The effects of adjuvant fibrin sealant on the surgical repair of segmental nerve defects in an animal model.

PURPOSE: Nerve repair after a segmental defect injury remains a challenge for surgeons. Fibrin glue can be used to expedite surgical procedures and maintain proper nerve spatial orientation to potentially optimize recovery, yet surgeons hesitate to use it owing to concerns about fibrin's inhibiting regeneration and increasing scar formation. The purpose of these experiments was to evaluate whether fibrin glue impedes nerve regeneration. METHODS: A critical-size defect of 10 mm was created in 32 Sprague-Dawley rats with 4 different forms of repair: a collagen type-I conduit (n = 8), a collagen type-I conduit filled with fibrin glue (n = 8), an autologous nerve graft (n=8), and an autologous nerve graft with fibrin glue (n = 8). Behavioral tests, including sciatic functional indices, were used to evaluate functional recovery. Neurophysiology, immunohistochemistry, and nerve morphometry were used to critically analyze nerve regeneration. RESULTS: Multiple outcome parameters for nerve regeneration, remyelination, behavior, and electrophysiology were used to determine that the addition of fibrin did not influence recovery for the autograft groups. Similarly, within the conduit group, behavioral tests showed comparable functional recovery and indistinguishable results in compound motor action potential and nerve morphometry. Immunohistochemistry revealed identical degrees of Wallerian degeneration and scarring between conduit groups. CONCLUSIONS: The addition of fibrin to either the conduit or the autograft group did not result in any meaningful differences in recovery. Our data demonstrate that fibrin glue does not impede nerve regeneration or functional recovery after surgical repair of a segmental nerve defect in a rat model. CLINICAL RELEVANCE: The clinical use of fibrin glue as an adjunct with peripheral nerve repair may be considered safe because it does not impair nerve regeneration with critical size defects in an animal model.

Improved rotorod performance and hyperactivity in mice deficient in a protein repair methyltransferase.

The protein L-isoaspartate (D-aspartate)-O-methyltransferase participates in the repair of age-induced protein damage by initiating the conversion of abnormal aspartyl residues within proteins to normal L-aspartyl residues. Previous studies have shown that mice deficient in the gene encoding this enzyme (Pcmt1-/-) accumulate damaged proteins, have altered levels of brain S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy), and suffer from epileptic seizures that result in death at an average age of about 42 days. In this study, we found that the behavior of Pcmt1-/- mice is abnormal in comparison to their wild-type (Pcmt1+/+) and heterozygous (Pcmt1+/-) littermates in two standard quantitative behavioral assays - the accelerating rotorod and the open-field test. On the accelerating rotorod, we found Pcmt1-/- mice actually perform significantly better than their heterozygous and wild-type littermates, a situation that has only been infrequently described in the literature and has not been described to date for epilepsy-prone mice. The Pcmt1-/- mice show, however, hyperactivity in the open-field test that becomes more pronounced with age, with a partial habituation with time in the chamber. Additionally, these mice demonstrate a strong thigmotaxic movement pattern. We present evidence that these phenotypes are not related to the alterations of the AdoMet/AdoHcy ratio in the brain and thus may be a function of the accumulation of damaged proteins. These results implicate a role for this enzyme in motor coordination and cerebellum development and suggest the importance of the function of the repair methyltransferase in hippocampal-dependent spatial learning.