Kinetics of facial motoneuron loss following facial nerve transection in severe combined immunodeficient mice

We have recently shown that cells of the acquired immune system are crucial components of motoneuron survival after injury (Serpe et al. [1999] J. Neu rosci. 19. RC7). The goal of the present study was to determine the kinetic s of facial motoneuron (FMN) loss in wild-type, scid, and reconstituted sci d mice after a right facial nerve axotomy at the stylomastoid foramen. Scid mice showed a significant decrease in FMN survival at all weekly postopera tive (wpo) times. One, two, four, and ten wpo, ipsilateral FMN survival in scid mice was 90% +/- 1.8%, 84% +/- 1.3%, 52% +/- 3.7%, and 45% +/- 2.5%, r espectively, of the contralateral, unoperated side. In contrast, FMN loss a fter axotomy in wild-type and reconstituted scid mice was not observed unti l 4 wpo (86% +/- 2.5% and 83% +/- 3.5%, respectively) relative to the contr alateral, unoperated side. However, the levels of FMN in both wild-type and reconstituted scid mice were significantly higher than those in the nonrec onstituted scid at 4 wpo. By 10 wpo, FMN survival in both wild-type and rec onstituted scid mice had continued to decline significantly (60% +/- 2.1% a nd 58% +/- 3.1%, respectively) relative to the contralateral, unoperated si de but were still significantly higher than that of the nonreconstituted sc id at 10 wpo. Several important controls were also added to this study. Bec ause the scid mutation is present in all cells (although it specifically re sults in a loss of V(D)J recombination mechanisms, we wanted to rule out th e actual DNA mutation as causal in FMN loss). To accomplish this, we used t he recombinase-activating gene-2 knockout (RAG-2 KO) mouse model, in which the RAG-2 has been disrupted and prevents maturation of T and B cells. As w ith the scid model, there was a significant loss of FMN at 4 wpo in the RAG -2 KO that could be reversed with whole splenocyte reconstitution. We also compared FMN numbers in nonaxotomized facial nuclei from both scid and RAG- 2 KO mice relative to wild-type controls. No differences in normal numbers of FMN were found in either the mutation or the gene knockout model. The ab ility of T and B lymphocytes to rescue FMN from cell death after peripheral nerve injury supports the hypothesis that cells of the acquired immune sys tem produce neurotrophic factors or neurocytokines to support neuronal surv ival until target reconnection occurs. (C) 2000 Wiley-Liss, Inc.