MECHANISMS OF MOTOR RECOVERY AFTER SUBTOTAL SPINAL-CORD INJURY - INSIGHTS FROM THE STUDY OF MICE CARRYING A MUTATION (WLD(S)) THAT DELAYS CELLULAR-RESPONSES TO INJURY

Partial lesions of the mammalian spinal cord result in an immediate mo tor impairment that recovers gradually over time; however, the cellula r mechanisms responsible for the transient nature of this paralysis ha ve not been defined. A unique opportunity to identify those injury-ind uced cellular responses that mediate the recovery of function has aris en from the discovery of a unique mutant strain of mice in which the o nset of Wallerian degeneration is dramatically delayed. In this strain of mice (designated Wld(s) for Wallerian degeneration, slow), many of the cellular responses to spinal cord injury are also delayed. We hav e used this experimental animal model to evaluate possible causal rela tionships between these delayed cellular responses and the onset of fu nctional recovery. For this purpose, we have compared the time course of locomotor recovery in C57BL/6 (control) mice and in Wld(s) (mutant) mice by hemisecting the spinal cord at T8 and evaluating locomotor fu nction at daily postoperative intervals. The time course of locomotor recovery (as determined by the Tarlov open-field walking procedure) wa s substantially delayed in mice carrying the Wld(S) mutation: C57BL/6 control mice began to stand and walk within 6 days (mean Tarlov score of 4), whereas mutant mice did not exhibit comparable locomotor functi on until 16 days postoperatively. Interpretation and conclusion: (a) T he rapid return of locomotor function in the C57BL/6 mice suggests tha t the recovery resulted from processes of functional plasticity rather than from regeneration or collateral sprouting of nerve fibers. (b) T he marked delay in the return of locomotor function in Wld(s) mice ind icates that the processes of neuroplasticity are induced by degenerati ve changes in the damaged neurons. (c) These strains of mice can be ef fectively used in future studies to elucidate the specific biochemical and physiological alterations responsible for inducing functional pla sticity and restoring locomotor function after spinal cord injury. (C) 1998 Academic Press.