Restorative Neurology and Neuroscience - Volume 18, issue 1

Authors: Riess, Peter | Bareyre, Florence M. | Saatman, Kathryn E. | Cheney, Jessica A. | Lifshitz, Jonathan | Raghupathi, Ramesh | Grady, M. Sean | Neugebauer, Edmund | McIntosh, Tracy K.

Article Type: Research Article

Abstract: Purpose: Cyclosporin A (CsA) is widely used in clinical situations to attenuate graft rejection following organ and central nervous system transplantation. Previous studies demonstrated that CsA administration is neuroprotective in models of traumatic brain injury (TBI). However, no studies, to date, have evaluated the influence of post-injury CsA administration on behavioral recovery after TBI. Methods: Rats (n = 33) were anesthetized and subjected to severe, lateral fluid percussion brain injury. Fifteen minutes …thereafter, animals were randomized to receive the first of 28 daily injections of either CsA (10 mg/kg, ip) or saline. Sham-operated animals (n = 14) were anesthetized and surgically prepared without injury and treated daily either with CsA or saline. Motor and sensorimotor functions were assessed at one day before and two days after injury, and weekly thereafter up to 4 wks post-injury. Cognition was assessed at 1 and 4 wks post-injury using a Morris Water Maze test. Results: Injured animals showed significant impairments in motor, sensorimotor and cognitive function over the 4-week post-injury period. Injured animals treated with CsA showed a significant improvement in motor function assessed using a composite neuroscore (at day 28) and in sensorimotor function assessed using a sticky paper test (at days 2, 14, and 28) (p < 0.05, when compared to vehicle treated, injured animals). No beneficial effects on cognitive function were observed following CSA administration. Conclusion: These data suggest that daily post-injury treatment with CsA improves certain aspects of motor and sensorimotor function following experimental TBI. Show more

Keywords: immunosuppressant, CsA, behavior

Citation: Restorative Neurology and Neuroscience, vol. 18, no. 1, pp. 1-8, 2001

Authors: Navarro, Xavier | Valderrama, Elena | Stieglitz, Thomas | Schüttler, Martin

Article Type: Research Article

Abstract: Purpose: To assess a new flexible, multicontact spiral-cuff electrode made of polyimide with integrated platinum contacts for selective stimulation of nerve fascicles. Methods: Polyimide cuff electrodes with 12 Pt sites in the spiral cuff were acutely implanted around the sciatic nerve of rats. Stimulation was applied through each one of the four tripoles of the cuff as single pulses of 10 µsec duration of increasing intensity The motor responses were monitored from EMG recordings of gastrocnemius …medialis (GM; innervated by the tibial nerve) and tibialis anterior (TA; innervated by the peroneal nerve) muscles. The torque developed in tbc ankle was simultaneously measured by means of a purposely designed apparatus. Recruitment curves were constructed for the CMAP of the GM and TA muscles and for the torque. Results: In all nerves evaluated stimulation through one or two of the tripoles initially evoked a dorsiflexion with parallel recruitment of the TA muscle at low stimulation intensity; at higher stimulation amplitude activation of the tibial innervated muscles prevailed and led to predominant plantarflexion. On the other hand, stimulating through the other two or three tripoles evoked plantarflexion from the beginning, with increasing force from low to high stimulus intensity. The effectiveness of selective stimulation was mildly increased by applying a simultaneous transverse steering current. The threshold for torque dorsiflexion decreased and the dynamic range of stimulation that resulted in a net dorsiflexion expanded. The effects of steering currents were more noticeable with pulses of 80 % than 40 % of threshold value, and when applied from an opposite than from an adjacent anode. Conclusions: Despite the relative small size of the rat sciatic nerve and the close apposition of tibial and peroneal fascicles, we proved the feasibility of using multipolar polyimide cuff electrodes to produce selective fascicular nerve stimulation. Show more

Keywords: selective electrical stimulation, peripheral nerve, cuff electrode, neural implant, polyimide, prosthesis

Citation: Restorative Neurology and Neuroscience, vol. 18, no. 1, pp. 9-21, 2001

Authors: Spilker, M.H. | Yannas, I.V. | Kostyk, S.K. | Norregaard, T.V. | Hsu, H-P. | Spector, M.

Article Type: Research Article

Abstract: Purpose: The purpose of this study was to characterize the effects of implantation of a collagen tube on healing and scar formation following transection of tbc adult rat spinal cord. Methods: The spinal cords of adult rats were completely transected at the mid-thoracic level. At 30 days after injury, the cellular and extra-cellular components of repair tissue present within tubulated and non-tubulated (control) wounds were compared using qualitative and quantitative histological techniques. Results: The presence of …the tube reduced fibrocollagenous scar invasion into the gap, promoted astrocyte migration, and oriented axonal and connective tissue components of the repair tissue. Tube implants supported the regeneration of a substantial number of myelinated axons. A notable finding was the identification of cells containing a contractile actin isoform in the healing spinal cord. Conclusions: The tubulation model allows for the study of spinal cord wound healing and axon elongation in a controlled experimental environment within the tube lumen. Using this model, it will be possible to study manipulation of the healing response by the introduction of exogenous agents within the tube Show more

Keywords: collagen tube irnplant, axon regeneration, myofibroblast

Citation: Restorative Neurology and Neuroscience, vol. 18, no. 1, pp. 23-38, 2001

Authors: Duconseille, Elee | Carrot, Sylvie-Noelle | Woerly, Stephane | Kelche, Christian | Will, Bruno | Cassel, Jean-Christophe

Article Type: Research Article

Abstract: Purpose: We studied the behavioral effects of an intracavitary implantation of poly[N-(2-hydroxypropyl)-methacrylamidel (PHPMA) hydrogels combined to intraseptal grafts of fetal septal cell suspensions in adult female rats subjected to aspirative fimbria-fornix lesions. The hydrogels were used as substrates for bridging the lesion cavity between the septum and the hippocampus. Methods: Control groups included sham-operated or lesion-only rats, as well as lesioned rats with only the hydrogel bridge in the lesion cavity, only …the graft in the septum, or an intrahippocampal graft of a septal cell suspension as a control for the standardly used ectopic transplantation strategy. Up to 10 months after grafting surgery, all rats were tested for locomotor activity in their home cage, sensorimotor performances using a beam-walking test, and cognitive performances in a radial maze, a water maze and a T-maze (rewarded alternation). Results: The lesions induced hyperlocomotion, sensorimotor disturbances and severe alterations of cognitive functions. We found that neither the grafts or the hydrogels, nor the combination of both, induced any significant enhancement of sensorimotor or cognitive performances. Nevertheless, in rats with both intraseptal (homotopic) grafts and a hydrogel implant, the locomotor activity did no longer differ from that found in sham-operated controls. Histological analysis showed that the hydrogels contained acetylcholinesterase(AChE)-positive fibers and that the hippocampal region in contact with the hydrogel exhibited AChE-positive reaction products over several hundreds of micrometers. Conclusions: These results are complementary to our previous report on electrophysiological evidence of septo-hippocampal reconnections (Duconseille et al., Rest. Neurol. Neurosci. 15, 1999, 305-317). They further suggest that septal neurons grafted homotopically and/or neurons from the host brain are able to elongate axonal processes through a PHPMA substrate up to the hippocampus. Although they did not affect the cognitive consequences of the lesion, the changes enabled by the homotopic grafts combined to the hydrogel have attenuated the lesion- induced hyperactivity. Show more

Keywords: Biomaterial, Grafts, Hippocampus, Homotopic, Hydrogels, Learning, Locomotor activity, Medial septum, Memory, Polymer, Regeneration, Sensorimotor, Septo-hippocampal system, Spatial, Transplants

Citation: Restorative Neurology and Neuroscience, vol. 18, no. 1, pp. 39-51, 2001