Nimodipine accelerates axonal sprouting after surgical repair of rat facial nerve

Abstract

Facial-facial anastomosis (FFA), i.e., suture of transected facial nerve, was performed in adult Wistar rats. For 10-112 d post-operation (DPO), half of the animals received standard food (placebo) and half received food pellets containing 1000 ppm nimodipine, a Ca2+ channel blocker. The time course of mimetic reinnervation between these two groups was compared by counting all retrogradely labeled motoneurons after injection of horseradish peroxidase (HRP) into the whiskerpad. In unoperated animals, injection of HRP labeled 1280 +/- 113 motoneurons. After FFA, this number dropped to zero, and the first HRP-labeled facial motoneurons reappeared in both placebo- and nimodipine-treated animals at 14 DPO. The treatment with nimodipine yielded two beneficial effects. (1) It accelerated axonal sprouting until 28 DPO. Whereas the number of HRP-labeled cells in the placebo group was 171 +/- 9 (mean +/- SD) at 16 DPO, 372 +/- 43 at 21 DPO, and 636 +/- 187 at 28 DPO, the number of sprouted motoneurons in nimodipine-treated rats was twice as high: 386 +/- 34 at 16 DPO, 620 +/- 28 at 21 DPO, and 756 +/- 257 at 28 DPO. (2) Nimodipine reduced the polyneuronal innervation of the target muscles. Whereas the number of HRP-labeled cells in the placebo group increased to 1430 +/- 36 at 56 DPO and 1600 +/- 31 at 112 DPO, the number of labeled motoneurons in nimodipine-treated rats remained almost within the normal range: 1315 +/- 31 at 56 DPO and 1354 +/- 33 at 112 DPO.

Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial

“…The beneficial effect of nimodipine treatment for the protection and regeneration of the facial and cochlear nerves is supported by animal experiments 1,6,8,9,[12][13][14][15] and clinical trials in VS surgery. 2,20,21,24,25 Furthermore, these positive results were also observed in laryngeal 8,14 and maxillofacial surgery 23 and may therefore be transferable to other surgical procedures with nerves at risk.…”

“…Although Voluven 6% is approved by the FDA and no adverse events related to HES (especially renal toxicity) were observed in the present study, the neuroprotective effect of HES is questionable, taking into consideration that animal experiments and clinical trials using nimodipine alone showed evidence of comparable neuroprotective efficacy. 1,6,8,9,[12][13][14][15]23 From a pharmacokinetic point of view, parenteral ni- modipine produces higher drug levels and has a higher neuroprotective efficacy compared with enteral administration. 22 Therefore, a central venous access is needed.…”

Intraoperative neurophysiological monitoring in vestibular schwannoma surgery: advances and clinical implications

“…1 The surgical approach used is either the middle fossa approach or retrosigmoid transmeatal approach. Intraoperative cochlear nerve monitoring has been traditionally performed with BAEPs.…”

Local Administration of Nimodipine and Improvement of Functional Recovery of the Transected Sciatic Nerve after Bridging with Inside-out Artery Graft

“…Nimodipine, a calcium channel blocker, is a US Food and Drug Administration approved drug used to reduce the morbidity and mortality associated with delayed ischemic deficits in patients with subarachnoid hemorrhage. In addition to its activity in the central nervous system, nimodipine has shown promise in multiple rodent models as a possible pharmacologic treatment for facial nerve injury (Angelov et al, 1996;Mattsson et al, 1999;Mattsson et al, 2001;Lindsay et al, 2010). To the best knowledge of the authors, the literature is poor regarding the beneficial local effects of nimodipine on transected sciatic nerve.…”