Nicorandil increased the cerebral blood flow via nitric oxide pathway and ATP-sensitive potassium channel opening in mice

Abstract

Purpose

Nicorandil has dual properties and acts as a nitric oxide donor and an ATP-sensitive potassium (K_ATP) channel opener. Considering its pharmacological profile, nicorandil might exert protective effects on the brain as well as on the heart. The purpose of this study was to directly evaluate the effect of nicorandil on cerebral blood flow (CBF) in mice using a transcranial Doppler method.

Methods

Under general anesthesia, the nicorandil groups received a single-bolus intraperitoneal injection of the respective doses of nicorandil (1, 5, or 10 mg/kg), while the control group received vehicle only. CBF was measured using a transcranial Doppler flowmeter. N^G-nitro-l-arginine methyl ester and glibenclamide were used to elucidate the underlying mechanisms.

Results

A single-bolus injection of 1 mg/kg of nicorandil increased the CBF (11.6 ± 3.6 vs. 0.5 ± 0.7%, p < 0.001) without affecting the heart rate and blood pressure. On the contrary, 5 and 10 mg/kg of nicorandil significantly decreased the cerebral blood flow by decreasing the mean blood pressure below the cerebral autoregulation range. The positive effect of 1 mg/kg of nicorandil on the cerebral blood flow was inhibited by co-administration of either N^G-nitro-l-arginine methyl ester or glibenclamide.

Conclusions

A clinical dose of nicorandil increases CBF without affecting systemic hemodynamics. The positive effect of nicorandil on CBF is most likely caused via both the nitric oxide pathway and K_ATP channel opening.

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Comparative genomics: Blood, guts and vampire bats

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The vulnerability of spinal motoneurons and soma size plasticity in a mouse model of amyotrophic lateral sclerosis

Abstract

Alpha-motoneuron soma size is correlated with the cell's excitability and function, and has been posited as a plastic property that changes during cellular maturation, injury, and disease. This study examined whether alpha-motoneuron somas change in size over disease progression in the G93A mouse model of amyotrophic lateral sclerosis (ALS), a disease characterized by progressive motoneuron death. We used 2D- and 3D-morphometric analysis of motoneuron size and measures of cell density at four key disease stages: Neonatal, P10 – with earliest known disease changes; young adult, P30 – presymptomatic with early motoneuron death; symptom onset, P90 – with death of 70–80% of motoneurons; and end-stage, P120+ – with full paralysis of hindlimbs. We additionally examined differences in lumbar vs. sacral vs. cervical motoneurons; in motoneurons from male vs. female mice; and in fast vs. slow motoneurons. We present the first evidence of plastic changes in the soma size of spinal α-motoneurons occurring throughout different stages of ALS with profound effects on motoneuron excitability. Somatic changes are time-dependent and are characterized by early-stage enlargement (P10 and P30); no change around symptom onset; and shrinkage at end-stage. A key finding in the study indicates that disease-vulnerable motoneurons exhibit increased soma sizes (P10 and P30). This pattern was confirmed across spinal cord regions, genders, and motoneuron types. This extends the theory of motoneuron size-based vulnerability in ALS: not only are larger motoneurons more vulnerable to death in ALS, but are also enlarged further in the disease. Such information is valuable for identifying ALS pathogenesis mechanisms.

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Virtual reality rehabilitation with functional electrical stimulation improves upper extremity function in patients with chronic stroke: a pilot randomized controlled study

Publication date: Available online 2 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Stephanie Hyeyoung Lee, Ji-Yeong Lee, Mi-Young Kim, Yu-Jin Jeon, Suyoung Kim, Joon-Ho Shin
ObjectiveTo compare virtual reality (VR) combined with functional electrical stimulation (FES) to cyclic FES for improving upper extremity function and health-related quality of life in patients with a chronic stroke.DesignA pilot, randomized, single blinded, controlled trial.SettingStroke rehabilitation inpatient unitParticipantsForty-eight participants with a hemiplegia secondary to a unilateral stroke for >3 months, with a hemiplegic wrist extensor Medical Research Council (MRC) scale score of 1–3.InterventionsFES was applied to the wrist extensors and finger extensors. A virtual-reality(VR) based wearable rehabilitation device was used, combined with FES and virtual activity-based training. The control group received cyclic FES only. Both groups completed 20 sessions, over a 4-week period.Main outcome measuresPrimary outcomes were the change in the Fugl–Meyer Assessment: upper extremity (FMA) and Wolf Motor Function Test (WMFT) scores. Secondary outcomes were the change in the Box and Block test (BB), Jebsen Taylor Hand Function Test (JTT), and Stroke Impact Scale (SIS) scores. Assessments were performed at baseline (T0) and at 2 weeks (T1), 4 weeks (T4), and 8 weeks (T8). Between-group comparisons were evaluated using a repeated measures analysis of variance.ResultsForty-one participants were included in the analysis. Compared to FES alone, VR-FES produced greater increase in FMA–distal score (p=0.011) and marginal improvement in JTT–gross score (p=0.057). VR-FES produced greater, although non-significant, improvements in all other outcome measures, except in the SIS–ADL/IADL score.ConclusionsFES with VR-based rehabilitation may be more effective than cyclic FES to improve distal gross upper extremity function post-stroke.



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Gait Training in Acute Spinal Cord Injury Rehabilitation – Utilization and Outcomes Among Non-Ambulatory Individuals: Findings from the SCIRehab Project

Publication date: Available online 3 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Stephanie Rigot, Lynn Worobey, Michael L. Boninger
ObjectivesTo investigate relation of gait training (GT) during inpatient rehabilitation (IPR) to outcomes of people with traumatic spinal cord injury (SCI).DesignProspective observational study using the SCIRehab database.SettingSix IPR facilities.ParticipantsPatients with new SCI receiving initial rehabilitation (n=1376).InterventionsPatients were divided into groups of who did and did not receive GT. Patients were further subdivided based on their primary mode of mobility as measured by the Functional Independence Measure (FIM).Outcome MeasuresPain rating scales; Patient Health Questionnaire Mood Subscale; Satisfaction with Life Scale (SWLS); and Craig Handicap Assessment and Reporting Technique (CHART).ResultsNearly 58% of all patients received GT, including 33.3% of patients who were primarily using a wheelchair 1-year after discharge from IPR. Those who used a wheelchair and received GT, received significantly less transfer and wheeled mobility training (p<.001). CHART physical independence (p=.002), mobility (p=.024), and occupation (p=.003) scores were significantly worse in patients who used a wheelchair at 1-year and received GT, compared to those who used a wheelchair and did not receive GT in IPR. Older age was also a significant predictor of worse participation as measured by the CHART.ConclusionsA significant percentage of individuals who are not likely to become functional ambulators are spending portions of their IPR stays performing GT, which is associated with less time allotted for other functional interventions. GT in IPR was also associated with participation deficits at 1-year for those who used a wheelchair, implying the potential consequences of opportunity costs, pain, and psychological difficulties of receiving unsuccessful GT. Clinicians should consider this data when deciding to implement gait training during initial inpatient rehabilitation.



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Effects of Intraneural Injection of Dexmedetomidine in Combination With Ropivacaine in Rat Sciatic Nerve Block

Background and Objectives Dexmedetomidine is known to have neural protection effect via attenuation of inflammatory responses induced by local anesthetics. We investigated whether intraneural dexmedetomidine is effective for attenuating or preventing neural injury resulting from inadvertent intraneural injection of local anesthetic. Methods Rats were randomly divided, and left sciatic nerve was surgically exposed. The rats received no injection (control group) or intraneural injections of 0.2 mL of normal saline (saline group), 0.2 mL of 0.5% ropivacaine (ropivacaine group), or 0.2 mL of 0.5% ropivacaine and 0.5 μg/kg of dexmedetomidine (ropivacaine plus dexmedetomidine group). Interleukin (IL)-6 and IL-1β messenger RNA (mRNA) levels were detected at 60 minutes after intraneural injection in experiment 1 (5 per group). Sensory and motor functions were assessed until the return of normal sensory and motor functions, and histopathological and ultrastructure analysis were performed at 4 weeks after intraneural injection in experiment 2 (8 per group). Results Dexmedetomidine with ropivacaine better enhanced sensory and motor blockade than ropivacaine alone. IL-6 (3.2 ± 1.0 vs 5.9 ± 2.1), IL-1β (1.1 ± 0.1 vs 2.2 ± 0.7) levels, scores of axon and myelinated fiber degeneration (1 [0–2] vs 2 [1–3]), and demyelinated fiber percentages (20.1 ± 10.4 vs 48.3 ± 12.7) were lower in the ropivacaine plus dexmedetomidine group than in the ropivacaine group. No animals showed any signs of permanent neurological deficit. Conclusions Intraneural dexmedetomidine has sensory and motor blockade-enhancing effects, anti-inflammatory properties, and protective effects against neural injury. These findings suggest that dexmedetomidine as an adjuvant has beneficial effects in rat when intraneural injection of local anesthetic occurs. Accepted for publication October 4, 2017. Address correspondence to: Deok-hee Lee, MD, PhD, Department of Anesthesiology and Pain Medicine, College of Medicine, Yeungnam University, 170, Hyeonchung-ro, Nam-gu, Daegu, Republic of Korea (e-mail: dhlee415@ynu.ac.kr). The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Intraoperative Neuromonitoring During Sciatic Nerve Schwanomma Excision: Utility of Evoked Potentials

No abstract available

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