Early methylprednisolone impact treatment for sensory and motor function recovery in patients with acute spinal cord injury A self-control study

BACKGROUND： For the treatment of spinal cord injury, any pathological changes of the injured tissue should be primarily corrected or reversed. Any remaining fibrous function and neurons with intact structure should be retained, and the toxic substances caused by ischemia-hypoxia following spinal cord injury, should be eliminated to create a favorable environment that would promote neural functional recovery. OBJECTIVE： This study was designed to investigate the effects of the impact of early methylprednisolone-treatment on the sensory and motor function recovery in patients with acute spinal cord injury. DESIGN： A self-control observation. SETTING： Department of Spine Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. PARTICIPANTS： Forty-three patients with acute spinal cord injury were admitted to the Department of Spine Surgery, First Affiliated Hospital of Nanjing Medical University, between October 2005 and September 2007. These patients were recruited for the present study. The patients comprised 33 males and 10 females, and all met with the inclusive criteria namely, the time between suffering from acute spinal cord injury and receiving treatment was less than or equal to eight hours. METHODS： According to the protocol determined by the State Second Conference of Acute Spinal Cord Injury of USA, all patients received the drop-wise administration of a 30-mg/kg dose of methylprednisolone （H200040339, 500 mg/bottle, Pharmacia N.V/S.A, Belgium） for 15 minutes within 8 hours post injury. After a 45-minute interval, methylprednisolone was administered at 5.4 mg/kg/h for 23 hours. MAIN OUTCOME MEASURES： Prior to and post treatment, acupuncture sense and light touch scoring were performed at 28 dermatomic area key points, including occipital tuberosity and supraclavicular fossa. At the same time, motor scoring of key muscles among 10 pairs of sarcomeres was also performed. RESULTS： All 43 patients participated in the final analysis. There was no significant difference of sensory and motor scores in patients with complete acute spinal cord injury between prior to and post methylprednisolone impact treatment （P 〉 0.05）. The motor score was significantly decreased in patients with incomplete acute spinal cord injury post methylprednisolone impact treatment （P 〈 0.01 ）. CONCLUSION： Early methylprednisolone impact may improve the motor function of patients with incomplete acute spinal cord injury. However, it has no influences on patients with complete acute spinal cord injury.

Anatomical changes in the somatosensory system after large sensory loss predict strategies to promote functional recovery after spinal cord injury

Among cases of spinal cord injury are injuries involving the dorsal column in the cervical spinal cord that interrupt the major cutaneous afferents from the hand to the cuneate nucleus（Cu）in the brainstem.Deprivation of touch and proprioceptive inputs consequently impair skilled hand use.

Establishment and Functional Evaluation of a Rat Model of Spinal Cord Injury

Objective:To explore the modified Allen impactor method in establishing a rat model of spinal cord injury,and to preliminarily evaluate the motor function of the forelimbs and hindlimbs of rats.Methods:Thirty female SD rats with a body weight of 255±21g were randomly divided into two groups,namely the sham-operated group and the operated group,with 15 rats in each group.The spinal cord injury SD rat model was established by exposing but not injuring the spinal cord in the sham-operated group,while the SD rat model was established by the modified Allen impactor method in the operated group.The Basso-Beattie-Bresnahan(BBB)rating scale was used to assess the rats’hindlimb motor neurobehavior.A rat model of spinal cord injury was established by the modified Allen impactor method.After the cells were transplanted,the BBB score was used to evaluate the motor function;the changes in the motor function of rats with spinal cord injury were detected.Results:The motor function and sensory function of the forelimbs and hindlimbs of the rats showed significant changes after five days.The motor function of the forelimbs and hindlimbs of the rats in the sham-operated group were essentially normal after three days(about 20 points);the sensory function of the rats in the operated group decreased significantly after five days;however,in the sham-operated group,it decreased to 0.The motor function scores of the rats in the operated group at each point of time were significantly lower than those in the sham-operated group(p<0.05),while the forelimb motor function scores were significantly higher than those in the sham-operated group(p<0.05).Conclusion:The modified Allen impactor method that was used to establish a rat model of spinal cord injury in this study can significantly reduce the motor function of rats.

Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injury

Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the field of nerve damage repair. In the present study, human placenta-derived mesenchymal stem ceils were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the restoration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.

Use of FK506 and bone marrow mesenchymal stem cells for rat hind limb allografts

Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance, bone marrow mesenchymal stem cells were intramuscularly （gluteus maximus） injected with FK506 （tacrolimus） daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 ＋ bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 ＋ bone marrow mesenchymal stem cells group. The FK506 ＋ bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.

Genomics and morphometrics reveal the adaptive evolution of pikas

Pikas(Lagomorpha: Ochotonidae) are small mouselike lagomorphs. To investigate their adaptation to different ecological environments during their dispersal from the Qinghai-Xizang(Tibet) Plateau(QTP), we collected 226 pikas and measured 20 morphological characteristics and recorded habitat information. We also sequenced the genome of 81specimens, representing 27 putative pika species.The genome-wide tree based on 4?090 coding genes identified five subgenera, i.e., Alienauroa, Conothoa,Lagotona, Ochotona, and Pika, consistent with morphometric data. Morphologically, Alienauroa and Ochotona had similar traits, including smaller size and earlier divergence time compared to other pikas.Consistently, the habitats of Alienauroa and Ochotona differed from those of the remaining subgenera. Phylogenetic signal analysis detected 83 genes significantly related to morphological characteristics, including several visual and hearingrelated genes. Analysis of shared amino acid substitutions and positively selected genes(PSGs) in Alienauroa and Ochotona identified two genes, i.e.,mitochondrial function-related TSFM(p.Q155E) and low-light visual sensitivity-related PROM1(p.H419Y).Functional experiments demonstrated that TSFM-155E significantly enhanced mitochondrial function compared to TSFM-155Q in other pikas, and PROM1-419Y decreased the modeling of dynamic intracellular chloride efflux upon calcium uptake. Alienauroa and Ochotona individuals mostly inhabit different environments(e.g., subtropical forests) than other pikas, suggesting that a shift from the larger ancestral type and changes in sensory acuity and energy enhancement may have been required in their new environments. This study increases our understanding of the evolutionary history of pikas.