Frontiers in neurology
-
Frontiers in neurology · Jan 2018
Silencing of Hypoglossal Motoneurons Leads to Sleep Disordered Breathing in Lean Mice.
Obstructive Sleep Apnea (OSA) is a prevalent condition and a major cause of morbidity and mortality in Western Society. The loss of motor input to the tongue and specifically to the genioglossus muscle during sleep is associated with pharyngeal collapsibility and the development of OSA. We applied a novel chemogenetic method to develop a mouse model of sleep disordered breathing Our goal was to reversibly silence neuromotor input to the genioglossal muscle using an adeno-associated viral vector carrying inhibitory designer receptors exclusively activated by designer drugs AAV5-hM4Di-mCherry (DREADD), which was delivered bilaterally to the hypoglossal nucleus in fifteen C57BL/6J mice. ⋯ Electrophysiology recording in brain slices showed that CNO inhibited firing frequency of DREADD-containing hypoglossal motoneurons. We conclude that chemogenetic approach allows to silence hypoglossal motoneurons in mice, which leads to sleep disordered breathing manifested by inspiratory flow limitation during NREM and REM sleep without oxyhemoglobin desaturation or sleep fragmentation. Other co-morbid factors, such as compromised upper airway anatomy, may be needed to achieve recurrent pharyngeal obstruction observed in OSA.
-
Frontiers in neurology · Jan 2018
Application of Machine Learning to Automated Analysis of Cerebral Edema in Large Cohorts of Ischemic Stroke Patients.
Cerebral edema contributes to neurological deterioration and death after hemispheric stroke but there remains no effective means of preventing or accurately predicting its occurrence. Big data approaches may provide insights into the biologic variability and genetic contributions to severity and time course of cerebral edema. These methods require quantitative analyses of edema severity across large cohorts of stroke patients. ⋯ This model demonstrated that CSF volume decreases over time (p < 2.2 × 10-13) and is lower in those with cerebral edema (p = 0.0004). We are now fully automating this pipeline to allow rapid analysis of even larger cohorts of stroke patients from multiple sites using an XNAT (eXtensible Neuroimaging Archive Toolkit) platform. Data on kinetics of edema across thousands of patients will facilitate precision approaches to prediction of malignant edema as well as modeling of variability and further understanding of genetic variants that influence edema severity.
-
Frontiers in neurology · Jan 2018
Case ReportsUsing Directional Deep Brain Stimulation to Co-activate the Subthalamic Nucleus and Zona Incerta for Overlapping Essential Tremor/Parkinson's Disease Symptoms.
This index case report describes a novel programming approach that utilizes the 8-contact directional Deep Brain Stimulation (DBS) lead to effectively control the akinesia, rigidity and tremor of Parkinson's Disease (PD), as well as a severe kinetic tremor of Essential Tremor (ET), in a patient with overlapping symptoms of both PD and ET. Through utilizing a bipolar directional montage on a single segmented contact, symptom control was attained via likely co-activation of the Subthalamic Nucleus (STN) and the adjacent Zona Incerta (ZI). The patient is a 67-year-old professional guitarist with a long-standing diagnosis of ET manifesting with bilateral kinetic tremor, who then developed right lateralizing symptoms indicative of PD. ⋯ At 6 months post initial programming, no montage changes have been made, and the patient has experienced a reduction in Motor UPDRS scores from 23 to 3 (evaluated off medication), full resolution of kinetic tremor and normalization of handwriting, as well as significant reduction in his medication requirements. This patient's response to a single segment bipolar directional montage, and lack of response from monopolar directional stimulation in the same area, does suggest the possibility of further axial asymmetric tissue activation and thus co-activation of both the dorsal STN and adjacent ZI. Further modeling and study are warranted.
-
Frontiers in neurology · Jan 2018
Administration of Bone Marrow-Derived Mononuclear Cells Contributed to the Reduction of Hypoxic-Ischemic Brain Injury in Neonatal Rats.
Background/Objective: Perinatal hypoxic-ischemia (HI) causes neonatal death and permanent neurological deficits. Cell therapy using various cell sources has been recently identified as a novel therapy for perinatal HI. Among the available types of cell sources, bone marrow-derived mononuclear cells (BMMNCs) have unique features for clinical application. ⋯ In gait analysis, the BMMNC normalized the contact area of the affected hind paw widened by HI. The volumes of the affected striata and globus pallidus were significantly larger in the BMMNC group than in the control group. Conclusion: These results indicated that the injection of BMMNCs ameliorated HI brain injury in a neonatal rat model.
-
Frontiers in neurology · Jan 2018
End-Tidal Hypocapnia Under Anesthesia Predicts Postoperative Delirium.
Background: Postoperative delirium (POD) might be associated with anesthetic management, but research has focused on choice or dosage of anesthetic drugs. We examined potential contributions of intraoperative ventilatory and hemodynamic management to POD. Methods: This was a sub-study of the ENGAGES-Canada trial (NCT02692300) involving non-cardiac surgery patients enrolled in Winnipeg, Canada. ⋯ There was no association between cumulative anesthetic agent exposure and POD. Conclusions: POD was associated with intraoperative ventilatory management, reflected by low end-tidal CO2 concentrations, but not with cumulative anesthetic drug exposure. These findings suggest that maintenance of intraoperative normocapnia might benefit patients at risk of POD.