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

Abstract

We have recently shown that cells of the acquired immune system are crucial components of motoneuron survival after injury (Serpe et al. [1999] J. Neurosci. 19:RC7). The goal of the present study was to determine the kinetics of facial motoneuron (FMN) loss in wild-type, scid, and reconstituted scid mice after a right facial nerve axotomy at the stylomastoid foramen. Scid mice showed a significant decrease in FMN survival at all weekly postoperative (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%, respectively, of the contralateral, unoperated side. In contrast, FMN loss after axotomy in wild-type and reconstituted scid mice was not observed until 4 wpo (86% +/- 2.5% and 83% +/- 3.5%, respectively) relative to the contralateral, unoperated side. However, the levels of FMN in both wild-type and reconstituted scid mice were significantly higher than those in the nonreconstituted scid at 4 wpo. By 10 wpo, FMN survival in both wild-type and reconstituted scid mice had continued to decline significantly (60% +/- 2.1% and 58% +/- 3.1%, respectively) relative to the contralateral, unoperated side but were still significantly higher than that of the nonreconstituted scid at 10 wpo. Several important controls were also added to this study. Because the scid mutation is present in all cells (although it specifically results in a loss of V(D)J recombination mechanisms, we wanted to rule out the actual DNA mutation as causal in FMN loss). To accomplish this, we used the 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 with 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 ability of T and B lymphocytes to rescue FMN from cell death after peripheral nerve injury supports the hypothesis that cells of the acquired immune system produce neurotrophic factors or neurocytokines to support neuronal survival until target reconnection occurs.