Critical period in muscle spindle regeneration in grafts of developing rat muscles

Abstract

Extensor digitorum longus (EDL) muscles from rats at various intervals after birth were grafted into EDL muscles of adult recipients. Three to twelve months after the operation, host muscles containing the grafts were removed and examined for the presence of muscle spindles in the graft. The aim of the study was to establish when muscle spindles become capable of regeneration during development. Regenerated muscles grafted during the first week after birth were virtually spindleless. Grafts of muscles transplanted 10 and 15 days postnatally contained only 5-8 muscle spindles on average. In contrast, the regenerated grafts originating from muscles of 24- and 28-day-old rats were spindle-rich as in mature muscle grafts; the number of spindles in the transplanted EDL muscles (25.0 +/- 2.3; mean +/- SE) attained values comparable to free standard autografts of these muscles in adult animals. Thus, the critical period after grafting, which also involves the loss of a vascular supply, is considerably longer than the critical period for muscle-spindle survival after nerve injury. Fifteen days after birth, when muscle spindles still survive denervation, only a few regenerated spindles were present in the individual muscle regenerates. We assume that the low resistance of immature spindle capsules to ischaemia accounts for their massive degeneration and abortive spindle regeneration in grafts from 10- to 15-day-old rats.

Expression of nestin, desmin and vimentin in intact and regenerating muscle spindles of rat hind limb skeletal muscles

“…It was shown (Jirmanová and Soukup 1995) that grafts of muscles transplanted 10 and 15 days postnatally contained only 5-8 regenerated spindles on average, due to the low resistance of immature spindle capsules to ischemia. This apparently accounts for the low number of muscle spindles analyzed on serial sections in our regenerated muscles grafted 15 days postnatally.…”

“…The maintenance and handling of experimental animals was in accordance with EU Council Directive (86/609EEC) and the investigation was approved by the Expert Committee of the Institute of Physiology, ASCR. In the heterochronous isotransplantation, we grafted EDL or soleus muscles of 15-day-old rats into the left EDL muscles of 2 to 3-monthold inbred Lewis female rats as described previously (Jirmanová and Soukup 1995). BrieXy, the animals were anesthetized with an intraperitoneal injection of Nembutal (sodium pentobarbital 40 mg/kg i.p.)…”

“…Surviving satellite cells become activated, divide and give rise to nascent myoblasts and subsequently new myoWbers with centrally localized nuclei are formed within 7-9 days after grafting. Intrafusal myoWbers of muscle spindles also degenerate and regenerate in grafted muscles (Milburn 1976;Rogers and Carlson 1981;Rogers 1982;Diwan and Milburn 1986;Jirmanová and Soukup 1995). These Wbers and their innervation undergo necrosis simultaneously with the extrafusal myoWbers, but the spindle capsule persists.…”

“…In order to achieve skeletal muscle regeneration, we used a model of intramuscular heterochronous isotransplantation (Jirmanová and Soukup 1995). Extensor digitorum longus (EDL) or soleus muscles from 15-day-old rats were transplanted into EDL muscles of adult female inbred Lewis rats.…”

Development & Plasticity

“…We have introduced a model of heterochronous allotransplantation (Jirmanova & Soukup, 1995), which enables us to study various combinations of muscle lineage (slow or fast muscle), type of innervation (axons with low or high impulse frequency) and level of thyroid hormones (hyper-, hypo-, euthyroid state).…”