Neurotherapeutic action of testosterone on hamster facial nerve regeneration: temporal window of effects

Abstract

Neurotherapeutic or neuroprotective effects of gonadal steroids on the injured nervous system have been demonstrated in our laboratory and others. We have previously demonstrated that testosterone propionate (TP) administered systemically at supraphysiological levels accelerates both recovery from facial paralysis and regeneration rates following facial nerve injury in the hamster. Initial temporal studies of steroidal enhancement of functional recovery from facial paralysis established that steroid exposure is necessary during the first postoperative week. Furthermore, accumulated evidence suggests that TP manifests its effects on neuronal regeneration in the immediate postoperative or preregenerative phase by altering the cellular stress response. The purpose of this study was to identify the effective temporal window of TP exposure sufficient to enhance regenerative properties of injured facial motoneurons and functional recovery from facial paralysis induced by facial nerve injury. Adult castrated male hamsters received a right facial nerve crush axotomy at the stylomastoid foramen and were divided into (1) short term, (2) delayed, (3) continuous, and (4) no TP treatment groups. Short term and continuous groups were implanted with 1 subcutaneous (sc) TP capsule each immediately after axotomy, with the capsule removed at 30 min, 2, 4, or 6 h in short-term groups and allowed to remain for the duration of the experiment in the continuous group. In the delayed TP group, 1 sc TP capsule was implanted 6 h after axotomy and allowed to remain for the duration of the experiment. For regeneration rate studies, postoperative times ranged from 4 to 7 days. For the behavioral studies, observations were made for 26 days postaxotomy. The results point to a critical 6-h interval immediately after injury when TP enhances nerve outgrowth distances and augments behavioral recovery.