Permanent denervation of rat Tibialis Anterior after bilateral sciatectomy: Determination of chronaxie by surface electrode stimulation during progression of atrophy up to one year

Permanent lack of motor innervation results in striking alterations of functional and structural properties of muscle. In SCI patients, direct Functional Electrical Stimulation of denervated muscles (FES of DDM) prevents or reverts muscle atrophy. FES is, however, believed to be effective when started early after SCI, since long term denervated muscle do not contract by commercial surface electrical stimulation. Whether this is the result of: 1. lack of muscle fibers; 2. their poor excitability, or 3. disarrangement of contractile machinery, is still an issue that deserves detailed time-course studies that are difficult in humans. In the present study, we investigated in a rat model, the progression of denervation-induced long term changes of Tibialis Anterior (TA). Muscle contraction elicited by external skin electrodes were studied up to 12 months after bilateral sciatectomy. Chronaxie analysis and histological structural findings showed that the sciatectomized TA undergoes: 1. a rapid atrophy process during the first month of denervation, accompanied by progressive increase of chronaxie that reached a stable increase during the second month after sciatectomy (early stage of rapid progressive atrophy); 2. a second phase of slow progressive atrophy up to 4 month-denervation, during which time no major changes in chronaxie or gross muscle mass occurred; 3. a third phase, during which the gross muscle mass remain stable, while the chronaxie either increased to infinite value (severe atrophy stage, from 4 to at least 12 months) or returned to the low values of reinnervated muscle. Histochemistry showed early disappearance of the slow type I fibers, followed by disappearance of the ATPase and of the SDH activities. On the other hand, the 9-month denervated muscle presents numerous “severely atrophic” muscle fibers. Our conclusion is that the lack of contractility of the long term denervated rat muscle is due to complete loss of contractile proteins long before muscle fibers decrease in number, a process that requires much more than 12 months in rat fast-twitch muscles.