Restorative Neurology and Neuroscience - Volume 39, issue 4

Authors: Wanni Arachchige, Pradeepa Ruwan | Karunarathna, Sadhani | Meidian, Abdul Chalik | Ueda, Ryo | Uchida, Wataru | Abo, Masahiro | Senoo, Atsushi

Article Type: Research Article

Abstract: Background: Although quite a very few studies have tested structural connectivity changes following an intervention, it reflects only selected key brain regions in the motor network. Thus, the understanding of structural connectivity changes related to the motor recovery process remains unclear. Objective: This study investigated structural connectivity changes of the motor execution network following a combined intervention of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) and intensive occupational therapy (OT) after a stroke using graph theory approach. Methods: Fifty-six stroke patients underwent Fugl-Meyer Assessment (FMA), Wolf Motor Function Test-Functional Ability Scale (WMFT-FAS), diffusion tensor imaging (DTI), and …T1 weighted imaging before and after the intervention. We examined graph theory measures related to twenty brain regions using structural connectomes. Results: The ipsilesional and contralesional hemisphere showed structural connectivity changes post-intervention after stroke. We found significantly increased regional centralities and nodal efficiency within the frontal pole and decreased degree centrality and nodal efficiency in the ipsilesional thalamus. Correlations were found between network measures and clinical assessments in the cuneus, postcentral gyrus, precentral gyrus, and putamen of the ipsilesional hemisphere. The contralesional areas such as the caudate, cerebellum, and frontal pole also showed significant correlations. Conclusions: This study was helpful to expand the understanding of structural connectivity changes in both hemispheric networks during the motor recovery process following LF-rTMS and intensive OT after stroke. Show more

Keywords: Low-frequency rTMS and OT intervention, stroke recovery, graph theory analysis, structural connectivity, motor execution network

DOI: 10.3233/RNN-211148

Citation: Restorative Neurology and Neuroscience, vol. 39, no. 4, pp. 237-245, 2021

Authors: Wu, Chun | Bendriem, Raphael M. | Freed, William J. | Lee, Chun-Ting

Article Type: Research Article

Abstract: Background: Motor and cognitive decline as part of the normal aging process is linked to alterations in synaptic plasticity and reduction of adult neurogenesis in the dorsal striatum. Neuroinflammation, particularly in the form of microglial activation, is suggested to contribute to these age-associated changes. Objective and Methods: To explore the molecular basis of alterations in striatal function during aging we analyzed RNA-Seq data for 117 postmortem human dorsal caudate samples and 97 putamen samples acquired through GTEx. Results: Increased expression of neuroinflammatory transcripts including TREM2 , MHC II molecules HLA-DMB , HLA-DQA2 , HLA-DPA1 , HLA-DPB1 …, HLA-DMA and HLA-DRA , complement genes C1QA , C1QB , CIQC and C3AR 1, and MHCI molecules HLA-B and HLA-F was identified. We also identified down-regulation of transcripts involved in neurogenesis, synaptogenesis, and synaptic pruning, including DCX , CX3CL1, and CD200 , and the canonical WNTs WNT7A , WNT7B , and WNT8A . The canonical WNT signaling pathway has previously been shown to mediate adult neurogenesis and synapse formation and growth. Recent findings also highlight the link between WNT/β-catenin signaling and inflammation pathways. Conclusions: These findings suggest that age-dependent attenuation of canonical WNT signaling plays a pivotal role in regulating striatal plasticity during aging. Dysregulation of WNT/β-catenin signaling via astrocyte–microglial interactions is suggested to be a novel mechanism that drives the decline of striatal neurogenesis and altered synaptic connectivity and plasticity, leading to a subsequent decrease in motor and cognitive performance with age. These findings may aid in the development of therapies targeting WNT/β-catenin signaling to combat cognitive and motor impairments associated with aging. Show more

Keywords: RNA sequencing, caudate, putamen, aging, WNT, striatal neurogenesis, synaptic plasticity, neuroinflammation

DOI: 10.3233/RNN-211161

Citation: Restorative Neurology and Neuroscience, vol. 39, no. 4, pp. 247-266, 2021

Authors: Keilhoff, Gerburg | Titze, Maximilian | Ebmeyer, Uwe

Article Type: Research Article

Abstract: Background: Stroke-related loss of vision is one of the residual impairments, restricting the quality of life. However, studies of the ocular manifestations of asphyxia cardiac arrest/resuscitation (ACA/R) have reported very heterogeneous results. Objective: We aimed to evaluate the ACA/R-induced degeneration pattern of the different retinal cell populations in rats using different immuno-histological stainings. Methods: The staining pattern of toluidine blue and the ganglion cell markers β-III-tubulin and NeuN; the calcium-binding protein parvalbumin, indicating ganglion, amacrine, and horizontal cells; calretinin D28k, indicating ganglion and amacrine cells; calbindin, indicating horizontal cells; Chx 10, indicating cone bipolar cells; PKCα, …indicating ON-type rod bipolar cells; arrestin, indicating cones; and rhodopsin, a marker of rods, as well as the glial cell markers GFAP (indicating astroglia and Müller cells) and IBA1 (indicating microglia), were evaluated after survival times of 7 and 21 days in an ACA/R rat model. Moreover, quantitative morphological analysis of the optic nerve was performed. The ACA/R specimens were compared with those from sham-operated and completely naïve rats. Results: ACA/R-induced effects were: (i) a significant reduction of retinal thickness after long-term survival; (ii) ganglion cell degeneration, including their fiber network in the inner plexiform layer; (iii) degeneration of amacrine and cone bipolar cells; (iv) degeneration of cone photoreceptors; (v) enhanced resistance to ACA/R by rod photoreceptors, ON-type rod bipolar and horizontal cells, possibly caused by the strong upregulation of the calcium-binding proteins calretinin, parvalbumin, and calbindin, counteracting the detrimental calcium overload; (vi) significant activation of Müller cells as further element of retinal anti-stress self-defense mechanisms; and (vii) morphological alterations of the optic nerve in form of deformed fibers. Conclusions: Regardless of the many defects, the surviving neuronal structures seemed to be able to maintain retinal functionality, which can be additionally improved by regenerative processes true to the “use it or lose it” dogma. Show more

Keywords: Keywords: Amacrine cells, bipolar cells, calcium-binding proteins, ganglion cells, horizontal cells, Müller cells, photoreceptors

DOI: 10.3233/RNN-211174

Citation: Restorative Neurology and Neuroscience, vol. 39, no. 4, pp. 267-289, 2021

Authors: Mendonça, Thyciane | Brito, Rodrigo | Luna, Plínio | Campêlo, Mayara | Shirahige, Lívia | Fontes, Luís | Dias, Rebeca | Piscitelli, Daniele | Monte-Silva, Kátia

Article Type: Research Article

Abstract: Background: Repetitive transcranial magnetic stimulation (rTMS) has been applied for modulating cortical excitability and treating spasticity in neurological lesions. However, it is unclear which rTMS frequency is most effective in modulating cortical and spinal excitability in incomplete spinal cord injury (SCI). Objective: To evaluate electrophysiological and clinical repercussions of rTMS compared to sham stimulation when applied to the primary motor cortex (M1) in individuals with incomplete SCI. Methods: A total of 11 subjects (35±12 years) underwent three experimental sessions of rTMS (10 Hz, 1 Hz and sham stimulation) in a randomized order at 90%intensity of the resting motor …threshold and interspersed by a seven-day interval between sessions. The following outcome measures were evaluated: M1 and spinal cord excitability and spasticity in the moments before (baseline), immediately after (T0), 30 (T30) and 60 (T60) minutes after rTMS. M1 excitability was obtained through the motor evoked potential (MEP); spinal cord excitability by the Hoffman reflex (H-reflex) and homosynaptic depression (HD); and spasticity by the modified Ashworth scale (MAS). Results: A significant increase in cortical excitability was observed in subjects submitted to 10 Hz rTMS at the T0 moment when compared to sham stimulation (p  = 0.008); this increase was also significant at T0 (p  = 0.009), T30 (p  = 0.005) and T60 (p  = 0.005) moments when compared to the baseline condition. No significant differences were observed after the 10 Hz rTMS on spinal excitability or on spasticity. No inter-group differences were detected, or in the time after application of 1 Hz rTMS, or after sham stimulation for any of the assessed outcomes. Conclusions: High-frequency rTMS applied to M1 was able to promote increased cortical excitability in individuals with incomplete SCI for at least 60 minutes; however, it did not modify spinal excitability or spasticity. Show more

Keywords: Spinal cord injury, transcranial magnetic stimulation, excitability, spasticity, physiotherapy

DOI: 10.3233/RNN-211167

Citation: Restorative Neurology and Neuroscience, vol. 39, no. 4, pp. 291-301, 2021

Authors: Uswatte, Gitendra | Taub, Edward | Lum, Peter | Brennan, David | Barman, Joydip | Bowman, Mary H. | Taylor, Andrea | McKay, Staci | Sloman, Samantha B. | Morris, David M. | Mark, Victor W.

Article Type: Research Article

Abstract: Background: Although Constraint-Induced Movement therapy (CIMT) has been deemed efficacious for adults with persistent, mild-to-moderate, post-stroke upper-extremity hemiparesis, CIMT is not available on a widespread clinical basis. Impediments include its cost and travel to multiple therapy appointments. To overcome these barriers, we developed an automated, tele-health form of CIMT. Objective: Determine whether in-home, tele-health CIMT has outcomes as good as in-clinic, face-to-face CIMT in adults ≥1-year post-stroke with mild-to-moderate upper-extremity hemiparesis. Methods: Twenty-four stroke patients with chronic upper-arm extremity hemiparesis were randomly assigned to tele-health CIMT (Tele-AutoCITE) or in-lab CIMT. All received 35 hours of treatment. …In the tele-health group, an automated, upper-extremity workstation with built-in sensors and video cameras was set-up in participants’ homes. Internet-based audio-visual and data links permitted supervision of treatment by a trainer in the lab. Results: Ten patients in each group completed treatment. All twenty, on average, showed very large improvements immediately afterwards in everyday use of the more-affected arm (mean change on Motor Activity Log Arm Use scale = 2.5 points, p  < 0.001, d′  = 3.1). After one-year, a large improvement from baseline was still present (mean change = 1.8, p  < 0.001, d′  = 2). Post-treatment outcomes in the tele-health group were not inferior to those in the in-lab group. Neither were participants’ perceptions of satisfaction with and difficulty of the interventions. Although everyday arm use was similar in the two groups after one-year (mean difference = –0.1, 95% CI  = –1.3–1.0), reductions in the precision of the estimates of this parameter due to drop-out over follow-up did not permit ruling out that the tele-health group had an inferior long-term outcome. Conclusions: This proof-of-concept study suggests that Tele-AutoCITE produces immediate benefits that are equivalent to those after in-lab CIMT in stroke survivors with chronic upper-arm extremity hemiparesis. Cost savings possible with this tele-health approach remain to be evaluated. Show more

Keywords: Stroke, upper extremity, hemiparesis, physical rehabilitation, telehealth, randomized controlled trial

DOI: 10.3233/RNN-201100

Citation: Restorative Neurology and Neuroscience, vol. 39, no. 4, pp. 303-318, 2021