Restorative Neurology and Neuroscience - Volume 23, issue 1

Authors: Thees, S. | Hubbard, G.B. | Winckler, J. | Schultz, C. | Rami, A.

Article Type: Research Article

Abstract: Purpose: During ageing, there may be an age-associated loss of particular nerve cells in specific brain areas. Recent studies highlight the role of apoptosis in the normal ageing of the brain, heart, and skeletal muscle. Particular attention is paid to the role of cytochrome c release from mitochondria and alterations in the pro- and anti-apoptotic proteins, Bax and Bcl-2, respectively. The aim of this study was to investigate the potential occurrence of apoptosis in the hippocampus …of aged baboons. Methods: we have used the baboon as a potential non-human primate model for age-related pathology which afflicts the human brain. The TUNEL staining method was used to characterise the apoptotic cell death. For immunocytochemistry, antibodies directed against activated caspase-3, cytochrome c, Bcl-2 and Bax proteins were used. Results: Our results show that in hippocampi of aged baboons the immunoreactivities of the antiapoptotic agent Bcl-2 was not prominently changed, of the proapoptotic agent Bax was upregulated, of the cytochrome c was redistributed, and that caspase-3 was not activated. The TUNEL-staining method revealed no apoptotic cell death in hippocampi of aged baboons. Conclusions: This demonstrates that a specific alteration of the Bax/Bcl2 ratio occurs in the ageing baboon hippocampus which may directly influence the release of cytochrome c even without commitment to apoptosis. Show more

Keywords: ageing, hippocampus, apoptosis, cytochrome c, Bcl-2, bax, baboon

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 1, pp. 1-9, 2005

Authors: Jang, Sung Ho | Cho, Sang-Hyun | Kim, Yun-Hee | Han, Bong Soo | Byun, Woo Mok | Son, Soo-Min | Kim, Seong Ho | Lee, Se Jin

Article Type: Research Article

Abstract: Purpose: This study examined whether the degree of impairment of diffusion anisotrophy in the early stages of a stroke can predict the motor function outcome. Methods: Thirty-one hemiplegic stroke patients were enrolled to this study. Diffusion anisotropy was measured by determining fractional anisotropy (FA) in the two ROIs (region of interests) at corona radiata (CR) and in the posterior limb of internal capsule (IC) during the early stages of stoke (average 7.9 days after …stroke onset) and compared with motor outcome of the affected hand 3 months after stroke onset. Results: Both ROIs (CR or IC) and lesion types (hemorrhage or infarction) did not have significant effect on the SBFA (symmetry of bilateral FA) and dMRC (medical research council score improvement), either. Patients with greater initial MRC score had significantly greater SBFA and dMRC. The regression equation between the dMRC (Y axis) and the SBFA (X axis) was semi-linear and significant (P < 0.05); for CR group, Y = 3.296 - 0.1192X + 0.0015X^{2} ; for IC group, Y = 2.342 - 0.0533X +0.0007^{2} . The regression lines had 'threshold points' where a minute SBFA change would make a steep increase in dMRC. Conclusion: The degree of impairment in diffusion anisotropy during the early stages of stroke appears to have the potential to predict motor outcome. Show more

Keywords: stroke, diffusion tensor imaging, anisotropy, MRI, motor function

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 1, pp. 11-17, 2005

Authors: Belkas, Jason S. | Munro, Catherine A. | Shoichet, Molly S. | Midha, Rajiv

Article Type: Research Article

Abstract: Purpose: As alternatives to nerve grafts for peripheral nerve repair, we have synthesized 12 mm long poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous tubes and studied their regenerative capacity for the repair of surgically-created 10 mm rat sciatic nerve gaps. We compared the in vivo regenerative efficacy of these artificial tubes with the gold standard, the nerve autograft. Methods: Tubes were assessed in vivo for their ability to support nerve regeneration at 4, 8, and 16 …weeks post-implantation by histology, electrophysiology, histomorphometry, and reinnervated lateral gastrocnemius (LG) dry muscle mass. Results: Axonal regeneration within the tubes was observed by 8 weeks, with outcome parameters comparable to autografts. This finding was further supported by the electrophysiological and histomorphometric results. The 16 week tube group had a bimodal response, with 60% of the tubes having a similar response to autografts and the other 40% having significantly lower (p < 0.05) outcome measures in several parameters. Conclusions: Axonal regeneration in artificial tubes was similar to that in autografts at 8 and 16 weeks, however, a bimodal distribution of regeneration was observed in 16 week tubes. Show more

Keywords: functional outcome measures, morphometry, poly(2-hydroxyethyl methacrylate-co-methyl methacrylate), rat, sciatic nerve

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 1, pp. 19-29, 2005

Authors: Marklund, Niklas | Keck, Carrie | Hoover, Rachel | Soltesz, Kristie | Millard, Marie | LeBold, David | Spangler, Zachary | Banning, Adrian | Benson, Jacqueline | McIntosh, Tracy K.

Article Type: Research Article

Abstract: Purpose: Although many previous studies have indicated that the acute inflammatory response following traumatic brain injury (TBI) is detrimental, inflammation may also positively influence outcome in the more chronic post-injury recovery period. We evaluated the effects of monoclonal antibodies (mAB), neutralizing either IL-6 (IL-6 mAB) or TNF-α (TNF mAB), administered intracerebroventricularly (i.c.v) on acute neurobehavioral outcome following TBI. Methods: Male Sprague-Dawley rats (n = 173) were anesthetized (sodium pentobarbital, 60 …mg/kg) and subjected to lateral fluid percussion (FP) brain injury of moderate severity (n = 123) or sham injury (n = 50). Beginning 1 h post-injury, TNF mAB (n = 41, of which 25 were brain-injured) or IL-6 mAB (n = 42, of which 25 were brain-injured) at a concentration of 2 mg/mL was infused i.c.v ipsilateral to the injury for 48 hours. Vehicle-treated animals (control IgG; n = 43, of which 26 were brain-injured) served as controls. In Study 1, cognitive function was evaluated in the Morris Water Maze (MWM) followed by evaluation of regional cerebral edema at 48 h post-injury. In Study 2, animals were evaluated for neurological motor function and post-injury learning in the MWM at one week post-injury. Results: FP brain injury caused significant cognitive (p < 0.05) and neurological motor (p < 0.05) deficits and increased regional brain water content in the injured hemisphere. Treatment with either TNF- or IL-6-mAB had no effect on neurological motor, cognitive function or brain edema during the first post-injury week. Conclusions: Evaluation of anti-inflammatory mABs on more chronic behavioral deficits appears warranted. Show more

Keywords: traumatic brain injury, lateral fluid percussion, tumor necrosis factor (TNF)-α, interleukin (IL)-6, Morris water maze, neuroscore, rotating pole, cerebral edema, inflammation

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 1, pp. 31-42, 2005

Authors: Almaguer, William | Capdevila, Vladimir | Ramírez, Magaly | Vallejo, Araceli | Rosillo, Juan C. | Bergado, Jorge A.

Article Type: Research Article

Abstract: Purpose: To evaluate the capacity of amygdala stimulation to improve neural plasticity in animals bearing lesions of the fimbria-fornix (FF) system. Methods: The animals were lesioned under narcosis (chloral hydrate, 420 mg/kg ip.) using a bilateral transection of the FF procedure. During the same surgery some animals were implanted with an electrode in the right basolateral amygdala (BLA) to allow the electrical stimulation of this structure. Training was carried out one week after surgery …using a Morris water maze. Animals were trained in four consecutive days (8 trials/day) in the non-visible platform condition except in the fourth day in which only 4 trials were performed followed by a probe trial in which the escape platform was removed. On day 5 of training 8 trials with visible platform were performed. After each of the first 3 training days one group of animals received trains of electrical stimulation to the BLA, while control groups were not stimulated. A group of non-lesioned animals served as control. The location of the electrode was confirmed histologically after the end of the experiments. Results: The learning capacity of the lesioned animals was improved by the electrical stimulation of the amygdala. The latency to find the submerged platform within this group approaches that of the non lesioned animals in the course of training (2-way ANOVA with repeated measures), while other lesioned animals continued to show severely impaired learning abilities. Conclusions: This is the first evidence that stimulating the BLA can positively influence the learning abilities of lesioned animals. Further experiments should contribute to improve the stimulation paradigms to make it more effective, if possible. Show more

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 1, pp. 43-50, 2005

Authors: Jang, Sung Ho | Cho, Sang-Hyun | Kim, Yun-Hee | You, Sung H. | Kim, Seong Ho | Kim, Oryong | Yang, Dong Suk | Son, Su min

Article Type: Research Article

Abstract: Purpose: The purpose of this study was to investigate the motor recovery mechanism following diffuse axonal injury (DAI) using transcranial magnetic stimulation (TMS) and functional MRI (fMRI). Methods: Twenty-six hands of 13 control subjects and 14 affected hands of 8 patients (two hemiparetics and six quadriparetics) were evaluated. All the patients were initially diagnosedwith DAIand were evaluated after they had reached their maximal motor recovery. fMRI was performed at 1.5 T using a hand …grasp-release movement paradigm and TMS was applied with a round coil over the vertex. Results: fMRI revealed that both normal subjects and patients with DAI showed increased contralateral primary sensori-motor cortex activation during affected hand movement.The motor evoked potentials (MEPs) of the patient group was slightly delayed in latency and significantly increased in duration and turns. The relative MEP amplitude, phase, and excitatory threshold were not significantly different between the groups. Conclusions: These findings may indicate the heterogeneity of the axons in the recovery process of the corticospinal tract. It seems that the motor recovery in patients who had suffered DAI was attributable to the recovery of the corticospinal tract. Show more

Keywords: diffuse axonal injury, functional MRI, Magnetic stimulation, Motor recovery

Citation: Restorative Neurology and Neuroscience, vol. 23, no. 1, pp. 51-56, 2005