Stereotactic surgery allows procedures on structures deep within the brain, while minimizing damage to tissue above and surrounding the target structure. Traditionally, neurosurgical intervention has involved the removal of pathological tissues. However, an emerging application of neurosurgical technique is the insertion of cells (neurotransplantation), trophic factors, genes, chemo-therapeutics, neuroactive compounds, or other therapeutic agents Neurotransplantation of fresh tissue or neural stem cells holds promise as a method of reconstituting cell populations, supplementing levels of locally produced brain chemicals, and re-establishing neural circuitry. Despite some successes, functional recovery following brain cell injections has to date been modest, with high variability. Marginal functional recovery is directly associated with poor survival of the implanted cells. Improvements in cell survival would contribute to the utility of this potentially powerful therapeutic approach. Numerous studies have demonstrated that cell survival is increased when the injection instrument is smaller and the injection volume is reduced. Cells delivered through a pulled glass micropipette have 250 percent increased survival over cells injected through a 0.5 mm. stainless steel cannula. Commonly used injectors for human surgery are 0.5-1 mm. in diameter. This proposal is to develop an intracerebral microinjection instrument for implanting small volumes of cells deep within the brain, at multiple injection sites, with a minimum of invasive damage. In Phase I, we developed an instrument and demonstrated proof of concept. This device will be scaled to human length, and tested again in animal models of disease. We will perform all testing necessary to obtain FDA approval as an investigational device in humans.
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| Cunningham, Miles G; Bolay, Hayrunnisa; Scouten, Charles W et al. (2004) Preclinical evaluation of a novel intracerebral microinjection instrument permitting electrophysiologically guided delivery of therapeutics. Neurosurgery 54:1497-507; discussion 1507 |
