Comparison of the Effects of Botulinum Toxin Doses on Nerve Regeneration in Rats with Experimentally Induced Sciatic Nerve Injury

Abstract

This study was designed to compare the effects of various doses of botulinum neurotoxin A (BoNT/A) on nerve regeneration. Sixty-five six-week-old rats with sciatic nerve injury were randomly allocated to three experimental groups, a control group, and a sham group. The experimental groups received a single session of intraneural BoNT/A (3.5, 7.0, or 14 U/kg) injection immediately after nerve-crushing injury. The control group received normal intraneural saline injections after sciatic nerve injury. At three, six, and nine weeks after nerve damage, immunofluorescence staining, an ELISA, and toluidine blue staining was used to evaluate the regenerated nerves. Serial sciatic functional index analyses and electrophysiological tests were performed every week for nine weeks. A higher expression of GFAP, S100β, GAP43, NF200, BDNF, and NGF was seen in the 3.5 U/kg and 7.0 U/kg BoNT/A groups. The average area and myelin thickness were significantly greater in the 3.5 U/kg and 7.0 U/kg BoNT/A groups. The sciatic functional index and compound muscle action potential amplitudes exhibited similar trends. These findings indicate that the 3.5 U/kg and 7.0 U/kg BoNT/A groups exhibited better nerve regeneration than the 14 U/kg BoNT/A and control group. As the 3.5 U/kg and the 7.0 U/kg BoNT/A groups exhibited no statistical difference, we recommend using 3.5 U/kg BoNT/A for its cost-effectiveness.

The proneurogenic and microglial modulatory properties of botulinum toxin in the hippocampus of aging experimental mice

“…Notably, suppression of neuroinflammation has been proposed to facilitate neurogenesis, synaptic plasticity, and neuroprotection in the brain. (Hwang et al 2023), Therefore, the increased number of immature neurons observed in the hippocampus of BoNT-treated groups could be attributed to BoNT-mediated neurotrophic support and its anti-neuroinflammatory properties.…”

“…Wang, L reported that following 48 hours of treatment with BoNT, SH-SY5Y cells exhibit induced expression transcripts related to neuronal cell development and metabolic processes (Wang et al 2020). BoNT has been shown to up-regulate the level of brain-derived neurotrophic factor (BDNF), which is a crucial neurotrophin involved in the differentiation, neuron survival, and synaptic plasticity of newborn neurons in the adult brain (Hwang et al 2023), Therefore, the increased number of immature neurons observed in the hippocampus of BoNT-treated groups could be attributed to BoNT-mediated neurotrophic support and its anti-neuroinflammatory properties.…”

Short-Term Effects of Botulinum Toxin-A Injection on the Medial Gastrocnemius Histological Features in Ambulant Children with Cerebral Palsy: A Longitudinal Pilot Study

“…The mechanisms involved in muscle recovery after (repeated) injections with BoNT-A are not well understood. In an experimental nerve injury model, BoNT-A has been shown to accelerate axonal growth and increase the regeneration of myelinated fibers [ 56 ] while also releasing neurotrophic factors [ 57 ]. Spontaneous recovery from BoNT-A-induced gastrocnemius muscle atrophy in mice is associated with a strong upregulation of the mTOR/S6 kinase signaling pathway with the upregulation of myotrophic factors such as IGF-I and IGF-II [ 58 ].…”