Reducing host aldose reductase activity promotes neuronal differentiation of transplanted neural stem cells at spinal cord injury sites and facilitates locomotion recovery.

Neural stem cell (NSC) transplantation is a promising strategy for replacing lost neurons following spinal cord injury. However, the survival and differentiation of transplanted NSCs is limited, possibly owing to the neurotoxic inflammatory microenvironment. Because of the important role of glucose metabolism in M1/M2 polarization of microglia/macrophages, we hypothesized that altering the phenotype of microglia/macrophages by regulating the activity of aldose reductase (AR), a key enzyme in the polyol pathway of glucose metabolism, would provide a more beneficial microenvironment for NSC survival and differentiation. Here, we reveal that inhibition of host AR promoted the polarization of microglia/macrophages toward the M2 phenotype in lesioned spinal cord injuries. M2 macrophages promoted the differentiation of NSCs into neurons in vitro. Transplantation of NSCs into injured spinal cords either deficient in AR or treated with the AR inhibitor sorbinil promoted the survival and neuronal differentiation of NSCs at the injured spinal cord site and contributed to locomotor functional recovery. Our findings suggest that inhibition of host AR activity is beneficial in enhancing the survival and neuronal differentiation of transplanted NSCs and shows potential as a treatment of spinal cord injury.

Selective anterior thoracolumbar/lumbar fusion and instrumentation in adolescent idiopathic scoliosis patients.

BACKGROUND: Selective anterior thoracolumbar/lumbar (TL/L) fusion and instrumentation in adolescent idiopathic scoliosis (AIS) patients with a structural major TL/L curve and a nonstructural minor thoracic curve is rarely reported. We investigate the correction results of these patients. METHODS: By reviewing the medical records and roentgenograms of AIS patients undergone selective anterior TL/L fusion and instrumentation, Cobb angle, correction rate of the major and minor curves, coronal balance, lowest instrumented vertebra (LIV) tilt, coronal disc angle immediately below the LIV (LIVDA) and radiographic shoulder height (RSH) were measured and analyzed. RESULTS: Forty patients were included. For the major TL/L curve, the mean coronal Cobb angle before and after operation were 43.9° and 8.7°, respectively, with an average correction rate of 80.2% (P = 0.000). While for the minor thoracic curve, the mean coronal Cobb angle before and after operation were 27.2° and 14.3°, respectively, with an average spontaneous correction rate of 47.4% (P = 0.000). At final follow-up, the coronal Cobb angles of the major and minor curves were 13.7° and 17.1°, respectively, with a mean correction loss of 5.0° and 2.9°, respectively. The coronal balance before and after operations was 13.2 mm and 11.5 mm, respectively. At the final follow-up, it turned to 5.6 mm, which was much better than that after operation (P = 0.001). The mean LIV tilt was 23.5° before operation, and was significantly improved after operation (8.3°, P = 0.000). At final follow-up, it was well maintained (10.6°). The LIVDA averaged 3.5° before operation, and aggravated to 5.5° after operation (P = 0.100) and 7.4° at final follow-up (P = 0.012), respectively. The RSH was 7.3 mm before operation, 5.6 mm after operation, and 2.2 mm at the final follow-up. The RSH at the final follow-up was significantly improved compared with that after operation (P = 0.002). CONCLUSIONS: Selective anterior TL/L fusion and instrumentation can get good correction results of both curves, with good results of the coronal balance and RSH in AIS patients, while a larger LIVDA.

[Selective anterior thoracolumbar or lumbar fusion for adolescent idiopathic scoliosis].

OBJECTIVE: To evaluate the outcomes of selective anterior thoracolumbar or lumbar (TL/L) fusion for adolescent idiopathic scoliosis (AIS) with PUMCIId1 curves (Lenke type 5). METHODS: Thirty-five consecutive AIS patients (PUMC type IId1, Lenke type 5) with selective anterior TL/L fusion with single solid rod instrumentation were reviewed. The average follow-up was 36 months (range, 18 - 42 months). Standing anteroposterior and lateral radiographs were measured and analyzed. RESULTS: The average preoperative Cobb angle of the TL/L curves was 45.6 degrees and corrected to 9.7 degrees postoperatively, with 79.7% curve correction. The thoracic curves decreased from 29.7 degrees preoperatively to 17.6 degrees postoperatively, with a spontaneous correction of 41.5%. There was an average 4.7 degrees and 2.5 degrees correction loss of the TL/L and the thoracic curves at the final follow-up respectively. Trunk shift deteriorated slightly from 14.0 mm preoperatively to 14.8 mm postoperatively, and improved significantly to 5.1 mm at the final follow-up. The lowest instrumented vertebra (LIV) tilt was significantly improved after surgery (from -21.8 degrees preoperatively to -1.5 degrees postoperatively) and well maintained at the final follow-up (-2.1 degrees). The coronal disc angle immediately above the upper instrumented vertebra (UIVDA) and below the LIV (LIVDA) averaged 0.5 degrees and 0.6 degrees respectively, and aggravated after surgery (0.9 degrees and 4.9 degrees, respectively). Both the UIVDA and LIVDA were significantly aggravated at the final follow-up (3.0 degrees and 7.8 degrees, respectively). The sagittal contours of T(5-12) and T(10)-L(2) were well maintained after surgery and at the final follow-up. The lumbar lordosis of L(1)-S(1) and the sagittal Cobb angle of the instrumented segments were reduced postoperatively and at the final follow-up. No pseudarthrosis or other complications were observed. CONCLUSION: Selective anterior TL/L fusion with single solid rod instrumentation is effective and safe for AIS with PUMCIId1 (Lenke type 5) curves, above and below the fusion and larger residual thoracic curve in some cases need further evaluated.

[Clinical diagnosis and surgical treatment of congenital contractural arachnodactyly: analysis of 6 cases].

OBJECTIVE: To discuss the clinical diagnosis and surgical treatment of congenital contractural arachnodactyly (CCA). METHODS: The clinical data of 6 CCA patients, 1 male and 5 female, aged 7.5 (5-14) were analyzed. All cases had kyphoscoliosis, 2 in the thoracic segments and 4 in the thoracolumbar segments. The average scoliosis Cobb angle was 88.6 degrees (85 degrees-117 degrees). The average kyphosis Cobb angle was 93.6 degrees (75 degrees-123 degrees). All of the cases underwent internal fixation with pedicle screw and lamina hooks instrumentation, in which 4 cases underwent posterior Smith-Petersen osteotomy. The diagnosis was based on a constellation of clinical findings. The clinical manifestations included marfanoid habitus, flexion contractures of multiple joints (elbow, knee, hip, and finger), kyphoscoliosis, muscular hypoplasia, and abnormal pinnae ("crumpled" outer helices). Molecular genetic testing showed mutation in the fibrillin-2 (FBN2) gene encoding the extracellular matrix microfibril. Four cases were followed up for 6-9 months. RESULTS: After operation the average Cobb angle of the scoliosis and kyphosis were 37.6 degrees (35 degrees-52 degrees) and 38.6 degrees (28 degrees-54 degrees) immediately, with 62.3% and 68.7% curve correction respectively. Three cases got excellent synostosis of posterior lamina, 1 case underwent revision with lamina hook because the distal screw was loose and hurt the nerve root, and the other 2 cases lost follow-up. The patients' body appearance and pulmonary function were obviously improved. CONCLUSION: The characteristic clinical manifestation include severe and stiff kyphoscoliosis, difficult to correct , and enhanced Cobb angle, and pedicle dysplasia of vertebral pedicle leading to difficulty in installing screws. Smith-Petersen osteotomy is often necessary. CCA should be differentiated with Marfan syndrome (MFS), Stickler syndrome, Homocystinuria, and distal arthrogryposis, especially MFS.