Current Neurovascular Research (v.10, #3)
Reacting to Stress: Radical Cellular Pathways for Novel Drug Development by Kenneth Maiese (195-196).
REM Sleep Loss and Recovery Regulates Blood-Brain Barrier Function by Beatriz Gomez-Gonzalez, Gabriela Hurtado-Alvarado, Enrique Esqueda-Leon, Rafael Santana- Miranda, Jose Angel Rojas-Zamorano, Javier Velazquez-Moctezuma (197-207).
The functions of rapid eye movement (REM) sleep have remained elusive since more than 50 years. Previousreports have identified several independent processes affected by the loss and subsequent recovery of REM sleep(hippocampal neurogenesis, brain stem neuronal cell death, and neurotransmitter content in several brain regions);however, a common underlying mechanism has not been found. We propose that altered brain homeostasis secondary toblood-brain barrier breakdown may explain all those changes induced by REM sleep loss. Therefore, the present reportaimed to study the consequences of REM sleep restriction upon blood-brain barrier permeability to Evans blue. REMsleep restriction was induced by the multiple platform technique; male rats were REM sleep restricted 20h daily (with 4hsleep opportunity) during 10 days; control groups included large platform and intact rats. To study blood-brain barrierpermeability Evans blue was intracardially administered; stained brains were sliced and photographed for optical densityquantification. An independent experiment was carried out to elucidate the mechanism of blood-brain breakdown bytransmission electron microscopy. REM sleep restriction increased blood-brain barrier permeability to Evans blue in thewhole brain as compared to both control groups. Brief periods of sleep recovery rapidly and effectively restored the severealteration of blood-brain barrier function by reducing blood-to-brain transfer of Evans blue. The mechanism of bloodbrainbarrier breakdown involved increased caveolae formation at brain endothelial cells. In conclusion, our data suggestthat REM sleep regulates the physical barrier properties of the blood-brain barrier.
Blockade of Ser16-Hsp20 Phosphorylation Attenuates Neuroprotection Dependent Upon Bcl-2 and Bax by Liuwang Zeng, Jieqiong Tan, Wei Lu, Zhiping Hu (208-215).
Ischemic stroke causes a significant amount of cell damage resulting from an insufficient supply of glucoseand oxygen to central nervous system tissue and finding more effective therapeutic neuroprotective agents has become apriority in the treatment of ischemic stroke. Hsp20, one of the small heat shock proteins, has been implicated in multiplephysiological and pathophysiological processes and is a potential neuroprotective agents. To investigate whether Hsp20exerts protective effects on in vitro ischemia-reperfusion injury, mouse neuroblastoma cells were subjected to oxygenglucosedeprivation/reoxygenation (OGDR) insult. The N2a cells transfected with Hsp20 and constitutivelyphosphorylated Hsp20 (S16D) had significantly less cell loss and less proportion of apoptotic cells compared to N2a cellstransfected with pEGFP-N1 after oxygen-glucose deprivation (OGD) 4 h plus 12 and 24 h reperfusion, which showed nodifference in N2a cells transfected with nonphosphorylatable Hsp20 (S16A). Meanwhile, transfected with Hsp20 andconstitutively phosphorylated Hsp20 (S16D) also significantly attenuated mitochondrial fragmentation and modulatedBcl-2 and Bax expression level after OGD 4 h plus 12 reperfusion, which were not affected in N2a cells transfected withHsp20 (S16A). In conclusion, our data demonstrated that increased Hsp20 and Hsp20 (S16D) expression in mouse N2Aneuroblastoma cells protected against ischemia-reperfusion injury, the neuroprotective mechanism may be related toregulate Bcl-2 and Bax expression. However, blockade of Ser16-Hsp20 phosphorylation attenuated the neuroprotectiveeffects of Hsp20. Therefore, Hsp20 and factors that contribute to regulation of phosphorylation on Ser16 of Hsp20 arepotential new therapeutic targets for the treatment of cerebral ischemia-reperfusion injury.
Electroacupuncture Reduces Hemiplegia Following Acute Middle Cerebral Artery Infarction with Alteration of Serum NSE, S-100B and Endothelin by Hong Zhang, Tao Kang, Li Li, Junjian Zhang (216-221).
Acupuncture may help motor recovery in chronic stroke survivors, but it is unclear whether it is useful foracute or subacute stroke patients. This study aimed to assess the effiency of electroacupuncture on hemiplegic patientscaused by acute first-ever middle cerebral artery infarction. Ninety-eight patients with hemiplegia after first-ever middlecerebral artery infarction were divided into the observation group and the control group. Electroacupuncture was appliedonce daily for three weeks seven days after symptom onset. The motor functions of the limbs and the activities of dailyliving (ADL) were evaluated by Fugl?Meyer assessment (FMA) and Barthel index (BI). Serum neuron -specific enolase(NSE), soluble protein-100B (S-100B) and endothelin (ET) were quantified before and after treatment.After treatment, theFMA and BI scores were improved in comparison to before treatment scores in the same group (P<0.01 or P<0.05), witha more significant improvement in the observation group (with electroacupuncture) than in the control group (P<0.01).After treatments, the amounts of serum NSE, S-100B and ET in the observation group were significantly decreased whencompared with those of the control group (P<0.01 or P<0.05). No adverse reactions occurred during electroacupuncture.This study showed that motor functions of the limbs and the activities of daily living in hemiplegic patients caused byacute cerebral infarction were improved significantly after treatment with electroacupuncture and this improvement wasassociated with reduced serum levels of NSE, S-100B and ET.
Mitochondrial Fusion and Fission Proteins Expression Dynamically Change in a Murine Model of Amyotrophic Lateral Sclerosis by Wentao Liu, Toru Yamashita, Fengfeng Tian, Nobutoshi Morimoto, Yoshio Ikeda, Kentaro Deguchi, Koji Abe (222-230).
Mitochondria dynamically change their shape through frequent fusion and fission to continuously perform theirfunction in the cell. Although a change in mitochondrial morphology was reported in amyotrophic lateral sclerosis (ALS),detailed changes of mitochondrial fusion and fission proteins have not been reported in ALS model mice. In transgenic(Tg) mice with the G93A human SOD1 mutation (G93ASOD1), both mitochondrial fusion proteins (Mfn1 and Opal) andfission proteins (Drp1 and Fis1) showed a significant increase in the anterior half of the lumbar spinal cord. Such changesin Tg mice were already noticeable at presymptomatic 10 week (W) compared with wildtype (WT) mice, detected throughimmunohistochemical as well as Western blot analyses. Furthermore, fusion protein levels of Mfn1 and Opa1 showed aprogressive decrease from 10 to 18 W in Tg mice while fission protein levels of P-Drp1 and Fis1 maintained a high levelof expression in Tg mice from 10 to 18 W. These data suggest that abnormal changes in mitochondrial morphology beganbefore the onset of ALS and that the balanced mitochondrial morphology becomes altered by fissions in motor neurons(MNs) in this ALS model.
Neuroprotection of Dietary Virgin Olive Oil on Brain Lipidomics During Stroke by Zahra Rabiei, Mohammad Reza Bigdeli, Bahram Rasoulian (231-237).
Recent studies suggest that dietary virgin olive oil reduces hypoxia-reoxygenation injury in rat brain. Thisstudy investigated the effect of pretreatment with different doses of dietary virgin olive oil on brain lipidomics duringstroke. In this experimental trial, 60 male Wistar rats were studied in 5 groups of 12 each. The control group receiveddistilled water while three treatment groups received oral virgin olive oil for 30 days (0.25, 0.5 and 0.75 ml/kg/dayrespectively). Also the sham group received distilled water. Two hours after the last dose, the animals divided two groups.The middle cerebral artery occlusion (MCAO) group subjected to 60 min of middle cerebral artery occlusion (MCAO)and intact groups for brain lipids analysis. The brain phosphatidylcholine, cholesterol ester and cholesterol levelsincreased significantly in doses of 0.5 and 0.75 ml/kg/day compare with control group. VOO in all three doses increasedthe brain triglyceride levels. VOO with dose 0.75 ml/kg increased the brain cerebroside levels when compared withcontrol group. VOO pretreatment for 30 days decreased the brain ceramide levels in doses of 0.5 and 0.75 ml/kg/day(p<0.05). Although further studies are needed, the results indicate that the VOO pretreatment improved the injury ofischemia and reperfusion and might be beneficial in patients with these disorders and seems to partly exert their effects viachange in brain lipid levels in rat.
Implementation of a Biocircuit Implants for Neurotransmitter Release During Neuro-Stimulation by Suw Young Ly, Dal woong Choi (238-246).
Neurotransmitter assay of epinephrine (EP) was sought using a modified carbon nanotube paste electrode (PE).Using optimum conditions, cyclic voltammetry (CV) and the square wave (SW) stripping voltammetric working rangeswere attained to 10-100 mgL-1 (CV) and 20-140 ngL-1 (SW). The relative standard deviation of 0.0549 (n=15) wasobtained at 20.0 mgL-1 EP constant. Here, the analytical detection limit (S/N) was reached with 4.60 ngL-1 (2.5?10-11molL-1) EP. The hand-made electrode was implanted into the in-vivo brain core of the animals and was used inchronoamperometric neuro detection. The results obtained are applicable in neuro sensing, physiological control, andother neuroscience fields.
The Role of Oxidative Stress in Cerebral Aneurysm Formation and Rupture by Robert M. Starke, Nohra Chalouhi, Muhammad S. Ali, Pascal M. Jabbour, Stavropoula I. Tjoumakaris, L. Fernando Gonzalez, Robert H. Rosenwasser, Walter J. Koch, Aaron S. Dumont (247-255).
Oxidative stress is known to contribute to the progression of cerebrovascular disease. Additionally, oxidativestress may be increased by, but also augment inflammation, a key contributor to cerebral aneurysm development andrupture. Oxidative stress can induce important processes leading to cerebral aneurysm formation including directendothelial injury as well as smooth muscle cell phenotypic switching to an inflammatory phenotype and ultimatelyapoptosis. Oxidative stress leads to recruitment and invasion of inflammatory cells through upregulation of chemotacticcytokines and adhesion molecules. Matrix metalloproteinases can be activated by free radicals leading to vessel wallremodeling and breakdown. Free radicals mediate lipid peroxidation leading to atherosclerosis and contribute tohemodynamic stress and hypertensive pathology, all integral elements of cerebral aneurysm development. Preliminarystudies suggest that therapies targeted at oxidative stress may provide a future beneficial treatment for cerebral aneurysms,but further studies are indicated to define the role of free radicals in cerebral aneurysm formation and rupture. The goal ofthis review is to assess the role of oxidative stress in cerebral aneurysm pathogenesis.
Alcoholism and its Effects on the Central Nervous System by Sukhes Mukherjee (256-262).
Alcohol abuse is a major health problem worldwide, resulting to extensive admissions in many generalhospitals. The overall economic cost of alcohol abuse is enormous worldwide. As a small molecule, alcohol can easilycross membrane barriers and reach different parts of the body very quickly. Attainment of its equilibrium concentration indifferent cellular compartments depends on the respective water content. Alcohol can affect several parts of the brain, but,in general, contracts brain tissues, destroys brain cells, as well as depresses the central nervous system. Excessivedrinking over a prolonged period of time can cause serious problems with cognition and memory. Alcohol interacts withthe brain receptors, interfering with the communication between nerve cells, and suppressing excitatory nerve pathwayactivity. Neuro-cognitive deficits, neuronal injury, and neurodegeneration are well documented in alcoholics, yet theunderlying mechanisms remain elusive. The effect can be both direct and/ or indirect. In this review we highlighted therole of alcoholism on the CNS and its impact on human health.
Hemodialysis Membranes for Acute and Chronic Renal Insufficiency by Jin-Gang Yu, Lin-Yan Yu, Xin-Yu Jiang, Xiao-Qing Chen, Li-Jian Tao, Fei-Peng Jiao (263-268).
As an incomplete renal replacement for the patients with either acute or chronic renal failure, membrane-basedhemodialysis therapy is progressing rapidly. However, the mortality and morbidity remain unacceptably high. Much efforthas been put into improving the biocompatibility of the hemodialysis membranes. To effectively remove small solutes and'middle molecules' in compact cartridges, the hydraulic and permselective properties of the hemodialysis membranes havealso been deeply investigated. An overview of recent progress of different kinds of hemodialysis membranes and theirpreparation technology, as well as their modification techniques, is presented. The advantages and deficiencies of manysynthetic membranes, including cellulose, cellulose acetate (CA), chitosan (CS), polysulfone (PS), poly(ether sulfone)(PES), polyacrylonitrile (PAN), ethylene-vinyl alcohol copolymer (EVOH), poly (methyl methacrylate) (PMMA) andpoly(vinyl alcohol) (PVA), etc. are elaborated upon.
Iron-Induced Fibrin in Cardiovascular Disease by Boguslaw Lipinski, Etheresia Pretorius (269-274).
Accumulating evidence within the last two decades indicates the association between cardiovascular disease(CVD) and chronic inflammatory state. Under normal conditions fibrin clots are gradually degraded by the fibrinolyticenzyme system, so no permanent insoluble deposits remain in the circulation. However, fibrinolytic therapy in coronaryand cerebral thrombosis is ineffective unless it is installed within 3-5 hours of the onset. We have shown that trivalent iron(FeIII) initiates a hydroxyl radical-catalyzed conversion of fibrinogen into a fibrin-like polymer (parafibrin) that isremarkably resistant to the proteolytic dissolution and thus promotes its intravascular deposition. Here we suggest that thepersistent presence of proteolysis-resistant fibrin clots causes chronic inflammation. We study the effects of certainamphiphilic substances on the iron- and thrombin-induced fibrinogen polymerization visualized using scanning electronmicroscopy. We argue that the culprit is an excessive accumulation of free iron in blood, known to be associated withCVD. The only way to prevent iron overload is by supplementation with iron chelating agents. However, administrationof free radical scavengers as effective protection against persistent presence of fibrin-like deposits should also beinvestigated to contribute to the prevention of cardiovascular and other degenerative diseases.