Introduction to spasticity and related mouse models

• Published in: Experimental neurology 2021-01, Vol.335, p.113491-113491, Article 113491
• Main Authors: Wieters, Frederique, Weiss Lucas, Carolin, Gruhn, Matthias, Büschges, Ansgar, Fink, Gereon R., Aswendt, Markus
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Animals; Cats; Corticospinal tract; Disease Models, Animal; H-reflex; Humans; Maladaptive plasticity; Mice; Multiple sclerosis; Muscle Hypotonia - physiopathology; Muscle Spasticity - physiopathology; Neuroinflammation; Rats; Reflex, Abnormal; Spasticity; Spinal cord injury; Stroke; Upper motor neuron syndrome
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2020.113491

Although spasticity is one of the most common causes of motor disability worldwide, its precise definition and pathophysiology remain elusive, which to date renders its experimental targeting tricky. At least in part, this difficulty is caused by heterogeneous phenotypes of spasticity-causing neurological disorders, all causing spasticity by involving upper motor neurons. The most common clinical symptoms are a series of rapid muscle contractions (clonus), an increased muscle tone (hypertonia), and augmented tendon reflex activity (hyperreflexia). This muscle overactivity is due to disturbed inhibition of spinal reflexes following upper motor neuron dysfunction. Despite a range of physical and pharmacological therapies ameliorating the symptoms, their targeted application remains difficult. Therefore, to date, spasticity impacts rehabilitative therapy, and no therapy exists that reverses the pathology completely. In contrast to the incidence and importance of spasticity, only very little pre-clinical work in animal models exists, and this research is focused on the cat or the rat spastic tail model to decipher altered reflexes and excitability of the motor neurons in the spinal cord. Meanwhile, the characterization of spasticity in clinically more relevant mouse models of neurological disorders, such as stroke, remains understudied. Here, we provide a brief introduction into the clinical knowledge and therapy of spasticity and an in-depth review of pre-clinical studies of spasticity in mice including the current experimental challenges for clinical translation.