Objective To review the research process of telomerase reverse transcriptase (TERT) in the restoration of neurological diseases. Methods The related l iterature on TERT in the restoration of neurological diseases was extensively reviewed and comprehensively analyzed. Results TERT was the significant component of telomerase and the critical regulator of telomerase activity. It played an important role in the pathomechanism of neurological diseases including tumors,neurodevelopmental deficits, and nerve injury. TERT was becoming a research focus in the reparative therapy of neurological diseases. Conclusion TERT has manifested its great academic significance and appl ication prospects in the reparative therapy of neurological diseases, which deserves a further investigation.
Peripheral nerve injury (PNI) is a common neurological dysfunction. In clinical practice, autologous nerve transplantation is used to solve problems related to PNI, such as limited donor resources, neuroma formation and high donor incidence rate. Therefore, searching for new nerve regeneration materials has become a hot research topic. The decellularized extracellular matrix (dECM) hydrogel provides a scaffold for nerve regeneration by removing the cellular components in biological tissues, preserving the extracellular matrix, and is a potential therapeutic material for nerve regeneration. This article reviews the research progress of dECM hydrogel for PNI and looks forward to the clinical prospects of this research direction.
Objective To analyze the therapeutic effect of olfactory ensheathing cells (OECs) transplantation for central nervous system diseases. Methods Between November 2001 and January 2008, 1 255 participants with central nervous system diseases were enrolled in this cl inical study for fetal OECs transplantation. There were 928 males and 327 femalesaged 1.2-87 (mean 40) years. The course of disease was (4.52 ± 4.67) years. Among them, 656 participants suffered from chronic spinal cord injury (SCI), 457 amyotrophic lateral sclerosis (ALS), 68 cerebral palsy (CP), 20 multiple sclerosis (MS), 11 the sequelae of stoke, 10 ataxia, and 33 residual diseases. The participants came from 71 countries or regions. Accidentally abortional fetal olfactory bulbs were donated voluntarily and were cultured for 2 weeks, then were transplanted. Results One thousand one hundred and twenty-eight cases were followed up for 2-8 weeks (mean 4 weeks) to obtain integrated data. Among them, the neurological functional amel ioration was noticed in 994 participants with the overall short-term improvement rate of 88.12%. Seventy-six patients experienced the various perioperative compl ications with the incidence rate of 6.74%. One hundred and twenty patients with SCI received over 1 year follow-up. And according to ASIA assessment, motor scores increased from (39.82 ± 20.25) to (44.55 ± 18.99) points, l ight touch scores from (51.56 ± 25.89) to (59.81 ± 27.72) points, pain scores from (50.36 ± 27.44) to (57.09 ± 28.51) points for foreign patients (P lt; 0.05); motor scores increased from (40.52 ± 20.80) to (46.45 ± 20.35) points, l ight touch scores from (55.64 ± 26.32) to (68.64 ± 25.89) points, pain scores from (57.05 ± 26.00) to (66.13 ± 24.29) points for good rehabil itation Chinese patients (overall P lt; 0.05); motor scores from (37.03 ± 18.52) to (38.03 ± 18.50 points (P lt;0.05), l ight touch scores from (45.88 ± 22.56) to (46.63 ± 23.09) points (P gt; 0.05), pain scores from (45.25 ± 23.68) to (45.28 ± 23.63) points (P gt; 0.05) for poor rehabil itation Chinese patients. Compared foreign patients and good rehabil itation Chinese patients with poor rehabil itation Chinese patients, difference in score change was remarkable (P lt; 0.05). One hundred and six cases of ALS, 32 CP, 8 MS, 7 ataxia, and 2 stroke sequelae were followed up for 3-48, 3-36, 2-20, 7-17, 6 and 24 months, One hundred and six cases of respectively. Majority of them (113/155, 72.9%）were benefited from OECs transplantation. Conclusion OECs transplantation into brain and spinal cord is feasible and safe . The therapeutic strategy is valuable treatment for such central nervous system diseases such as chronic SCI, ALS, CP and stroke sequelae and can improve the patients’ neurological functions and/or decrease the progressive deterioration.
The peripheral nerve group of the reparative and reconstructive surgery committee (branch of Chinese association of rehabilitation medicine) was established in 1995. Major research progress has been made in the repair, regeneration, and reconstruction of peripheral nerve injury. Professor GU Yudong initiated the contralateral cervical7 root (CC7) transfer for the treatment of total brachial plexus root injury in 1986. Now this method has been applied safely and effectively for 30 years with profound progress and refinement. In addition, the repair and reconstruction of peripheral nerve injury had achieved great development such as the treatment of spastic paralysis of upper limb, CC7 transfer using a modified prespinal route, the reconstruction of bladder function after spinal cord injury, the development of acellular allograft nerve, the small gap suture technique, the functioning free gracilis muscle transplantation, and contralateral S1 transfer which have been widely used in clinical application with good outcomes. With the progress of the biological manufacturing of peripheral nerve bio-materials and the remodeling of central nervous system after brachial plexus injury, a novel peripheral neuroscience research field was growing up. It is still a challenge for surgeons and scholars in this field to insist on the popularization and improvement of peripheral nerve repair and reconstruction by microsurgical technique, and to make efforts to transform the results of peripheral nerve research into clinical practice.
OBJECTIVE In order to investigate the opportunity of repair and prognosis of recurrent laryngeal nerve injuries after thyroidectomy. METHODS Twelve cases with recurrent laryngeal nerve injuries after thyroidectomy were immediately and delayed operated on nerve repair and reinnervation. In immediate operation, 5 cases were repaired by direct recurrent laryngeal nerve suture, and 1 case was treated by transposition of the phrenic nerve to the recurrent laryngeal nerve and sutured the adductor branch to the branch of ansa cervicalis. In delayed operation, 3 cases were treated by anastomosis the main trunk of ansa cervicalis to the adductor branch of recurrent laryngeal nerve, and 3 cases were operated on neuromuscular pedicle to reinnervate posterior cricoarytenoid muscle. RESULTS Followed up 6 months, the effect was excellent in 1 case who was immediately operated by selective reinnervation of the abductor and adductor muscles of the larynx, better in 9 cases, and poor in 2 cases who were delayed operated over 12 months. CONCLUSION It can be concluded that the earlier reinnervation is performed, the better prognosis is.
ObjectiveTo construct recombinant adenovirus expressing nerve growth factor (NGF) and myelin associated glycoprotein (MAG) (Ad-NGF-MAG) and to investigate its effect on repair and regeneration of sciatic nerve injury in rats. MethodsNGF and MAG gene sequences were cloned into shuttle plasmid pCA13 of adenovirus type 5. After packed in HEK293 cells, the recombinant Ad-NGF-MAG underwent sequence and identification. Thirty-two male Sprague Dawley rats were randomly divided into 4 groups (n=8): control group (normal control), adenovirus vector group (Ad group), Ad-NGF group, and Ad-NGF-MAG group. The sciatic nerve injury model was established by transection of the right sciatic nerve; then, the empty adenovirus vector, Ad-NGF, and Ad-NGF-MAG were injected into the gastrocnemius muscle of the affected limb at a dose of 1×108 PFU every other day for 3 times in Ad group, AdNGF group, and Ad-NGF-MAG group, respectively. The right sciatic nerve was exposed only, and then the incision was closed in the control group. The sciatic nerve function index (SFI) was measured, and neuro-electrophysiology was observed; mRNA and protein expressions of NGF and MAG were detected by RT-PCR and Western blot; and histological examination was performed at 31 days after operation. ResultsRecombinant adenovirus vectors of Ad-NGF and Ad-NGF-MAG were constructed successfully. All rats survived and incision healed by first intension. The SFI, nerve conduction velocity, evoked potential amplitude, and latent period of Ad-NGF-MAG group were significantly better than those of Ad group and Ad-NGF group (P < 0.05). MAG mRNA and protein expressions of Ad-NGF-MAG group were the highest in all the groups (P < 0.05). The expressions of NGF mRNA and protein increased in Ad-NGF group and AdNGF-MAG group when compared with control group and Ad group (P < 0.05). Histological examination showed that the nerve had good continuity in control group; nerve fibers disarranged in Ad group; neurons connections formed in some nerve fibers of Ad-NGF group, but nerve fibers arrange disorderly; and the growth of the nerve were ordered and wellstructured in Ad-NGF-MAG group. ConclusionAd-NGF-MAG can effectively promote the growth of the nerve and inhibit the form of abnormal branches, facilitating the repair of sciatic nerve injury in rats.
Objective To investigate the effectiveness of heterodigital antegrade digital artery island flap innervated by proper digital nerve and the dorsal branch of proper digital nerve for repairing digital volar complex soft tissue defects. Methods Between May 2014 and January 2018, 27 patients with digital volar complex soft tissue defects were treated. There were 17 males and 10 females with an average age of 37 years (range, 18-60 years). The causes included electric saw injury in 8 cases, twisted injury in 12 cases, and heavy pound injury in 7 case. There were 9 thumbs, 5 index fingers, 6 middle fingers, 3 ring fingers, and 4 little fingers. The interval between injury and admission ranged from 1 to 4 hours (mean, 2.5 hours). The defect size ranged from 2.2 cm×1.4 cm to 3.8 cm×2.3 cm. The mean length of unilateral proper digital nerve defect was 2.9 cm (range, 2-4 cm). All defects were repaired with heterodigital antegrade digital artery island flap innervated by the proper digital nerve and the dorsal branch of the proper digital nerve. The proper digital nerve and the dorsal branch of the proper digital nerve in the flap were anastomosed with the proper digital nerve stumps in the wound. The flap size ranged from 2.4 cm×1.6 cm to 4.1 cm×2.6 cm. A segment of dorsal branch of the proper digital nerve was intercalated into the defect of the proper digital nerve in donor site. And the defect of donor site was repaired with the full-thickness skin graft. Results All flaps and skin grafts survived, and the wounds healed by first intention. All patients were followed up 12-24 months (mean, 17 months). The appearance, color, and texture of the flaps were similar to the surrounding tissue. There was no pain and double sensibility in any flap. At last follow-up, the static two-point discrimination of the flaps ranged from 4 to 8 mm (mean, 5.3 mm). And the two-point discrimination of digital pulps of recipient and donor fingers ranged from 4 to 10 mm with the average of 6.2 mm and 6.0 mm, respectively. According to the functional assessment criteria of the upper limb formulated by the Hand Surgery Society of the Chinese Medical Association, the results were excellent in 18 cases and good in 9 cases. No scar contracture was observed in donor site. Conclusion The heterodigital antegrade digital artery island flap innervated by the proper digital nerve and the dorsal branch of the proper digital nerve provides a safe and simple technique with minimal donor site cost and satisfactory effectiveness, which could be an ideal option for repairing digital volar defect, especially for the defect complicated with digital nerve defect.
Objective To investigate the neuroprotective effect of conducting hydrogel loaded with tetramethylpyrazine sustained-release microparticles (hereinafter referred to as “TGTP hydrogel”) on spinal cord injury rats. Methods Forty-eight adult female Sprague Dawley rats were randomly divided into 4 groups: sham operation group (group A), model group (group B), conductive hydrogel group (group C), and TGTP hydrogel group (group D), with 12 rats in each group. Only laminectomy was performed in group A, and complete spinal cord transection was performed in groups B, C, and D. Basso-Bettie-Bresnahan (BBB) score was used to evaluate the recovery of hind limb motor function of each group before modeling and at 1, 3, 7, 14, and 28 days after modeling, respectively. At 28 days after modeling, the rats were sacrificed for luxol fast blue (LFB) staining to detect myelin regeneration. Nissl staining was used to detect the survival of neurons. Immunohistochemical staining was used to evaluate the expression of inflammation-related factors [nuclear factor кB (NF-кB), tumor necrosis factor α (TNF-α), and interleukin 10 (IL-10)]. Immunofluorescence staining and Western blot were used to evaluate the expression of neurofilament 200 (NF200). RseultsBBB scores of group A were significantly better than those of the other three groups at all time points after modeling (P<0.05); at 14 and 28 days after modeling, there was no significant difference in BBB scores between groups C and D (P>0.05), but the BBB score of group D was significantly better than that of group B (P<0.05). LFB staining and Nissl staining showed that the structure of neurons and myelin in group A was intact, and the myelin integrity and survival number of neurons in group D were significantly better than those in groups B and C. Immunohistochemical staining showed that the absorbency (A) value of NF-кB and TNF-α in group A were significantly lower than those in groups B and C (P<0.05), the A value of IL-10 was significantly higher than that in the other three groups (P<0.05); the A value of NF-κB in group D was significantly lower than that in groups B and C, the A value of TNF-α in group D was significantly lower than that in group B, while the A value of IL-10 in group D was significantly higher than that in group B (P<0.05). Immunofluorescence staining showed that the structure of neurons and nerve fibers in group A was clear and the fluorescence intensity was high. The fluorescence intensity of NF200 in group D was higher than that in groups B and C, and some nerve fibers could be seen. Western blot analysis showed that the relative expression of NF200 in group A was the highest, and the relative expression of NF200 in group D was significantly higher than that in groups B and C (P<0.05). Conclusion The TGTP hydrogel can effectively promote the recovery of motor function in rats with spinal cord injury, and its mechanism may be related to the regulation of inflammatory response.
Objective To analyze the therapy and effectiveness of ulnar styloid fracture complicated with wrist dorsal branch of ulnar nerve injury. Methods Between October 2005 and October 2012, 16 cases of ulnar styloid fracture complicated with wrist dorsal branch of ulnar nerve injury were treated. There were 14 males and 2 females with an average age of 42 years (range, 22-58 years). Fracture was caused by traffic accident in 8 cases, by mechanical crush in 5 cases, and by falling in 3 cases. According to the anatomical features of the ulnar styloid and imaging findings, ulnar styloid fractures were classified as type I (ulnar styloid tip fracture) in 1 case and type II (ulnar styloid base fracture) in 15 cases. The skin sensation of ulnar wrist was S0 in 5 cases, S1 in 1 case, S2 in 7 cases, and S3 in 3 cases according to the criteria of the British Medical Research Council in 1954 for the sensory functions of the ulnar wrist. The time from injury to operation was 6-72 hours (mean, 18 hours). Fracture was treated by operative fixation, and nerve was repaired by epineurium neurolysis in 13 cases of nerve contusion and by sural nerve graft in 3 cases of complete nerve rupture. Results All incisions healed by first intention. Sixteen patients were followed up for an average time of 14 months (range, 6-24 months). The X-ray films showed that all of them achieved bone union at 4-10 weeks after operation (mean, 6 weeks). No patient had complications such as ulnar wrist chronic pain and an inability to rotate. According to Green-O’Brien wrist scoring system, the results were excellent in 13 cases and good in 3 cases; according to the criteria of the British Medical Research Council in 1954 for the sensory functions of the ulnar wrist, the results were excellent in all cases, including 11 cases of S4 and 5 cases of S3+. Two-point discrimination of the ulnar wrist was 5-9 mm (mean, 6.6 mm). Conclusion For patients with ulnar styloid fracture complicated with wrist dorsal branch of ulnar nerve injury, internal fixation and nerve repair should be performed. It can prevent ulnar wrist pain and promote sensory recovery.
Objective To review the basic researches and the cl inical appl ication of the nano-neural tissue engineering materials, especially the electrically conductive carbon nanotubes (CNT). Methods The l iterature concerning the basic and cl inical researches of the conductive materials of nano-neural tissue engineering, especially the electrically conductive CNT were reviewed. Results The researches of conductive materials of nano-neural tissue engineering have made some progress, the electrically conductive CNT can not only promote Schwan cells’ adhension, migration, and prol iferation, but also mimic the function of electric conductivity of neural myel in and enhance neurite growth and regeneration. So the electrically conductive CNT make great sense in stimulating and directing the growth of neurite and the regeneration of axons. Conclusion Because of these unique properties, the electrically conductive CNT have great advantages in peripheral nerve repair and function reconstruction, and are promising to provide a novel method for cl inical peri pheral nerve repair and function reconstruction after injury.