Restorative Neurology and Neuroscience - Volume 17, issue 1

Authors: Hesse, S. | Brandl-Hesse, B. | Seidel, U. | Doll, B. | Gregoric, M.

Article Type: Research Article

Abstract: Purpose: The study investigated the effect of Botulinum toxin A on the gait and lower limb muscle activity of ambulatory CP children. Methods: 19 spastic diplegic and 4 left hemiparetic CP children were injected with a mean dose of 23.5 units of Botulinum toxin A/kg body weight into the gastrocnemius and hamstring muscles. Muscle tone and gait analysis including the kinesiological electromyogram of the shank and thigh muscles were assessed before and four weeks after injection …and compared with the help of a multivariate analysis (p < 0.05). Results: Botulinum toxin A caused a definite reduction of plantarflexor, knee and hip hypertonia in 21 children, resulting in a more plantar grade and erect gait in 17 children four weeks after injection. Gait analysis showed a statistically significant improvement in peak ankle dorsi-flexion and knee extension during stance, and the length of the force point of action under both feet increased. Electromyography revealed sig-nificantly less co-contraction of the lower leg muscles, due to a more phasic instead of a tonic activity of the tibialis anterior muscle, and an improved activation pattern of the left rectus and biceps femoris muscles. Conclusions: The present study demonstrated that the injection of Botulinum toxin A resulted in a more mature muscle activation pattern of CP children. Most of the children walked more plantigrade and erect, the functional gait parameters, however, did not change. Show more

Keywords: spasticity , children, botulinum toxin, gait analysis, ICP, EMG

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 1, pp. 1-8, 2000

Authors: Fukuyama, Ryuichi | Ohta, Mitsuhiro | Ohta, Kiyoe | Saiwaki, Takuya | Fushiki, Shinji | Awaya, Akira

Article Type: Research Article

Abstract: Purpose: We evaluated the effects of the drug MS-818 (2-piperadino-6-methyl-5-oxo-5,6-dihydro-(7H) pyrrolo-[3,4-d] pyrimidine maleate), a synthesized pyrimidine compound, on regeneration in crush-injured sciatic nerves of rats. Methods: MS-818 at 1.0 or 10 mg/kg or the vehicle was intraperitoneally injected into rats daity. The pinch test (PT) was performed 5 days after the operation. Walking function recovery was assessed by the sciatic nerve functional index (SFI). Time-dependent changes in the levels of transcripts of …nerve growth factor (NGF) and apolipoprotein E (ApoE) genes were monitored by RT-PCR. NGF peptide levels retained in the crushed nerves of rats 5 days after surgery and in the culture medium of IMS32 cells, a mouse Schwann cell line, incubated for 24 h with high or low doses of MS-818, were measured by enzyme immunoassay. Results: The PT showed that MS-818 injection promoted axonal elongation by 19.3 % compared to the vehicle injected control (n = 7, *p < 0.03). The SFIs 3 weeks after injection of MS-818 at 1.0 mg/kg and 1 0 mg/kg were significantly increased to the control level (n = 5-6, **p < 0.006 and *p < 0.03, respectively). Injection of MS-818 at 1.0 mg/kg induced NGF gene expression more than twofold compared to that of the control at 5 to 6 days after surgery (n = 4). NGF levels in crushed nerves after MS-818 injection at 1.0 and 10 mg/kg tended to be higher than those of the vehicle-injected controls by approximately 20 %, although it did not reach statistical significance. Treatment of IMS32 cells with MS-818 failed to give rise to NGF overproduction and its secretion into the culture medium. Conclusions: These present evidences suggest that MS-818 enhances functional recovery of damaged sciatic nerves by promoting axonal sprouting through indirect activation of Schwann cells and that local production of NGF rnay be activated by MS-818. Show more

Keywords: MS-818, sciatic nerve, pinch test, SFI, crush, NGF, RT-PCR, rat

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 1, pp. 9-16, 2000

Authors: Segal, Richard L. | Wolf, Steven L. | Catlin, Pamela A. | Gilliand, Rebecca L. | Taffs, Jamie K. | Bass, Helen C. | Vickers, Elizabeth F.

Article Type: Research Article

Abstract: Purpose: Successful operant conditioning of the biceps brachii spinal stretch reflex (SSR) has resulted in concurrent changes in the magnitude of long latency reflex responses (LLRRs). This finding suggests a coupling of the SSR and LLRR. The purpose of the present study was to downtrain the LLRR using operant conditioning and to observe any concurrent change in the SSR. Methods: Fourteen, able-bodied, human subjects were randomly assigned to either the control group or the training group. …The LLRR and SSR responses were measured as magnitude of electromyographic response to a quick stretch of the elbow flexors, delivered by a torque motor. All the subjects attended fourteen sessions. The first six sessions were baseline sessions during which no conditioning or feedback occurred. The next eight sessions were the same as the baseline sessions (extended baseline sessions) for the control group; no feedback or operant conditioning of the LLRR occurred. The next eight sessions for the training group comprised the operant conditioning. Results: Operant conditioning of the LLRR resulted in a statistically significant reduction of that response within the training group and between the two groups. Also, operant conditioning of the biceps brachii LLRR did not result in concurrent changes in the magnitude of the SSR suggesting an uncoupling of these responses. Conclusions: The LLRR of the biceps brachii could be operantly conditioned without significant changes in the SSR which suggests that these two responses can be volitionally uncoupled. Show more

Keywords: plasticity, spinal cord, biceps brachii, electromyography, upper extremity, motor control,

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 1, pp. 17-22, 2000

Authors: Inoue, Tetsu | Sasaki, Hitoshi | Hosokawa, Mizuho | Fukuda, Yutaka

Article Type: Research Article

Abstract: Purpose: Retinal ganglion cells (RGCs) of adult mammals can regenerate their axons along a segment of the peripheral nerve (PN) that is transplanted to the cut optic nerve. There have been many trials of PN transplantation to induce axonal regeneration of RGCs in adult rodents, cats and ferrets. However, because of the technical difficulty in transplant operation, PN transplantation in adult mice has not been carried out in spite of the availability of many kinds of …gene-manipulated animals. Here we report the procedures for successful PN transplantation in this species. Methods: We made intraretinal (IR) and retrobulbar (RB) approaches for PN transplantation. Four weeks after PN transplantation, RGCs with regenerated axons were identified by retrograde labeling with rhodamine or horseradish peroxidase applied into the PN segment. Results: A quantitative survey showed that the mean regeneration ratio was 1.0 % (n = 8) in IR transplantation, whereas it was only 0.1 % in RB transplantation (n = 11). As previously shown in other species, the regenerated RGCs were predominantly larger-bodied cells in com-parison to intact cells. Conclusion: Possible reasons for the difference in regeneration ratio between the two transplant approaches and the feature of soma size of regenerated RGCs are discussed. Show more

Keywords: Axonal regeneration, Retinal ganglion cells, Peripheral nerve transplantation, Optic nerve, Retrograde labeling, Mice

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 1, pp. 23-29, 2000

Authors: Aoi, Mizuho | Date, Isao | Tomita, Susumu | Ohmoto, Takashi

Article Type: Research Article

Abstract: Purpose: Neurotrophic factor delivery into the brain is a promising approach in the treatment of Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent neurotrophic factors for dopaminergic neurons. Although multiple injections of GDNF into the brain are commonly performed in experimental studies, the present study investigates the efficacy of using a single injection of GDNF, which may be useful in elinically applying this treatment. Methods: Unilateral 6-hydroxydoparnine (6-OHDA) …administration into the striatum was perforrned in Sprague-Dawley rats to create a partial lesion of the nigrostriatal DA system. These parkinsonian model rats received a single injection of human recombinant GDNF into the same portion of the striatum either 24 h before or 4 weeks after 6-OHDA treatrnent. Results: GDNF injected into the striatum before 6-OHDA administration potently protected the dopaminergic system, as shown by the numbers of mesencephalic dopaminergie neuron cell bodies and dopaminergic nerve terminal densities in the striatum. Dopaminergic neuron cell bodies and fiber densities were also significantly restored when GDNF was given after 6-OHDA administration, although the degree of restoration was lower than in the protective experiment. ODNF administration ameliorated apomorphine-induced rotational behavior in animals receiving it either before or after 6-OHDA treatment. However, the degree of improvement was less prominent when GDNF was iniected after 6-OHDA. Conclusion: Intracerebral GDNF adininistration exerts both protective and regenerative effects on the nigrostriatal dopaminergic system, a finding which may have implications for the development of new treatment strategies for Parkinson's disease. Show more

Keywords: GDNF, Parkinson's disease, dopamine, regeneration, protection

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 1, pp. 31-38, 2000

Authors: Jost,, Sarah C. | Doolabh, Vaishali B. | Mackinnon, Susan E. | Lee, Michelle | Hunter, Daniel

Article Type: Research Article

Abstract: Purpose: The severe functional and sensory deficits seen following injury to peripheral nerves makes facilitation of nerve regeneration a primary goal of the reconstructive surgeon. This study examines whether daily administration of FK506 or Cyclosporin A expedites peripheral nerve regeneration following neurotmetic injury in a rat model Methods: Inbred Buffalo rats were randomized to three experimental groups. Group I rats served as untreated controls. Rats in groups II and III received daily subcutaneous …CsA (5 mg/kg), and FK506 (1 mg/kg), respectively. Each animal underwent unilateral posterior tibial nerve transection with immediate epineurial reapproximation. Functional recovery of the injured limb was assessed by serial walking track analysis. Nerve regeneration was assessed histomorphometrically via light microscopy. Results: Return of hindlimb function in control animals occurred at 32 days post injury. CsA and FK506-treated transection animals recovered at 26 and 18 days post injury, respectively. Statistically significant greater fiber density and percent neural tissue were seen in FK506- treated animals compared to control animals four weeks post transection. Conclusions: This data suggest that the daily systemic administration of both CsA and FK506 accelerate the rate of functional regeneration, following neurotmetic injuries in tbc rat model. FK506's effect on nerve growth is significantly greater than that of CsA. Show more

Keywords: FK506, CsA, peripheral nerve, nerve regeneration, immunophilin, FKBP-12

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 1, pp. 39-44, 2000

Authors: Turski, Lechoslaw | Schneider, Herbert H. | Neuhaus, Roland | McDonald, Fiona | Jones, Graham H. | Löfberg, Boel | Schweinfurth, Hermann | Huth, Andreas | Krüger, Martin | Ottow, Eckhard

Article Type: Other

Abstract: In the Western world, over 350,000 deaths and $30 billion in medical costs are attributed annually to stroke. Head and spinal cord trauma cause an estimated 250,000 deaths annually and result in medical costs of $15 billion. Although stroke and head/spinal cord trauma are leading causes of disability and death in humans, no adequate neuroprotective treatment is available. Glutamate antagonists derived from the quinoxa-linedione scaffold are as drug candidates for neuroprotection in stroke and trauma. Quinoxalinedione …derivatives such as 2,3-dihydroxy-6- nitro-7-sulfamoylbenzo(f)quinoxaline and 6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione failed clinical trials because of insolu-bility and resulting nephrotoxicity. Introduction of a phosphonate group into the quinoxalinedione skeleton improves solubility and leaves potency for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor unchanged. Phosphonate quinoxalinedione derivatives ZK202000 and ZK200775 protected rodent brain against sequelae of permanent occlusion of the middle cerebral artery and head trauma. No major deleterious effects on motor coordination, cardiovascular, or respiratory systems were detected in doses required for neuroprotection. No psychotomimetic and no neurotoxic side effects, typical for N-methyl-D-aspartate antagonists, were observed following treatment with phosphonate quinoxalinediones. Show more

Keywords: glutamate, antagonists , anxiety , analgesia , muscle tone , seizures , stroke, traumatic brain injury, neuroprotection

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 1, pp. 45-59, 2000