Direct Delivery of GDNF Into the Non-Human Primate and Human Parkinsonian Brain: Success and Road Blocks

Grondin, Richard; Zhang, Z; Ai, Yi; Slevin, John T.; Young, A. W.; Gash, D.; Gerhardt, Ga

doi:10.1016/b978-012373994-0.50011-7

Cited by 1 publication

(2 citation statements)

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“…Several factors have been shown to produce significant beneficial effects in the laboratory [81]. Only glial cell line-derived neurotrophic factor (GDNF) has been shown to dramatically protect and enhance the function of dopamine neurons in animal models of PD [82]- [84].…”

Section: A Introductionmentioning

confidence: 99%

“…The biologically active form is a glycosylated homodimer of kDa [86]. This section is a review of studies carried out in a nonhuman primate model of PD and in humans with PD involving site-specific delivery of GDNF by computer-controlled pumps coupled to infusion catheters [84]. While this work focuses on studies of GDNF and its potential use in treating PD, these studies lay the foundation for the site-specific delivery of many drugs to the brain that may be beneficial for treatment of neurodegenerative diseases and brain disorders.…”

Section: A Introductionmentioning

confidence: 99%

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The Impact of Neurotechnology on Rehabilitation

Berger

Gerhardt

Liker

et al. 2008

IEEE Rev. Biomed. Eng.

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This paper present results of a multi-disciplinary project that is developing a microchip-based neural prosthesis for the hippocampus, a region of the brain responsible for the formation of long-term memories. Damage to the hippocampus is frequently associated with epilepsy, stroke, and dementia (Alzheimer's disease) and is considered to underlie the memory deficits related to these neurological conditions. The essential goals of the multi-laboratory effort include: (1) experimental study of neuron and neural network function--how does the hippocampus encode information? (2) formulation of biologically realistic models of neural system dynamics--can that encoding process be described mathematically to realize a predictive model of how the hippocampus responds to any event? (3) microchip implementation of neural system models--can the mathematical model be realized as a set of electronic circuits to achieve parallel processing, rapid computational speed, and miniaturization? and (4) creation of hybrid neuron-silicon interfaces-can structural and functional connections between electronic devices and neural tissue be achieved for long-term, bi-directional communication with the brain? By integrating solutions to these component problems, we are realizing a microchip-based model of hippocampal nonlinear dynamics that can perform the same function as part of the hippocampus. Through bi-directional communication with other neural tissue that normally provides the inputs and outputs to/from a damaged hippocampal area, the biomimetic model could serve as a neural prosthesis. A proof-of-concept will be presented in which the CA3 region of the hippocampal slice is surgically removed and is replaced by a microchip model of CA3 nonlinear dynamics--the "hybrid" hippocampal circuit displays normal physiological properties. How the work in brain slices is being extended to behaving animals also will be described.

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Section: A Introductionmentioning

confidence: 99%

Section: A Introductionmentioning

confidence: 99%