Neural Tissue Engineering - Tissue Engineering
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Who won the nobel prize in chemistry for PCR?
Kary Mullis in 1993
What is the basic idea for PCR?
- Elevated temperature to melt doublestranded DNA
- DNA polymerase - enzyme for polymerizing bases
- Enzyme will recognize certain "ques" or "primers"
- Specific DNA strand or "primer" to recognize certain sequences at both ends of the DNA of interest
- Comes at it from different ends, repeats 25x and eventually have pure amplified DNA strand
- Use polymerase from thermophile bacteria - Taq was first but caused errors. Didn't have to replace enzyme each time.
- Use of Pwo or Pfu from archera bacteria has internal proof-reading mechanism to reduce errors
Prior to Taq, the protein would denature
What are some applications for Neuronal tissue engineering?
- Enhancing regeneration after injury
- Cell replacement therapy in neurodegenerative diseases
- Replacement of sensor inputs
- Replacement of motor control
- "Interactive interfaces" - Deep brain stimulation
- Brain-Machine interface
- Replacement of brain areas/functions
What is an example applications for enhancing regeneration after injury with neuronal tissue engineering?
- Spinal cord injury
- Brain trauma
- Scaffolds with neurons/stem cells/helper cells/growth factors
What is an example of a neurodegenerative disease that tissue engineering may assist with?
What are examples of sensory inputs that may be aided with tissue engineering?
- Cochlear implant
- Artificial vision
What would deep simulation assist in for tissue engineering?
It would assist in stimulating the brain against epilepsy and parkinson disease
What are some issues with neuronal tissue engineering?
- We do not clearly understand how the brain processes information.
- We do not have parallel interface to the brain similar to computers
- We do not have a chronic, non-invasive method to communicate with the brain.
- Bio-(in)compativity (physical, chemical, biological)
- Brain works more on efficiency rather than parallel processes
What direction does information from the nervous system flow?
Neuronal cellular structure. Information in the nervous system generally, but not always, flows from the dendrites to the axon.
What is the role of the hippocampus?
It plays an important role in converting short-term memories to long term memories and spatial navigation.
What is the intention of the biomimetic neuronal interface for the hippocampus?
By-pass the damaged brain region with a biomimetic device that mimics signal processing function of hippocampal neurons and circuits.
What is the role of the hippocampus in associative memory?
- Involved in establishing long-term "declarative" memories such as facts and names.
- Also includes associations of high-order features
- A hierachy of features generated within each sensory system.
- Highest order features are those inputs to hippocampus.
What is the pathway for short-term memories to be converted into the long-term memory in the hippocampus?
- Multi-modal representation
- Re-encoding for long-term storage
What area of the hippocampus is typically damaged?
DG or CA3 is typically damaged.
What is a coclear implant? How many electrodes are used to replace the 16,000 delivate hair cells that are typically used in this function?
The surgical implantation of a device that enables a person that has damaged or loss of hearing to hear sounds and noises. At most, 24 electrodes to replace the 16,000 hairs.
This includes the case in which the hammer/anvil/stirrup are damaged.
What is the perilymph? What is the process and it's location in the process of hearing?
The perilymph is extracellular fluid located in the cochlear.
The motion of the perilymph virbrates the endolyph in the scala media and causes movements of the hair bundles of the hair cells.
The hair cells convert vibration into electrical potentials. The hair cells in the Organ of Corti are tuned to certain sound freqencies (high vs low)
How are the hair cells arranged in the Organ of Corti?
The hair cells are arranged in four rows along the entire length of the cochlear coil. Three rows consist of outer hair cells and one row consists of inner hair cells.
The inner hair cells provide the main neural output of the cochlea. The outer cells main receive neural input from the brain and influences their motility as part of the cochlear's mechanical pre-amplifier. The input to the OHC is from the olivary body via the medial olivocochlear bundle.
How many rows does the out hair cell consist of?
- Three rows consist of the outer hair cells.
- One row consists of the inner hair cells.
What does the inner hair cells do in their role in hearing? What does the outer hair cells do in their role in hearing?
- The inner hair cells provide the main neural output of the cochlea.
- The outer hair cells mainly receive neural input from the brain.
(T/F) There are different growth factors for the different frequencies of hair cells and the inner vs outer hair cells.
What the four methods of cortical implants (vision implants)?
- Infront of the retina - Attached to inner surface of retina and stimulates inner retinal layer based on signals received by a camera and signal processor
- Behind the retina - Photodiodes are implanted underneath the retina and used to generate currents that stimulate directly the retina
- Optic nerve approach - Simulation of optic nerve by implanting a cuff electrode around nerve
- Cortical approach - Bioinspired retina to perform pre-processing function of retina and turns into signals that can exite the visual cortex in real time.
Describe the cortical implant approach of implanting infront of the retina.
Infront of the retina - Attached to inner surface of retina and stimulates inner retinal layer based on signals received by a camera and signal processor
Describe the cortical implant approach of implanting behind the retina.
Behind the retina - Photodiodes are implanted underneath the retina and used to generate currents that stimulate directly the retina
Describe the cortical implant approach of implanting on the optic nerve.
Optical nerve approach - Simulation of optic nerve by implanting a cuff electrode around nerve
Describe the cortical implant approach of implanting via the cortical approach.
Cortical approach - Bioinspired retina to perform pre-processing function of retina and turns into signals that can exite the visual cortex in real time.
Who developed a pair of glasses with a camera that sends images to a microchip attached to the eyeball?
John Wyatt at MIT.
(T/F) John Wyatt developed a pair of glasses with a camera that sends images to a microchip attached to the eyeball. The glasses also contained a coil that wirelessly transmits power to receiving coils surrounding the eyeball.
In John Wyatt's eyeball/glasses research, what does the microchip do upon receiving the images?
The microchip activates electrodes that stimulate nerve cells in the areas of the retina corresponding to the features of the visual scene. The electrode directly activate optical nerves that carry signals to the brain, bypassing the damaged layers of retina.
It has shown to have produced organized vision in the blind.
(T/F) Deep Brain Stimulation (DBS) is used to help control tremors and chronic movement disorders.
(T/F) Tiny electrodes are surgically implanted in the brain and are connected via a subcutaneous wire to a neurostimulator implanded under the skine near the clavicle.
(T/F) Over 2,00 people with Parkinson's disease in the US have had DBS systems implanted. For most people, DBS has relieved many symptoms and improved their ability to walk and do the activities of daily life.
What is a brain computer interface device (BCID)?
An external device that communicates with the brain of humans or animals through neuron silicon interfaces.
What are types of brain computer interface devices?
- Direct neuronal contact (invasive)
- Electroencephalography (EEG): First non-invasive neuroimaging technique (measures electrical activity)
- Magnetoencephalography (MEG): Records the magnetic fields produced by electrical activity
- Functional Magnetic Resonance Imaging (fMRI): Measures the haemodynamic response (blood flow and blood oxygenation) related to neural activity in the brain by the use of MRI.
- VEP interface (Vision envoked potential): Caused by visual stimulation
- ERS/ERD (Event related synchronization/desynchronization) : Signal type that can be measured when the subject imagines a hand or foot movement.
What is EEG?
Electroencephalography - First non-invasive neuroimaging technique (mesures electrical activity)
What is MEG?
Magnetoencephalography - records the magnetic fields produced by electric activity
What is fMRI?
Functional magnetic resonance imaging - measures the haemodynamic response (blood flow and blood oxygenation) related to neural activity in the brain by the use of MRI
What is VEP interfacing?
Visual Evoked Potential - which is caused by a visual stimulation.
What is ERS/ERD?
Event Related Synchronization/ Desynchronization - a signal type that can be measured when the subject imagines a hand or food movement.
(T/F) It has been demonstrated that primates can reach and grasp virtual objects by controlling a robotic arm through a closed-loop brain-machine interface (BMIc) that uses multiple mathematical models to extract several motor parameters (ie hand position, gripping etc) from the electrical activity of frontoparietal neuronal esembles.
True. Read that.
In the paper in 1998 Chronic recording capability of the Utah Intracortical Electrode Array, what was shown concerning the use of the array?
Even though the array itselfwas functional over the chronic implant periods studied, the location of the electrode tips was constantly changing as the fibrous tissue accumulated between thearray and the cortex.
The accumulation of fibrous tissue was believed to be associated to hitting blood vessels during implantation.
What has been shown to reduce the response in neural prosthetic devices. What cell has a reduced response?
dexamethasone slowly released by EVAc-polymer ribbons.
The astrocyte responses are greatly reduced and brain tissue conforms directly to the polymer ribbon.
Reactive responses of astrocytes can be controlled by slow releaseof dexamethasone from EVAc polymer. (A)–(B) Significant astrocyticresponse and enlargements of the insertion site are observed around insertedEVAc-polymer ribbons. (C)–(D) When dexamethasone is incorporated into the EVAc-polymer ribbons, astrocyte responses are greatly reduced and braintissue conforms directly to the polymer ribbon.
What is an astrocyte?
Star-shaped glia cells that have a role in scarring in the brain and the spinal cord.
They perform many functions, including biochemical support of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a role in the repair and scarring process of the brain and spinal cord following traumatic injuries.
What is a demyelinating disease?
Any disease of the nervous system in which the myelin sheath of neurons is damaged.
This impairs the conduction of signals in the affected nerves, causing impairment in sensation, movement, cognition, or other functions depending on which nerves are involved.
What are functional in vitro systems?
Assays or systems between single cell assays (ie proliferation, metabolic, live/dead) and an animal or human test.
What are factors affecting tissue reaction to implanted electrodes?
- Mechanical trauma
- Foreign body reaction
- Implantation method
- Physical properties of the electrode (size, shape and surface characteristics)
Main cell types involved in the inflammatory and wound healing response to the brain injury and materials implanted in the CNS are _________________________ which respond very rapidly.
microglia/blood-borne macrophages, oligodendrocyte precursors (OPCs) and astrocytes
(T/F) Astrocyte activation is also mediated by blood-borne factors including growth factors and hormones, albumin, thrombin, angiotensin II and cAMP.
Astrocyte activation is also mediated by blood-borne factors including growth factors and hormones, albumin, _______, angiotensin II and cAMP.
What are two different approaches to reduce the inflammatory response to implanted electrodes?
- Material science approach involving modifying the electrode size, shape and materials.
- Bioactive molecule strategies look at the administration of anti-inflammatory agents
- Using electrode coatings (ie nitrocellulose coatings as a polymer matrix for storage and sustained release of the anti-inflammatory agent Dexamethasone)
- Direct injections from embedded microchannels (microfluidic drug delivery)
- Systemic injections - not viable due to difficulties in crossing the blood-brain barrier and side effects in peripheral metabolism
What is an anti-inflammatory agent for the brain? What cells have shown a reduction in scarring with this agent?
Dexamethasone has shown a reduction in scarring done by astrocytes.
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