Restorative Neurology and Neuroscience - Volume 33, issue 5

Authors: Chang, Won Hyuk | Kim, Hyun | Sun, Woong | Kim, Joo Yeon | Shin, Yong-Il | Kim, Yun-Hee

Article Type: Research Article

Abstract: Purpose: Previous studies demonstrated that administering extradural cortical stimulation (ECS) to rats during the acute phase of a photothrombotic infarct enhances motor recovery. However, the effect of ECS during the subacute phase was unknown. We aimed to evaluate the effects of ECS on motor recovery in a rat model of subacute photothrombotic stroke. Methods: Photothrombotic ischemic injury to the left sensorimotor cortex (SMC) was induced in 41 male Sprague-Dawley rats using Rose-bengal dye (20 mg/kg) and cold light. The rats were randomly divided into two groups: ECS on infarcted SMC (ECS group) and no ECS on …infarcted SMC (non-stimulated group). The ECS group received continuous ECS for 14 days starting from day 5 after the stroke onset. Behavioral training with the single-pellet reaching task (SPRT) was performed daily for all of the rats from the fifth day after stroke onset. After 19 days, brain sections were immunostained to allow the quantification of infarct volumes and the evaluation of the neuronal markers. Results: The SPRT scores showed significantly faster and greater improvement in the ECS group than in the non-stimulated group. There were no significant differences in infarct size. However, in the ECS group, significantly more doublecortin-labeled cells were identified close to the penumbra region of the cerebral cortex. Conclusions: ECS in the subacute phase improved the behavior motor function in the stroke rat model, and induced a significant axonal sprouting in the peri-infarct area. Show more

Keywords: Axonal sprouting, extradural cortical stimulation, motor recovery, stroke

DOI: 10.3233/RNN-140445

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 589-596, 2015

Authors: Bocci, Tommaso | Santarcangelo, Enrica | Vannini, Beatrice | Torzini, Antonio | Carli, Giancarlo | Ferrucci, Roberta | Priori, Alberto | Valeriani, Massimiliano | Sartucci, Ferdinando

Article Type: Research Article

Abstract: Purpose: The cerebellum is involved in a wide number of integrative functions, but its role in pain experience and in the nociceptive information processing is poorly understood. In healthy volunteers we evaluated the effects of transcranial cerebellar direct current stimulation (tcDCS) by studying the changes in the perceptive threshold, pain intensity at given stimulation intensities (VAS:0-10) and laser evoked potentials (LEPs) variables (N1 and N2/P2 amplitudes and latencies). Methods: Fifteen subjects were studied before and after anodal, cathodal and sham tcDCS. LEPs were obtained using a neodymium:yttrium–aluminium–perovskite (Nd:YAP) laser and recorded from the dorsum of …the left hand. VAS was evaluated by delivering laser pulses at two different intensities, respectively two and three times the perceptive threshold. Results: Cathodal polarization dampened significantly the perceptive threshold and increased the VAS score, while the anodal one had opposite effects. Cathodal tcDCS increased significantly the N1 and N2/P2 amplitudes and decreased their latencies, whereas anodal tcDCS elicited opposite effects. Motor thresholds assessed through transcranial magnetic stimulation were not affected by cerebellar stimulation. Conclusions: tcDCS modulates pain perception and its cortical correlates. Since it is effective on both N1 and N2/P2 components, we speculate that the cerebellum engagement in pain processing modulates the activity of both somatosensory and cingulate cortices. Present findings prompt investigation of the cerebellar direct current polarization as a possible novel and safe therapeutic tool in chronic pain patients. Show more

Keywords: Pain cerebellum, cerebellar direct current stimulation, tDCS, laser evoked potentials, pain modulation

DOI: 10.3233/RNN-140453

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 597-609, 2015

Authors: Tremblay, Sara | Vernet, Marine | Bashir, Shahid | Pascual-Leone, Alvaro | Théoret, Hugo

Article Type: Research Article

Abstract: Purpose: Recent studies investigating the effects of mild traumatic brain injury (mTBI) suggest the presence of unbalanced excitatory and inhibitory mechanisms within primary motor cortex (M1). Whether these abnormalities are associated with impaired synaptic plasticity remains unknown. Methods: The effects of continuous theta burst stimulation (cTBS) on transcranial magnetic stimulation-induced motor evoked potentials (MEPs) were assessed on average two weeks and six weeks following mTBI in five individuals. Results: The procedure was well-tolerated by all participants. Continuous TBS failed to induce a significant reduction of MEP amplitudes two weeks after the injury, …but response to cTBS normalized six weeks following injury, as a majority of patients became asymptomatic. Conclusions: These preliminary results suggest that cTBS can be used to assess M1 synaptic plasticity in subacute phase following mTBI and may provide insights into neurobiological substrates of symptoms and consequences of mTBI. Show more

Keywords: Traumatic brain injury, concussion, transcranial magnetic stimulation, plasticity, motor cortex

DOI: 10.3233/RNN-140459

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 611-620, 2015

Authors: Ernst, Alexandra | Blanc, Frédéric | De Seze, Jérôme | Manning, Liliann

Article Type: Research Article

Abstract: Purpose: The co-occurrence of autobiographical memory (AM) and episodic future thinking (EFT) impairment has been documented in relapsing-remitting multiple sclerosis (RR-MS) patients. On these bases, we aimed at probing the efficacy of a mental visual imagery (MVI)-based facilitation programme on AM and EFT functioning in the context of a randomised-controlled trial study in RR-MS patients. Methods: Using the Autobiographical Interview (AI), 40 patients presenting with an AM/EFT impairment were randomly assigned in three groups: (i) the experimental (n  = 17), who followed the MVI programme, (ii) the verbal control (n  = 10), who followed a sham verbal …programme, and (iii) the stability groups (n  = 13), who underwent the AM/EFT test twice, with no intervention in between. Results: AI’s second assessment scores showed a significant improvement of AM and EFT performance only for the experimental group, with a long-term robustness of treatment benefits. Conclusions: The control and stability groups’ results ruled out nursing and test learning effects as explanations of AM/EFT improvement. These benefits were corroborated by the patients’ comments, which indicated an effective MVI strategy transfer to daily life. Our results suggest that the MVI programme tackles a common cognitive process of scene construction present in AM and EFT. Show more

Keywords: Autobiographical memory, episodic future thinking, neuropsychological rehabilitation, mental visual imagery, multiple sclerosis

DOI: 10.3233/RNN-140461

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 621-638, 2015

Authors: González-Tapia, David | Velázquez-Zamora, Dulce A. | Olvera-Cortés, María Esther | González-Burgos, Ignacio

Article Type: Research Article

Abstract: Purpose: The presynaptic stimulatory activity of parallel fibers on the dendritic spines of cerebellar Purkinje cells (PC) has a strong influence on the organization of motor learning. Motor learning has been shown to modify the synapses established on PC dendritic spines but the plastic changes of the different spine types, possibly underlying motor learning, have not been studied. Methods: Adult male Sprague-Dawley rats were trained daily for 26 days using an acrobatic paradigm (AC), at the end of which dendritic spine density and the proportion of the different types of spines was assessed. …Results: The learning curves of AC rats reflected a robust decrease in the latency for resolution and in the errors committed during the first week of training, which subsequently stabilized until the end of training. Dendritic spine density was greater in these AC rats, reflected in a larger proportion of thin, mushroom and stubby spines. Conclusions: Since thin spines are associated with acquiring novel information whilst mushroom spines are associated with long-term information storage, there appears to be a strong relationship between AC motor learning and consolidation. The increase in stubby spines could be related to the regulation of excitatory stimulation underlying motor overactivity. Show more

Keywords: Cerebellum, Purkinje, motor learning, plasticity, dendritic spines

DOI: 10.3233/RNN-140462

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 639-645, 2015

Authors: Làdavas, Elisabetta | Giulietti, Sara | Avenanti, Alessio | Bertini, Caterina | Lorenzini, Eleonora | Quinquinio, Cristina | Serino, Andrea

Article Type: Research Article

Abstract: Background and objective: The aim of the study is to compare the effects of multiple sessions of cathodal (c-tDCS) or anodal tDCS (a-tDCS) in modulating the beneficial effects of prism adaptation (PA) treatment in neglect patients. Methods: 30 neglect patients were submitted to 10 daily sessions of PA treatment. Patients were pseudo-randomly divided into 3 groups. In the c-tDCS-group, each PA session was coupled with 20 minutes of cathodal stimulation of the left, intact PPC; in the a-tDCS-group, anodal stimulation was applied to PPC of the damaged hemisphere; in the Sham group, sham stimulation was …applied. Neglect was evaluated before and after treatment with the Behavioral Inattention Test. Results: Combined tDCS-PA treatment induced stronger neglect improvement in the a-tDCS group as compared to the Sham group. No improvement was found in the c-tDCSgroup, with respect to that normally induced by PA and found in the Sham group. Conclusions: c-tDCS abolished neglect amelioration after PA, possibly because stimulation affected the sensorimotor network controlling prism adaptation. Instead, a-tDCS PPC boosted neglect amelioration after PA probably thanks to increased excitability of residual tissue in the lesioned hemisphere, which in turn might reduce dysfunctional over-excitability of the intact hemisphere. Show more

Keywords: Neglect, Prism Adaptation, tDCS

DOI: 10.3233/RNN-140464

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 647-662, 2015

Authors: Dutta, Anirban | Krishnan, Chandramouli | Kantak, Shailesh S. | Ranganathan, Rajiv | Nitsche, Michael A.

Article Type: Research Article

Abstract: Purpose: Recent evidence indicates that anodal transcranial direct current stimulation (tDCS) can selectively alter the EMG/force relationship of agonist arm muscles; however, the mechanisms mediating those changes are less clear. The purpose of this study was to evaluate the effect of anodal tDCS on motor unit synchronization by using a sophisticated non-linear EMG analysis called recurrence quantification analysis (RQA). Methods: Surface EMG signals were collected from the biceps brachii muscle of eighteen healthy young adults (9 tDCS and 9 control) at various force levels (12.5%, 25%, 37.5%, and 50% maximum) before and after the application …of anodal tDCS over the primary motor cortex. RQA was employed to quantify the changes in percentage of determinism (% DET) and laminarity (% LAM) of the surface EMG signals, which are surrogate measures of motor unit synchronization. Results: RQA analyses indicated that the changes in % DET and % LAM scores were significantly higher in the tDCS group than in the control group (p  <  0.05) and this effect was particularly pronounced at higher force levels. Conclusion: The results of this study provide novel evidence supporting that anodal tDCS significantly alters motor unit firing strategies (i.e., the degree of synchronization) of the biceps brachii muscle. Show more

Keywords: Recurrence analysis, electromyography, nonlinear analysis, brain stimulation, motor unit, synchronization

DOI: 10.3233/RNN-140469

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 663-669, 2015

Authors: Calabrò, Rocco Salvatore | Naro, Antonino | Russo, Margherita | Leo, Antonino | Balletta, Tina | Saccá, Ileana | De Luca, Rosaria | Bramanti, Placido

Article Type: Research Article

Abstract: Background: Tilt-table equipped with the dynamic foot-support (ERIGO) and the functional electric stimulation could be a safe and suitable device for stabilization of vital signs, increasing patient’s motivation for further recovery, decreasing the duration of hospitalization, and accelerating the adaptation to vertical posture in bedridden patients with brain-injury. Moreover, it is conceivable that verticalization may improve cognitive functions, and induce plastic changes at sensory motor and vestibular system level that may in turn facilitate motor functional recovery. Objective: To test the safety and effectiveness of ERIGO treatment on motor and cognitive functions, cortical plasticity within …vestibular and sensory-motor systems in a bedridden post-stroke sample. Methods: 20 patients were randomly divided in two groups that performed ERIGO training (30 sessions) (G1) or physiotherapist-assisted verticalization training (same duration) (G2), beyond conventional neurorehabilitation treatment. Motor and cognitive functions as well as sensory-motor and vestibular system plasticity were investigated either before (T0 ) or after (T1 ) the rehabilitative protocols. Results: Both the verticalization treatments were well-tolerated. Notably, the G1 patients had a significant improvement in cognitive function (p  = 0.03), global motor function (p  = 0.006), sensory-motor (p  <  0.001) and vestibular system plasticity (p  = 0.02) as compared to G2. Conclusions: ERIGO training could be a valuable tool for the adaptation to the vertical position with a better global function improvement, as also suggested by the sensory-motor and vestibular system plasticity induction. Show more

Keywords: ERIGO, verticalization, stroke, vestibular system, sensory-motor plasticity, bedridden condition

DOI: 10.3233/RNN-140475

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 671-681, 2015

Authors: Gálvez, Javier | Estrada-Reyes, Rosa | Benítez-King, Gloria | Araujo, Gabriela | Orozco, Sandra | Fernández-Mas, Rodrigo | Almazán, Salvador | Calixto, Eduardo

Article Type: Research Article

Abstract: Purpose: Characterization of sedative, possible anticonvulsant, and protective effects of Acacetin-7-O -glucoside (7-ACAG). Methods: 7-ACAG was separated and its purity was analyzed. Its sedative and anti-seizure effects (1, 10, 20, and 40 mg/kg) were evaluated in male mice. Synaptic responses were acquired from area CA1 of hippocampal slices obtained from male Wistar rats. Rats were subjected to stereotaxic surgeries to allow Electroencephalographic (EEG) recordings. Functional recovery was evaluated by measuring the time rats spent in completing the motor task. Then the rats were subjected to right hemiplegia and administered 7-ACAG (40 mg/kg) 1 h or 24 h after surgery. …Brains of each group of rats were prepared for histological analysis. Results: Effective sedative doses of 7-ACAG comprised those between 20 and 40 mg/kg. Latency and duration of the epileptiform crisis were delayed by this flavonoid. 7-ACAG decreased the synaptic response in vitro , similar to Gamma-aminobutyric acid (GABA) effects. The flavonoid facilitated functional recovery. This data was associated with preserved cytoarchitecture in brain cortex and hippocampus. Conclusions: 7-ACAG possesses anticonvulsive and sedative effects. Results suggest that GABAergic activity and neuroprotection are involved in the mechanism of action of 7-ACAG and support this compound’s being a potential drug for treatment of anxiety or post-operative conditions caused by neurosurgeries. Show more

Keywords: Flavonoids, GABAA, hemiplegia, functional recovery

DOI: 10.3233/RNN-140486

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 683-700, 2015

Authors: Dettmers, Christian | Nedelko, Violetta | Ariel Schoenfeld, Mircea

Article Type: Research Article

Abstract: Purpose: Mental training appears to be an attractive tool in stroke rehabilitation. The objective of this study was to investigate whether any differences in the processing of action observation and imagery might exist between patients with left and right hemisphere subcortical strokes. Methods: Eighteen patients with strictly subcortical stroke (nine right-hemispheric) underwent a functional magnetic resonance imaging (fMRI) study with an experimental paradigm in which motor acts had to be observed and/or imagined from a first person perspective. Changes in hemodynamic activity were measured using fMRI. Results: The activity level was found …to be higher in the non-lesioned compared to the lesioned hemisphere. Patients with lesions in the left hemisphere had a higher activation level in visual (fusiform and lingual gyri), superior temporal areas and dorsal premotor regions across all performed comparisons than those with right hemisphere lesions. Furthermore they had more vivid imagery experiences and lower scores on the Stroke Impact Scale. Conclusions: Patients with left hemisphere subcortical lesions recruit more cortical regions in the processing of action pictures and videos. This recruitment was further enhanced during imagery. This is most likely related to the fact that the lesion touched the dominant hemisphere. Show more

Keywords: Motor observation, motor imagery, subcortical strokes, handedness, functional imaging

DOI: 10.3233/RNN-140487

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 701-712, 2015

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