In post‐mitotic tissues, damaged cells are not replaced by new cells and hence effective local tissue repair mechanisms are required. In skeletal muscle, which is a syncytium, additional nuclei are ...obtained from muscle satellite (stem) cells that multiply and then fuse with the damaged fibres. Although insulin‐like growth factor‐I (IGF‐I) had been previously implicated, it is now clear that muscle expresses at least two splice variants of the IGF‐I gene: a mechanosensitive, autocrine, growth factor (MGF) and one that is similar to the liver type (IGF‐IEa). To investigate this activation mechanism, local damage was induced by stretch combined with electrical stimulation or injection of bupivacaine in the rat anterior tibialis muscle and the time course of regeneration followed morphologically. Satellite cell activation was studied by the distribution and levels of expression of M‐cadherin (M‐cad) and related to the expression of the two forms of IGF‐I. It was found that the following local damage MGF expression preceded that of M‐cad whereas IGF‐IEa peaked later than M‐cad. The evidence suggests therefore that an initial pulse of MGF expression following damage is what activates the satellite cells and that this is followed by the later expression of IGF‐IEa to maintain protein synthesis to complete the repair.
Recent reports indicate that walking capabilities in spinal cord damaged persons significantly improve--as compared to conventional rehabilitation therapy--after intensive training of aided ...(Laufband) treadmill-stepping. In the present report, follow up investigations on two collectives of spinal cord injured (sci) persons are described who had undergone (Laufband) treadmill therapy either during a period of renewed rehabilitation months or years after spinal cord injury (35 chronic patients) or during their first postacute rehabilitation period (41 acute patients). Among the initially chronic patients, 20 from 25 still wheelchair-bound before the onset of (Laufband) treadmill therapy, ie not capable of raising from the wheelchair and walking without help by other persons, became independent walkers after therapy. Assessment of voluntary muscle activity in resting position before and after the period of therapy had shown only small increases in most patients, indicating the involvement of motor automatisms and better utilisation of remaining muscle function during walking. Follow-up assessments performed 6 months to 6 1/2 years after discharge from the hospital revealed that the walking capabilities achieved by (Laufband) treadmill therapy in the 35 initially chronic patients were maintained in 31 persons, in three they had further improved, in only one it was reduced. These results indicate that the improvements achieved under clinical conditions can be maintained in every day life under domestic surroundings. From 41 initially acute patients, 15 had further improved and none had reduced his walking capability 6 months to 6 years after discharge from the hospital.
Recent reports indicate that intensive training of upright walking on a treadmill (German: Laufband, LB), significantly improves walking capability in spinal cord-damaged persons. The aids provided ...initially are body weight support by a harness and passive setting of one or both limbs by therapists. To facilitate stepping and evoke motor automatisms, "rules of spinal locomotion" need to be applied during training. The effects of this novel locomotion therapy on patients with chronic and acute incomplete paralysis are summarized and discussed here. Many patients with chronic paralysis, still wheelchair-bound and not capable of walking without help from others, became independent and learned to walk for some distance without help. Assessment of voluntary muscle activity in resting position before and after the period of therapy often showed only small increases, rendering the involvement of complex motor reflexes (motor programs) and better utilization of remaining muscle function during walking as main sources for the improvements in locomotion. This idea is supported by electromyographic recordings. Follow-up assessments performed 0.5 to 6.5 years after discharge from the hospital show that the significant improvements achieved by LB-therapy in patients with initially chronic paralysis can be maintained under domestic surrounding. Patients with initially acute paralysis improved their walking capabilities even further. It is suggested that LB therapy may be generally applied in the motor rehabilitation of persons with acute and chronic incomplete paraplegia and tetraplegia. Its use in other diseases is discussed.
We investigated the activation of lower limb motor pools by supraspinal and spinal networks after human spinal cord injury (SCI). We compared electromyographic (EMG) activity from six muscles during ...voluntarily attempted non-weight-bearing single-joint movements, multijoint movements approximating stepping in a supine position, and weight-bearing stepping on a treadmill with body weight support (BWST) in seven clinically incomplete and three clinically complete SCI subjects. Seven SCI subjects had previously completed Laufband therapy (a specific step training using variable levels of body weight support and manual assistance). Significant coactivation of agonists and antagonists and multijoint flexion or extension movements of the entire limb occurred during attempts at isolated knee or ankle single-joint movements in clinically incomplete SCI subjects. Further, some muscles that were not recruited during voluntary attempts at single-joint movements were activated during voluntary step-like multijoint movements (5/16 comparisons). This suggests that the residual voluntary motor control in incomplete SCI subjects evokes more generalized motor patterns (limb flexion or extension) rather than selective activation of individual muscles. Clinically incomplete and clinically complete SCI subjects could achieve greater activation of motor pools and more reciprocal patterns of activity between agonists and antagonists during weight bearing stepping than during non-weight-bearing voluntary movements. The EMG mean amplitudes were higher during stepping than during voluntary movements in 50/60 muscles studied (p < 0.05). These results suggest that stepping with knee and hip extension and flexion and alternating lower limb loading and unloading provides proprioceptive inputs to the spinal cord that increases motor recruitment and improves reciprocity between agonists and antagonists compared to voluntary efforts.
Pretreatment of muscles with ionising radiation enhances tissue formation by transplanted myoblasts but little is known about
the effects on muscle function. We implanted myoblasts from an expanded, ...male-donor-derived, culture (i28) into X-ray irradiated
(16 Gy) or irradiated and damaged soleus muscles of female syngeneic mice (Balb/c). Three to 6 months later the isometric
contractile properties of the muscles were studied in vitro , and donor nuclei were visualised in muscle sections with a Y chromosome-specific DNA probe.
Irradiated sham-injected muscles had smaller masses than untreated solei and produced less twitch and tetanic force (all by
about 18 %). Injection of 10 6 myoblasts abolished these deficiencies and innervation appeared normal.
Cryodamage of irradiated solei produced muscle remnants with few (1â50) or no fibres. Additional myoblast implantation led
to formation of large muscles (25 % above normal) containing numerous small-diameter fibres. Upon direct electrical stimulation,
these muscles produced considerable twitch (53 % of normal) and tetanic forces (35 % of normal) but innervation was insufficient
as indicated by weak nerve-evoked contractions and elevated ACh sensitivity.
In control experiments on irradiated muscles, reinnervation was found to be less complete after botulinum toxin paralysis
than after nerve crush indicating that proliferative arrest of irradiated Schwann cells may account for the observed innervation
deficits.
Irradiation appears to be an effective pretreatment for improving myoblast transplantation. The injected cells can even produce
organised contractile tissue replacing whole muscle. However, impaired nerve regeneration limits the functional performance
of the new muscle.
1. Myoblasts from expanded primary cultures were implanted into cryodamaged soleus muscles of adult BALB/c mice. One to four
months later isometric tension recordings were performed in vitro, and the ...male donor cells implanted into female hosts were
traced on histological sections using a Y-chromosome-specific probe. The muscles were either mildly or severely cryodamaged,
which led to reductions in tetanic muscle force to 33% (n = 9 muscles, 9 animals) and 70% (n = 11) of normal, respectively.
Reduced forces resulted from deficits in regeneration of muscle tissue as judged from the reduced desmin-positive cross-sectional
areas (34 and 66% of control, respectively). 2. Implantation of 10(6) myogenic cells into severely cryodamaged muscles more
than doubled muscle tetanic force (to 70% of normal, n = 14), as well as specific force (to 66% of normal). Absolute and relative
amount of desmin-positive muscle cross-sectional areas were significantly increased indicating improved microarchitecture
and less fibrosis. Newly formed muscle tissue was fully innervated since the tetanic forces resulting from direct and indirect
(nerve-evoked) stimulation were equal. Endplates were found on numerous Y-positive muscle fibres. 3. As judged from their
position under basal laminae of muscle fibres and the expression of M-cadherin, donor-derived cells contributed to the pool
of satellite cells on small- and large-diameter muscle fibres. 4. Myoblast implantation after mild cryodamage and in undamaged
muscles had little or no functional or structural effects; in both preparations only a few Y-positive muscle nuclei were detected.
It is concluded that myoblasts from expanded primary cultures-unlike permanent cell lines-significantly contribute to muscle
regeneration only when previous muscle damage is extensive and loss of host satellite cells is severe.
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