Restorative Neurology and Neuroscience - Volume 36, issue 5

Authors: Chen, Hongyan | Tang, Yingli | Wang, Hanyan | Chen, Weibing | Jiang, Hong

Article Type: Research Article

Abstract: Background/Objective: Curcumin exerts multiple functions including antioxidant and anti-inflammation, and has been shown protective potential on neurological disorders. Maternal or intrauterine infection/inflammation is one of the major factors underlying perinatal brain damage. This study aimed to determine whether maternal administration of curcumin has attenuation on neuroinflammation in fetal brain caused by lipopolysaccharide (LPS) administration. Methods: LPS was used to establish mouse fetal brain injury model, and we investigated the effects of curcumin (40 mg/kg) on the fetal mouse brain by evaluating the morphological change of the neuronal cells and the expression of different pro-inflammatory cytokines and chemokines at …protein and mRNA levels in the fetal brains, the maternal serum and amniotic fluid. Results: Our results demonstrated that maternal administration of curcumin has attenuation on neuroinflammation in the fetal brain induced by LPS. Pretreatment of curcumin in the LPS-induced mice effectively reestablished the neuronal cell morphology, attenuated the expression of soluble intercellular adhesion molecule-1, sE-Selectin, macrophage chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1 in the maternal serum, decreased the expression of cyclooxygenase-2, interleukin-1 beta and chemokine (C-C motif) ligand 2 in the brain, and suppressed interleukin-6 (IL-6) mRNA transcription in the amniotic fluid. In addition, curcumin suppressed the LPS-induced microglia activation. Conclusions: Our study in animal models indicates that maternal administration of curcumin alleviates neuroinflammation in the fetal brain caused by LPS. Long-term consumption of curcumin might improve the neurological outcomes of premature neonates delivered from dams suffering from infection/ inflammation. Show more

Keywords: Curcumin, premature brain injury, anti-inflammation, lipopolysaccharide, neuroprotection, infection

DOI: 10.3233/RNN-180834

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 5, pp. 583-592, 2018

Authors: Li, Chen | Cao, Xuhua | Ma, Zhizhao | Sun, Xiaofeng | Hu, Fuguang | Wang, Liqun

Article Type: Research Article

Abstract: Background: Extracranial-intracranial (EC-IC) bypass surgery has been used to improve the conditions of cerebral ischemia symptoms for selected patients resulting from diverse complications such as stroke and atherosclerotic disease. However, several clinical trials showed EC-IC bypass surgery failed to prevent recurrent ischemic stroke in certain patients. Objective: Our clinical trial aimed to investigate whether there is a correlation between pre-surgery assessments and prognosis of patients received EC-IC bypass operation. Methods: We divided all patients into 4 groups according to their compensatory stages of cerebral ischemia. The values of cerebral blood flow (CBF), cerebral blood volume (CBV), …mean transit time (MTT), time to peak (TTP), and oxygen extraction fraction (OEF) were obtained by computed tomography perfusion (CTP), single photon emission computed tomography (SPECT), and positron emission tomography (PET) at different time points before and after EC-IC bypass surgery. We assessed the correlations between the compensatory stage with modified Rankin scale (mRS) scores, survival rates, stroke and TIA incidences over the 12 months after surgery. Results: Patients with normal CBF, normal or increased CBV, and normal OEF tended to have a better prognosis after the EI-CI bypass operation than patients with abnormal CBF, CBV and OEF. However, patients with abnormal CBF and CBV, and increased OEF showed elevated mRS, less survival rates, and higher stroke and TIA incidences over the 12 months after surgery, compared to the groups with normal CBF, CBV and OEF. Conclusions: Our results suggest that a defined compensatory stage of cerebral ischemia might be useful for the prognosis of patients receiving EI-CI bypass surgery. Show more

Keywords: Extracranial-intracranial (EC-IC) bypass surgery, oxygen extraction fraction (OEF), cerebral ischemic, stroke, transient ischemic attack (TIA)

DOI: 10.3233/RNN-180848

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 5, pp. 593-604, 2018

Authors: Jiang, Naifu | Li, Guangsheng | Wei, Jinsong | Wei, Bo | Zhu, Frank F. | Hu, Yong

Article Type: Research Article

Abstract: Background: Transcranial direct current stimulation (tDCS) on primary motor cortex (M1) provides a new way to relieve postoperative pain. Previous studies only found postoperative analgesia dosage significantly reduced in tDCS group while the patient-controlled analgesia (PCA) was applied. However, there lacks the study about the effect of M1-tDCS on pain intensity and brain activity while the analgesia dosage is the same for both groups. Objective: To investigate whether M1-tDCS can (1) reduce pain intensity and (2) change spontaneous electroencephalography (EEG) oscillations in prefrontal cortex, in patients with postoperative pain, after taking the constant dosage of analgesics. …Methods: A prospective, single-blind, randomized, sham-controlled study was conducted. 32 patients with postoperative pain after lumbar spine surgery were recruited. All patients received same dosage of dezocine before intervention. In the morning of the first day after surgery and before dezocine injection, a single 20-minute session of anodal M1-tDCS was applied to ‘tDCS’ group while sham stimulation to ‘sham’ group. Numeric rating scale (NRS) and resting-state EEG with eyes-closed were measured and analyzed. EEG spectral powers were analyzed using repeated measures analysis of variance (ANOVA). Correlation analysis was conducted between the change of NRS and the change of spectral power. Results: The NRS in “tDCS” group significantly decreased (p < 0.01) while not in “sham” group after intervention. Only spectral power within alpha2 band (10–13 Hz) in Fp1 and beta1 band (13–20 Hz) in Fp1 showed significant Time×Intervention interaction effect. These changes of the spectral power also showed significant correlation with the change of NRS. Conclusions: The postoperative pain intensity in patients receiving surgery could reduce after a single session of anodal M1-tDCS compared to sham M1-tDCS. The effect to the top-down dimension of postoperative pain might account for the analgesic effect of M1-tDCS, which reflecting slow oscillations in left prefrontal EEG. Show more

Keywords: Transcranial direct current stimulation, postoperative pain, resting-state electroencephalography, primary motor cortex, dry electrode, lumbar spine surgery

DOI: 10.3233/RNN-180816

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 5, pp. 605-620, 2018

Authors: Walker, Chandler L. | Meadows, Rena M. | Merfeld-Clauss, Stephanie | Du, Yansheng | March, Keith L. | Jones, Kathryn J.

Article Type: Research Article

Abstract: Background: Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ∼47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A ) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treatment could ameliorate neuromuscular junction (NMJ) disruption. Objective: To determine whether pre-symptom administration of ASC-CM prevents early NMJ disconnection. Methods: We …confirmed the NMJ denervation time course in mSOD1G93A mice using co-labeling of neurofilament and post-synaptic acetylcholine receptors (AchR) by α -bungarotoxin. We determined whether ASC-CM ameliorates early NMJ loss in mSOD1G93A mice by systemically administering 200μl ASC-CM or vehicle medium daily from post-natal days 35 to 47 and quantifying intact NMJs through co-labeling of neurofilament and synaptophysin with α -bungarotoxin in gastrocnemius muscle. Results: Intact NMJs were significantly decreased in 47 day old mSOD1G93A mice (p  < 0.05), and daily systemic ASC-CM prevented disease-induced NMJ denervation compared to vehicle treated mice (p  < 0.05). Conclusions: Our results lay the foundation for testing the long-term neurological benefits of systemic ASC-CM therapy in the mSOD1G93A mouse model of ALS. Show more

Keywords: Amyotrophic lateral sclerosis, ALS, neuromuscular junctions, adipose-derived stem cells, conditioned medium

DOI: 10.3233/RNN-180820

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 5, pp. 621-627, 2018

Authors: Chen, Yan | Hou, Yiwei | Ge, Ruli | Han, Jianmei | Xu, Jing | Chen, Jinbo | Wang, Hongcai

Article Type: Research Article

Abstract: Background: Protective effect of roscovitine and deregulation of the p-RB/E2F1 have not been well studied in PD models generated by repeated oral administration of rotenone. Objective: These experiments evaluated the effects of repeated oral gavage of rotenone on the activation of p-RB/E2F1 and the effects of roscovitine on the regulation of dopaminergic neuronal injury and the behavior of PD in mice. Methods: Using 2.5% carboxymethylcellulose and 1.25% chloroform as a vehicle solution, rotenone (30 mg/kg) was administered via oral gavage once daily for 30 days in C57 mice. Behavioral profiles (pole test and traction test) were assessed …in these PD models, and oxidative stress levels were evaluated in the midbrain. The immunoreactivities of TH, α -synuclein (α -syn), p-RB, E2F1 and cleaved caspase-3 in the substantia nigra were examined with a laser confocal microscope. Pharmacological inhibition of cyclin-dependent kinase with roscovitine was achieved by intraperitoneal (IP) injection at a dose of 50 mg/kg daily. Results: All rotenone-administered C57 mice showed the typical behavioral features of PD: stiffness, bradykinesia, or hypokinesia. Behavioral testing with the pole test and traction test indicated that the rotenone group, but not the vehicle group, was affected. Spectrophotometric analysis demonstrated that glutathione (GSH) and superoxide dismutase (SOD) activity was decreased, and the generation of malondialdehyde (MDA) was elevated in the midbrain of the rotenone-treated group. After oral administration of rotenone, a loss of nigral tyrosine hydroxylase (TH)-positive neurons was observed. The immune response of α -syn was enhanced in the cytoplasm of dopaminergic neurons from the rotenone-induced neurotoxicity. Rb phosphorylation at serine 780, which affected Rb binding to E2F, was induced after rotenone treatment. The activation of E2F1, which is involved in the regulation of the cell cycle, was also induced from chronic exposure to rotenone. Moreover, administration of the cell cycle inhibitor roscovitine protected against rotenone-induced nigral dopaminergic neuronal injury and inhibited cleaved caspase-3 activation. Roscovitine also markedly ameliorated the behavior of PD mice. Conclusions: Mouse models of Parkinson’s disease were established by oral rotenone administration and reproduced some of the features of dopaminergic neuronal degeneration. Roscovitine protects against rotenone-induced parkinsonism. Show more

Keywords: Roscovitine, Parkinson’s disease (PD), dopaminergic neuron, rotenone, cell cycle, p-RB, E2F1

DOI: 10.3233/RNN-180817

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 5, pp. 629-638, 2018

Authors: Kang, Eun Kyoung | Shin, Dabi | Yun, Jeong-Yeon | Park, Wanjoo | Park, Hee-Won

Article Type: Research Article

Abstract: Background: Specific investigation of dual task-interference (DTI) may help researchers to develop the optimal training exercise for enhancing the performance of daily activities. Objectives: To reveal the DTI by comparing the performances between personalized single tasks (cognitive or motor task) and dual task with serial decomposition in normal healthy adults. Methods: After a preliminary period, healthy participants randomly (n  = 46) performed three computerized experiments of cognitive (CT), motor (MT) and dual tasks (DT). In CT, participants were required to release button 1 (BT1) as rapidly as possible when the font color of a word and its …meaning were congruent (Go), and in MT, they had to release BT1 and then tap button 2 (BT2) 10 times as rapidly as possible if the symbol “○” was presented (Go). The DT consisted of a combination of CT and MT elements. The reaction time (RT) of correct releases (RTCR) of BT1 in all tasks was measured, as well as the button shifting time between releasing BT1 and pressing BT2, and the finger tapping rate in MT and DT. To obtain the DTI values, we calculated the RTCR ratio in CT and MT and divided the outcome by the RTCR of DT. Results: The ratio of RTCR in CT (% CT/DT, 78.6±13.0%) and MT (% MT/DT, 74.2±10.1%) were significantly lower than the ratio of RTCR in DT (% DT/DT, 100%). The button shifting time of MT was at 92.0±23.7% of baseline, and the finger tapping rate of MT was 106.1±19.1%, which was significantly higher than baseline. Conclusions: The % DT/DT is significantly higher than both % CT/DT and % MT/DT, which suggests that the cognitive load depends on the type of cognitive task that is being performed. Additionally, the significant increase of % DT/DT compared to % CT/DT indicated that there is a cognitive load prior to a motor task. The increased button shifting time and decreased tapping rate in DT may indicate that a residual cognitive load and a concurrent motor load were present. Show more

Keywords: Dual task, cognition, motor, task, interference

DOI: 10.3233/RNN-180825

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 5, pp. 639-646, 2018

Authors: Oda, Hiroki | Ohta, Souichi | Ikeguchi, Ryosuke | Noguchi, Takashi | Kaizawa, Yukitoshi | Yurie, Hirofumi | Takeuchi, Hisataka | Mitsuzawa, Sadaki | Matsuda, Shuichi

Article Type: Research Article

Abstract: Background: Replantation of the avulsed nerve root has been proposed for the treatment of severe brachial plexus injury for several decades. However, due to the complexity of the technique and limited functional improvement, practical applications are yet to be implemented. Objective: In the present study, we investigated the effect of pretreatment with resveratrol on nerve autografts used for replantation surgery in a rat model of nerve root avulsion. Methods: Resveratrol pretreatment was performed using an explant culture technique. Two surgical procedures were performed. During the first surgery, Sprague-Dawley rats were subjected to left C6 nerve root …avulsion, and nerves were harvested for autografting. The harvested grafts were explant-cultured for 1 week. A second procedure was performed to replant the C6 nerve root using the explant-cultured nerve graft 1 week after the first procedure. Histological and immunohistochemical analyses were performed 8 weeks after the second procedure. We first compared findings between explant-cultured nerve grafts and fresh nerve grafts, following which we compared findings between explant-cultured grafts pretreated with and without resveratrol. Changes induced within nerve grafts by 1 week of explant culture with or without resveratrol were investigated in vitro . Results: There was no significant difference in outcomes between 1 week-explant-cultured and fresh nerve grafts. Addition of resveratrol to the explant culture medium resulted in a significant increase in the number and myelin thickness of regenerated axons, and in the number of regenerating motor neurons in the C6 spinal cord segment. In vitro analyses revealed that nerve grafts pretreated with resveratrol exhibited significant increases in glial cell line-derived neurotrophic factor (GDNF) expression and the number of dedifferentiated Schwann cells. Conclusions: Resveratrol may promote axonal regeneration following replantation surgery for the treatment of nerve root avulsion injury; however, further studies are required to verify these findings in humans. Show more

Keywords: Autografts, nerve root avulsions, nerve regeneration, resveratrol, tissue culture techniques

DOI: 10.3233/RNN-180844

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 5, pp. 647-658, 2018

Authors: Ma, Lili | Mu, Ying | Zhang, Zhaobo | Sun, Qiansan

Article Type: Research Article

Abstract: Background: Eugenol, a natural phenolic compound found in essential oils, shows a variety of remedial properties, while its effect on spinal cord injury (SCI) is still unknown. Objective: To study the effects of Eugenol on SCI-related impairments in rats. Methods: Rats received SCI or sham surgery were administered by oral gavage with Eugenol or physiological saline 6 hours following SCI and once a day for seven consecutive weeks. Basso, Beattie, Bresnahan (BBB) score and inclined plane test were used to assess locomotion function, while mechanical allodynia and thermal hyperalgesia were used to evaluate the withdrawal response …to painful stimuli. Spinal cord water content was counted and permeability of the blood-spinal cord barrier was assessed by Evans blue extravasation. Serum tumor necrosis factor (TNF)-α , interleukin (IL)-1β , interleukin (IL)-6, nuclear factor (NF)-κ B p65, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were determined by ELISA (enzyme-linked immunosorbent assay), while NF-κ B p65, p38 mitogen-activated protein kinase (MAPK), inducible nitric oxide synthase (iNOS), and Caspase-3 in the spinal cord were detected by Western blot. Results: Eugenol markedly improved locomotor function and alleviated neuropathic pain, accompanied by decreased inflammation, oxidative stress, and neural apoptosis-associated molecules in the serum and injured spinal cord. Downregulated pathway molecules NF-κ B and p38 MAPK were also found in the spinal cord. Conclusions: These findings suggest that down-regulating NF-κ B and MAPK signaling pathway may support the neuroprotective effect of Eugenol against traumatic SCI. Show more

Keywords: Eugenol, oxidative stress, inflammation, apoptosis, NF-κB, p38 MAPK

DOI: 10.3233/RNN-180826

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 5, pp. 659-668, 2018