Model of Rat Blood-brain Barrier (BBB): A Focus on BBB Impermeability and Receptor-mediated Transport

Setting-up an In Vitro Model of Rat Blood-brain Barrier BBB: A Focus on BBB Impermeability and Receptor-mediated Transport

Etablering af en<em&gt; In Vitro</em&gt; Model of Rat blod-hjerne barrieren (BBB): Fokus på BBB Uigennemtrængelighed og receptor-medieret transport

The blood brain barrier (BBB) specifically regulates molecular and cellular flux between the blood and the nervous tissue. Our aim was to develop and ...

Oxygen-Glucose Deprivation and Reoxygenation as an In Vitro Ischemia-Reperfusion Injury Model for Studying Blood-Brain Barrier Dysfunction

Oxygen-Glucose Deprivation and Reoxygenation as an In Vitro Ischemia-Reperfusion Injury Model for Studying Blood-Brain Barrier Dysfunction

Ilt-Glucose afsavn og reoxygenering som en<em&gt; In vitro</em&gt; Iskæmireperfusion Skade Model for studere blod-hjerne barrieren dysfunktion

Ischemia-Reperfusion (IR) injury is known to contribute significantly to the morbidity and mortality associated with ischemic strokes. Ischemic ...

A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics

En Rat carotis ballon Skade Model til Test Anti-vaskulære Remodeling Therapeutics

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is ...

Retroductal Submandibular Gland Instillation and Localized Fractionated Irradiation in a Rat Model of Salivary Hypofunction

Retroductal Submandibularis Gland Instillation og Lokaliseret Fraktioneret Bestråling i en rotte model af spyt hypofunktion

Normal tissues that lie within the portals of radiation are inadvertently damaged. Salivary glands are often injured during head and neck radiotherapy. ...

In Vitro Assays to Assess Blood-brain Barrier Mesh-like Vessel Formation and Disruption

In Vitro Assays to Assess Blood-brain Barrier Mesh-like Vessel Formation and Disruption

I Vitro Assays at vurdere blod-hjerne barriere mesh-lignende fartøj dannelse og afbrydelse

Blood-brain barrier (BBB) coverage plays a central role in the homeostasis of the central nervous system (CNS). The BBB is dynamically maintained by ...

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

Forbedret metode til etablering af et In Vitro blod - hjerne barrieren Model baseret på svin hjernen Endothelial Cells

The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

Isometrisk kontraktilitet måling af musen mesenterica arterie ved hjælp af Wire blodkar

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model

Levering af kardioaktive lægemidler i en porcin myokardieinfarktmodel

Myocardial infarction is one of the leading causes of death and disability worldwide, and there is an urgent need for novel cardioprotective or ...