Connecting the dots: Sensory cueing enhances functional connectivity between pre-motor and supplementary motor areas in Parkinson's disease.

People with Parkinson's disease often exhibit improvements in motor tasks when exposed to external sensory cues. While the effects of different types of sensory cues on motor functions in Parkinson's disease have been widely studied, the underlying neural mechanism of these effects and the potential of sensory cues to alter the motor cortical activity patterns and functional connectivity of cortical motor areas are still unclear. This study aims to compare changes in oxygenated haemoglobin, deoxygenated haemoglobin and correlations among different cortical regions of interest during wrist movement under different external stimulus conditions between people with Parkinson's disease and controls. Ten Parkinson's disease patients and 10 age- and sex-matched neurologically healthy individuals participated, performing repetitive wrist flexion and extension tasks under auditory and visual cues. Changes in oxygenated and deoxygenated haemoglobin in motor areas were measured using functional near-infrared spectroscopy, along with electromyograms from wrist muscles and wrist movement kinematics. The functional near-infrared spectroscopy data revealed significantly higher neural activity changes in the Parkinson's disease group's pre-motor area compared to controls (p = 0.006), and functional connectivity between the supplementary motor area and pre-motor area was also significantly higher in the Parkinson's disease group when external sensory cues were present (p = 0.016). These results indicate that external sensory cues' beneficial effects on motor tasks are linked to changes in the functional connectivity between motor areas responsible for planning and preparation of movements.

The Effect of Exosomes Derived from Bone Marrow Stem Cells in Combination with Rosuvastatin on Functional Recovery and Neuroprotection in Rats After Ischemic Stroke.

Rosuvastatin, known as a cholesterol-lowering agent, has been used as an alternative therapy after the onset of stroke. In this study, neuroprotection and functional recovery of exosomes in combination with rosuvastatin have been investigated. Sixty adult male Wistar rats were subjected to middle cerebral artery occlusion (MCAO). Exosome at the dose of 100 µg and/or rosuvastatin at the dose of 20 mg/kg/day for 7 days were administered to rats as a therapeutic strategy. The elevated body swing test (EBST) and Garcia score were conducted as behavioral tests for the measurement of functional recovery. The histopathological and immunohistochemical analyses were also performed for the assessment of infarcted volume and neuroprotection in the brain of rats. The real-time PCR method was carried out to determine the relative expressions of the NLRP-3 and NLRP1 genes. After 7 days of treatment with exosome and rosuvastatin in rats which underwent MCAO, the decrease in infarct volume of the animals treated with exosome was more pronounced compared with those treated only with exosome. The combination therapy remarkably lowered the size of infarct volume. Our observation was confirmed by the downregulation of the NLRP1 and NLRP3 genes in response to combinatory treatment of rats induced by MCOA, denoting a lower rate of cell death. The number of GFAP-positive cells were reduced in the exosome-treated group compared with the MCAO group. The rate of lipid peroxidation was measured by malondialdehyde (MDA) levels which demonstrated a significant reduction of MDA in the exosome- and rotuvastatin-treated groups when compared with the MCAO group. However, the levels of the SOD enzyme did not significantly alter when the treatment groups were compared with the MCAO group. According to our findings, it seems that the use of exosomes and rosuvastatin, as a novel treatment regimen, might promote neurological recovery after the onset of stroke.

A Novel Intervention Technology for Cerebral Palsy: Brain Stimulation.

A common pediatric disorder with posture and motor dysfunction in neurological diseases is known as cerebral palsy (CP). Recently, a series of effective techniques have been developed for treatment of CP. These promising methods need high-tech equipment for brain stimulation and mainly classified into invasive and no-invasive approaches. This study aimed to introduce these techniques for treatment of patients who suffer from CP. The potential and performance of currently available brain stimulation techniques have been mentioned in detail. Moreover, the clinical application, safety, efficacy and challenges of these methods have been discussed. Here we review the recent advances in the CP treatment with an emphasis on brain stimulation techniques.

A new rat model of neonatal bilirubin encephalopathy (kernicterus).

INTRODUCTION: Hemolytic kernicterus, an indirect bilirubin-induced brain dysfunction, is associated with hyper-bilirubinemia in mammalian neonates. In this study, a new model of kernicterus has been developed using intra-peritoneal injections of phenyl hydrazine and subcutaneous injections of sulfisoxazole. These drugs can potentially induce kernicterus in neonatal through changes in hemolysis and hypo-albumin. METHODS: For this purpose, 7-day-old male Wistar rats (n=72; mean weight 11±1g) were used. The animals have been divided into six different groups which received the drugs alone and their combination, and the drugs' solvents and their combination. Biochemical parameters, brain iron and bilirubin, behavioural performance, auditory function and apoptosis were measured using auto-analyser instruments; atomic absorption spectroscopy, Sawasaki, footprint, auditory brainstem response (ABR) and TUNEL test, respectively. RESULT: The drug-injected groups showed a significant reduction in serum haematocrit and an increase in the concentration of brain bilirubin, total and indirect bilirubin as well as TUNEL positive cells in basal ganglia. In addition, the obtained results showed that there was a significant increase in behavioural disturbance and auditory dysfunction in the group injected with the combination of two drugs. CONCLUSION: This kernicterus-induced rat model could perfectly mimic the common conditions of the hyperbilirubinemia in human neonates. This study offers an easy technique to develop more stable models for follow-up studies.

Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats.

Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.