Restorative Neurology and Neuroscience - Volume 34, issue 6

Authors: Kalaani, Joanna | Roche, Joëlle | Hamade, Eva | Badran, Bassam | Jaber, Mohamed | Gaillard, Afsaneh | Prestoz, Laetitia

Article Type: Research Article

Abstract: Background: Cell therapy is a promising approach for Parkinson’s disease (PD). Others and we have previously shown that transplantation of ventral mesencephalic fetal cells into substantia nigra (SN) in an animal model of PD enables anatomical and functional repair of the degenerated pathway. However, the molecular basis of this repair is still largely unknown. Objective: In this work, we studied the expression of several axon guidance molecules that may be implicated in the repair of the degenerated nigrostriatal pathway. Methods: The expression of axon guidance molecules was analyzed using qRT-PCR on five specific regions surrounding …the nigrostriatal pathway (ventral mesencephalon (VM), thalamus (Thal), medial forebrain bundle (MFB), nucleus accumbens (NAcc) and caudate putamen (CPu)), one and seven days after lesion and transplantation. Results: We showed that mRNA expression of specific axon guidance molecules and their receptors is modified in structures surrounding the nigrostriatal pathway, suggesting their involvement in the axon guidance of grafted neurons. Moreover, we highlight a possible new role for semaphorin 7A in this repair. Conclusion: Overall, our data provide a reliable basis to understand how axons of grafted neurons are able to navigate towards their targets and interact with the molecular environment in the adult brain. This should help to improve the efficiency of cell replacement approaches in PD. Show more

Keywords: Axon guidance molecule expression, substantia nigra, transplantation, adult brain plasticity

DOI: 10.3233/RNN-150587

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 877-895, 2016

Authors: Khedr, Eman Mohamed | Badry, Reda | Ali, Anwer Mohamed | Abo El-Fetoh, Noha | El-Hammady, Dina Hatem | Ghandour, Abeer Mohamed | Abdel-Haleem, Ahmed

Article Type: Research Article

Abstract: Background: A large number of patients with Bell’s palsy fail to recover facial function completely after steroid therapy. Only a few small trials have been conducted to test whether outcomes can be improved by the addition of antiviral therapy. Objective: To evaluate the efficacy of treatment with steroid alone versus steroid + antiviral in a group of patients with moderately severe to severe acute Bell’s palsy. Methods: Fifty eligible patients out of a total of 65 with acute onset Bell’s palsy were randomized to receive the two treatments. Evaluation was performed before starting treatment, after …2 weeks of treatment and 3 months after onset, using the House and Brackmann facial nerve grading system (HB) and the Sunnybrook grading system. This study was registered with ClinicalTrials.gov, number NCT02328079. Results: Both treatments had comparable demographics and clinical scores at baseline. There was greater improvement in the mean HB and Sunnybrook scores of the steroid + antiviral group in comparison to steroid group at 3 months. At the end of the 3rd month, 17 patients (68%) had good recovery and 8 patients (32%) had poor recovery in the steroid group compared with 23 patients (92%) and 2 (8%) respectively in the steroid and antiviral group (p  = 0.034). Conclusion: The combination of steroid and antiviral treatment increases the possibility of recovery in moderately severe to complete acute Bell’s palsy. Show more

Keywords: Bell’s palsy, steroid/antiviral, electroneurography, prognosis

DOI: 10.3233/RNN-150605

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 897-905, 2016

Authors: Liepert, Joachim | Büsching, Imke | Sehle, Aida | Schoenfeld, Mircea Ariel

Article Type: Research Article

Abstract: Background: Motor imagery is used for treatment of motor deficits after stroke. Clinical observations suggested that motor imagery abilities might be reduced in patients with severe sensory deficits. This study investigated the influence of somatosensory deficits on temporal (mental chronometry, MC) and spatial aspects of motor imagery abilities. Methods: Stroke patients (n  = 70; <6 months after stroke) were subdivided into 3 groups according to their somatosensory functions. Group 1 (n  = 31) had no sensory deficits, group 2 (n  = 27) had a mild to moderate sensory impairment and group 3 (n  = 12) had severe sensory deficits. Patients and …a healthy age-matched control group (n  = 23) participated in a mental chronometry task (Box and Block Test, BBT) and a mental rotation task (Hand Identification Test, HIT). MC abilities were expressed as a ratio (motor execution time–motor imagery time/motor execution time). Results: MC for the affected hand was significantly impaired in group 3 in comparison to stroke patients of group 1 (p  = 0.006), group 2 (p  = 0.005) and healthy controls (p  < 0.001). For the non-affected hand MC was similar across all groups. Stroke patients had a slower BBT motor execution than healthy controls (p  < 0.001), and group 1 executed the task faster than group 3 (p  = 0.002). The percentage of correct responses in the HIT was similar for all groups. Conclusion: Severe sensory deficits impair mental chronometry abilities but have no impact on mental rotation abilities. Future studies should explore whether the presence of severe sensory deficits in stroke patients reduces the benefit from motor imagery therapy. Show more

Keywords: Motor imagery, mental chronometry, hand identification task, stroke, somatosensory function

DOI: 10.3233/RNN-160640

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 907-914, 2016

Authors: Kwon, Tae Gun | Park, Eunhee | Kang, Chung | Chang, Won Hyuk | Kim, Yun-Hee

Article Type: Research Article

Abstract: Background: Both transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), when provided to stroke patients in combination with motor training, enhance therapeutic efficacy and motor function. However, the majority of previous studies have only examined a single treatment modality. Objective: The authors investigated the modulating influence of combination dual-mode brain stimulation upon bihemispheric stimulation with motor training in stroke patients. Methods: Twenty stroke patients with hemiparesis underwent five randomly arranged sessions of diverse combinations of rTMS and tDCS. We applied cathodal or anodal tDCS over the contralesional primary motor cortex (cM1) and 10 Hz …rTMS over the ipsilesional primary motor cortex (iM1) in a simultaneous or preconditioning method including sham stimulation. Immediately after dual-mode stimulation, sequential hand motor training was performed for 5 minutes. The total pulses of rTMS and the duration of tDCS and motor training were the same for all sessions. Cortical excitability and sequential motor performance were evaluated before and after each session. Results: Motor function and corticomotor excitability following simultaneous stimulation via cathodal tDCS over the cM1 combined with 10 Hz rTMS over the iM1 were significantly increased after the intervention, with significantly greater motor improvement than seen with other treatment conditions (P  < 0.05). Conclusion: For the combination of bihemispheric rTMS and tDCS, simultaneous stimulation of cathodal tDCS and 10 Hz rTMS results in better motor performance in stroke patients than other combination methods. This result seemed to be related to effective modulation of interhemispheric imbalance of cortical excitability by dual-mode stimulation. Show more

Keywords: Stroke, motor recovery, transcranial magnetic stimulation, transcranial direct current stimulation

DOI: 10.3233/RNN-160654

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 915-923, 2016

Authors: Kim, Bo-Ram | Kim, Hahn Young | Chun, Young Il | Yun, Yeo-Min | Kim, Hyuntae | Choi, Dong-Hee | Lee, Jongmin

Article Type: Research Article

Abstract: Background: The dopamine system plays a key role in motor learning and neuroplasticity. Several studies have studied the efficacy of dopaminergic drugs in enhancing motor recovery after stroke, but the effects are controversial. Although genetic variations in plasticity-related genes influence each individual’s capacity for recovery after stroke, limited studies have investigated the effects of polymorphism of dopamine-related genes. Objective: We aimed to investigate the association between motor recovery in stroke patients and polymorphisms in the dopamine-related genes catechol-O-methyltransferase (COMT ), dopamine receptor D1 (DRD1 ), DRD2 , and DRD3 . Methods: We enrolled 74 patients …with first-ever stroke (42 males, 32 females, mean age: 61.4±14.1 y). During admission, blood samples were collected, and the genotypes of COMT , DRD1 , DRD2 , and DRD3 were analyzed. The primary outcome was assessed with Fugl-Meyer Assessment (FMA) at 1 week, 3 months, and 6 months after stroke; secondary outcomes were assessed with Functional Independence Measure (FIM) and mini-mental state examination at 3 and 6 months after stroke. The association between polymorphisms and functional outcome was analyzed. Results: There were no significant associations between COMT polymorphisms and FMA or FIM scores at 1 week after stroke or between DRD1 , DRD2 , or DRD3 genotypes and FMA or FIM scores at any point. COMT genotypes were significantly associated with FMA and FIM at 3 months (p  < 0.01 and p  < 0.05, respectively) and at 6 months (p  < 0.01 and p  < 0.05, respectively). Conclusion: These data suggest that genetic variation of dopamine-related genes may affect motor recovery after stroke and that COMT polymorphism could be useful for predicting motor recovery. Show more

Keywords: Stroke, single-nucleotide polymorphism, dopamine, rehabilitation

DOI: 10.3233/RNN-160667

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 925-934, 2016

Authors: Ilić, Nela V. | Dubljanin-Raspopović, Emilija | Nedeljković, Una | Tomanović-Vujadinović, Sanja | Milanović, Sladjan D. | Petronić-Marković, Ivana | Ilić, Tihomir V.

Article Type: Research Article

Abstract: Background: A growing body of evidence supports the effectiveness of using transcranial direct current stimulation (tDCS) in patients with chronic hand motor impairment resulting from stroke. Objective: In this study, we investigate and compare the combined effects of anodal tDCS and occupational therapy (OT) to sham stimulation with OT (control) on fine motor skill deficits of chronic stroke patients. Methods: A total of 26 stroke patients (at ≥ 9 months) were randomly assigned to an active treatment or a control group in a double-blinded, sham-controlled, parallel design study. Each group received OT for 45 min/day (10 …sessions for 2 weeks). Treatment was preceded by either 20 minutes of 2 mA anodal tDCS over ipsilesional M1 or sham tDCS. A modified Jebsen-Taylor Hand Function Test (mJTHFT) was administered as primary outcome measure, and handgrip dynamometer and upper limb Fugl-Meyer (ULFM) assessments were performed as secondary outcomes. The assessment was done at baseline (T0), after the interventions on day 1(T1), day 10 (T2) and day 40 (T3). Results: We observed a statistically significant effect in the tDCS group when the results were compared to the sham group. The mJTHFT times were significantly shorter immediately after treatment and at day 40. The intervention had no effect on handgrip strength or ULFM score. Conclusion: Fine motor skill deficits in chronic stroke survivors can be improved when intensive OT is primed with anodal tDCS over the ipsilesional hemisphere. Show more

Keywords: Stroke recovery, rehabilitation, non-invasive brain stimulation, transcranial direct current stimulation, occupational therapy

DOI: 10.3233/RNN-160668

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 935-945, 2016

Authors: Allen, Rachael S. | Sayeed, Iqbal | Oumarbaeva, Yuliya | Morrison, Katherine C. | Choi, Paul H. | Pardue, Machelle T. | Stein, Donald G.

Article Type: Research Article

Abstract: Background/Objective: To determine whether inflammation increases in retina as it does in brain following middle cerebral artery occlusion (MCAO), and whether the neurosteroid progesterone, shown to have protective effects in both retina and brain after MCAO, reduces inflammation in retina as well as brain. Methods: MCAO rats treated systemically with progesterone or vehicle were compared with shams. Protein levels of cytosolic NF-κ B, nuclear NF-κ B, phosphorylated NF-κ B, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane X receptor were assessed in retinas and brains at 24 and 48 h using western blots. Results: …Following MCAO, significant increases were observed in the following inflammatory markers: pNF-κ B and CD11b at 24 h in both brain and retina, nuclear NF-κ B at 24 h in brain and 48 h in retina, and TNF-α at 24 h in brain. Progesterone treatment in MCAO animals significantly attenuated levels of the following markers in brain: pNF-κ B, nuclear NF-κ B, IL-6, TNF-α, and CD11b, with significantly increased levels of cytosolic NF-κ B. Retinas from progesterone-treated animals showed significantly reduced levels of nuclear NF-κ B and IL-6 and increased levels of cytosolic NF-κ B, with a trend for reduction in other markers. Post-MCAO, progesterone receptors A and B were upregulated in brain and downregulated in retina. Conclusion: Inflammatory markers increased in both brain and retina after MCAO, with greater increases observed in brain. Progesterone treatment reduced inflammation, with more dramatic reductions observed in brain than retina. This differential effect may be due to differences in the response of progesterone receptors in brain and retina after injury. Show more

Keywords: Focal ischemia, inflammation, middle cerebral artery occlusion, NF-kB, progesterone, progesterone receptor, rat, retina, retinal ischemia

DOI: 10.3233/RNN-160672

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 947-963, 2016

Authors: Lee, Chun-Ting | Boeshore, Kristen L. | Wu, Chun | Becker, Kevin G. | Errico, Stacie L. | Mash, Deborah C. | Freed, William J.

Article Type: Research Article

Abstract: Purpose: Astrocytes perform a plethora of important functions in the central nervous system (CNS) and are involved in cocaine-evoked synaptic plasticity. Previously, we showed that while cocaine decreased cyclin A2 expression in primary human neural progenitor cells, it increased cyclin A2 expression in human astrocytes. Since cyclin A2 is an essential regulator of the cell cycle, the aim of the present study is to clarify the effect of cocaine on proliferation of human astrocytes and elucidate the underlying molecular mechanisms. Methods: Primary human astrocytes were treated with either 1, 10, or 100 μM cocaine for …48 hr, and cell proliferation was measured using the CyQUANT cell proliferation assay. To elucidate the molecular mechanisms through which cocaine affects the proliferation of astrocytes, we analyzed gene expression profiles in cocaine-treated primary human astrocytes using a human focused cDNA array. Gene ontology/pathway enrichment analysis, STRING protein-protein interaction analysis, RT-qPCR, and western blotting were used to identify signal transduction pathways that are involved in cocaine-induced astrocyte dysfunction. Results: Cocaine at 10 and 100 μM significantly increased human astrocyte proliferation. Gene expression profiling revealed the JNK MAP kinase pathway as a driver of cell proliferation affected by cocaine in human astrocytes. Further experiments showed that cocaine-induced JNK activation induced up-regulation of cyclin A2, leading to enhanced proliferation of human astrocytes. Conclusion: Cocaine-induced abnormal increases in the number of astrocytes may cause disruption in neuron-glia signaling and contribute to synaptic impairment in the CNS. Understanding the mechanisms of cocaine’s effects on human astrocytes may help to reveal the involvement of glial cells in addictive behaviors. Show more

Keywords: Astrocytes, cocaine, reactive astrogliosis, addiction, JNK, cyclin A

DOI: 10.3233/RNN-160676

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 965-976, 2016

Authors: Morris, Timothy | Gomes Osman, Joyce | Tormos Muñoz, Jose Maria | Costa Miserachs, David | Pascual Leone, Alvaro

Article Type: Research Article

Abstract: Background: There is a growing body of evidence revealing exercise-induced effects on brain structure and cognitive function across the lifespan. Animal models of traumatic brain injury also suggest exercise is capable of modulating not only the pathophysiological changes following trauma but also the associated cognitive deficits. Objective: To evaluate the effect of physical exercise on cognitive impairment following traumatic brain injury in humans. Methods: A systematic search of the PubMed database was performed using the search terms “cognition” and “executive function, memory or attention”, “traumatic brain injury” and “physical exercise”. Adult human traumatic brain injury studies …that assessed cognitive function as an outcome measure (primary or secondary) and used physical exercise as a treatment (single or combined) were assessed by two independent reviewers. Data was extracted under the guidance of the population intervention comparison outcome framework wherein, characteristics of included studies (exercise duration, intensity, combined or single intervention, control groups and cognitive measures) were collected, after which, methodological quality (Cochrane criteria) was assessed. Results: A total of 240 citations were identified, but only 6 met our inclusion criteria (3 from search records, 3 from reference lists. Only a small number of studies have evaluated the effect of exercise on cognition following traumatic brain injury in humans, and of those, assessment of efficacy is difficult due to low methodological strength and a high risk of different types of bias. Conclusion: Evidence of an effect of physical exercise on cognitive recovery suggests further studies should explore this treatment option with greater methodological approaches. Recommendations to reduce risk of bias and methodological shortfalls are discussed and include stricter inclusion criteria to create homogenous groups and larger patient pools, more rigorous cognitive assessments and the study and reporting of additional and combined rehabilitation techniques. Show more

Keywords: Traumatic brain injury, physical exercise, cognition, rehabilitation

DOI: 10.3233/RNN-160687

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 977-988, 2016

Article Type: Other

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 989-996, 2016