Restorative Neurology and Neuroscience - Volume 33, issue 5

Authors: Hubacher, Martina | DeLuca, John | Weber, Peter | Steinlin, Maja | Kappos, Ludwig | Opwis, Klaus | Penner, Iris-Katharina

Article Type: Research Article

Abstract: Purpose: To assess possible effects of working memory (WM) training on cognitive functionality, functional MRI and brain connectivity in patients with juvenile MS. Methods: Cognitive status, fMRI and inter-network connectivity were assessed in 5 cases with juvenile MS aged between 12 and 18 years. Afterwards they received a computerized WM training for four weeks. Primary cognitive outcome measures were WM (visual and verbal) and alertness. Activation patterns related to WM were assessed during fMRI using an N-Back task with increasing difficulty. Inter-network connectivity analyses were focused on fronto-parietal (left and right), default-mode (dorsal and ventral) …and the anterior salience network. Cognitive functioning, fMRI and inter-network connectivity were reassessed directly after the training and again nine months following training. Results: Response to treatment was seen in two patients. These patients showed increased performance in WM and alertness after the training. These behavioural changes were accompanied by increased WM network activation and systematic changes in inter-network connectivity. The remaining participants were non-responders to treatment. Effects on cognitive performance were maintained up to nine months after training, whereas effects observed by fMRI disappeared. Conclusions: Responders revealed training effects on all applied outcome measures. Disease activity and general intelligence may be factors associated with response to treatment. Show more

Keywords: Connectivity, cognitive rehabilitation, working memory, juvenile multiple sclerosis

DOI: 10.3233/RNN-150497

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 713-725, 2015

Authors: Subramanian, Sandeep K | Chilingaryan, Gevorg | Sveistrup, Heidi | Levin, Mindy F.

Article Type: Research Article

Abstract: Purpose: Sensorimotor impairments and depressive symptoms (PSD) influence arm motor recovery post-stroke. Feedback provision improves upper limb motor learning in patients with chronic stroke but factors including PSD may affect ability to use feedback. We evaluated the influence of PSD on the ability to use auditory feedback for upper limb recovery and motor learning in patients with chronic stroke. Methods: Participants (n  = 24) practiced 72 pointing movements/session (6 targets, 12 sessions, randomized) with auditory feedback on movement speed and trunk displacement. The presence of PSD (Beck’s Depression Inventory; BDI-II) was assessed at pre-intervention (PRE). Arm …motor impairment (Fugl-Meyer Assessment, shoulder horizontal adduction, shoulder flexion, elbow extension ranges, trunk displacement) and arm use (Motor Activity Log) were assessed at PRE, immediately after (POST) and retention (3mos; RET). Participants were divided into two groups based on BDI-II scores: ≥14/63 (DEP group; n  = 8; score: 20.5 ± 7.5) and ≤13/63 (no PSD (ND) group; n  = 16; score: 5.0 ± 3.8). Changes in impairment and arm use levels were assessed (mixed-model ANOVAs). Results: All participants improved arm use. DEP had lower Fugl-Meyer scores, used more compensatory trunk displacement and had lower shoulder horizontal adduction range compared to ND. Conclusion: The presence of PSD diminished the ability to use auditory feedback for arm motor recovery and motor learning. Show more

Keywords: Rehabilitation, kinematics, upper limb, mood, knowledge of performance, knowledge of results, cerebrovascular accident

DOI: 10.3233/RNN-150508

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 727-740, 2015

Authors: Zhang, Rui | Yang, Nan | Ji, Chao | Zheng, Ji | Liang, Zhen | Hou, Chun-Ying | Liu, Yan-Yong | Zuo, Ping-Ping

Article Type: Research Article

Abstract: Purpose: To investigate the effect and underlying mechanism of Aceglutamide on motor dysfunction in rats after cerebral ischemia-reperfusion. Methods: Adult male Sprague-Dawley rats were subjected to 2 h transient middle cerebral artery occlusion (MCAO). Aceglutamide or vehicle was intraperitoneally given to rats at 24 h after reperfusion and lasted for 14 days. Subsequently functional recovery was assessed and number of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) was analyzed. Tumor necrosis factor receptor-associated factor 1(TRAF1), P-Akt and Bcl-2/Bax were determined in mesencephalic tissue by Western blot method. PC12 cells and primary cultured mesencephalic neurons were employed …to further investigate the mechanism of Aceglutamide. Results: Aceglutamide treatment improved behavioral functions, reduced the infarction volume, and elevated the number of TH-positive neurons in the SN. Moreover, Aceglutamide significantly attenuated neuronal apoptosis in the SN. Meanwhile Aceglutamide treatment significantly inhibited the expression of TRAF1 and up-regulated the expression of P-Akt and Bcl-2/Bax ratio both in vitro and in vivo . Conclusions: Aceglutamide ameliorated motor dysfunction and delayed neuronal death in the SN after ischemia, which involved the inhibition of pro-apoptotic factor TRAF1 and activation of Akt/Bcl-2 signaling pathway. These data provided experimental information for applying Aceglutamide to ischemic stroke treatment. Show more

Keywords: Aceglutamide, neuroprotection, cerebral ischemia and reperfusion, motor function, substantia nigra, TNF receptor associated factor 1 (TRAF1), apoptosis

DOI: 10.3233/RNN-150509

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 741-759, 2015

Authors: Sergeeva, Elena G. | Henrich-Noack, Petra | Gorkin, Alexander G. | Sabel, Bernhard A.

Article Type: Research Article

Abstract: Purpose: Transcorneal alternating current stimulation (tACS) has become a promising tool to modulate brain functions and treat visual diseases. To understand the mechanisms of action a suitable animal model is required. However, because existing animal models employ narcosis, which interferes with brain oscillations and stimulation effects, we developed an experimental setup where current stimulation via the eye and flicker light stimulation can be applied while simultaneously recording local field potentials in awake rats. Method: tACS was applied in freely-moving rats (N  = 24) which had wires implanted under their upper eye lids. Field potential recordings were made in …visual cortex and superior colliculus. To measure visual evoked responses, rats were exposed to flicker-light using LEDs positioned in headset spectacles. Results: Corneal electrodes and recording assemblies were reliably operating and well tolerated for at least 4 weeks. Transcorneal stimulation without narcosis did not induce any adverse reactions. Stable head stages allowed repetitive and long-lasting recordings of visual and electrically evoked potentials in freely moving animals. Shape and latencies of electrically evoked responses measured in the superior colliculus and visual cortex indicate that specific physiological responses could be recorded after tACS. Conclusions: Our setup allows the stimulation of the visual system in unanaesthetised rodents with flicker light and transcorneally applied current travelling along the physiological signalling pathway. This methodology provides the experimental basis for further studies of recovery and restoration of vision. Show more

Keywords: Noninvasive brain stimulation, animal model, freely-moving animal, vision restoration, visual evoked potential, electrically evoked response

DOI: 10.3233/RNN-150513

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 761-769, 2015

Authors: Zhang, Qihui | Yang, Ying | Saver, Jeffrey L.

Article Type: Research Article

Abstract: Purpose: Final global disability 3 months post-stroke is the cardinal endpoint in acute stroke clinical trials. The most similar variable available in administrative datasets is discharge destination at end of the acute hospitalization. We investigated the predictive value of discharge destination for final global disability. Methods: In the public dataset of the two NINDS-TPA trials, we characterized discharge destination as a 4 level ordinal variable. Correlation coefficients and logistic models probed the relation with the modified Rankin Scale (mRS) of global disability at 3 months. Results: Among the 624 ischemic stroke patients, discharge destination was …home in 42.1% , rehabilitation in 33.0% , skilled nursing facility in 9.8% , and in hospital-death in 12.4% . A strong correlation was noted between hospital discharge destination and 3 month mRS, r  = 0.71, P  <  0.001. Length of stay showed a weaker correlation with 3 month mRS, r  = 0.29, p  <  0.0001. A multiple logistic regression model identified 4 categories of independent predictors of 3 month global disability outcome, with discharge destination as the strongest independent variable. Conclusions: Discharge destination is a powerful predictor of final 3 month global disability outcomes and a valid outcome measure for use in local and national quality improvement programs. Show more

Keywords: Hospital discharge destination, Ischemic stroke, Modified rankin score

DOI: 10.3233/RNN-150531

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 771-775, 2015

Authors: Koyuncuoglu, Turkan | Turkyilmaz, Mesut | Goren, Bulent | Cetinkaya, Merih | Cansev, Mehmet | Alkan, Tulin

Article Type: Research Article

Abstract: Purpose: A significant cause of neurological disability in newborns is hypoxic-ischemic encephalopathy (HIE), a disorder which involves an enhancement in histone deacetylase (HDAC) activity among underlying pathological mechanisms. We showed recently that exogenous administration of uridine to newborn rats with HIE reduced brain injury in a dose-dependent manner. The present study was performed to investigate whether uridine modulates histone acetylation/deacetylation balance in a neonatal rat model of HIE. Methods: Newborn rats that were subjected to hypoxic-ischemic (HI) insult on postnatal day 7 (P7) were injected intraperitoneally with either saline or uridine (500 mg/kg) for three consecutive days. One …day after completion of treatment, brains of pups were collected for evaluation of brain infarct volume, apoptosis, HDAC activity and acetylated-Histone H3 (Ac-H3) and H4 (Ac-H4) protein levels. Results: Results revealed that uridine administration reduced infarct volume, active Caspase-3 levels and HDAC activity while increasing the expressions of Ac-H3 and Ac-H4 proteins. Conclusions: We conclude that one mechanism by which uridine provides neuroprotection in neonatal rat HIE model involves reduction in HDAC activity. Show more

Keywords: Hypoxic-ischemic encephalopathy, neonatal, rat, uridine, histone deacetylase, neuroprotection

DOI: 10.3233/RNN-150549

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 777-784, 2015