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Abstract
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Bioengenharia

Gnaver adfærdsmæssige test for at vurdere funktionelle mangler forårsaget af mikroelektrode Implantation i rotte motoriske Cortex

Published: August 18, 2018
doi:
10.3791/57829
, , , , , ,
1Advanced Platform Technology Center, Rehabilitation Research and Development,Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 2Department of Biomedical Engineering,Case Western Reserve University

Summary

Vi har vist, at en mikroelektrode implantation i den motoriske hjernebark af rotter forårsager øjeblikkelig og varig motor underskud. Metoderne, der foreslås heri disposition en mikroelektrode implantering og tre gnaver adfærdsmæssige opgaver at belyse eventuelle ændringer i den fin eller grov motorik på grund af implantation-forårsaget skade på den motoriske hjernebark.

Abstract

Medicinsk udstyr implanteret i hjernen hold kolossalt potentiale. Som en del af en hjerne Machine Interface (BMI) demonstrere intracortical microelectrodes evnen til at optage handling potentialer fra individuelle eller små grupper af neuroner. Sådanne optagede signaler med held været anvendt til at tillade patienter at interface med eller styre computere, robot lemmer og deres egne lemmer. Dog har tidligere animalsk undersøgelser vist at en mikroelektrode implantation i hjernen ikke kun skader det omkringliggende væv, men kan også resultere i funktionelle mangler. Her diskuterer vi en række adfærdsmæssige test at kvantificere potentielle motoriske funktionsnedsættelser efter implantation af intracortical microelectrodes i den motoriske hjernebark af en rotte. Metoderne til åben feltgitteret, stigen passage og greb styrke test giver værdifulde oplysninger om de potentielle komplikationer som følge af en mikroelektrode implantation. Resultaterne af de adfærdsmæssige test er korreleret med slutpunkt histologi, giver yderligere oplysninger om de patologiske resultater og virkninger af denne procedure på tilstødende væv.

Introduction

Intracortical microelectrodes blev oprindeligt brugt til at knytte kredsløb i hjernen, og har udviklet sig til et værdifuldt værktøj til at muliggøre påvisning af motor intentioner, som kan bruges til at fremstille funktionelle udgange1. Detekterede funktionelle udgange kan tilbyde personer lider af rygmarvsskader, cerebral parese, amyotrofisk lateral sklerose (ALS) eller andre bevægelse-begrænsende betingelser en computer markøren2,3 , eller robot arm4,5,6, eller gendanne funktion til deres egen handicappede lemmer7. Derfor opstået intracortical mikroelektrode teknologi som en lovende og hurtigt voksende felt8.

På grund af de gode resultater set i feltet, er kliniske undersøgelser undervejs for at forbedre og bedre at forstå mulighederne for BMI technology5,9,10. Af at realisere det fulde potentiale af kommunikation med neuroner i hjernen, er rehabilitering programmer opfattet som ubegrænsede8. Selvom der er stor optimisme for fremtiden for intracortical mikroelektrode teknologi, er det også velkendt, at microelectrodes i sidste ende ikke11, muligvis på grund af en akut neuroinflammatory svar efter implantation. Implantation af en udenlandsk materiale i hjernen medfører øjeblikkelig skader til det omgivende væv og fører til yderligere skade som følge af den neuroinflammatory reaktion, som varierer afhængigt af egenskaber af implantatet12. Derudover et implantat i hjernen kan forårsage en microlesion effekt: en reduktion af glukose stofskifte menes at være forårsaget af akut ødem og blødning på grund af enheden indsættelse13. Derudover er signalkvaliteten og længden af tid, nyttige signaler kan registreres inkonsekvent, uanset dyremodel11,14,15,16. Flere undersøgelser har påvist forbindelsen mellem neuroinflammation og mikroelektrode ydeevne17,18,19. Konsensus i Fællesskabet er derfor, at den inflammatoriske reaktion af neurale væv, der omgiver microelectrodes, i det mindste delvis, kompromiser elektrode pålidelighed.

Mange studier har undersøgt lokale betændelse11,20,21,22 eller udforsket metoder til at reducere skader på hjernen forårsaget af indsættelse11,23, 24,25, med et mål om outplacement recording over tid14,26. Derudover har vi for nylig vist, at en iatrogen skade forårsaget af en mikroelektrode indsættelse i den motoriske hjernebark af rotter forårsager en øjeblikkelig og varig fine motor underskud27. Formålet med de protokoller, der præsenteres her er derfor at give forskere en kvantitativ metode til at vurdere mulige motor underskud som følge af hjernen traumer efter implantation og vedvarende tilstedeværelse af intracortical enheder (microelectrodes i den tilfælde af dette manuskript). Adfærd prøverne her var designet til at drille ud både grov og fin motorik funktionshæmninger og kan bruges i mange modeller af hjerneskade. Disse metoder er ligetil, reproducerbar, og kan nemt implementeres i en gnaver model. Yderligere, de metoder, der præsenteres her tillader en korrelation på motor adfærd til histologisk resultater, en fordel, der indtil for nylig, forfatterne ikke har set offentliggjort i feltet BMI. Endelig, da disse metoder var designet til at teste fin motorik28, grov motorik29og stress og angst adfærd29,30, de metoder, der præsenteres her kan også gennemføres i en række hovedskade modeller hvor forskerne vil regere ud (eller i) enhver motorik underskud.

Protocol

Alle procedurer og dyrs pleje praksis blev godkendt og udført i overensstemmelse med Louis Stokes Cleveland afdeling af veteraner anliggender medicinsk Center institutionelle dyrs pleje og brug udvalg. Bemærk: For at uddanne forskere på beslutningen om brugen af en stab skade model som en kontrol, anbefales det at gennemgå Potter et al. arbejde 21. 1. mikroelektrode Implantation kirurgisk Procedure Pre kirurgis…

Representative Results

Ved hjælp af de metoder, der præsenteres her, er en mikroelektrode implantering i den motoriske hjernebark afsluttet følgende fastlagte procedurer39,40,41,42, efterfulgt af åben gitteret feltafprøvning for at vurdere grov motorik og stigen og greb fungere styrke test til at vurdere den fine motor27. Motorik test blev afsluttet 2 x pr…

Discussion

Den protokol, der er skitseret her har været brugt til effektivt og reproducerbar måling af både fint og groft motor underskud i en model af gnaver hjerneskade. Desuden, det giver mulighed for korrelation af fine motor adfærd til histologisk resultater efter en mikroelektrode implantation i den motoriske cortex. Metoderne er let at følge og billig at etablere, og kan ændres til at passe en forsker individuelle behov. Yderligere, opførsel test ikke forårsager stor stress eller smerte til dyr; Forskerne tror snarer…

Declarações

The authors have nothing to disclose.

Acknowledgements

Denne undersøgelse var delvist understøttet af Merit anmeldelse Award #B1495-R (Capadona) og den præsidentielle tidlige karriere Award for forskere og ingeniører (PECASE, Capadona) fra de Forenede Stater (USA) Institut for veteraner anliggender rehabilitering forskning og Udvikling af Service. Derudover blev dette arbejde støttet i en del af kontor for Assistant Secretary of Defense for sundhed anliggender gennem Peer Reviewed medicinske forskningsprogrammet under Award No. W81XWH-15-1-0608. Oplysningerne repræsenterer ikke synspunkter US Department of veterananliggender eller de Forenede Staters regering. Forfatterne vil gerne takke Dr. Hiroyuki Arakawa i CWRU gnaver adfærd kerne til hans vejledning i at designe og teste gnaver adfærdsmæssige protokoller. Forfatterne ønsker også at takke James Drake og Kevin Talbot fra den CWRU afdeling af mekanisk og astronautik for deres hjælp i design og fremstilling gnaver stigen test.

Materials

Sprague Dawley rats, male, 201-225g Charles River CD
Compac5 anesthesia system Vetequip 901812
Electric trimmers Wahl 9918-6171
Stereotaxic frame David Kopf Instruments 1760
Gaymar heated water pad and pump Braintree Scientific Inc  TP-700
Vetbond tissue adhesive 3M 07-805-5031
Dental drill Pearson Dental O60-0045
Dura pick Fine Science Tools 10064-14
Silicon shank microelectrode Made in-house at Cleveland VA Medical Center N/A
KwikCast silicone elastomer World Precision Instruments KWIK-CAST
Teets dental cement  A-M Systems 525000
Webcam HD Pro c920 Logitec 960-000764
Grip strength meter Harvard Apparatus 565084
Minitab 17 statistical software Minitab Inc
Open field grid test Made in-house at Case Western Reserve University N/A
Ladder test Made in-house at Case Western Reserve University N/A
Rabbit anti rat IgG antibody Bio-Rad 618501
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Tags

RodentBehavioral TestingFunctional DeficitsMicroelectrode ImplantationRat Motor CortexNeural EngineeringMotor FunctionSurgical ProcedureStereotaxic FrameCephalosporin AntibioticBupivacaineBetadineCyanoacrylateDental CementDuraMotor CortexForepaw Movement

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Goss-Varley, M., Shoffstall, A. J., Dona, K. R., McMahon, J. A., Lindner, S. C., Ereifej, E. S., Capadona, J. R. Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex. J. Vis. Exp. (138), e57829, doi:10.3791/57829 (2018).
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