This review summarizes current information regarding the changes in structure or function that occur in skeletal muscle secondary to spasticity. Most published studies have reported an increase in fiber size variability in spastic muscle. There is no general agreement regarding any shift in fiber type distribution secondary to spasticity. Mechanical studies in whole limbs as well as in isolated single cells support the notion of an intrinsic change in the passive mechanical properties of muscle after spasticity in addition to the more widely reported neural changes that occur. Evidence is presented for changes within both the muscle cell and extracellular matrix that contribute to the overall changes in the tissue. Taken together, the literature supports the notion that, although spasticity is multifactorial and neural in origin, significant structural alterations in muscle also occur. An understanding of the specific changes that occur in the muscle and extracellular matrix may facilitate the development of new conservative or surgical therapies for this problem.

Eccentric contractions (ECs), in which a muscle is forced to lengthen while activated, result in muscle injury and, eventually, muscle strengthening and prevention of further injury. Although the mechanical basis of EC-induced injury has been studied in detail, the biological response of muscle is less well characterized. This study presents the development of a minimally invasive model of EC injury in the mouse, follows the time course of torque recovery after an injurious bout of ECs, and uses Affymetrix microarrays to compare the gene expression profile 48 h after ECs to both isometrically stimulated muscles and contralateral muscles. Torque dropped by approximately 55% immediately after the exercise bout and recovered to initial levels 7 days later. Thirty-six known genes were upregulated after ECs compared with contralateral and isometrically stimulated muscles, including five muscle-specific genes: muscle LIM protein (MLP), muscle ankyrin repeat proteins (MARP1 and -2; also known as cardiac ankyrin repeat protein and Arpp/Ankrd2, respectively), Xin, and myosin binding protein H. The time courses of MLP and MARP expression after the injury bout (determined by quantitative real-time polymerase chain reaction) indicate that these genes are rapidly induced, reaching a peak expression level of 6-11 times contralateral values 12-24 h after the EC bout and returning to baseline within 72 h. Very little gene induction was seen after either isometric activation or passive stretch, indicating that the MLP and MARP genes may play an important and specific role in the biological response of muscle to EC-induced injury.

Thirty eccentric contractions (ECs) were imposed upon rat dorsiflexors (n= 46) by activating the peroneal nerve and plantarflexing the foot ≈40 deg, corresponding to a sarcomere length change over the range 2.27‐2.39 μm for the tibialis anterior and 2.52‐2.66 μm for the extensor digitorum longus. Animals were allowed to recover for one of 10 time periods ranging from 0.5 to 240 h, at which time muscle contractile properties, immunohistochemical labelling and gene expression were measured. Peak isometric torque dropped significantly by ≈40 % from an initial level of 0.0530 ± 0.0009 Nm to 0.0298 ± 0.0008 Nm (P < 0.0001) immediately after EC, and then recovered in a linear fashion to control levels 168 h later. Immunohistochemical labelling of cellular proteins revealed a generally asynchronous sequence of events at the cellular level, with the earliest event measured being loss of immunostaining for the intermediate filament protein, desmin. Soon after the first signs of desmin loss, infiltration of inflammatory cells occurred, followed by a transient increase in membrane permeability, manifested as inclusion of plasma fibronectin. The quantitative polymerase chain reaction (QPCR) was used to measure transcript levels of desmin, vimentin, embryonic myosin heavy chain (MHC), myostatin, myoD and myogenin. Compared to control levels, myostatin transcripts were significantly elevated after only 0.5 h, myogenic regulatory factors significantly elevated after 3 h and desmin transcripts were significantly increased 12 h after EC. None of the measured parameters provide a mechanistic explanation for muscle force loss after EC. Future studies are required to investigate whether there is a causal relationship among desmin loss, increased cellular permeability, upregulation of the myoD and desmin genes, and, ultimately, an increase in the desmin content per sarcomere of the muscle.

Spasticity, a neurological problem secondary to an upper motor neuron lesion, has a significant effect on skeletal muscle. The upper motor neuron lesions may be secondary to a cerebral vascular accident, head injury, spinal cord injury, or degenerative diseases such as multiple sclerosis, or perinatal brain injuries such as cerebral palsy. Functional ability in these patients can be severely compromised but the basic mechanisms underlying these deficits are not clearly understood. In this review we evaluate the current evidence in the literature that suggests that skeletal muscle tissue itself is altered in spastic conditions. Experimental studies were evaluated that included a variety of methods encompassing joint mechanics, tissue mechanics, and muscle morphology. Taken together, the literature strongly supports the assertion that 'spastic muscles' are altered in a way that is unique among muscle plasticity models and inconsistent with simple transformation due to chronic stimulation or disuse. Further studies are required to detail the intra- and extracellular modifications of skeletal muscle that occur secondary to spasticity so that novel therapeutic treatments can be developed for this impairment.

The biological response of muscle to eccentric contractions (ECs) results in strengthening and protection from further injury. However, the cellular basis for this response remains unclear. Previous studies identified the muscle ankyrin repeat protein (MARP) family, consisting of cardiac ankyrin repeat protein (CARP), ankyrin repeat domain 2/ankyrin repeat protein with PEST and proline-rich region (Ankrd2/Arpp), and diabetes-associated ankyrin repeat protein (DARP), as rapidly and specifically upregulated in mice after a single bout of EC. To determine the role of these genes in skeletal muscle, a survey of skeletal muscle structural and functional characteristics was performed on mice lacking all three MARP family members (MKO). There was a slight trend toward MKO muscles having a slower fiber type distribution but no differences in muscle fiber size. Single MKO fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that these proteins may play a role in the passive mechanical behavior of muscle. Finally, MKO mice showed a greater degree of torque loss after a bout of ECs compared with wild-type mice, although they recovered from the injury with the same or even improved time course. This recovery was associated with enhanced expression of the muscle regulatory genes MyoD and muscle LIM protein (MLP), suggesting that the MARP family may play both important structural and gene regulatory roles in skeletal muscle.