Magnetic Insertion System for Flexible Electrode Implantation.

J Neurosci Methods. 2009 Jul 8; Jaroch DB, Ward MP, Chow EY, Rickus JL, Irazoqui PPChronic recording electrodes are a vital tool for brain research and neural prostheses. Despite decades of advances in recording technology, probe structures and implantation methods have changed little over time. Then as now, compressive insertion methods require probes to be constructed from hard, stiff materials, such as silicon, and contain a large diameter shank to penetrate the brain, particularly for deeper structures. The chronic presence of these probes results in an electrically-isolating glial scar, degrading signal quality over time. This work demonstrates a new magnetic tension-based insertion mechanism that allows for the use of soft, flexible, and thinner probe materials, overcoming the materials limitations of modern electrodes. Probes are constructed from a sharp magnetic tip attached to a flexible tether. A pulsed magnetic field is generated in a coil surrounding a glass pipette containing the electrode. The applied field pulls the electrode tip forward, accelerating the probe into the neural tissue with a penetration depth that is calibrated against the charge voltage. Mathematical modeling and agar gel insertion testing demonstrate that the electrode can be implanted to a predictable depth given system specific parameters. Trial rodent implantations resulted in discernible single-unit activity on one of the probes. The current prototype demonstrates the feasibility of a tension based, magnetically driven implantation system and opens the door to a wide variety of new minimally invasive probe materials and configurations.

Osteogenesis induced by extracorporeal shockwave in treatment of delayed osteotendinous junction healing.

J Orthop Res. 2009 Jul 14; Qin L, Wang L, Wan-Nar Wong M, Wen C, Wang G, Zhang G, Chan KM, Cheung WH, Leung KSHealing at the osteotendinous junction (OTJ) is challenging in orthopedic surgery. The present study aimed to test extracorporeal shockwave (ESW) in treatment of a delayed OTJ healing. Twenty-eight rabbits were used for establishing a delayed healing (DH) model at patella-patellar-tendon (PPT) complex after partial patellectomy for 4 weeks and then were divided into DH and ESW groups. In the ESW group, a single ESW treatment was given at postoperative week 6 to the PPT healing complex. The samples were harvested at week 8 and 12 for radiographic and histological evaluations with seven samples for each group at each time point. Micro-CT results showed that new bone volume was 1.18 +/- 0.61 mm(3) in the ESW group with no measurable new bone in the DH group at postoperative week 8. Scar tissue formed at the OTJ healing interface of the DH group, whereas ESW triggered high expression of VEGF in hypertrophic chondrocytes at week 8 and regeneration of the fibrocartilage zone at week 12 postoperatively. The accelerated osteogenesis could be explained by acceleration of endochondral ossification. In conclusion, ESW was able to induce osteogenesis at OTJ with delayed healing with enhanced endochondral ossification process and regeneration of fibrocartilage zone. These findings formed a scientific basis to potential clinical application of ESW for treatment of delayed OTJ healing. (c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Prospective Study on Neck Dissection after Primary Chemoradiation Therapy in Stage IV Pharyngeal Cancer.

Anticancer Res. 2009 Jul; 29(7): 2645-53Bremke M, Barth PJ, Sesterhenn AM, Budach V, Engenhart-Cabillic R, Werner JABACKGROUND: Definitive chemoradiation is a well-established option in the treatment of locally advanced squamous cell carcinoma of the head and neck. The intention of this study was to evaluate its efficacy on cervical lymph node metastases in a prospective study after a standardized protocol for chemoradiation (CRT) and histopathological evaluation, respectively. PATIENTS AND METHODS: The data of 25 patients (10 oropharynx, 15 hypopharynx) who received planned neck dissection after definitive chemoradiation for UICC stage IV carcinomas of the pharynx were analyzed. All patients were sonomorphologically staged positive for lymph nodes (3 patients: N1; 2 patients N2a; 7 patients N2b; 9 patients N2c and 4 patients N3). A neck dissection was carried out 8.9+/-1.5 weeks (range 6-13) post treatment. The specimens obtained from the different neck levels were histologically examined for viable tumour cells. RESULTS: Local control was achieved in 100% of all patients on endoscopy 9 weeks after the chemoradiation. In 14/25 patients (56%), still viable tumour tissue was found in the neck dissection (ND) specimen. Only one of these 14 patients (7%) was deemed suspicious for residual lymphadenopathy from clinical and diagnostic findings at re-staging after chemoradiation, the others were staged yN0. Postsurgical complications occurred in six patients (24%) such as bleeding and prolonged wound healing in one patient each and functional deficits in an additional four patients. One patient developed a scar recurrence seven months after surgery. CONCLUSION: Based on these findings, the ultimate efficacy of primary CRT should not be judged 8-10 weeks after the treatment. Therefore planned neck dissection should be performed no earlier than 12 weeks after primary CRT.

[Blocking of Notch signaling decreased scar formation in rabbit ear hypertrophic scar model]

Zhonghua Yi Xue Za Zhi. 2009 Apr 28; 89(16): 1088-92Diao JS, Zhang X, Ren J, Zeng HF, Liu B, Ma FC, Wang YM, Yang XT, Guo SZ, Xia WOBJECTIVE: To investigate the effects of Notch signaling on scars in a rabbit ear model of hypertrophic scarring. METHODS: The hypertrophic scar of rabbits' ears was reproduced. The left rabbit's ear wounds as the N-[N-(3,5-difluorophenacetyl-L-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT) treated group were treated intradermally with the gamma-secretase inhibitor DAPT to inhibit the activation of Notch at 1, 3, 7 and 14 day time points. The right ears as the control group were treated with normal saline at the same time points. Experimental and control wounds were harvested on days 14, 21, 28 and 35 post wounding, and then examined histologically to quantify hypertrophic index and fibroblasts. The expression of epidermal differentiation markers-keratin 14 (K14), keratin 19 (K19), Involucrin and Notch downstream molecules-P21, P63 were examined and analyzed with immunohistochemistry staining. RESULTS: Both hypertrophic index (1.93 +/- 0.32, 1.82 +/- 0.36, 1.79 +/- 0.25) and number of fibroblasts [(4.08 +/- 0.88), (3.30 +/- 0.53), (3.19 +/- 0.73) x 10(3)/mm(2)] in the DAPT treated group were significantly reduced on days 21, 28 and 35, compared with the control group [2.56 +/- 0.29, 2.61 +/- 0.30, 2.58 +/- 0.39, and (5.45 +/- 0.99), (4.80 +/- 1.13), (4.43 +/- 1.17) x 10(3)/mm(2), all P < 0.01)]. The K19, K14 and P63 increased their expression in the DAPT treated group (28.6% +/- 5.7%, 53.1% +/- 4.5%, 57.0% +/- 5.8%) relative to the control group (10.1% +/- 2.8%, 30.8% +/- 4.9%, 16.5% +/- 2.2%, all P < 0.01) on day 14 post wounding, while the Involucrin and P21 decreased their expression in the DAPT treated group (12.3% +/- 1.9%, 11.0% +/- 1.7%) relative to the control group (29.3% +/- 4.6%, 44.3% +/- 3.5%, both P < 0.01). CONCLUSION: Inactivation of Notch signaling will inhibit scar epidermis to over-differentiation, and thereby inhibit proliferation of hypertrophic scars in the rabbit ears.

NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury.

BMC Neurol. 2009 Jul 15; 9(1): 32Buss A, Pech K, Kakulas BA, Martin D, Schoenen J, Noth J, Brook GAABSTRACT: BACKGROUND: A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). Experimental spinal cord injury (SCI) has demonstrated rapid re-expression of CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery. The potential therapeutic relevance of interfering with CSPG expression or function following experimental injuries seems clear, however, the spatio-temporal pattern of expression of individual members of the CSPG family following human spinal cord injury is only poorly defined. In the present correlative investigation, the expression pattern of CSPG family members NG2, neurocan, versican and phosphacan was studied in the human spinal cord. METHODS: An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type. RESULTS: In sections from control spinal cord, NG2 immunoreactivity was restricted to stellate-shaped cells corresponding to oligodendrocyte precursor cells. The distribution patterns of phosphacan, neurocan and versican in control human spinal cord parenchyma were similar, with a fine reticular pattern being observed in white matter (but also located in gray matter for phosphacan. Neurocan staining was also associated with blood vessel walls. Furthermore, phosphacan, neurocan and versican were present in the myelin sheaths of ventral and dorsal nerve roots axons. After human SCI, NG2 and phosphacan were both detected in the evolving astroglial scar. Neurocan and versican were detected exclusively in the lesion epicentre, being associated with infiltrating Schwann cells in the myelin sheaths of invading peripheral nerve fibres from lesioned dorsal roots. CONCLUSIONS: NG2 and phosphacan were both present in the evolving astroglial scar and, therefore, might play an important role in the blockade of successful CNS regeneration. Neurocan and versican, however, were located at the lesion epicentre, associated with Schwann cell myelin on regenerating peripheral nerve fibres, a distribution that was unlikely to contribute to failed CNS axon regeneration. The present data points to the importance of such correlative investigations for demonstrating the clinical relevance of experimental data.