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Diffusion of Nerve Growth Factor in Rat Striatum as Determined by Multiphoton Microscopy

Mark Stroh ^*, Warren R. Zipfel , Rebecca M. Williams , Watt W. Webb  and W. Mark Saltzman ^*

Departments of ^* Chemical and Biomolecular Engineering and Applied and Engineering Physics, Cornell University, Ithaca, New York 14853

Correspondence: Address reprint requests to Prof. W. Mark Saltzman, Yale University, P. O. Box 208284, New Haven, CT 06520. E-mail: mark.saltzman{at}yale.edu.

Neurotrophins such as nerve growth factor (NGF) may be useful for treating diseases in the central nervous system; our ability to harness the potential therapeutic benefit of NGF is directly related to our understanding of the fate of exogenously supplied factors in brain tissue. We utilized multiphoton microscopy to quantify the dynamic behavior of NGF in coronal, 400-µm thick, fresh rat brain tissue slices. We administered a solution containing bioactive rhodamine nerve growth factor conjugate via pressure injection and monitored the dispersion in the striatal region of the coronal slices. Multiphoton microscopy facilitated repeated imaging deep (200 µm) into tissue slices with minimal photodamage of tissue and photobleaching of label. The pressure injection paradigm approximated diffusion from a point source, and we therefore used the corresponding solution to the diffusion equation to estimate an apparent diffusion coefficient in brain tissue (D_b(34°C)) of 2.75 ± 0.24 x 10^-7 cm²/s (average ± SE). In contrast, we determined a corresponding free diffusion coefficient in buffered solution (D_f(34°C)) of 12.6 ± 0.9 x 10^-7 cm²/s using multiphoton fluorescence photobleaching recovery. The tortuosity, defined as the square root of the ratio of D_f to D_b, was 2.14 and moderate in magnitude.

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