N Bouche | PubMed Health

PubMed2001

Nerve growth factor- and neurotrophin-3-releasing guidance channels promote regeneration of the transected rat dorsal root.

Dorsal roots have a limited regeneration capacity after transection. To improve nerve regeneration, the growth-promoting effects of the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were evaluated. The proteins were continuously released by synthetic nerve guidance channels bridging a 4-mm gap in the transected dorsal root. Four weeks after lesion, the regenerated nerve cables were analyzed for the presence of myelinated and unmyelinated axons. While BDNF showed a limited effect on axonal regeneration (863 +/- 39 axons/regenerated nerve, n = 6), NGF (1843 +/- 482) and NT-3 (1495 +/- 449) powerfully promoted regeneration of myelinated axons compared to channels releasing the control protein bovine serum albumin (293 +/- 39). In addition, NGF, but not BDNF nor NT-3, had a potent effect on the regeneration of unmyelinated axons (NGF, 55 +/- 1.4; BDNF, 4 +/- 0.3; NT-3, 4.7 +/- 0.3 axons/100 microm(2); n = 6). The present study suggests that synthetic nerve guidance channels slowly and continuously releasing the neurotrophins NGF and NT-3 can overcome the limited regeneration of transected dorsal root.

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PubMed1995

Hydrogel-based three-dimensional matrix for neural cells.

The ability to organize cells in three dimensions (3D) is an important component of tissue engineering. This study sought to develop an extracellular matrix (ECM) equivalent with a physicochemical structure capable of supporting neurite extension from primary neural cells in 3D. Rat embryonic day 14 striatal cells and chick embryonic day 9 dorsal root ganglia extended neurites in 3D in agarose hydrogels in a gel concentration-dependent manner. Primary neural cells did not extend neurites above a threshold agarose gel concentration of 1.25% wt/vol. Gel characterization by hydraulic permeability studies revealed that the average pore radius of a 1.25% agarose gel was 150 mm. Hydraulic permeability studies for calculating average gel pore radius and gel morphology studies by environmental and scanning electron micrography showed that the average agarose gel por size decreased exponentially as the gel concentration increased. It is hypothesized that the average gel porosity plays an important role in determining the ability of agarose gels to support neurite extension. Lamination of alternating nonpermissive, permissive, and nonpermissive gel layers facilitated the creation of 3D neural tracts in vitro. This ability of agarose hydrogels to organize, support, and direct neurite extension from neural cells may be useful for applications such as 3D neural cell culture and nerve regeneration. Agarose hydrogel substrates also offer the possibility of manipulating cells in 3D, and may be used as 3D templates for tissue engineering efforts in vitro and in vivo.

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