Functional recovery and facial motoneuron survival are influenced by immunodeficiency in crush-axotomized mice

Taylor Beahrs, Lisa Tanzer, Virginia M. Sanders, Kathryn J. Jones

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Facial nerve axotomy is a well-described injury paradigm for peripheral nerve regeneration and facial motoneuron (FMN) survival. We have previously shown that CD4+ T helper (Th) 1 and 2 effector subsets develop in the draining cervical lymph node, and that the IL-4/STAT-6 pathway of Th2 development is critical for FMN survival after transection axotomy. In addition, delayed behavioral recovery time in immunodeficient mice may be due to the absence of T and B cells. This study utilized a crush axotomy paradigm to evaluate FMN survival and functional recovery in WT, STAT-6 KO (impaired Th2 response), T-Bet KO (impaired Th1 response), and RAG-2 KO (lacking mature T and B cells) mice to elucidate the contributions of specific CD4+ T cell subsets in motoneuron survival and recovery mechanisms. STAT-6 KO and RAG-2 KO mice exhibited decreased FMN survival after crush axotomy compared to WT, supporting a critical role for the Th2 effector cell in motoneuron survival before target reconnection. Long term FMN survival was sustained through 10 wpo after crush axotomy in both WT and RAG-2 KO mice, indicating that target derived neurotrophic support maintains FMN survival after target reconnection. In addition, RAG-2 KO mice exhibited delayed functional recovery compared to WT mice. Both STAT-6 and T-Bet KO mice exhibited partially delayed functional recovery compared to WT, though not to the extent of RAG-2 KO mice. Collectively, our findings indicate that both pro- and anti-inflammatory CD4+ T cell responses contribute to optimal functional recovery from axotomy-induced facial paralysis, while FMN survival is supported by the anti-inflammatory Th2 response alone.

Original languageEnglish (US)
Pages (from-to)225-230
Number of pages6
JournalExperimental Neurology
Volume221
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Keywords

  • Facial nerve axotomy
  • Functional recovery
  • Motoneuron survival
  • T helper cells

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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