The protective effect of ginko bilboa leaves injection on the brain dopamine in the rat model of cerebral ischemia/reperfusion injury

Background

Ginkgo Bilboa injection has had been clinically applied to restore the damaged cells and tissues due to the ischemia through improving the cerebral blood supply and decreasing the oxygen consumption.

Objective Aim

To evaluate the Ginkgo Bilboa injection''s therapeutic role towards ischemia/ reperfusion (I/R) injury through determination of monoamine neurotransmitter dopamine (DA) in corpus striatum.

Methods

After the incomplete global cerebral ischemia and reperfusion models were prepared, rats were randomly assigned into four groups: sham-operated group, ischemia-reperfusion group, nimodipine injection group, and Ginkgo Biloba injection group. The cerebrospinal fluid in the rat brain striatum at different time points was collected with microdialysis, and the level of monoamine neurotransmitters dopamineDA was determined by high performance liquid chromatography (HPLC) with electrochemical detector (ECD).

Results

The dopamineDA content in cerebral ischemia model group was significantly higher than that in the sham-operated group (P<0.05) at the 30 min. However, the DA level in nimodipine injection group and Ginkgo Biloba injection group were lower than the model group (P<0.05). The dopamineDA level in Ginkgo Biloba injection group gradually decreased, and was significantly different from the model group (P<0.05).

Conclusion

Ginkgo Biloba injection can could significantly inhibit brain I/R injury, as demonstrated by prevention of excessive release of dopamineDA in striatum.     

Metabolic Response of the Cerebral Cortex Following Gentle Sleep Deprivation and Modafinil Administration

Study Objectives:

The main energy reserve of the brain is glycogen, which is almost exclusively localized in astrocytes. We previously reported that cerebral expression of certain genes related to glycogen metabolism changed following instrumental sleep deprivation in mice. Here, we extended our investigations to another set of genes related to glycogen and glucose metabolism. We also compared the effect of instrumentally and pharmacologically induced prolonged wakefulness, followed (or not) by 3 hours of sleep recovery, on the expression of genes related to brain energy metabolism.

Design:

Sleep deprivation for 6–7 hours.

Setting:

Animal sleep research laboratory.

Participants:

Adults OF1 mice.

Interventions:

Wakefulness was maintained by “gentle sleep deprivation” method (GSD) or by administration of the wakefulness-promoting drug modafinil (MOD) (200 mg/kg i.p.).

Measurements and Results:

Levels of mRNAs encoding proteins related to energy metabolism were measured by quantitative real-time PCR in the cerebral cortex. The mRNAs encoding protein targeting to glycogen (PTG) and the glial glucose transporter were significantly increased following both procedures used to prolong wakefulness. Glycogenin mRNA levels were increased only after GSD, while neuronal glucose transporter mRNA only after MOD. These effects were reversed after sleep recovery. A significant enhancement of glycogen synthase activity without any changes in glycogen levels was observed in both conditions.

Conclusions:

These results indicate the existence of a metabolic adaptation of astrocytes aimed at maintaining brain energy homeostasis during the sleep-wake cycle.

Citation:

Petit, JM; Tobler I; Kopp C; Morgenthaler F; Borbély AA; Magistretti PJ. Metabolic response of the cerebral cortex following gentle sleep deprivation and modafinil administration. SLEEP 2010;33(7):901–908.     

Ceramide from sphingomyelin hydrolysis differentially mediates mitogen-activated protein kinases (MAPKs) activation following cerebral ischemia in rat hippocampal CA1 subregion

Objective

To explore the role that ceramide plays in the activation of mitogen-activated protein kinases (MAPKs) during cerebral ischemia and reperfusion.

Methods

Rats were subjected to ischemia by the four-vessel occlusion (4-VO) method. The sphingomyelinase inhibitor TPCK was administered to the CA1 subregion of the rat hippocampus before inducing ischemia. Western blot was used to examine the activity of extracellular-signal regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) using antibodies against ERK, JNK and diphosphorylated ERK and JNK.

Results

At 1h reperfusion post-ischemia, JNK reached its peak activity while ERK was undergoing a sharp inactivation (P < 0.05). The level of diphosphorylated JNK was significantly reduced but the sharp inactivation of ERK was visibly reversed (P < 0.05) by the sphingomyelinase inhibitor.

Conclusion

The ceramide signaling pathway is up-regulated through sphingomyelin hydrolysis in brain ischemia, promoting JNK activation and suppressing ERK activation, culminating in the ischemic lesion.     

Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice: Ischemia and Reparixin

OBJECTIVE:

Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice.

METHODS:

C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-1β was measured by ELISA.

RESULTS:

Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-1β were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment.

CONCLUSIONS:

Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.     

Sleep Disruption Aggravates Focal Cerebral Ischemia in the Rat

Study Objectives:

Sleep changes are frequent in stroke patients and predict a poor outcome. It remains unclear how sleep influences stroke evolution and recovery. We assessed effects of sleep disruption on brain damage and on the expression of axon sprouting genes after focal cerebral ischemia in rats.

Design:

12 h after ischemia induced by occlusion of the middle cerebral artery, rats were subjected to sleep disruption including sleep deprivation for 12h (SDpv12h) and sleep disturbances (SDis) by SDpv12h for consecutive 3 days. Control groups included ischemia without SDpv12h or SDis, sham surgery plus SDis and sham surgery without SDis. Sleep changes were evaluated based on EEG and EMG recordings.

Measurements and Results:

SDpv12h increased the infarct volume by 40% (SDpv12h 82.8 ± 10.9 vs. control 59.2 ± 13.9 mm³, P = 0.008) and SDis by 76% (SDis 58.8 ± 20.4 vs. control 33.8 ± 6.3 mm³, P = 0.017). SDpv12h also increased the number of damaged cells, visualized by TUNEL staining, by 137% (SDpv12h 46.8 ± 15 vs. control 19.7 ± 7.7/mm², P < 0.001) and SDis by 219% (SDis 32.9 ± 13.2 vs. control 10.3 ± 2.5/mm², P = 0.002). In addition, SDis significantly elevated the expression of the axonal extension inhibitory molecule neurocan (SDis 14.3 ± 0.4 vs. control 6.2 ± 0.1-fold of change, P < 0.001) in the injured hemisphere.

Conclusions:

These results provide the first direct evidence for a detrimental impact of sleep disruption on stroke evolution and suggest a potential role of sleep modulating treatments on stroke outcomes.

Citation:

Gao B; Cam E; Jaeger H; Zunzunegui C; Sarnthein J; Bassetti CL. Sleep disruption aggravates focal cerebral ischemia in the rat. SLEEP 2010;33(7):879-887.     

Study on the Anti-Cerebral Ischemia Effect of Borneol and Its Mechanism

Background

Borneol is the processed item from resin of Dryobalanops aromatica Gaertn. f. It can enhance the activity of antioxidant enzymes in brain tissue and reduce inflammatory response by improving the energy metabolism of ischemic brain regions, and thereby reduces brain tissue damage. The objective of this paper was to study the anti-cerebral ischemia effect of borneol and its mechanism.

Materials and Methods

The anti-cerebral ischemia effect of borneol was studied by ligation of bilateral common carotid arteries (CCA), and vagus nerves in mice and the acute cerebral ischemia-reperfusion experiment in rats.

Results

Compared with the blank and solvent control groups, the borneol low-; medium-; and high-dose groups can significantly prolong the gasping time of mice after decapitation, and extend the survival time of mice after ligation of bilateral CCA, and vagus nerves.

Conclusion

Compared with the Xueshuantong injection group, the prolongation of survival time of mice after ligation of bilateral CCA, and vagus nerves was more apparent in the high-dose borneol experimental group; each experimental group can significantly reduce the number of leukocyte infiltration, the number of ICAM-1-positive vessels, as well as the number of TNF-α-positive cells.

Conclusion

Borneol has an anti-cerebral ischemia effect.     

Polysomnographic Abnormalities in Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

Objectives:

Patients with SSADH deficiency, a disorder of chronically elevated endogenous GABA and GHB, were studied for sleep symptoms and polysomnography. We hypothesized that patients would have excessive daytime somnolence and decreased REM sleep.

Design:

Polysomnography and MSLT were performed on patients enrolled for comprehensive clinical studies of SSADH deficiency.

Setting:

Sleep studies were obtained in the sleep laboratories at CNMC and NIH.

Patients:

Sleep recordings were obtained in 10 patients with confirmed SSADH deficiency.

Interventions:

Thirteen overnight polysomnograms were obtained in 10 patients (7 male, 3 female, ages 11-27 y). Eleven MSLT studies were completed in 8 patients.

Measurements and Results:

Polysomnograms showed prolongation of REM stage latency (mean 272 ± 89 min) and decreased percent stage REM (mean 8.9%, range 0.3% to 13.8%). Decreased mean sleep latency was present in 6 of 11 MSLTs.

Conclusions:

SSADH deficiency is associated with prolonged latency to stage REM and decreased percent stage REM. This disorder represents a model of chronic GABA and GHB accumulation associated with suppression of REM sleep.

Citation:

Pearl PL; Shamim S; Theodore WH; Gibson M; Forester K; Combs SE; Lewin D; Dustin I; Reeves P; Jakobs C; Sato S. Polysomnographic abnormalities in succinic semialdehyde dehydrogenase (SSADH) deficiency. SLEEP 2009;32(12):1645-1648.     

Ulinastatin attenuates oxidation,inflammation and neural apoptosis in the cerebral cortex of adult rats with ventricular fibrillation after cardiopulmonary resuscitation

OBJECTIVE:

The role of Ulinastatin in neuronal injury after cardiopulmonary resuscitation has not been elucidated. We aim to evaluate the effects of Ulinastatin on inflammation, oxidation, and neuronal injury in the cerebral cortex after cardiopulmonary resuscitation.

METHODS:

Ventricular fibrillation was induced in 76 adult male Wistar rats for 6 min, after which cardiopulmonary resuscitation was initiated. After spontaneous circulation returned, the rats were split into two groups: the Ulinastatin 100,000 unit/kg group or the PBS-treated control group. Blood and cerebral cortex samples were obtained and compared at 2, 4, and 8 h after return of spontaneous circulation. The protein levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were assayed using an enzyme-linked immunosorbent assay, and mRNA levels were quantified via real-time polymerase chain reaction. Myeloperoxidase and Malondialdehyde were measured by spectrophotometry. The translocation of nuclear factor-κB p65 was assayed by Western blot. The viable and apoptotic neurons were detected by Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).

RESULTS:

Ulinastatin treatment decreased plasma levels of TNF-α and IL-6, expression of mRNA, and Myeloperoxidase and Malondialdehyde in the cerebral cortex. In addition, Ulinastatin attenuated the translocation of nuclear factor-κB p65 at 2, 4, and 8 hours after the return of spontaneous circulation. Ulinastatin increased the number of living neurons and decreased TUNEL-positive neuron numbers in the cortex at 72 h after the return of spontaneous circulation.

CONCLUSIONS:

Ulinastatin preserved neuronal survival and inhibited neuron apoptosis after the return of spontaneous circulation in Wistar rats via attenuation of the oxidative stress response and translocation of nuclear factor-κB p65 in the cortex. In addition, Ulinastatin decreased the production of TNF-α, IL-6, Myeloperoxidase, and Malondialdehyde.     

Previous mild traumatic brain injury and postural-control dynamics

Context:

Postural control and cognitive function are adversely affected by acute mild traumatic brain injury (mTBI). Whether postural-control deficits persist beyond the acute stage in individuals with a history of mTBI is unclear.

Objective:

To determine if postural-control deficits persist in individuals with a history of mTBI.

Design:

Retrospective cross-sectional study.

Setting:

University research laboratory.

Patients or Other Participants:

As part of an ongoing investigation examining cognitive and motor deficits associated with mTBI, 224 individuals participated in the study. Of these, 62 participants self-reported at least 1 previous physician-diagnosed mTBI.

Intervention(s):

Postural control was assessed using the NeuroCom Sensory Organization Test (SOT) postural-assessment battery.

Main Outcome Measure(s):

The SOT postural assessment yields 4 indices of postural control: a composite balance score, a visual ratio score, a somatosensory score, and a vestibular score. Postural dynamics were also examined by calculating approximate entropy of center-of-pressure excursions in the anteroposterior and mediolateral axis for each test condition.

Results:

Minimal differences in the SOT indices were noted among individuals with and without a history of previous mTBI (P > .05). In the group with a history of mTBI, anteroposterior postural irregularity decreased as postural difficulty increased. In contrast, the group without a history of mTBI displayed increased postural irregularity in the mediolateral direction.

Conclusions:

Individuals with a history of mTBI exhibited altered postural dynamics compared with individuals without a history of mTBI. These findings support the notion that changes in cerebral functioning that affect postural control may persist long after acute injury resolution.     

Polysomnographic and Health-related Quality of Life Correlates of Restless Legs Syndrome in the Sleep Heart Health Study

Study Objectives:

Sleep disturbance is the primary clinical morbidity of restless legs syndrome (RLS). To date, sleep disturbance in RLS has been measured in (1) clinical samples with polysomnography (PSG) or (2) population-based samples by self-report. The objective of this study was to analyze sleep by PSG in a population-based sample with symptoms of RLS.

Design:

Cross-sectional observational study

Setting:

Community-based

Participants:

3433 older men and women

Interventions:

None

Measurements and Results:

RLS was evaluated using an 8-item self-administered questionnaire based on NIH diagnostic criteria and required symptoms occurring ≥ five times per month and associated with at least moderate distress. Health-related quality of life (HRQOL) was determined using the SF-36. Unattended, in-home PSG was performed. Data were assessed using general linear models with adjustment for demographic, health-related variables, and apnea-hypopnea index (AHI). Subjects with RLS had longer adjusted mean sleep latency (39.8 vs 26.4 min, P < 0.0001) and higher arousal index (20.1 vs 18.0, P = 0.0145) than those without RLS. Sleep latency increased progressively as the frequency of RLS symptoms increased from 5-15 days per month to 6-7 days per week. No differences in sleep stage percentages were observed between participants with and without RLS. Subjects with RLS also reported poorer HRQOL in all physical domains as well as in the Mental Health and Vitality domains.

Conclusions:

These novel PSG data from a nonclinical, community-based sample of individuals with RLS document sleep disturbance in the home even in individuals with intermittent symptoms.

Citation:

Winkelman JW; Redline S; Baldwin CM; Resnick HE; Newman AB; Gottlieb DJ. Polysomnographic and health-related quality of life correlates of restless legs syndrome in the sleep heart health study. SLEEP 2009;32(6):772-778.     

Human prefrontal layer II interneurons in areas 46, 10 and 24

Background:

Prefrontal cortex (PFC) represents the highest level of integration and control of psychic and behavioral states. Several dysfunctions such as autism, hyperactivity disorders, depression, and schizophrenia have been related with alterations in the prefrontal cortex (PFC). Among the cortical layers of the PFC, layer II shows a particular vertical pattern of organization, the highest cell density and the biggest non-pyramidal/pyramidal neuronal ratio. We currently characterized the layer II cytoarchitecture in human areas 10, 24, and 46.

Objective:

We focused particularly on the inhibitory neurons taking into account that these cells are involved in sustained firing (SF) after stimuli disappearance.

Methods:

Postmortem samples from five subjects who died by causes different to central nervous system diseases were studied. Immunohistochemistry for the neuronal markers, NeuN, parvalbumin (PV), calbindin (CB), and calretinin (CR) were used. NeuN targeted the total neuronal population while the rest of the markers specifically the interneurons.

Results:

Cell density and soma size were statically different between areas 10, 46, 24 when using NeuN. Layer II of area 46 showed the highest cell density. Regarding interneurons, PV+-cells of area 46 showed the highest density and size, in accordance to the proposal of a dual origin of the cerebral cortex. Interhemispheric asymmetries were not identified between homologue areas.

Conclusion:

First, our findings suggest that layer II of area 46 exhibits the most powerful inhibitory system compared to the other prefrontal areas analyzed. This feature is not only characteristic of the PFC but also supports a particular role of layer II of area 46 in SF. Additionally, known functional asymmetries between hemispheres might not be supported by morphological asymmetries.     

Neuroprotective effect of atorvastatin in spinal cord ischemia-reperfusion injury

OBJECTIVES:

Prevention of the development of paraplegia during the repair of the damage caused by descending thoracic and thoracoabdominal aneurysms remains an important issue. Therefore, we investigated the protective effect of atorvastatin on ischemia-induced spinal cord injury in a rabbit model.

METHOD:

Thirty-two rabbits were divided into the following four equally sized groups: group I (control), group II (ischemia-reperfusion), group III (atorvastatin treatment) and group IV (atorvastatin withdrawal). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the iliac bifurcation. Seventy-two hours postoperatively, the motor function of the lower limbs of each animal was evaluated according to the Tarlov score. Spinal cord and blood samples were obtained for histopathological and biochemical analyses.

RESULTS:

All of the rabbits in group II exhibited severe neurological deficits. Atorvastatin treatment (groups III and IV) significantly reduced the level of motor dysfunction. No significant differences were observed between the motor function scores of groups III and IV at the evaluated time points. Light microscopic examination of spinal cord tissue samples obtained at the 72^nd hour of reperfusion indicated greater tissue preservation in groups III and IV than in group II.

CONCLUSION:

This study demonstrates the considerable neuroprotective effect of atorvastatin on the neurological, biochemical and histopathological status of rabbits with ischemia-induced spinal cord injury. Moreover, the acute withdrawal of atorvastatin therapy following the induction of spinal cord ischemia did not increase the neuronal damage in this rabbit model.     

Local and remote ischemic preconditioning protect against intestinal ischemic/reperfusion injury after supraceliac aortic clamping

OBJECTIVES:

This study tests the hypothesis that local or remote ischemic preconditioning may protect the intestinal mucosa against ischemia and reperfusion injuries resulting from temporary supraceliac aortic clamping.

METHODS:

Twenty-eight Wistar rats were divided into four groups: the sham surgery group, the supraceliac aortic occlusion group, the local ischemic preconditioning prior to supraceliac aortic occlusion group, and the remote ischemic preconditioning prior to supraceliac aortic occlusion group. Tissue samples from the small bowel were used for quantitative morphometric analysis of mucosal injury, and blood samples were collected for laboratory analyses.

RESULTS:

Supraceliac aortic occlusion decreased intestinal mucosal length by reducing villous height and elevated serum lactic dehydrogenase and lactate levels. Both local and remote ischemic preconditioning mitigated these histopathological and laboratory changes.

CONCLUSIONS:

Both local and remote ischemic preconditioning protect intestinal mucosa against ischemia and reperfusion injury following supraceliac aortic clamping.     

Multilevel Botulinum Toxin Type A as a Treatment for Spasticity in Children with Cerebral Palsy: A Retrospective Study

INTRODUCTION:

Cerebral palsy is the most common cause of physical disability in children. Spasticity is a disabling clinical symptom that is prevalent among patients suffering from cerebral palsy. The treatment of spasticity with botulinum toxin type A (BTX-A) is a well-established option in the interdisciplinary management of spasticity, providing focal reductions in muscle tone in cerebral palsy patients.

OBJECTIVE:

The aim of this retrospective study was to describe the effect of multilevel BTX-A injections in the lower extremities, focusing mainly on gross motor function and functional status in cerebral palsy patients.

METHODS:

Data from 71 cerebral palsy patients (64% male, 36% female, mean age 6.7 ±3.2 years) were analyzed retrospectively. We used the Ashworth and Tardieu scales to evaluate the degree of spasticity. Motor function was measured by the Gross Motor Function Measure (GMFM–88), and functional status was classified by the Gross Motor Function Classification System (GMFCS I-V). Multilevel BTX-A injections were applied after sedation and with electrostimulation guidance. The evaluations were repeated every three months, and the patients were followed for six months.

RESULTS:

We found that the Ashworth and Tardieu scores decreased significantly at the three-month evaluation (p<0.05) but not at the six-month evaluation (p>0.05). Although the improvement in spasticity was not maintained at the six-month evaluation, GMFM-88 scores increased significantly at the three- and six-month assessments. GMFSC levels showed no change in the three- and six-month assessments.

CONCLUSION:

We believe that a single multilevel BTX-A injection reduces spasticity and improves motor function in children with cerebral palsy.     

Preconditioning of the response to ischemia/ reperfusion-induced plasma leakage in hamster cheek pouch microcirculation

OBJECTIVE:

Ischemic preconditioning and some drugs can protect tissues from injury by preserving microcirculation. This study evaluated vascular permeability in a hamster cheek pouch preparation using either short ischemic periods or bradykinin as preconditioning stimuli followed by 30 min of ischemia/reperfusion.

METHOD:

Sixty-six male hamsters were divided into 11 groups: five combinations of different ischemic frequencies and durations (one, three or five shorts periods of ischemia, separated by one or five minutes) with 10 min intervals between the ischemic periods, followed by 30 min ischemia/reperfusion; three or five 1 min ischemic periods with 10 min intervals between them followed by the topical application of histamine (2 µM); bradykinin (400 nM) followed by 30 min of ischemia/reperfusion; and three control groups (30 min of ischemia/reperfusion or histamine or bradykinin by themselves). Macromolecular permeability was assessed by injection of fluorescein-labeled dextran (FITC-dextran, MW = 150 kDa; 250 mg/Kg body weight), and the number of leaks/cm2 was counted using an intravital microscope and fluorescent light in the cheek pouch.

RESULTS:

Plasma leakage (number of leaks/cm²) was significantly reduced by preconditioning with three and five 1 min ischemic periods, one and three 5 min ischemic periods and by bradykinin. Histamine-induced macromolecular permeability was also reduced after three periods of 5 min of ischemia.

CONCLUSION:

Short ischemic periods and bradykinin can function as preconditioning stimuli of the ischemia/reperfusion response in the hamster cheek pouch microcirculation. Short ischemic periods also reduced histamine-induced macromolecular permeability.     

The protective effect of cilostazol on isolated rabbit femoral arteries under conditions of ischemia and reperfusion: the role of the nitric oxide pathway

OBJECTIVES:

The clinical significance of ischemia/reperfusion of the lower extremities demands further investigation to enable the development of more effective therapeutic alternatives. This study investigated the changes in the vascular reactivity of the rabbit femoral artery and nitric oxide metabolites under partial ischemia/reperfusion conditions following cilostazol administration.

METHODS:

Ischemia was induced using infrarenal aortic clamping. The animals were randomly divided into seven groups: Control 90 minutes, Ischemia/Reperfusion 90/60 minutes, Control 120 minutes, Ischemia/Reperfusion 120/90 minutes, Cilostazol, Cilostazol before Ischemia/Reperfusion 120/90 minutes, and Ischemia 120 minutes/Cilostazol/Reperfusion 90 minutes. Dose-response curves for sodium nitroprusside, acetylcholine, and the calcium ionophore A23187 were obtained in isolated femoral arteries. The levels of nitrites and nitrates in the plasma and skeletal muscle were determined using chemiluminescence.

RESULTS:

Acetylcholine- and {"type":"entrez-nucleotide","attrs":{"text":"A23187","term_id":"833253","term_text":"A23187"}}A23187-induced relaxation was reduced in the Ischemia/Reperfusion 120/90 group, and treatment with cilostazol partially prevented this ischemia/reperfusion-induced endothelium impairment. Only cilostazol treatment increased plasma levels of nitrites and nitrates. An elevation in the levels of nitrites and nitrates was observed in muscle tissues in the Ischemia/Reperfusion 120/90, Cilostazol/Ischemia/Reperfusion, and Ischemia/Cilostazol/Reperfusion groups.

CONCLUSION:

Hind limb ischemia/reperfusion yielded an impaired endothelium-dependent relaxation of the femoral artery. Furthermore, cilostazol administration prior to ischemia exerted a protective effect on endothelium-dependent vascular reactivity under ischemia/reperfusion conditions.     

Limb blood flow after class 4 laser therapy

Context:

Laser therapy is purported to improve blood flow in soft tissues. Modulating circulation would promote healing by controlling postinjury ischemia, hypoxia, edema, and secondary tissue damage. However, no studies have quantified these responses to laser therapy.

Objective:

To determine a therapeutic dose range for laser therapy for increasing blood flow to the forearm.

Design:

Crossover study.

Setting:

Controlled laboratory setting.

Patients or Other Participants:

Ten healthy, college-aged men (age = 20.80 ± 2.16 years, height = 177.93 ± 3.38 cm, weight = 73.64 ± 9.10 kg) with no current history of injury to the upper extremity or cardiovascular conditions.

Intervention(s):

A class 4 laser device was used to treat the biceps brachii muscle. Each grid point was treated for 3 to 4 seconds, for a total of 4 minutes. Each participant received 4 doses of laser therapy: sham, 1 W, 3 W, and 6 W.

Main Outcome Measure(s):

The dependent variables were changes in blood flow, measured using venous occlusion plethysmography. We used a repeated-measures analysis of variance to analyze changes in blood flow for each dose at 2, 3, and 4 minutes and at 1, 2, 3, 4, and 5 minutes after treatment. The Huynh-Feldt test was conducted to examine differences over time.

Results:

Compared with baseline, blood flow increased over time with the 3-W treatment (F_3,9 = 3.468, P < .011) at minute 4 of treatment (2.417 ± 0.342 versus 2.794 ± 0.351 mL/min per 100 mL tissue, P = .032), and at 1 minute (2.767 ± 0.358 mL/min per 100 mL tissue, P < .01) and 2 minutes (2.657 ± 0.369 mL/min per 100 mL tissue, P = .022) after treatment. The sham, 1-W, and 6-W treatment doses did not change blood flow from baseline at any time point.

Conclusions:

Laser therapy at the 3-W (360-J) dose level was an effective treatment modality to increase blood flow in the soft tissues.     

Obstructive Sleep Apnea Leads to Transient Uncoupling of Coronary Blood Flow and Myocardial Work in Humans

Study Objectives:

Obstructive Sleep Apnea (OSA) is associated with a poor prognosis in patients with coronary artery disease. We hypothesized that abnormalities of coronary blood flow (CBF) associated with obstructive apneas may predispose patients to ischemia. We aimed to determine CBF during respiratory events in patients with OSA.

Setting:

University Hospital.

Patients:

Ten subjects undergoing elective percutaneous coronary intervention

Design:

We measured CBF and myocardial work (rate-pressure product [RPP]) in a non-culprit coronary artery in patients sleeping in the cardiac catheterization laboratory. Hemodynamic responses were matched to spontaneously occurring respiratory events.

Measurements and Results:

Events comprised a mixture of obstructive apneas, central apneas and hypopneas. RPP increased at the termination of each type of respiratory event. Following the rise in RPP, there was a delay, identified with breakpoint analysis, before CBF began to increase (P < 0.001) that differed in duration with event type: 8 sec for obstructive apnea, 5 sec for central apnea, and 4 sec for hypopnea. The delay in CBF with obstructive apnea was associated with an increase in coronary vascular resistance of 16% ± 4% (P < 0.05). Stepwise multilinear regression analysis showed the increase in CBF was predicted by the rise in RPP (R = 0.52, P < 0.001) and presence of arousal from sleep (R = 0.30, P < 0.05), but not the degree of O₂ desaturation.

Conclusion:

Following obstructive apneas there is a transient uncoupling of CBF from myocardial work and an increase in CVR. This disturbed flow-metabolic coupling may lead to nocturnal myocardial ischemia in patients with both OSA and coronary artery disease.

Citation:

Hamilton GS; Meredith IT; Walker AM; Solin P. Obstructive sleep apnea leads to transient uncoupling of coronary blood flow and myocardial work in humans. SLEEP 2009;32(2):263-270.     

Effect of vitamin A adjunct therapy for cerebral malaria in children admitted to Mulago hospital: a randomized controlled trial

Background

Malaria is a leading cause of mortality in Uganda accounting for 25% of deaths among children. Hitherto no adjunct therapy has been identified to improve outcome of cerebral malaria. Retinol suppresses growth of P.falciparum, scavenges free radicals, and exhibits synergistic action with quinine in parasite clearance.

Objective

To determine the effect of vitamin A supplementation on treatment outcome of cerebral malaria

Methods

In this randomised double-blind placebo controlled clinical trial we studied 142 children aged 6–59 months admitted with cerebral malaria in Mulago Hospital, Kampala. Children were randomised to either vitamin A or placebo and followed for 7 days. The main outcome measures were coma recovery time, time for convulsions to stop, and parasite and fever clearance. Secondary outcomes were overall mortality and time taken to start oral feeds.

Results

There was no difference in the coma recovery time (p=0.44), resolution of convulsions (p=0.37), fever clearance (p=0.92), parasite clearance (p=0.12), and starting oral feeds between the two treatment groups. Mortality was higher (16.2%) in the placebo than in the vitamin A group (8.1%): RR 1.4; 95% CI 1.0–2.1.

Conclusions

Vitamin A as adjunct therapy did not significantly reduce coma duration but there were fewer deaths in the vitamin A arm.     

A Gene and Neural Stem Cell Therapy Platform Based on Neuronal Cell Type-Inducible Gene Overexpression

Purpose

Spinal cord injury (SCI) is associated with permanent neurological damage, and treatment thereof with a single modality often does not provide sufficient therapeutic outcomes. Therefore, a strategy that combines two or more techniques might show better therapeutic effects.

Materials and Methods

In this study, we designed a combined treatment strategy based on neural stem cells (NSCs) introduced via a neuronal cell type-inducible transgene expression system (NSE::) controlled by a neuron-specific enolase (NSE) promoter to maximize therapeutic efficiency and neuronal differentiation. The luciferase gene was chosen to confirm whether this combined system was working properly prior to using a therapeutic gene. The luciferase expression levels of NSCs introduced via the neuronal cell type-inducible luciferase expression system (NSE::Luci) or via a general luciferase expressing system (SV::Luci) were measured and compared in vitro and in vivo.

Results

NSCs introduced via the neuronal cell type-inducible luciferase expressing system (NSE::Luci-NSCs) showed a high level of luciferase expression, compared to NSCs introduced via a general luciferase expressing system (SV::Luci-NSCs). Interestingly, the luciferase expression level of NSE::Luci-NSCs increased greatly after differentiation into neurons.

Conclusion

We demonstrated that a neuronal cell type-inducible gene expression system is suitable for introducing NSCs in combined treatment strategies. We suggest that the proposed strategy may be a promising tool for the treatment of neurodegenerative disorders, including SCI.