Implantation of neuronal suspensions into contusive injury sites in the adult rat spinal cord

Summary Implants of various types of neuronal and nonneuronal tissue have shown promise for the amelioration of certain disorders of the adult mammalian brain. Implants may also have therapeutic potential for some lesions of the spinal cord. To examine the feasibility of implantation for clinically relevant spinal cord injuries, we have implanted cells into injury sites produced by a well-characterized and standardized rat model of contusive injury. To reduce the possibility of the implantation procedure itself causing damage to the spinal cord, the tissue was dissociated and a suspension of cells introduced into the cord via a small bore needle. To test the implantation procedure, dissociated adult rat dorsal root ganglia were used because of the ease with which these neurons could be distinguished after implantation. The extent to which functional deficits were produced or exacerbated by the implantation procedure was assessed by behavioral tests of groups of rats that had been implanted (implant controls), contused (injury only) or contused and implanted (injury-implant). Survival of the implanted neurons was assessed by quantitative morphological analysis of histological sections taken through the injury/implant sites at different times following injury. In addition, the histopathology of the contusive injury sites was compared for rats that had or had not received immediate or delayed implants. Results indicated that cell suspensions could be implanted into the spinal cord without causing a functional deficit in an otherwise uninjured animal or exacerbating a standardized incomplete contusive injury. Implanted neurons survived for at least 4 weeks in all contusion sites whether implantation was performed immediately following injury or after a delay or 1 week. There was no significant difference in neuron survival among the groups at 2 h, 18 h or 1 week after implantation. The average number of surviving neurons expressed as a percentage of those counted immediately after implantation was about 90% at 2 h, 50% at 18 h and 30% at 1 week. However, at 4 weeks after implantation, significantly more neurons survived in the delayed group as compared to the immediate group. The results demonstrate the feasibility of implanting dissociated nervous tissue into the sites of clinically relevant experimental contusive injuries and lay the groundwork for investigating possible beneficial effects of implants of different types of neural or glial cell suspensions in the treatment of contusive spinal cord injuries.Suported by the Stroke and Trauma Program, NIH NINCDS, NO1-NS-2-2310 and NO1-NS-7-2301