Fetal Transplants Alter the Development of Function after Spinal Cord Transection in Newborn Rats

Abstract

Pieces of fetal spinal tissue were transplanted into the site of complete midthoracic spinal transections in neonatal rat pups (transplant rats). The development of locomotion in these animals was compared with that of unoperated control rats and rats that received spinal transections alone (spinal rats). Reflex, treadmill and overground locomotion, staircase descent, and horizontal ladder crossing for a water reward were tested in control, spinal, and transplant rats from 3 weeks to adulthood. All tests were readily performed by control animals. Most spinal rats were unable to make many linked weight-supported steps on these tasks. Transplant rats were variable in their locomotor capabilities, but a subset of rats were able to demonstrate coordinated and adaptable locomotion on these tasks. Some transplant rats performed better on more challenging tasks, suggesting that motor strategies for these tasks used different information, perhaps from descending systems. Transplanted tissue survived, and in most cases there was immunocytochemical staining of serotonergic fibers passing into and caudal to the transplant, supporting the conclusion that descending systems grew through the transplanted tissue. Integration with the host tissue was often poor, suggesting that nonspecific or trophic effects of the transplant might also contribute to the development of locomotor function. Therefore several mechanisms may contribute to the repair of injured spinal cord provided by transplants that permit the development of useful locomotion.

Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence

“…Thus, together, of the total 56 NTX rats prepared, we found 13 (23%) were WS and 43 (77%) NWS. These proportions of WS and NWS match many prior published data for such NTX rats from our laboratory and others (Stelzner et al, 1975;Miya et al, 1997;Giszter et al, 2008a). The large sample size and relative stability of proportions between iterations of surgeries give statistical force to the later effects of robot training that we observed.…”

“…With the exception of anesthetic method (we used isoflurane as opposed to hypothermia), spinal transection surgery is largely as described in detail in Miya et al (1997) and Giszter et al (1998Giszter et al ( , 2008a. Neonates were placed under isoflurane anesthesia and maintained on an anesthetic plane (0.75%-2% mixed in oxygen), and sterile procedures were used throughout the surgery.…”

“…We classified the animals' locomotion into one of two categories: (1) weight-supporting (WS) or 2) non-weight-supporting (NWS). This was accomplished in a manner similar to Miya et al (1997) and Giszter et al (1998) by determining the proportion of autonomous hindlimb weight-supporting steps (%WSS) taken compared with the sum of hindlimb steps attempted (i.e., sum of weight-supported and non-weight-supported steps) (Miya et al, 1997;Giszter et al, 1998). The classification we used here was based on observations (Giszter et al, 2008a; see Materials and Methods) that most NTX rats showed either good consistent weight-supported stepping of Ͼ50%WSS (weight-supporting NTX rats or WS, usually ϳ20% of rats prepared) or poor weight-supported stepping of Ͻ50%WSS, which was often accompanied with frequent hindlimb scissoring action (NWS) (Giszter et al, 2008a) (usually ϳ80% of rats prepared).…”

“…The classification we used here was based on observations (Giszter et al, 2008a; see Materials and Methods) that most NTX rats showed either good consistent weight-supported stepping of Ͼ50%WSS (weight-supporting NTX rats or WS, usually ϳ20% of rats prepared) or poor weight-supported stepping of Ͻ50%WSS, which was often accompanied with frequent hindlimb scissoring action (NWS) (Giszter et al, 2008a) (usually ϳ80% of rats prepared). In prior work, the WS and NWS rats generated after neonatal spinal transection differed in a range of ways, with a "no-man's land" between the function levels of 20%-25%WSS and 45%-50% or better WSS (Miya et al, 1997;Giszter et al, 1998Giszter et al, , 2007. Of the 18 NTX rats prepared for robotic rehabilitation training, 4 (22%) were considered WS and 14 (78%) were considered NWS.…”

“…The total number of hindlimb weight-supported steps was expressed as a percentage of total hindlimb steps (i.e., sum of weight-supported and non-weight-supported steps) attempted (%WSS). This technique for quantifying autonomous weight-supported stepping (%WSS) was adopted from details by Miya et al (1997). A hindlimb step was considered as a weight-supported step if the hindlimb was seen to be raised above the surface of the treadmill with no contact of the belly, or proximal hindlimb joints (knee or hip), with the treadmill during the swing and stance phases of the hindlimb step cycle.…”