ABSTRACT
This study aimed to investigate changes in attention processing after low-frequency repetitive transcranial magnetic stimulation (rTMS) over the left posterior parietal cortex to better understand its role in visuospatial neglect (VSN) rehabilitation. The current study included 10 subacute stroke patients with VSN consecutively recruited from the inpatient stroke rehabilitation center at Xuanwu Hospital (the teaching hospital affiliated with Capital Medical University) between March and November 2019. All patients performed a battery of tasks (including line bisection, line cancellation, and star cancellation tests) two weeks before treatment and at the beginning and end of treatment; the attentive components of the test results were analyzed. In addition, low-frequency rTMS was used to stimulate the left posterior parietal cortex for 14 days and event-related potential data were collected before and after the stimulation. Participants were evaluated using a target-cue paradigm and pencil-paper tests. No significant differences were detected on the battery of tasks before rTMS. However, we found that rTMS treatment significantly improved the response times and accuracy rates of patients with VSN. After rTMS, the treatment side (left) amplitude of P300 following an event-related potential was higher than that before treatment (left target, p = 0.002; right target, p = 0.047). Thus, our findings suggest that rTMS may be an effective treatment for VSN. The observed increase in event-related potential amplitude supports the hypothesized compensational role of the contralesional hemisphere in terms of residual performance. Our results provide electrophysiological evidence that may help determine the mechanisms mediating the therapeutic effects of rTMS.
ABSTRACT
BACKGROUND: Visual-spatial neglect (VSN) is a neuropsychological syndrome, and right-hemisphere stroke is the most common cause. The pathogenetic mechanism of VSN remains unclear. This study aimed to investigate the behavioral and event-related potential (ERP) changes in patients with or without VSN after right-hemisphere stroke. METHODS: Eleven patients with VSN with right-hemisphere stroke (VSN group) and 11 patients with non-VSN with right-hemisphere stroke (non-VSN group) were recruited along with one control group of 11 age- and gender-matched healthy participants. The visual-spatial function was evaluated using behavioral tests, and ERP examinations were performed. RESULTS: The response times in the VSN and non-VSN groups were both prolonged compared with those of normal controls (Pâ<â0.001). In response to either valid or invalid cues in the left side, the accuracy in the VSN group was lower than that in the non-VSN group (Pâ<â0.001), and the accuracy in the non-VSN group was lower than that in controls (Pâ<â0.05). The P1 latency in the VSN group was significantly longer than that in the control group (F[2, 30]â=â5.494, Pâ=â0.009), and the N1 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30]â=â4.343, Pâ=â0.022). When responding to right targets, the left-hemisphere P300 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30]â=â4.255, Pâ=â0.025). With either left or right stimuli, the bilateral-hemisphere P300 latencies in the VSN and non-VSN groups were both significantly prolonged (all Pâ<â0.05), while the P300 latency did not differ significantly between the VSN and non-VSN groups (all Pâ>â0.05). CONCLUSIONS: Visual-spatial attention function is impaired after right-hemisphere stroke, and clinicians should be aware of the subclinical VSN. Our findings provide neuroelectrophysiological evidence for the lateralization of VSN.
Subject(s)
Cerebral Infarction/physiopathology , Perceptual Disorders/physiopathology , Stroke/physiopathology , Adult , Aged , Electrophysiology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Nitric Oxide Synthase Type III/genetics , PPAR gamma/genetics , Perceptual Disorders/genetics , Perceptual Disorders/metabolism , Polymorphism, Genetic/genetics , Reaction Time/genetics , Reaction Time/physiology , Reactive Oxygen Species/metabolism , Stroke/genetics , Stroke/metabolism , Superoxide Dismutase/geneticsABSTRACT
Intervertebral discs (IVDs) provide stability and flexibility to the spinal column; however, IVDs, and in particular the nucleus pulposus (NP), undergo a degenerative process characterized by changes in the disc extracellular matrix (ECM), decreased cell viability, and reduced synthesis of proteoglycan and type II collagen. Here, we investigated the efficacy and feasibility of stem cell therapy using bone marrow mesenchymal stem cells (BMSCs) over-expressing bone morphogenetic protein 7 (BMP7) to promote ECM remodeling of degenerated IVDs. Lentivirus-mediated BMP7 over-expression induced differentiation of BMSCs into an NP phenotype, as indicated by expression of the NP markers collagen type II, aggrecan, SOX9 and keratins 8 and 19, increased the content of glycosaminoglycan, and up-regulated ß-1,3-glucuronosyl transferase 1, a regulator of chondroitin sulfate synthesis in NP cells. These effects were suppressed by Smad1 silencing, indicating that the effect of BMP7 on ECM remodeling was mediated by the Smad pathway. In vivo analysis in a rabbit model of disc degeneration showed that implantation of BMSCs over-expressing BMP7 promoted cell differentiation and proliferation in the NP, as well as their own survival, and these effects were mediated by the Smad pathway. The results of the present study indicate the beneficial effects of BMP7 on restoring ECM homeostasis in NP cells, and suggest potential strategies for improving cell therapy for the treatment of disc diseases.
Subject(s)
Bone Morphogenetic Protein 7/genetics , Intervertebral Disc Degeneration/therapy , Lentivirus/genetics , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Aggrecans/genetics , Aggrecans/metabolism , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Bone Morphogenetic Protein 7/metabolism , Chondrocytes/metabolism , Chondrocytes/pathology , Collagen Type II/genetics , Collagen Type II/metabolism , Disease Models, Animal , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Gene Expression Regulation , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Glucuronosyltransferase/genetics , Glucuronosyltransferase/metabolism , Glycosaminoglycans/metabolism , Humans , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , Keratin-19/genetics , Keratin-19/metabolism , Keratin-8/genetics , Keratin-8/metabolism , Lentivirus/metabolism , Mesenchymal Stem Cells/cytology , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Rabbits , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Signal Transduction , Smad1 Protein/antagonists & inhibitors , Smad1 Protein/genetics , Smad1 Protein/metabolismABSTRACT
The aim of the study was to investigate the fate of donor osteocytes in fine particulate bone powders during repair of bone defects in experimental rats. The iliac bone of male inbred DA rats was harvested and used as the larger bone grafts and also prepared as fine particulate (granulated) bone powders (300-500µm size particles) for transplantation into radial defects in female rats. The presence and relative amounts of genes specific to the sex-determining region of the Y-chromosome (Sry) originating from the bone grafts were evaluated by polymerase chain reaction and by in situ hybridization, respectively. Additional samples were evaluated histologically. In the larger bone grafts, the expression of Sry decreased relatively early, disappeared by 1 week, reappeared at 4 weeks and continued to increase with time. In the fine particulate bone powders, Sry was detected all the time and its expression was statistically greater than in the larger bone grafts at each time point. Both bone grafts provided donor cells to repair the defects. The donor cells seemed to function differently between the two groups. The fine particulate bone powders contained more living osteocytes in comparison with the larger bone grafts and may accelerate the healing of bone defects compared with conventional autografts.
