Botulinum Toxin and Neuronal Regeneration after Traumatic Injury of Central and Peripheral Nervous System

Abstract

<jats:p>Botulinum neurotoxins (BoNTs) are toxins produced by the bacteria Clostridium botulinum, the causing agent for botulism, in different serotypes, seven of which (A–G) are well characterized, while others, such as H or FA, are still debated. BoNTs exert their action by blocking SNARE (soluble N-ethylmale-imide-sensitive factor-attachment protein receptors) complex formation and vesicle release from the neuronal terminal through the specific cleavage of SNARE proteins. The action of BoNTs at the neuromuscular junction has been extensively investigated and knowledge gained in this field has set the foundation for the use of these toxins in a variety of human pathologies characterized by excessive muscle contractions. In parallel, BoNTs became a cosmetic drug due to its power to ward off facial wrinkles following the activity of the mimic muscles. Successively, BoNTs became therapeutic agents that have proven to be successful in the treatment of different neurological disorders, with new indications emerging or being approved each year. In particular, BoNT/A became the treatment of excellence not only for muscle hyperactivity conditions, such as dystonia and spasticity, but also to reduce pain in a series of painful states, such as neuropathic pain, lumbar and myofascial pain, and to treat various dysfunctions of the urinary bladder. This review summarizes recent experimental findings on the potential efficacy of BoNTs in favoring nerve regeneration after traumatic injury in the peripheral nervous system, such as the injury of peripheral nerves, like sciatic nerve, and in the central nervous system, such as spinal cord injury.</jats:p>

Botulinum Neurotoxins in Central Nervous System: An Overview from Animal Models to Human Therapy

“…Regarding the spinal cord, although BoNTs have been considered as an off-label adjuvant therapy in treatment of both spasticity and bladder compliance in spinal cord injured patients [117,118], only a few studies have analyzed the effect of BoNTs directly injected in the spinal cord [24]. Marinelli et al [119] performed i.th.…”

“…level or intracerebral in specific brain structures. As an example, much evidence has been produced, mainly in animal models for safety reasons, in favor of a possible role of BoNTs in the treatment of spinal cord injuries or cerebral neurodegenerative processes [22][23][24]. Possible routes of administration of BoNTs are depicted in Figure 1.…”

Effect of Botulinum Toxin Injection and Extracorporeal Shock Wave Therapy on Nerve Regeneration in Rats with Experimentally Induced Sciatic Nerve Injury

“…Methods of surgical treatment include primary end-to-end repair and nerve grafts, and non-surgical treatments include physical therapy, electrical stimulation, hydrotherapy, and medications [5]. Attention has predominantly been focused on non-surgical therapeutic approaches, including new pharmacological or physical therapies to treat traumatic peripheral nerve injuries [6]. Two widely-used novel treatments, botulinum neurotoxin A (BoNT/A) and extracorporeal shock wave treatment (ESWT), have shown promise in modulating nerve regeneration after neural injury.…”

Preclinical Evidence for the Role of Botulinum Neurotoxin A (BoNT/A) in the Treatment of Peripheral Nerve Injury

“…Related topics such as the role of BoNT in the treatment of neuropathic pain will only be dealt with briefly, since they have been covered thoroughly elsewhere [ 44 , 47 , 48 ]. For a recent review on the effects of BoNT on injuries to the nervous system that includes the CNS, the reader is referred to Luvisetto [ 49 ].…”