EBME201: Finishingtheeye,visualprosthetics, andneuroinflammationinresponse toneuralprosthetics

JeffCapadona 10/9/2012

Peripheralareafoveal area

Transmission

light

 Howdoweseemorethat3colors?

 Whydoesthiswork???

Visualprosthesis
TheProblem:Iftherodsandconesdie off,lightcannolongerbeconverted intoelectricalsignalsandtransferredto theopticnerve.Therefore,thepatient becomesblind. Historyofthedevice:1929 electricalstimulationofthevisual cortexledtoperceptionoflight;1968 contactlenselectrode=blindcan senseelectricallyexcited PopulationAffected:Nearly1M legallyblindinUSA,Australiaand Europe Researchworldwide:onlyabout20 groupsandcompaniesworldwide workingonthesetypesofdevices

Visualprosthesis:BionicEye

Itsasifyourethrowingatelevisionintotheoceanandexpectingittowork

Biomaterials and Devices for the Nervous System

a)

b)

c)

2 mm

d)

5 mm 10 mm f) 200 um 5 mm g) 200 um 10 mm 2 mm

e) 5 mm 5 mm

h)

2 mm

i)

k)

10 mm

j)

2 mm

Ordonez, J. et al. (2012) MRS Bulletin 37:6; 590-598 Zhong, Y. et al. (2011) J Roy Soc Inter 5:957 Hamann M.C. et al. (2003) Exper Neuro 182:2; 300-309

Deguchi et al. (2006) Cere Blood Flow 26:10; 1263-1273 http://www.ima.umn.edu/industrial/97_98/hamlen/Image3.jpg http://neuroanimations.com/Hydrocephalus/Shunts/Complications

BrainMachineInterfacesRequireProximitytoNeuronalCellBodies

http://news.brown.edu/pressreleases/2009/06/braingate2;Buzski,G,NatNeurosci 2004;Normann etal.JNeuroscienceMethods 1998

Cortical Neuroprostheses implantation causes insult:

Infection Hemorrhage Damaged brain barriers Inflammation

Cut through soft tissue & expose skull

Drill through skull to expose cortical tissue

Insert electrodes into the cortical tissue

Abbot Nat. Rev. Neurosci, 2006

ChronicInflammatoryResponseleadstoNeurodegeneration

Microglia

Healthy Neuron

Dying Neuron

Activated Microglia

Astrocyte

Soluble Factors

Blood

Scalebar=100m
He,W.W.Reichert,CRCPress, 2008;Potter,KA.JournalofNeuroscienceMethods 2012;Winslow,B.D.andP.A.Tresco (2010).Biomaterials 2010;McConnell,G.C.,etal.JournalofNeuralEngineering 2009

 Variabilityfromtwoshanksononedevice oneshowsnoscaring,and theothershowsdenseglialscar Resultsarejustasvariableforpreventativemeasures

Trescoetal2005;StensaasandStensaas,1976;Reieretal.,1983;Turneretal.,1999;Edelletal.,1992

Stab/removevs.chronicimplanthealing
StabChronic Microglia 4wks2wks StabChronic Astrocytes

GlialScar

Stab=Healsinweeks,withnoresidualactivatedmicroglia orastrocytes Chronic=Scargetsmoredensewithtime,stayaslongas probeisimplanted

Biranetal.ExpNeurol 2005

Stab/removevs.chronicimplanthealing
StabChronic StabChronic

GlialScar

4wks2wks

NeuralFilament Stab=Nolongtermeffectson neurons Chronic=Neuronalfilamentdoes notregenerate,andneuronalcell bodiesdonotsurviveinclose proximitytotheinterface.

NeuronalCellBodies

2wks4wks Deadzone=>100m (4weeks);Recordingsitemustbe<20m

Biranetal.ExpNeurol 2005

fromcellbodytodeterminebetweenneurons

ChronicInflammatoryResponseleadstoNeurodegeneration

Microglia

Healthy Neuron

Morphology
Shape,Size,Roughness

Dying Neuron

Porosity Chemistry Modulus

Activated Microglia

Astrocyte

Soluble Factors

Blood

Micromotion CausesContinualStrainandTissueDamage

100GPa

1GPa

1MPa

CompliantMaterialsReduceStrain

1030m =pressurechanges,respiration 24m =vascularpulsatility 1060m=administrationofanesthesia

Highmodulusenablesinsertion Lowmodulusreducesstrain

Kipke etal.JNeuralEng 2005.

SeaCucumberInspiredMechanicallyAdaptiveNanocomposite

Relaxed Soft SeaCucumberDermis Matrix:Lowmodulus biomatrix Nanofiller:Collagen FillerInteractions: Glycoprotein

Threatened Stiff AdaptivePolymerNanocomposite Matrix:Lowmodulus polymer(PVAc) Nanofiller:Cellulosewhiskers FillerInteractions:Hydrogen bonds

Capadonaet al.NatureNanotech.2007;Capadonaetal.Science 2008;Capadonaetal.Biomacromolecules 2009,2010;Capadonaetal. MaterialsResearchBulletin 2012

GlialScar MajorPlayers:CellTypes Foreignobjectsneedtoberemoved phagocytosis

Microglia inthenormalbrainareinaquiescent state,withshort branchedprocesses.(510%glialpopulation,nomacrophagelike receptors. Followinginjurytheyexhibitvariousbehaviors,includingactivation, celldivision,andmigration totheinjury.Also,upregulateenzymes, receptors,andreleaseinflammatoryfactors MHCI,II(leakyBBB= macrophagerecruitment).Activationpersistininjurysitesformany weeks untilhealed.

Macrophages=Wherethereisvasculardamage,therewillalsobe massivemacrophagerecruitmentfromtheblood.Elevatednumbers ofmicroglial/macrophagecellspersistuntilinjuryisphagocytosed.

GlialScar

MajorPlayers:CellTypes

Whatcantberemoved,mustbewalledoff

RestingAstrocytes =810nmindiameterGFAPfilaments,round neucleus,maintainnueronalenvironment,gapjunctionswithother astrocytes,3065%ofglialpopulation

ReactiveAstrocyte =largeincreaseinGFAPfilaments,irregular nucleus,proliferates,phagocytosis,migration,secretionofECM proteins,producesneurotrophicandinflammatorycues

GlialScar Noninflammatory,residentcells

MajorPlayers:CellTypes

Myelindebrisisslowlyremovedbymicroglia.Someofthe oligodendrocytesdie,butsomesurviveandglialscarstherefore generallycontainsomeoligodendrocytesandforsometimecontain myelindebris.Whethertheseoligodendrocyescanregeneratetheir processestomakenewmyeliniscontroversial.

MeningealCells =Anyinjurythatpenetratesthemeningealsurfaceofthe brainorspinalcordisrapidlyinvadedbymigratingmeningealcells,whichre createthecontinuouslayerofcellsthatcoverstheCNS.Thesecellsalsoplay apartthroughtheirinteractionswithastrocytesinthereformationofthe glialimitansthatsurroundstheCNS. Sources??? TheextenttowhichtheyparticipateinCNSinjuriesisnotclear, sincethereisatpresentnoreliablemarkerthatallowsthesecellstobe identified.