Neuroprotective and Neuroregenerative Effects of Nimodipine in a Model System of Neuronal Differentiation and Neurite Outgrowth

Abstract

Nimodipine is a Ca 2+ -channel antagonist mainly used for the management of aneurysmal subarachnoid hemorrhage (aSAH) to prevent cerebral vasospasms. However, it is not clear if the better outcome of nimodipine-treated patients is mainly due to vasodilatation or whether other cellular neuroprotective or neuregenerative effects of nimodipine are involved. We analysed PC12 cells after different stress stimuli with or without nimodipine pretreatment. Cytotoxicity of 200 mM EtOH and osmotic stress (450 mosmol/L) was significantly reduced with nimodipine pretreatment, while nimodipine has no influence on the hypoxia-induced cytotoxicity in PC12 cells. The presence of nimodipine also increased the NGF-induced neurite outgrowth in PC12 cells. However, nimodipine alone was not able to induce neurite outgrowth in PC12 cells. These results support the idea that nimodipine has general neuroprotective or neuregenerative effect beside its role in vasodilatation and is maybe useful also in other clinical applications beside aSAH.

Prophylactic nimodipine treatment and improvement in hearing outcome after vestibular schwannoma surgery: a combined analysis of a randomized, multicenter, Phase III trial and its pilot study

“…Several retrospective and prospective clinical trials have pointed to a beneficial effect of nimodipine on longterm outcome of cranial nerve functions following VS, laryngeal, and maxillofacial surgery. 3,9,12,14,19,20,22,25,27,28 The beneficial effect of nimodipine treatment for the protection and regeneration of nerve tissue is also supported by animal experiments. 1,6,10,13,15 Additionally, basic research points to an underlying neuroprotective mechanism of nimodipine.…”

“…This work was based on a series of studies with nimodipine and HES treatment in VS surgery, each forming the basis for the next. First, a beneficial effect of the intraoperative start of nimodipine and HES for hearing preservation was reported in 2001, 3,27 and was later also noticed for facial nerve outcome. 20,28 The concept of a prophylactic administration of nimodipine and HES arose from these observations.…”

“…1,6,10,13,15 Additionally, basic research points to an underlying neuroprotective mechanism of nimodipine. 3,7,29 In principle, prophylactic treatment with neuroprotective drugs prior to interventions in which nerve tissue is at risk seems to be a novel and promising concept.…”

“…17 The beneficial impact of nimodipine on protection and regeneration of nerve tissue is supported by animal experiments, 1,6,10,13,15 and it has been used in combination with hydroxyethyl starch (HES) by several retrospective and prospective clinical trials. 3,19,20,27,28 A pilot study showed superiority of prophylactic nimodipine compared with an intraoperative start or no treatment. 19 A Phase III trial with facial nerve function assessed 12 months after surgery as the primary outcome showed no significant results.…”

A bout analysis reveals age-related methylmercury neurotoxicity and nimodipine neuroprotection

“…Nimodipine attenuated or blocked deficits in an incremental repeated acquisition (IRA) procedure [25], wheel-running and rotarod performance, and mortality [26]. CCBs, including nimodipine, also attenuate or block selective signs of normal aging [27,28,29,30,31] and other CNS insults [32,33,34,35,36,37; c.f. 38).…”