Sabrina Jedlicka 9/20/2010 NEUROENGINEERING

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1 Sabrina Jedlicka 9/20/2010 NEUROENGINEERING

2 What is neuroengineering? Neuroengineering is an interdisciplinary field, combining engineering and computational approaches to problems in basic and clinical neuroscience Biomedical Engineering i Neuro engineering BioMEMS

3 Highly Interdisciplinary Field Research and education in neuroengineering i encompasses the fields of engineering, mathematics, and computer science This is coupled with molecular, cellular, and systems neurosciences

4 Neurological Disorders Over 600 known neurological disorders Diseases of the CNS and PNS Epilepsy Alzheimer s Stroke Diseases that attack the nervous system Infections Cancers Physical Injury For most, treatment options are extremely limited These disorders range from a loss of cells or tissue, to faulty electrical signaling

5 Primary Goals of Neuroengineering Analyze the function of the nervous system Develop methods to restore damaged neurological lfunctions Create artificial neuronal systems

6 Several Neuroengineering Subfields Diagnostic Devices and Systems Assistive Devices Smart Prosthetics Neural Cell/Tissue Engineering Brain Computer Interfaces Neural Stimulators Neural Prosthesis: Implanted Sensors and Devices Artificial cochlea Artificial retina Hippocampal prosthesis

7 Neural Prosthetics Bridging the gap between neuroprosthetic design, tissue engineering, and neurobiology Hochberg, 2006, Cyberkinetics Corp

8 New Devices to Treat Epilepsy What is Epilepsy? ~1% of industrialized population 5 10% of non industrialized population ~60 million people worldwide Treatments? Surgery Not all patients are candidates Not all patients are candidates Pharmacological Treatment 2.7 million patients have seizures resistant to pharmacological treatment Other patients suffer intolerable drug side effects

9 Glutamate/GABA Imbalance Transporter Biology/2918/0/

10 New Approach The 2000 National Institutes t of Health Curing Epilepsy Conference: "successfully use a biosensor device (comprised of a biodetector, mini pump, microstimulator, or other detector systems) that reliably anticipates or identifies seizures, and applies targeted treatment to abort seizures in at least one form of epilepsy."

11 Closed Loop Approach

12 New Approaches Being Tested Implanted drug pumps: These provide temporal and spatial delivery Implanted Neural Recorder/Stimulator: Record EEG and Attenuate to stop seizures The biological approach: The transplantation of g pp p biomolecule releasing cells provides spatial delivery of drug

13 The Interface: One Type of Electrode Used Julien Modolo, Basabdatta Bhattacharya, Roderick Edwards, Julien Campagnaud, Alexandre Legros and Anne Beuter (2010) Frontiers in Neuroprosthetics

14 Ongoing Research in Electrode Array Technology Smaller, more sensitive ii Algorithm Development for Seizure Prediction Feedback Loop Control Location of Device Implantation Techniques Control of False Positives

15 Major Interest Area Controlling host response Long term stable electrode/neuron interface Gliosis Biomaterial Coatings Cone Electrodes/NGF Cage Electrodes

16 Gliosis Asya Rolls, Ravid Shechter & Michal Schwartz Nature Reviews Neuroscience 10, (March 2009)

17 Gliosis upon Electrode Implantation Acute Chronic Jennie B. Leach, Anil Kumar H. Achyuta, and Shashi K. Murthy (2010) Frontiers in Neuroengineering.

18 Some of the molecules Secreted in Response to CNS Injury ART_DOI= /neuro

19 Gliosis Effects Jennie B. Leach, Anil Kumar H. Achyuta, and Shashi K. Murthy (2010) Frontiers in Neuroengineering.

20 How to Combat Gliosis? Bioactive Coatings Cell Adhesion Molecules Anti Inflammatory Agents Encapsulated cells Coating the Electrodes Target and draw in NPCs Jennie B. Leach, Anil Kumar H. Achyuta, and Shashi K. Murthy (2010) Frontiers in Neuroengineering.

21 Cell Adhesion Molecules NCAM 1 Integral membrane protein Inhibits attachment of astrocytes, etc. Supported Neurite Outgrowth Webb, et al. Biomaterials 22(10): 1017 (2001).

22 Anti Inflammatory Agents Immobilized anti Inflammatory Tridecapeptide He, et al. Advanced Materials 19(21): 3529 (2007)

23 Cell Encapsulation for Neurite Guidance Schwann Cells were encapsulated within a fibrin gel. The gel was placed in contact with rat spinal cord coated with fibroblast sieve filled coating Neurites penetrated the sieves Schlosshauer et al. Brain Research 903(1 2): 237 (2001)

24 Stimulate NPCs When microglia are treated with Interferon γ or Interleukin 4, NPCs differentiate into neurons Butovsky et al. Molecular and Cellular Neuroscience 31(1): 149 (2006)

25 How to combat Gliosis? Mechanical Camofluoge Limit micromotion Transcranial Intracranial

26 Limiting Micromotion Stimuli Responsive Polymers that can change stiffness Capadona et al. Science 319(5868): 1370 (2008)

27 Transcranial vs. Intracranial Tethered microelectrodes (to the cortical brain tissue) elicit greater response.

28 A couple more approaches Jennie B. Leach, Anil Kumar H. Achyuta, and Shashi K. Murthy (2010) Frontiers in Neuroengineering.

29 How to Combat Gliosis Need a Multi Tiered Approach Modify Surface of Implant Enhance Neuronal Growth Discourage Microglia/Macrophage/Astrocytic /A i Response Add Soluble Cues Modify the Mechanics of the Implant Implant Placement Jennie B. Leach, Anil Kumar H. Achyuta, and Shashi K. Murthy (2010) Frontiers in Neuroengineering.

30 So, in Epilepsy Closed Loop Devices What is Downstream of the Electrode? Drug Pumps Drug Producing Active Cells Glutamate Attenuation Many other approaches

31 Much more work to be done Will require collaboration at the intersection i of neuroprosthetics, tissue engineering and neurobiology.