Acetazolamide Therapy for Metabolic Alkalosis in Pediatric Intensive Care Patients.

Science.gov (United States)

López, Carolina; Alcaraz, Andrés José; Toledo, Blanca; Cortejoso, Lucía; Gil-Ruiz, Maite Augusta

2016-12-01

Patients in PICUs frequently present hypochloremic metabolic alkalosis secondary to loop diuretic treatment, especially those undergoing cardiac surgery. This study evaluates the effectiveness of acetazolamide therapy for metabolic alkalosis in PICU patients. Retrospective, observational study. A tertiary care children's hospital PICU. Children receiving at least a 2-day course of enteral acetazolamide. None. Demographic variables, diuretic treatment and doses of acetazolamide, urine output, serum electrolytes, urea and creatinine, acid-base excess, pH, and use of mechanical ventilation during treatment were collected. Patients were studied according to their pathology (postoperative cardiac surgery, decompensated heart failure, or respiratory disease). A total of 78 episodes in 58 patients were identified: 48 were carried out in cardiac postoperative patients, 22 in decompensated heart failure, and eight in respiratory patients. All patients received loop diuretics. A decrease in pH and PCO2 in the first 72 hours, a decrease in serum HCO3 (mean, 4.65 ± 4.83; p alkalosis secondary to diuretic therapy. Cardiac postoperative patients present a significant increase in urine output after acetazolamide treatment.

The phosphaturic effect of sodium bicarbonate and acetazolamide in dogs

Science.gov (United States)

Fulop, Milford; Brazeau, Paul

1968-01-01

Urinary inorganic phosphate excretion was studied before and during the administration of sodium bicarbonate and acetazolamide in dogs that were not given infusions of phosphate. The excretion fraction of filtered phosphate increased after sodium bicarbonate or acetazolamide was given. This phosphaturia was attributed to decreased tubular reabsorption of phosphate consequent to alkalinization of either tubular urine or cells. PMID:5645865

Use of acetazolamide in lithium-induced nephrogenic diabetes insipidus: a case report.

Science.gov (United States)

Macau, Ricardo A; da Silva, Tiago Nunes; Silva, Joana Rego; Ferreira, Ana Gonçalves; Bravo, Pedro

2018-01-01

Lithium-induced nephrogenic diabetes insipidus (Li-NDI) is a rare and difficult-to-treat condition. A study in mice and two recent papers describe the use of acetazolamide in Li-NDI in 7 patients (a case report and a 6 patient series). We describe the case of a 63-year-old woman with bipolar disorder treated with lithium and no previous history of diabetes insipidus. She was hospitalized due to a bowel obstruction and developed severe dehydration after surgery when she was water deprived. After desmopressin administration and unsuccessful thiazide and amiloride treatment, acetazolamide was administrated to control polyuria and hydroelectrolytic disorders without significant side effects. To our knowledge, this is the third publication on acetazolamide use in Li-NDI patients. Treatment of lithium-induced nephrogenic diabetes insipidus might be challenging.Vasopressin, amiloride and thiazide diuretics have been used in lithium-induced nephrogenic diabetes insipidus treatment.Acetazolamide might be an option to treat lithium-induced nephrogenic diabetes insipidus patients who fail to respond to standard treatment.The use of acetazolamide in lithium-induced nephrogenic diabetes insipidus must be monitored, including its effects on glomerular filtration rate.

Acetazolamide in cerebral diagnosis: Physiological and pathophysiological aspects. Acetazolamid in der zerebrovaskulaeren Diagnostik: Physiologische und pathophysiologische Aspekte

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Lerch, H.; Franke, W.G.; Templin, A. (Medizinische Akademie ' Carl Gustav Carus' , Klinik fuer Nuklearmedizin, Dresden (Germany) Medizinische Akademie ' Carl Gustav Carus' , Klinik fuer Psychiatrie und Neurologie, Abt. Neurologie, Dresden (Germany))

1990-01-01

The sensitivity in the diagnosis of cerebrovascular diseases using radiotracers can be enhanced by the use of the acetazolamide test. In this paper we present and discuss some physiological and pathophysiological aspects of its mechanism. The physiological action of the carboanhydrase inhibitor is like the action of enhanced pCO{sub 2} in the tissue, thus acting at the site of metabolic regulation. The reaction of the vascular bed is influenced in part by subcortical structures. Pathologically the reaction can be disturbed at first by an altered regulation with the vessels being mechanically intact, e.g. in hypoxia or transient ischemia. Secondly, the mechanics of the vessels may be not intact e.g., in atherosclerosis or surrounding edema. Lastly, the vessels have already dilated, e.g. poststenotically. All these facts have to be taken into consideration interpreting an acetazolamid test. (orig.).

Population pharmacodynamic model of bicarbonate response to acetazolamide in mechanically ventilated chronic obstructive pulmonary disease patients

Science.gov (United States)

2011-01-01

Introduction Acetazolamide is commonly given to chronic obstructive pulmonary disease (COPD) patients with metabolic alkalosis. Little is known of the pharmacodynamics of acetazolamide in the critically ill. We undertook the pharmacodynamic modeling of bicarbonate response to acetazolamide in COPD patients under mechanical ventilation. Methods This observational, retrospective study included 68 invasively ventilated COPD patients who received one or multiple doses of 250 or 500 mg of acetazolamide during the weaning period. Among the 68 investigated patients, 207 time-serum bicarbonate observations were available for analysis. Population pharmacodynamics was modeled using a nonlinear mixedeffect model. The main covariates of interest were baseline demographic data, Simplified Acute Physiology Score II (SAPS II) at ICU admission, cause of respiratory failure, co-prescription of drugs interfering with the acid-base equilibrium, and serum concentrations of protein, creatinin, potassium and chloride. The effect of acetazolamide on serum bicarbonate levels at different doses and in different clinical conditions was subsequently simulated in silico. Results The main covariates interacting with acetazolamide pharmacodynamics were SAPS II at ICU admission (P = 0.01), serum chloride (P 500 mg twice daily is required to reduce serum bicarbonate concentrations > 5 mmol/L in the presence of high serum chloride levels or coadministration of systemic corticosteroids or furosemide. Conclusions This study identified several covariates that influenced acetazolamide pharmacodynamics and could allow a better individualization of acetazolamide dosing when treating COPD patients with metabolic alkalosis. PMID:21917139

SPECT measurements of cerebral blood volume before and after acetazolamide in occlusive cerebrovascular diseases

International Nuclear Information System (INIS)

Inoue, Yusuke; Momose, Toshimitsu; Machida, Kikuo; Honda, Norinari; Nishikawa, Junichi; Sasaki, Yasuhito.

1994-01-01

Cerebral blood volume before and after acetazolamide was measured by SPECT to evaluate cerebral vasodilatory capacity in eight patients with cerebrovascular disease and five control subjects. Two SPECT measurements were performed serially, and acetazolamide was administered between them. The ratio of increase in hemispheric blood volume was calculated, and it was compared with the results of cerebral blood flow and cerebral blood volume measurements. A cerebral vasodilatory capacity map, the image after acetazolamide minus the baseline image, was also produced. Acetazolamide increased hemispheric blood volume in all subjects. The ratio of increase was lower in the involved hemispheres of the patients with unilateral carotid disease than in the uninvolved hemispheres of the patients and control subjects. The ratio of concordance with blood flow and blood volume measurements was approximated at 80%. Cerebral vasodilatory capacity mapping revealed three defects compatible with the clinical data. SPECT measurements of cerebral blood volume after acetazolamide can be performed following baseline SPECT with no additional radiotracer, and may be helpful to assess hemodynamic status. (author)

Population pharmacodynamic modeling and simulation of the respiratory effect of acetazolamide in decompensated COPD patients.

Directory of Open Access Journals (Sweden)

Nicholas Heming

Full Text Available Chronic obstructive pulmonary disease (COPD patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis.619 time-respiratory (minute ventilation, tidal volume and respiratory rate and 207 time-PaCO2 observations were obtained from 68 invasively ventilated COPD patients. We modeled respiratory responses to acetazolamide in mechanically ventilated COPD patients and then simulated the effect of increased amounts of the drug.The effect of acetazolamide on minute ventilation and PaCO2 levels was analyzed using a nonlinear mixed effect model. The effect of different ventilatory modes was assessed on the model. Only slightly increased minute ventilation without decreased PaCO2 levels were observed in response to 250 to 500 mg of acetazolamide administered twice daily. Simulations indicated that higher acetazolamide dosage (>1000 mg daily was required to significantly increase minute ventilation (P0.75 L min(-1 in 60% of the population. The model also predicts that 45% of patients would have a decrease of PaCO2>5 mmHg with doses of 1000 mg per day.Simulations suggest that COPD patients might benefit from the respiratory stimulant effect after the administration of higher doses of acetazolamide.

Association of acetazolamide infusion with headache and cranial artery dilation in healthy volunteers

DEFF Research Database (Denmark)

Arngrim, Nanna; Schytz, Henrik Winther; Asghar, Mohammad Sohail

2014-01-01

under the curve for headache was increased after acetazolamide compared to placebo in the delayed phase (2-12 h) (P=.005). Compared to placebo, arterial circumference increased after acetazolamide in the basilar artery (P=.002) as well as the cerebral (P=.003), cavernous (P=.002), and cervical (P=.005...

Use of acetazolamide in lithium-induced nephrogenic diabetes insipidus: a case report

Directory of Open Access Journals (Sweden)

Ricardo A Macau

2018-02-01

Full Text Available Lithium-induced nephrogenic diabetes insipidus (Li-NDI is a rare and difficult-to-treat condition. A study in mice and two recent papers describe the use of acetazolamide in Li-NDI in 7 patients (a case report and a 6 patient series. We describe the case of a 63-year-old woman with bipolar disorder treated with lithium and no previous history of diabetes insipidus. She was hospitalized due to a bowel obstruction and developed severe dehydration after surgery when she was water deprived. After desmopressin administration and unsuccessful thiazide and amiloride treatment, acetazolamide was administrated to control polyuria and hydroelectrolytic disorders without significant side effects. To our knowledge, this is the third publication on acetazolamide use in Li-NDI patients.

Development of a topical niosomal preparation of acetazolamide: preparation and evaluation.

Science.gov (United States)

Aggarwal, Deepika; Garg, Alka; Kaur, Indu P

2004-12-01

Orally administered acetazolamide has a limited use in glaucoma due to the systemic side effects associated with its use. No topical formulation of acetazolamide is available, mainly because of it having a limited aqueous solubility and poor corneal permeation. To enhance the bioavailability of acetazolamide by the topical route and to improve the corneal permeability of the drug, niosomes of acetazolamide were prepared (employing span 60 and cholesterol) by different methods. Transmission electron microscopy (TEM) of the selected formulation was carried out to study the morphology. Niosomes were also prepared in the presence of dicetyl phosphate and stearylamine to obtain negatively and positively charged vesicles, respectively. It was found that the reverse-phase evaporation method (REV) gave the maximum drug entrapment efficiency (43.75%) as compared with ether injection (39.62%) and film hydration (31.43%) techniques. Drug entrapment efficiency varied with the charge and the percent entrapment efficiency for the REV method was 43.75, 51.23 and 36.26% for neutral, positively charged and negatively charged niosomes, respectively. Corneal permeability studies, however, showed that the percent permeation and the apparent permeability coefficient for the charged niosomes were less than for the neutral ones. A bioadhesive niosomal formulation of acetazolamide was also prepared and compared with the positively charged formulation, considering that both of them would have a prolonged stay in the cul-de-sac because of their expected interactions with mucin. The formulations were also compared based on their intraocular pressure (IOP)-lowering capacity. The positively charged niosomes (REV2), although showing good corneal permeability and pharmacodynamics, were however found to be inappropriate in terms of the corneal cell toxicity. The bioadhesive coated formulation (REV1bio) compared well with REV2 and also showed a much lesser toxicity. Further, the IOP

Acetazolamide improves oxygenation in patients with respiratory failure and metabolic alkalosis.

Science.gov (United States)

Gulsvik, Ragnhild; Skjørten, Ingunn; Undhjem, Kenneth; Holø, Lars; Frostad, Anne; Saure, Eirunn Waatevik; Lejlic, Vasvija; Humerfelt, Sjur; Hansen, Gunnar; Bruun Wyller, Torgeir

2013-10-01

Coexistent respiratory failure and metabolic alkalosis is a common finding. Acidotic diuretics cause a fall in pH that may stimulate respiration. The purpose of the study was to evaluate the effectiveness of short-term treatment with acetazolamide for combined respiratory failure and metabolic alkalosis. A randomised, placebo-controlled and double-blind parallel group trial where oral acetazolamide 250 mg three times a day for 5 days were administered to patients hospitalised for respiratory failure because of a pulmonary disease (Pa O2 ≤ 8 kPa and/or Pa CO2 ≥ 7 kPa) who had concurrent metabolic alkalosis [base excess (BE) ≥ 8 mmol/L]. Pa O2 after 5 days was the primary effect variable. Secondary effect variables were Pa CO2 , BE and pH on day 5, and the total number of days in hospital. Of 70 patients enrolled (35 in each group), data from 54 were analysed per protocol, while last observation carried forward was used for the remaining 16. During the 5-day treatment, Pa O2 increased on average 0.81 kPa in the placebo group and 1.41 kPa in the acetazolamide group. After adjustment for baseline skewness, the difference was statistically significant (adjusted mean difference 0.55 kPa, 95% confidence interval 0.03-1.06). Pa CO2 decreased in both groups, but the difference was not statistically significant. As expected, pH and BE decreased markedly in the acetazolamide group. Acetazolamide may constitute a useful adjuvant treatment mainly to be considered in selected patients with respiratory failure combined with prominent metabolic alkalosis or where non-invasive ventilation is insufficient or infeasible. © 2013 John Wiley & Sons Ltd.

The early diagnostic value of oral acetazolamide load combined with SPECT rCBF imaging in patients with transient ischemia attack in brain

International Nuclear Information System (INIS)

Liu Xintong; Zheng Zhiping; Qiao Suixian; Tang Anwu

2001-01-01

Objective: In order to assess the diagnostic value of acetazolamide (ACZ) combined with rCBF-SPECT imaging in patients with transient ischemia attack (TIA). Methods: SPECT imaging was performed before and after oral ACZ with visual and semiquantitative analysis of the images. Blood gas analysis was done before and after ACZ administration either. Results: After ACZ loading, in normal group, 99 Tc m -ECD was distributed symmetrically on correspondent parts of the brain and rCBF was generally increased. The blood pH was decreased and blood PCO 2 was increased, respectively in TIA group, the positive rate of hypoperfusion foci on SPECT images were increased from 5/6 to 6/6 in symptomatic patients and from 60% to 92% in asymptomatic patients. The total positive rate was 93%. Conclusion: Oral ACZ before SPECT imaging is a simple, reliable way for early diagnosis in patients with TIA

Acetazolamide in cerebral diagnosis: Physiological and pathophysiological aspects

International Nuclear Information System (INIS)

Lerch, H.; Franke, W.G.; Templin, A.

1990-01-01

The sensitivity in the diagnosis of cerebrovascular diseases using radiotracers can be enhanced by the use of the acetazolamide test. In this paper we present and discuss some physiological and pathophysiological aspects of its mechanism. The physiological action of the carboanhydrase inhibitor is like the action of enhanced pCO 2 in the tissue, thus acting at the site of metabolic regulation. The reaction of the vascular bed is influenced in part by subcortical structures. Pathologically the reaction can be disturbed at first by an altered regulation with the vessels being mechanically intact, e.g. in hypoxia or transient ischemia. Secondly, the mechanics of the vessels may be not intact e.g., in atherosclerosis or surrounding edema. Lastly, the vessels have already dilated, e.g. poststenotically. All these facts have to be taken into consideration interpreting an acetazolamid test. (orig.) [de

Acetazolamide lowers intracranial pressure and modulates the cerebrospinal fluid secretion pathway in healthy rats

DEFF Research Database (Denmark)

Uldall, Maria; Botfield, Hannah; Jansen-Olesen, Inger

2017-01-01

a maximum reduction at 55min 66±4% (P... in the amount of AQP1 (p=0.0152) and Na/K ATPase (p=0.0411) protein in the membrane fraction of the CP, but not AQP4 (p=0.0649). A single dose of acetazolamide lowers ICP and modulates the CSF secretion pathway in healthy rats - Firstly, by inhibiting the Na/K ATPase to slow the CSF production, secondly...... was collected for qPCR and western blot analysis. The effect of acetazolamide on the Na/K ATPase activity was evaluated in an in vitro assay of primary CP epithelial cells isolated from rats. Acetazolamide significantly lowered ICP within 10min of injection compared to the vehicle group (P

Acetazolamide: a second wind for a respiratory stimulant in the intensive care unit?

Science.gov (United States)

Heming, Nicholas; Urien, Saïk; Faisy, Christophe

2012-08-07

Patients with chronic obstructive pulmonary disease (COPD) are affected by episodes of respiratory exacerbations, some of which can be severe and may necessitate respiratory support. Prolonged invasive mechanical ventilation is associated with increased mortality rates. Persistent failure to discontinue invasive mechanical ventilation is a major issue in patients with COPD. Pure or mixed metabolic alkalosis is a common finding in the intensive care unit (ICU) and is associated with a worse outcome. In patients with COPD, the condition is called post-hypercapnic alkalosis and is a complication of mechanical ventilation. Reversal of metabolic alkalosis may facilitate weaning from mechanical ventilation of patients with COPD. Acetazolamide, a non-specific carbonic anhydrase inhibitor, is one of the drugs employed in the ICU to reverse metabolic alkalosis. The drug is relatively safe, undesirable effects being rare. The compartmentalization of the different isoforms of the carbonic anhydrase enzyme may, in part, explain the lack of evidence of the efficacy of acetazolamide as a respiratory stimulant. Recent findings suggest that the usually employed doses of acetazolamide in the ICU may be insufficient to significantly improve respiratory parameters in mechanically ventilated patients with COPD. Randomized controlled trials using adequate doses of acetazolamide are required to address this issue.

Cerebral blood flow and cerebrovascular response to acetazolamide in patients with chronic alcoholism

OpenAIRE

Oishi, M; Mochizuki, Y; Takasu, T

1997-01-01

Cerebral blood flow and cerebrovascular response to acetazolamide were studied in 12 patients with chronic alcoholism and 12 age matched healthy controls. Blood flows in the cerebral cortex, thalamus, and putamen were significantly lower in the chronic alcoholic group than in the healthy control group. The increase in blood flow caused by acetazolamide did not show any significant difference between the two groups. These findings suggest that the decreased cerebral blood flow i...

Simplified quantitative determination of cerebral perfusion reserve with H215O PET and acetazolamide

International Nuclear Information System (INIS)

Arigoni, M.; Kneifel, S.; Burger, C.; Buck, A.; Fandino, J.; Khan, N.

2000-01-01

The measurement of regional cerebral blood from (rCBF) and perfusion reserve (PR) with H 2 15 O positron emission tomography (PET) and acetazolamide challenge is of importance in evaluating patients with cerebrovascular disease and is thought to be useful in selecting patients for possible vascular surgery. Full quantitative assessment of rCBF with PET requires arterial blood sampling, which is inconvenient in a clinical setting. In this work, we present a simple non-invasive method with which to quantitatively evaluate PR in one PET session lasting no more than 30 min. In ten patients with cerebrovascular disease, rCBF was measured with H 2 15 O PET under the baseline condition and after administration of 1 g acetazolamide using a standard technique involving arterial blood sampling. The activity accumulated over 60 s was normalized to injected activity per kilogram body weight (nAA) and compared with rCBF in eight different brain regions. A high linear correlation was found for PR based on nAA (PR nAA ) and rCBF (PR rCBF ) (PR nAA =0.843 PR rCBF + 0.092, r=0.83, Pearson's correlation coefficient). Bland-Altman analyses further confirmed that PR nAA reflects PR in a quantitative manner. These results demonstrate that the method based on normalized counts allows the quantitative assessment of PR without blood sampling. (orig.)

Prediction of cerebral ischemia due to cerebral vasospasm in SAH using SPECT and 123I-IMP with acetazolamide test

International Nuclear Information System (INIS)

Nakagawara, Jyoji; Wada, Keiji; Takeda, Rihei; Usami, Takashi; Hashimoto, Ikuo; Shimazaki, Mitsuteru; Tanaka, Chiharu; Nakamura, Jun-ichi; Suematsu, Katsumi.

1989-01-01

To investigate the possibility of predicting cerebral ischemia due to cerebral vasospasm in subarachnoid hemorrhage (SAH), serial evaluation of the cerebral vasodilatory capacity by the acetazolamide test was conducted, using single photon emission computed tomography (SPECT) and N-isopropyl 123 I-p-iodoamphetamine (IMP), in 17 patients with cerebral vasospasm following early surgery for ruptured aneurysms. The degree of vasospasm measured on the angiograms was classified into the following three types; mild degree (25%>stenosis), moderate degree (25∼50% stenosis), and severe degree(50%acetazolamide was limited until the release of the cerebral vasospasm. Therefore, assessment of cerebral vasodilatory capacity in SAH by the acetazolamide test might predict the appearance and continuation of potential ischemia of the brain caused by the reduction of perfusion pressure due to cerebral vasospasm. (J.P.N.)

Prediction of cerebral ischemia due to cerebral vasospasm in SAH using SPECT and sup 123 I-IMP with acetazolamide test

Energy Technology Data Exchange (ETDEWEB)

Nakagawara, Jyoji; Wada, Keiji; Takeda, Rihei; Usami, Takashi; Hashimoto, Ikuo; Shimazaki, Mitsuteru; Tanaka, Chiharu; Nakamura, Jun-ichi (Nakamura Memorial Hospital, Sapporo (Japan)); Suematsu, Katsumi

1989-11-01

To investigate the possibility of predicting cerebral ischemia due to cerebral vasospasm in subarachnoid hemorrhage (SAH), serial evaluation of the cerebral vasodilatory capacity by the acetazolamide test was conducted, using single photon emission computed tomography (SPECT) and N-isopropyl {sup 123}I-p-iodoamphetamine (IMP), in 17 patients with cerebral vasospasm following early surgery for ruptured aneurysms. The degree of vasospasm measured on the angiograms was classified into the following three types; mild degree (25%>stenosis), moderate degree (25{approx}50% stenosis), and severe degree(50%acetazolamide was limited until the release of the cerebral vasospasm. Therefore, assessment of cerebral vasodilatory capacity in SAH by the acetazolamide test might predict the appearance and continuation of potential ischemia of the brain caused by the reduction of perfusion pressure due to cerebral vasospasm. (J.P.N.).

Effect of acetazolamide on the otolith growth of goldfish

International Nuclear Information System (INIS)

Mugiya, Yasuo

1977-01-01

In order to clarify the involvement of a functional carbonic anhydrase (CA) system in the otolith formation of the goldfish, Carassius auratus, acetazolamide, a specific CA inhibitor, was injected intraperitoneally every 3 or 4 days, and its inhibitory effect on the otolith growth was examined by means of a tetracycline labelling technique. Calcium-45 deposition on the otolith was also examined after a single injection of the drug. Given in multiple doses of 50 mg per Kg of body weight, acetazolamide did not reduce the growth rate of the otolith on either dorsal or ventral side. With multiple doses of 100 mg, however, the dorsal growth was significantly depressed by 17%. The ventral growth was not affected. Similarly, calcium-45 deposition on the otolith was effectively reduced (39%) only when a dose of 100 mg was given. These results suggest that, if involved, the enzyme-catalyzed hydration or hydroxylation of CO 2 is not indispensable to the carbonate formation of the otolith. (auth.)

Prevention of acute mountain sickness by acetazolamide in Nepali porters: a double-blind controlled trial.

Science.gov (United States)

Hillenbrand, Peter; Pahari, Anil K; Soon, Yuen; Subedi, Deepak; Bajracharya, Rajan; Gurung, Puncho; Lal, Barun K; Marahatta, Ramesh; Pradhan, Santosh; Rai, Dilip; Sharma, Shailendra

2006-01-01

This study aimed to determine the efficacy, tolerability, and practicality of acetazolamide for the prevention of acute mountain sickness (AMS) in Nepali trekking porters early in the trekking season. This study was a randomized, double-blind controlled trial with 400 male Nepali porters in the Mount Everest region of Nepal, trekking from Namche Bazaar (3440 m) to Lobuche (4930 m), the study endpoint. Participants were randomized to receive 250 mg acetazolamide daily or placebo, and AMS symptom scores (Lake Louise) were compared in highlanders vs lowlanders. Only 109 (27.2%) of the 400 porters completed the trial (28 highlanders, 81 lowlanders). The rest either dropped out (275/400 porters, 68.8%) or were excluded (16/400 porters, 4%). Acute mountain sickness occurred in 13 (11.9%) of 109 porters; all were lowlanders; 7 were taking acetazolamide, 6 taking placebo. Birthplace, acclimatization in the week before the trial, ascent rate, and rest days were the most important variables affecting the incidence of AMS. No highlanders, but 13 (16.1%) of 81 lowlanders had AMS (P = .016). Acclimatization in the pretrial week reduced AMS incidence (P = .013), as did a slower ascent rate (P = .0126), but rest days were the most potent prophylactic variable (P = .0001). Side effects were more frequent in porters taking acetazolamide than in the placebo group (P = .0001), but there were no serious side effects. Acetazolamide was tolerable, but impractical for the routine prevention of AMS in Nepali porters. A good trekking schedule and adequate acclimatization remain the most effective preventive measures. This study identified lowland porters as a high-risk group for developing AMS.

Acetazolamide improves cerebral oxygenation during exercise at high altitude

NARCIS (Netherlands)

Vuyk, J.; Bos, J. van den; Terhell, K.; Bos, R. de; Vletter, A.; Valk, P.; Beuzekom, M. van; Kleef, J. van; Dahan, A.

2006-01-01

Acute mountain sickness is thought to be triggered by cerebral hypoxemia and be prevented by acetazolamide (Actz). The effect of Actz on cerebral oxygenation at altitude remains unknown. In 16 members of the 2005 Dutch Cho Oyu (8201 m, Tibet) expedition, the influence of Actz and exercise (750 mg PO

A highly selective and sensitive Tb3+-acetylacetone photo probe for the assessment of acetazolamide in pharmaceutical and serum samples

Science.gov (United States)

Youssef, A. O.

2018-04-01

A novel, simple, sensitive and selective spectrofluorimetric method was developed for the determination of Acetazolamide in pharmaceutical tablets and serum samples using photo probe Tb3+-ACAC. The Acetazolamide can remarkably quench the luminescence intensity of Tb3+-ACAC complex in DMSO at pH 6.8 and λex = 350 nm. The quenching of luminescence intensity of Tb3+-ACAC complex especially the electrical band at λem = 545 nm is used for the assessment of Acetazolamide in the pharmaceutical tablet and serum samples. The dynamic range found for the determination of Acetazolamide concentration is 4.49 × 10-9-1.28 × 10-7 mol L-1, and the limit of detection (LOD) and limit of quantification (LOQ) are (4.0 × 10-9 and 1.21 × 10-8) mol L-1, respectively.

The effect of oral acetazolamide on cystoid macular edema in hydroxychloroquine retinopathy: a case report.

Science.gov (United States)

Hong, Eun Hee; Ahn, Seong Joon; Lim, Han Woong; Lee, Byung Ro

2017-07-12

Hydroxychloroquine (HCQ) retinopathy can accompany other retinal complications such as cystoid macular edema (CME), which leads to central visual loss. We report a case of CME with HCQ retinopathy that improved with the use of oral acetazolamide, and discussed the possible mechanisms of CME in HCQ retinopathy using multimodal imaging modalities. A 62-year-old patient with systemic lupus erythematosus (SLE) and HCQ retinopathy developed bilateral CME with visual decline. Fluorescein angiography (FA) showed fluorescein leakage in the macular and midperipheral area. After treatment with oral acetazolamide (250 mg/day) for one month, CME was completely resolved, best corrected visual acuity (BCVA) improved from 20/50 to 20/25, and FA examination showed decreased dye leakage in the macular and midperipheral areas. In cases of vision loss in HCQ retinopathy, it is important to consider not only progression of maculopathy, but also development of CME, which can be effectively treated with oral acetazolamide.

Indomethacin abolishes cerebral blood flow increase in response to acetazolamide-induced extracellular acidosis

DEFF Research Database (Denmark)

Wang, Qian; Paulson, O B; Lassen, N A

1993-01-01

by acetazolamide (Az), a drug that induces brain extracellular acidosis, which triggers its effect on CBF. We compared the results to the inhibitory effect of indomethacin on the CBF increase during hypercapnia. Indomethacin but not diclofenac, another potent cyclooxygenase inhibitor, was found to block almost...... completely the CBF increase caused by Az-induced extracellular acidosis or by CO2, but it did not influence the CBF increase produced by sodium nitroprusside or papaverine. The results suggest that indomethacin exerts its action on CO2 reactivity by a nonprostaglandin-mediated mechanism that directly......Indomethacin is known to attenuate quite markedly the increase in CBF during hypercapnia. Hypercapnia is, in all likelihood, mediated by the acid shift at the level of the smooth muscle cells of the cerebral arterioles. We therefore investigated the effect of indomethacin on the CBF increase caused...

Comparison of acetazolamide-enhanced brain SPECT using Tc-99m ECD with cerebral angiography in patients with cerebrovascular disease

International Nuclear Information System (INIS)

Choi, Y. Y.; Moon, D. H.; Ryu, J. S.; Yang, S. H.; Lee, H. K.; Lee, J. H.; Kim, J. S.; Kim, K. A.

1997-01-01

Cerebral vascular reserve can be assessed by development of collateral channels (DCC) on cerebral angiography(CA) or vasoreactivity (VR) on acetazolamide-enhanced brain SPECT (ACZ-SPECT). The purpose of this study was to compare Tc-99m ECD ACZ-SPECT with CA in the evaluation of vascular reserve in patients (pts) with cerebrovascular disease(CVD). Twenty seven patients with CVD, including TIA (n=13), infarction (n=11) and asymptomatic pts (AS, n=3), underwent CA and ACZ-SPECT. Basal and ACZ-SPECT was obtained consecutively, and image subtraction was performed. On CA, degree of DCC was scored 0-3 (0: normal, 3: poor) according to parenchymal staining on delayed film. In ACZ-SPECT, decrease of VR was graded 0-3 (0: normal, 3: more than 30% decrease). The correlation between degree of stenosis, DCC and VR were analyzed. 1) Variable degree of VR or DCC was observed in totally occluded or stenotic cerebral arterial territories. 2) In arterial territories with poor DCC, ACZ-SPECT showed poor VR. However, in 5 out of 11 TIA or AS with good DCC, poor VR was observed. These data suggests that 1) cerebral hemodynamic status cannot be assessed by the degree of stenosis on CA alone. 2) DCC may overestimate the cerebral vascular reserve in patients with TIA or AS. 3) ACZ-SPECT plays a complementary role to CA for evaluation of cerebral hemodynamic status in pts with CVD

SPECT study of cerebral blood flow reactivity after acetazolamide in patients with transient ischemic attacks

International Nuclear Information System (INIS)

Chollet, F.; Celsis, P.; Clanet, M.; Guiraud-Chaumeil, B.; Rascol, A.; Marc-Vergnes, J.P.

1989-01-01

We investigated 15 patients with one or more transient ischemic attacks (TIAs) in the internal carotid artery territory within the month following the most recent TIA. Cerebral blood flow (CBF) was measured by single-photon emission computed tomography, using intravenous xenon-133 before and after injection of 1 g acetazolamide. Six patients had severe carotid stenosis or occlusion; the other nine patients had no significant carotid lesions. Twenty age-matched volunteers free of neurologic symptoms or history were used as controls. Mean CBF in the sylvian region was not significantly different between patients and controls. Seven patients exhibited a focal hypoperfusion at rest in the symptomatic hemisphere, and their hypoperfused areas were hyporeactive after administration of acetazolamide. Seven other patients exhibited hyporeactive areas after acetazolamide administration while their CBF tomograms at rest were normal. Thus, CBF abnormalities were detected in 14 of the 15 patients. Our findings suggest that CBF measured early after acetazolamide administration could be useful to confirm the clinical diagnosis of TIA. In the nine patients with no significant lesion of the internal carotid artery, the areas of hypoperfusion were small and were probably related to the focal ischemic event. In the six patients with severe lesions of the internal carotid artery, abnormalities were of variable size and intensity but were often large and pronounced. The discrepancy between these two subgroups of patients could be ascribed to the hemodynamic influence of the internal carotid artery lesions. Moreover, our findings may provide some insight into the pathophysiology of TIAs

Assessment of cerebral blood flow reserve using blood oxygen level-dependent echo planar imaging after acetazolamide administration in patients post-STA-MCA anastomosis surgery

International Nuclear Information System (INIS)

Zenke, Kiichiro; Kusunoki, Katsusuke; Saito, Masahiro; Sadamoto, Kazuhiko; Ohta, Shinsuke; Kumon, Yoshiaki; Sakaki, Saburo; Nagasawa, Kiyoshi

1998-01-01

Recently, blood oxygen level-dependent (BOLD) echo planar imaging (EPI) has been used to estimate blood flow changes. Theoretically, a relative decrement of deoxyhemoglobin in cerebral blood supply induces a MR signal change after neuronal stimulation. In the present study, we have attempted to evaluate CBF reserve capacity by the BOLD EPI in patients who had undergone STA-MCA anastomosis surgery. Then, we compared with the signal intensity changes obtained by this procedure with the CBF changes by Xe-SPECT after acetazolamide administration. Six patients, post-STA-MCA anastomosis surgery, were studied. Pre-operatively, MR signal intensity and CBF, by Xe-SPECT, were increased in the intact side after acetazolamide administration in all patients, and MR signal intensities were decreased in low flow regions after acetazolamide administration in all four patients in whom so-called steal phenomenon was demonstrated by Xe-SPECT study. Post-operatively, poor response was shown after acetazolamide administration with both Xe-SPECT and BOLD EPI in the two patients who had unsuccessful anastomoses. In the successfully anastomosed patients, improved vascular reactivity was demonstrated on BOLD EPI after acetazolamide administration in 3 of 4 patients in whom an improvement of vascular reactivity was demonstrated on Xe-SPECT. In one patient, MRI studies were considered to have technical artifacts, because the MR signal intensity did not increase, even in the intact side after acetazolamide administration. In conclusion, BOLD EPI after acetazolamide administration is an useful procedure for the pre- and post-operative of vascular reserve in patients with ischemic stroke. (author)

Ventilatory oscillations at exercise: effects of hyperoxia, hypercapnia, and acetazolamide.

Science.gov (United States)

Hermand, Eric; Lhuissier, François J; Larribaut, Julie; Pichon, Aurélien; Richalet, Jean-Paul

2015-06-01

Periodic breathing has been found in patients with heart failure and sleep apneas, and in healthy subjects in hypoxia, during sleep and wakefulness, at rest and, recently, at exercise. To unravel the cardiorespiratory parameters liable to modulate the amplitude and period of ventilatory oscillations, 26 healthy subjects were tested under physiological (exercise) and environmental (hypoxia, hyperoxia, hyperoxic hypercapnia) stresses, and under acetazolamide (ACZ) treatment. A fast Fourier transform spectral analysis of breath-by-breath ventilation (V˙E) evidenced an increase in V˙E peak power under hypercapnia (vs. normoxia and hyperoxia, P power was positively related to cardiac output (Q˙c) and V˙E in hyperoxia (P oscillations by increasing Q˙c and V˙E, whereas ACZ decreases ventilatory instability in part by a contrasting action on O2 and CO2 sensing. An intrinsic oscillator might modulate ventilation through a complex system where peripheral chemoreflex would play a key role. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

The Selfish Brain: Stress and Eating Behavior

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Achim ePeters

2011-05-01

Full Text Available The brain occupies a special hierarchical position in human energy metabolism. If cerebral homeostasis is threatened, the brain behaves in a "selfish" manner by competing for energy resources with the body. Here we present a logistic approach, which is based on the principles of supply and demand known from economics. In this "cerebral supply chain" model, the brain constitutes the final consumer. In order to illustrate the operating mode of the cerebral supply chain, we take experimental data which allow to assess the supply, demand and need of the brain under conditions of psychosocial stress. The experimental results show that the brain under conditions of psychosocial stress actively demands energy from the body, in order to cover its increased energy needs. The data demonstrate that the stressed brain uses a mechanism referred to as "cerebral insulin suppression" to limit glucose fluxes into peripheral tissue (muscle, fat and to enhance cerebral glucose supply. Furthermore psychosocial stress elicits a marked increase in eating behavior in the post-stress phase. Subjects ingested more carbohydrates without any preference for sweet ingredients. These experimentally observed changes of cerebral demand, supply and need are integrated into a logistic framework describing the supply chain of the selfish brain.

ACETAZOLAMIDE IS A MEDICINE FOR THE MEDICATED CORRECTION OF THE SLEEP APNEA AND HYPOPNEA SYNDROME AMONG CHILDREN AND ADULTS

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O.V. Bykova

2006-01-01

Full Text Available Sleep apnea and hypopnea syndrome is a life bendangering sleep dis order among both adults and children. The prevalence of the sleep apnea and hypopnea syndrome both in adult and pediatric population may be evaluated only approximately, as not all of the patients, suffering from this pathology, may call some adequate complaints, which, in their turn, help diagnose the disease. For example, only obstructive sleep apnea syndrome according to the data of British epidemiologists is met among the adults at the frequency rate, which can be compared with the prevalence of the bronchial asthma. Since metabolic acidosis caused by the carbonic anhydrase inhibitor of acetazolamide stimulates the ventilation of lungs, the researchers have set forth a supposition that the application of this medicine can be efficient to treat the respiratory disturbances in sleep. There is wide application of acetazolamide for the medicated correction of sleep apnea and hypopnea syndrome of the central genesis among both adults and children. When using acetazolamide for the long term therapy of respiratory disturbances among adult patients, the main issue is the probable growth of tolerance towards the carbonic anhydrase inhibitor along with the continuous longbterm application of the medicine. In pediatry, quite on the contrary, the sleep apnea and hypopnea syndrome is usually a transit problem of the early infancy and it does not require any longbterm drug therapy, which defines specifically high perspectives of the efficient and safe application of acetazolamide for the medicated correction of respiratory disturbances in sleep precisely within this category of patients.Key words: apnea, hypopnea, sleep disorder, acetazolamide, children.

[Reduction of omalgia in laparoscopic cholecystectomy: clinical randomized trial ketorolac vs ketorolac and acetazolamide].

Science.gov (United States)

Figueroa-Balderas, Lorena; Franco-López, Francisco; Flores-Álvarez, Efrén; López-Rodríguez, Jorge Luis; Vázquez-García, José Antonio; Barba-Valadez, Claudia Teresa

2013-01-01

Laparoscopy cholecystectomy for the surgical treatment of cholelithiasis has been considered the gold standard. The referred pain to the shoulder (omalgia) may be present to 63% of the patients and limits outpatient management. The study was to evaluate the usefulness of acetazolamide associated with ketorolac for reduction of the omalgia to minimally invasive treatment. We performed a clinical trial, randomized, double blind in patients undergoing laparoscopic cholecystectomy to assess the reduction of post-operative omalgia comparing ketorolac and ketorolaco+acetazolamida. 31 patients in each group were studied. The study group: 250 mg of acetazolamide before anesthetic induction and 30 mg of ketorolac in the immediate postoperative period. one tablet of placebo prior to the anesthetic induction and 30 mg of ketorolac in the immediate postoperative. The presence of omalgia was assessed using the analog visual scale. The variables recorded included: age, sex, flow of carbon dioxide intra-abdominal pressure, surgical time, urgent or elective surgery, omalgia, severity of pain evaluated by analog visual scale, addition analgesia. Both groups were homogeneous and statistical analysis showed no differences in the variables studied. The omalgia in the study group was presented at 9.67% and in the group control was the 58.06% (p < 0.001). 250 mg oral acetazolamide associated 30 mg of ketorolac reduces significantly the development of omalgia in patients undergoing laparoscopic cholecystectomy.

Brain SPECT using dipyridamole for evaluation of vascular reserve

International Nuclear Information System (INIS)

Kim, Su Zy; Park, Chan Hee; Yoon, Soo Hwan; Pai, Moon Sun; Yoon, Suk Nam; Cho, Kyung Kee

1997-01-01

Baseline and stress brain SPECT studies using CO 2 inhalation, acetazolamide (Diamox R ) and adenosine administrations have been used in the evaluation of cerebral vascular reserve. Recently dipyridamole (Persantine R ) which is one of the pharmacologic myocardial perfusion SPECT agents as a potent vasodilator is suggested as another cerebral vasodilator. IV Diamox R is not available in Korea. Therefore, the purpose of our study was to evaluate dipyridamole in stress brain SPECT in patients with Moya Moya disease. Eight patients with angiographically proven Moya Moya disease were studied. Their ages ranged from 7 to 62 year old. There were 4 males and 4 females. Each patient had a baseline and persantine brain SPECT studies with 1 to 3 days' interval. Dipyridamole was given intravenously at a dose of 0.56 mg/kg over 4 minutes while watching vital signs such as blood pressure, heart rate, and electrocardiogram. Three minutes after the completion of the infusion, 99mTc-ECD (0.2 mCi/Ib body weight) was injected. Brain SPECT was performed 30 minutes later using a tripple head gamma camera equipped with LEHR collimators. A total of 128 projections with an acquisition time of 30 second per projection was obtained and reconstructed by filtered back projections without attenuation correction. The difference between the baseline and persantine studies was analysed by visual and semiquantitavely. During the infusion of persantine, heart rate, blood pressure and side effects such as headache, chest discomfort were similar to the persantine myocardial SPECT studies. Five of eight patients showed a significant decrease in rCBF on persantine brain SPECT in comparison to the baseline study. The remaining three revealed no significant change in rCBF. Our study suggests that the dipyridamole stress brain SPECT is feasible and useful in assessing cerebral blood flow reserve. However we need to evaluate more number of patients in the future

Binary and ternary cocrystals of sulfa drug acetazolamide with pyridine carboxamides and cyclic amides.

Science.gov (United States)

Bolla, Geetha; Nangia, Ashwini

2016-03-01

A novel design strategy for cocrystals of a sulfonamide drug with pyridine carboxamides and cyclic amides is developed based on synthon identification as well as size and shape match of coformers. Binary adducts of acetazolamide (ACZ) with lactams (valerolactam and caprolactam, VLM, CPR), cyclic amides (2-pyridone, labeled as 2HP and its derivatives MeHP, OMeHP) and pyridine amides (nicotinamide and picolinamide, NAM, PAM) were obtained by manual grinding, and their single crystals by solution crystallization. The heterosynthons in the binary cocrystals of ACZ with these coformers suggested a ternary combination for ACZ with pyridone and nicotinamide. Novel supramolecular synthons of ACZ with lactams and pyridine carboxamides are reported together with binary and ternary cocrystals for a sulfonamide drug. This crystal engineering study resulted in the first ternary cocrystal of acetazolamide with amide coformers, ACZ-NAM-2HP (1:1:1).

ACETAZOLAMIDE IN PEDIATRIC NEUROLOGY: HISTORY AND PERSPECTIVE OF CILNICAL USE

OpenAIRE

A.N. Boyko; E.I. Gusev; O.V. Bykova; L.M. Kuzenkova; O.I. Maslova

2006-01-01

Resume the up tob date pharmacological and clinical findings have revealed new opportunities for the use of known for a long time pharmaceutical agents in various fields of practical medicine. For more than 50 years acetozolamide, systemic carbonic anhydrase inhibitor, has been used in neurology to correct liquorodynamic disorders. High clinical efficacy and good tolerb ability in longbterm use has made acetazolamide an essential agent in pediatric neurology, along with this the true therapeu...

Acetazolamide on the ventral medulla of the cat increases phrenic output and delays the ventilatory response to CO sub 2

Energy Technology Data Exchange (ETDEWEB)

Coates, E.L.; Aihua Li; Nattie, E.E. (Dartmouth College, Hanover, NH (United States))

1991-03-11

Acetazolamide applied to the surface of the rostral ventrolateral medulla or microinjected beneath the medullary surface in chloralose-urethan-anesthetized, vagotomized, carotid denervated, paralyzed, servo-ventilated cats produced a long-lasting increase in phrenic minute ventilation. Extracellular pH measured beneath the rostral ventrolateral medulla exhibited a long-lasting decrease after surface acetazolamide but was not a good predictor, in each individual animal, of changes in phrenic activity. Medullary carbonic anhydrase inhibition reduced the slope and the half-time of the phrenic response to rapid step CO{sub 2} increases. Conversely, acetazolamide did not effect the phrenic response to steady state CO{sub 2} increases. These data indicate that localized inhibition of medullary carbonic anhydrase causes a centrally mediated increase in ventilation that the authors attribute to medullary tissue acidosis. In addition, these data indicate that medullary carbonic anhydrase may play a role in central CO{sub 2} chemotransduction.

Binary and ternary cocrystals of sulfa drug acetazolamide with pyridine carboxamides and cyclic amides

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Geetha Bolla

2016-03-01

Full Text Available A novel design strategy for cocrystals of a sulfonamide drug with pyridine carboxamides and cyclic amides is developed based on synthon identification as well as size and shape match of coformers. Binary adducts of acetazolamide (ACZ with lactams (valerolactam and caprolactam, VLM, CPR, cyclic amides (2-pyridone, labeled as 2HP and its derivatives MeHP, OMeHP and pyridine amides (nicotinamide and picolinamide, NAM, PAM were obtained by manual grinding, and their single crystals by solution crystallization. The heterosynthons in the binary cocrystals of ACZ with these coformers suggested a ternary combination for ACZ with pyridone and nicotinamide. Novel supramolecular synthons of ACZ with lactams and pyridine carboxamides are reported together with binary and ternary cocrystals for a sulfonamide drug. This crystal engineering study resulted in the first ternary cocrystal of acetazolamide with amide coformers, ACZ–NAM–2HP (1:1:1.

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis.

Science.gov (United States)

Kempuraj, Duraisamy; Selvakumar, Govindhasamy P; Thangavel, Ramasamy; Ahmed, Mohammad E; Zaheer, Smita; Raikwar, Sudhanshu P; Iyer, Shankar S; Bhagavan, Sachin M; Beladakere-Ramaswamy, Swathi; Zaheer, Asgar

2017-01-01

Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

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Duraisamy Kempuraj

2017-12-01

Full Text Available Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases

Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.

Science.gov (United States)

Faisy, Christophe; Meziani, Ferhat; Planquette, Benjamin; Clavel, Marc; Gacouin, Arnaud; Bornstain, Caroline; Schneider, Francis; Duguet, Alexandre; Gibot, Sébastien; Lerolle, Nicolas; Ricard, Jean-Damien; Sanchez, Olivier; Djibre, Michel; Ricome, Jean-Louis; Rabbat, Antoine; Heming, Nicholas; Urien, Saïk; Esvan, Maxime; Katsahian, Sandrine

2016-02-02

Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach. To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis. The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis. Acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality. Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (-16.0 hours; 95% CI, -36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (-0.9 hours; 95% CI, -4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation (-0.0 L/min; 95% CI, -0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (-0.3 mm Hg; 95% CI, -0.8 to 0.2 mm

13 reasons why the brain is susceptible to oxidative stress

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James Nathan Cobley

2018-05-01

Full Text Available The human brain consumes 20% of the total basal oxygen (O2 budget to support ATP intensive neuronal activity. Without sufficient O2 to support ATP demands, neuronal activity fails, such that, even transient ischemia is neurodegenerative. While the essentiality of O2 to brain function is clear, how oxidative stress causes neurodegeneration is ambiguous. Ambiguity exists because many of the reasons why the brain is susceptible to oxidative stress remain obscure. Many are erroneously understood as the deleterious result of adventitious O2 derived free radical and non-radical species generation. To understand how many reasons underpin oxidative stress, one must first re-cast free radical and non-radical species in a positive light because their deliberate generation enables the brain to achieve critical functions (e.g. synaptic plasticity through redox signalling (i.e. positive functionality. Using free radicals and non-radical derivatives to signal sensitises the brain to oxidative stress when redox signalling goes awry (i.e. negative functionality. To advance mechanistic understanding, we rationalise 13 reasons why the brain is susceptible to oxidative stress. Key reasons include inter alia unsaturated lipid enrichment, mitochondria, calcium, glutamate, modest antioxidant defence, redox active transition metals and neurotransmitter auto-oxidation. We review RNA oxidation as an underappreciated cause of oxidative stress. The complex interplay between each reason dictates neuronal susceptibility to oxidative stress in a dynamic context and neural identity dependent manner. Our discourse sets the stage for investigators to interrogate the biochemical basis of oxidative stress in the brain in health and disease.

{sup 18}FDG PET and acetazolamide-enhanced {sup 99m}Tc-HMPAO SPET in systemic lupus erythematosus

Energy Technology Data Exchange (ETDEWEB)

Gruenwald, F. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Schomburg, A. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Badali, A. [Dept. of Dermatology, Univ. of Bonn (Germany); Ruhlmann, J. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Pavics, L. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Biersack, H.J. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin

1995-09-01

In this report, we present the case of a 70-year-old female patient, suffering from SLE without symptoms of CNS involvement. In addition to a SPET study using technetium-99m hexamethylpropylene amine oxime ({sup 99m}Tc-HMPAO) and a PET scan with fluorine-18 deoxyglucose ({sup 18}FDG), a SPET study after acetazolamide injection was performed in order to assess the cerebral perfusion reserve. While the PET scan showed no major abnormalities, and the baseline SPET study revealed only minor changes, the acetazolamide-enhanced SPET study revealed a marked reduction of the cortical perfusion reserve, particularly in both frontal lobes. It is concluded that ``preclinical`` CNS involvement, mainly caused by pathological mechanisms involving the cerebral blood vessels, can be considered to exist in this patient with SLE. (orig.). With 2 figs.

Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family

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Galantuomo MS

2016-11-01

Full Text Available Maria Silvana Galantuomo,1,* Maurizio Fossarello,1 Alberto Cuccu,1 Roberta Farci,1 Markus N Preising,2 Birgit Lorenz,2 Pietro Emanuele Napoli1,* 1Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy; 2Department of Ophthalmology, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany *These authors contributed equally to this work Background: Juvenile X-linked retinoschisis (RS1, OMIM: 312700 is a hereditary vitreoretinal dystrophy characterized by bilateral foveal schisis and, in half of the patients, splitting through the nerve fiber layer in the peripheral retina. In the first decade of life, patients usually develop a decrease in visual acuity. Long-term visual outcomes can be poor due to the limited number of known successful treatments. Purpose: The purposes of this study were to present, for the first time, a p.Arg197Cys missense mutation in the RS1 gene (OMIM: 300839 in a four-generation Italian family with RS1 and to examine the clinical response to the treatment with acetazolamide tablets alone or in combination with dorzolamide eye drops as assessed by spectral-domain optical coherence tomography (SD-OCT. Methods: Eleven individuals, including two brothers with RS1 (patients 1 and 2, underwent a full medical history examination and a comprehensive ocular assessment that involved SD-OCT, fluorescein angiography, electroretinography and DNA analysis. Each RS1 patient received oral acetazolamide (375 mg daily during the first three months. Thereafter, patient 1 continued only with dorzolamide eyedrops three times a day for a period of three months, while patient 2 spontaneously stopped both medications. Results: Sequence analysis of the RS1 gene identified a hemizygous c.589C>T (p.Arg197Cys missense mutation in exon 6, which has not been previously reported in an Italian family. A different response to the medical therapy was observed in the four eyes of the two affected brothers hemizygous for

Comparative study of acetazolamide and spironolactone on body fluid compartments on induction to high altitude

Science.gov (United States)

Singh, M. V.; Jain, S. C.; Rawal, S. B.; Divekar, H. M.; Parshad, Rajinder; Tyagi, A. K.; Sinha, K. C.

1986-03-01

Studies were conducted on 29 male healthy subjects having no previous experience of living at high altitude. These subjects were divided into three groups, i.e., subjects treated with placebo, acetazolamide and spironolactone. These subjects were first studied in Delhi. The drug schedule was started 24 hour prior to the airlift of these subjects to an altitude of 3,500 m and was continued for 48 hour after arrival at high altitude. Total body water, extra cellular water, plasma volume, blood electrolytes, pH, pO2, pCO2 and blood viscosity were determined on 3rd and 12th day of their stay at high altitude. Total body water, extra cellular water intracellular water and plasma volume decreased on high altitude exposure. There was a further slight decrease in these compartments with acetazolamide and spironolactone. It was also observed that spironolactone drives out more water from the extracellular compartment. Loss of plasma water was also confirmed by increased plasma osmolality. Increase in arterial blood pH was noticed on hypoxic exposure but the increase was found less in acetazolamide and spironolactone cases. This decrease in pH is expected to result in better oxygen delivery to the tissues at the low oxygen tension. It was also confirmed because blood pO2 increased in both the groups. No significant change in plasma electrolytes was observed in subjects of various groups. Blood viscosity slightly increased on exposure to high altitude. The degree of rise was found less in the group treated with spironolactone. This study suggests that both the drugs are likely to be beneficial in ameliorating/prevention of AMS syndrome.

Evaluation of the cerebral vasodilatory capacity by the acetazolamide test before EC-IC bypass surgery in patients with occlusion of the internal carotid artery

DEFF Research Database (Denmark)

Vorstrup, S; Brun, B; Lassen, N A

1986-01-01

Cerebral blood flow (CBF) was measured by xenon-133 inhalation tomography in 18 patients with cerebrovascular disease before and 4 months after extracranial-intracranial bypass surgery. Only patients who showed a reduced CBF in areas that were intact on the CT scan and relevant to the clinical...... the patients with a compromised collateral circulation and hence reduced CBF due to reduced perfusion pressure, a cerebral vasodilatory stress test was performed using acetazolamide (Diamox). In normal subjects, Diamox has been shown to increase tomographic CBF without change of the flow distribution...... pathways. However, an increase in the regional vasodilatory capacity was observed postoperatively in the majority of patients....

Predicting parenting stress in caregivers of children with brain tumours.

Science.gov (United States)

Bennett, Emily; English, Martin William; Rennoldson, Michael; Starza-Smith, Arleta

2013-03-01

The purpose of the study was to identify factors that contribute to parenting stress in caregivers of children diagnosed with brain tumours. The study was cross-sectional and recruited 37 participants from a clinical database at a specialist children's hospital. Parents were sent questionnaires, which were used to measure factors related to stress in caregivers of children diagnosed with a brain tumour. Stress levels were measured using the Parenting Stress Index-Short Form (PSI/SF). Correlation analysis and multiple linear regression were used to examine the associations between parenting stress and coping styles, locus of control, parent-perceived child disability and time since diagnosis. Results revealed that 51% of parents were experiencing clinically significant levels of stress. The mean stress level of parents in the study was significantly higher than the PSI/SF norms (t = 4.7, p parenting stress. Other styles of coping, child behaviour problems and the amount of time since diagnosis were not found to be predictive of levels of parenting stress. There was a high prevalence of parenting stress in caregivers of children with a brain tumour. An external locus of control and coping by accepting responsibility increased the likelihood of elevated levels of stress. Results emphasised the importance of ongoing support for parents of children with brain tumours. Intervention might helpfully be centred on strategies to increase parents' internal locus of control. Copyright © 2012 John Wiley & Sons, Ltd.

The neuroendocrinological sequelae of stress during brain ...

African Journals Online (AJOL)

Severe stress during the sensitive periods of neurodevelopment, (which include the prenatal period, infancy, childhood and adolescence), has a long-lasting organizing effect on the brain and stress axes. Child abuse and neglect thus exert a cumulative harmful effect on neuroendocrinological development, which persists ...

Pharmacological modulation of the BOLD response: a study of acetazolamide and glyceryl trinitrate in humans

DEFF Research Database (Denmark)

Asghar, Mohammed Sohail; Hansen, Adam E; Pedersen, Simon

2011-01-01

To examine the effect of acetazolamide, known to increase cerebral blood flow (CBF) and glyceryl trinitrate (GTN), known to increase cerebral blood volume (CBV) on the blood oxygenation level-dependent (BOLD) response in humans using 3 T magnetic resonance imaging (MRI), and to evaluate how...... pharmacological agents may modulate cerebral hemodynamic and thereby possibly the BOLD signal....

Restraint stress-induced morphological changes at the blood-brain barrier in adult rats

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Petra eSántha

2016-01-01

Full Text Available Stress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3 and 21 days were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occludin and glucose transporter-1 and astroglia (GFAP. Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, one-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5 and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes

13 reasons why the brain is susceptible to oxidative stress

OpenAIRE

James Nathan Cobley; Maria Luisa Fiorello; Damian Miles Bailey

2018-01-01

The human brain consumes 20% of the total basal oxygen (O2) budget to support ATP intensive neuronal activity. Without sufficient O2 to support ATP demands, neuronal activity fails, such that, even transient ischemia is neurodegenerative. While the essentiality of O2 to brain function is clear, how oxidative stress causes neurodegeneration is ambiguous. Ambiguity exists because many of the reasons why the brain is susceptible to oxidative stress remain obscure. Many are erroneously understood...

Comment on the case report “Possible association between acetazolamide administration during pregnancy and multiple congenital malformations”

Directory of Open Access Journals (Sweden)

Keskin-Arslan E

2016-11-01

Full Text Available Elif Keskin-Arslan,1,2 Yusuf Cem Kaplan1,2 1Department of Pharmacology, School of Medicine, Izmir Katip Celebi University, 2Terafar – Izmir Katip Celebi University Teratology Information, Training and Research Center, Izmir, Turkey We read with interest the case report in the April 2016 issue of Drug Design Development and Therapy by Al-Saleem and Al-Jobair.1 The authors have presented a boy with oligodontia, ectrodactyly, and syndactyly who was exposed to acetazolamide in utero. Although the discussion was well balanced with a mention to possible confounders such as family and obstetric history and lack of a genetic analysis, two important papers regarding prenatal exposure to acetazolamide were not cited by the authors. In this letter, we would like to mention these studies in order to expand the current context provided by Al-Saleem and Al-Jobair.1View the original paper by Al-Saleem and Al-Jobair

Critical brain circuits at the intersection between stress and learning.

Science.gov (United States)

Bangasser, Debra A; Shors, Tracey J

2010-07-01

The effects of stressful life experience on learning are pervasive and vary greatly both within and between individuals. It is therefore unlikely that any one mechanism will underlie these complicated processes. Nonetheless, without identifying the necessary and sufficient circuitry, no complete mechanism or set of mechanisms can be identified. In this review, we provide two anatomical frameworks through which stressful life experience can influence processes related to learning and memory. In the first, stressful experience releases stress hormones, primarily from the adrenals, which directly impact brain areas engaged in learning. In the second, stressful experience indirectly alters the circuits used in learning via intermediary brain regions. Importantly, these intermediary brain regions are not integral to the stress response or learning itself, but rather link the consequences of a stressful experience with circuits used to learn associations. As reviewed, the existing literature provides support for both frameworks, with somewhat more support for the first but sufficient evidence for the latter which involves intermediary structures. Once we determine the circumstances that engage each framework and identify which one is most predominant, we can begin to focus our efforts on describing the neuronal and hormonal mechanisms that operate within these circuits to influence cognitive processes after stressful life experience.

Biochemical and ultrastructural changes in rabbit sclera after treatment with 7-methylxanthine, theobromine, acetazolamide, or L-ornithine

Science.gov (United States)

Trier, K.; Olsen, E. B.; Kobayashi, T.; Ribel-Madsen, S. M.

1999-01-01

AIMS—To examine a possible effect of 7-methylxanthine, theobromine, acetazolamide, or L-ornithine on the ultrastructure and biochemical composition of rabbit sclera.
METHODS—Groups of pigmented rabbits, six in each group, were dosed during 10 weeks with one of the substances under investigation, and one untreated group was the control. Samples of anterior and posterior sclera were taken for determination of hydroxyproline, hydroxylysine, proline, proteoglycans, uronic acids and dermatan sulphate, chondroitin sulphate, and hyaluronic acid. Sections were examined with electron microscopy, and the diameter of the individual collagen fibrils was measured.
RESULTS—Treatment with theobromine produced a significant increase in the contents of hydroxylysine, hydroxyproline, and proline in both anterior and posterior sclera, while 7-methylxanthine increased the contents of hydroxyproline and proline selectively in posterior sclera. Acetazolamide, on the other hand, significantly decreased the contents of hydroxyproline and proline in samples from anterior sclera. Uronic acids in both anterior and posterior sclera were significantly reduced by treatment with 7-methylxanthine, and L-ornithine significantly reduced uronic acids in posterior sclera. An inverse correlation between contents of hydroxyproline and uronic acids was found. The mean diameter of collagen fibrils was significantly higher in the posterior sclera from rabbits treated with 7-methylxanthine or theobromine, and significantly lower in rabbits treated with acetazolamide or L-ornithine compared with controls. In the anterior sclera, fibril diameter was significantly reduced in all treatment groups compared with controls. A positive, significant correlation between fibril diameter and content of hydroxyproline and proline was found in posterior sclera.
CONCLUSION—7-Methylxanthine, a metabolite of caffeine, increases collagen concentration and the diameter of collagen fibrils in the posterior

Brain neurotransmitters and hippocampal proteome in pigs under stress and environmental enrichment

Directory of Open Access Journals (Sweden)

Laura Arroyo

2017-06-01

Full Text Available Stress and wellbeing are psychological conditions that are mediated by the central nervous system. In the brain, stress is mediated mainly by the hypothalamus, which will activate the hypothalamic-pituitary-adrenal (HPA axis, leading to the secretion of cortisol, the paradigmatic stress hormone. Other brain areas as the amygdala, the hippocampus or the prefrontal cortex (PFC are involved in emotions such as happiness, anxiety and fear. Communication between brain areas is achieved by chemical neurotransmitters (NTs, which are secreted by presynaptic neurons to reach postsynaptic neurons, where they will cause a variation in membrane polarization and other cell signaling actions, leading to physiological responses. Amongst these NTs, catecholamines (noradrenaline and dopamine and serotonin play an important role. On the other hand, the adverse effects of stress may be counteracted by housing the individuals under environmental enrichment conditions. This long-term situation should have an effect, not only on NTs, but also on the brain proteome. Under the hypothesis that different stress situations will lead to changes in NT composition that will be specific for crucial brain areas, we have tested the effects of transport stress, handling stress at the slaughterhouse, and the stress-susceptible genotype (Ryr1 on the amine NT concentration in amygdala, hippocampus, PFC and hypothalamus of pigs. The effects of living under environmentally enriched or control conditions on the NT concentration in several brain regions and on the hippocampus proteome has been also analyzed. In conclusion, genetic factors as well as management conditions related to housing, transport and slaughterhouse alter in different degree the catecholaminergic and the serotoninergic neurotransmission in the brain, and give clues about how different individual types are able to react to external challenges. Likewise, environmental enrichment leads to changes in the proteome

Brain structure across the lifespan: the influence of stress and mood

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Jose Miguel Soares

2014-11-01

Full Text Available Normal brain aging is an inevitable and heterogeneous process characterized by a selective pattern of structural changes. Such heterogeneity arises as a consequence of cumulative effects over the lifespan, including stress and mood effects, which drive different micro- and macro-structural alterations in the brain. Investigating these differences in healthy age-related changes is a major challenge for the comprehension of the cognitive status. Herein we addressed the impact of normal aging, stress, mood and their interplay in the brain gray and white matter structure. We showed the critical impact of age in the white matter volume and how stress and mood influence brain volumetry across the lifespan. Moreover, we found a more profound effect of the interaction of aging/stress/mood on structures located in the left hemisphere. These findings help to clarify some divergent results associated with the aging decline and to enlighten the association between abnormal volumetric alterations and several states that may lead to psychiatric disorders.

Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats.

Science.gov (United States)

Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Borji, Abasalt; Samini, Mohammad; Farkhondeh, Tahereh

2017-05-04

Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research focused the protective effect of carnosol against the brain injury induced by the restraint stress. The restraint stress induced by keeping animals in restrainers for 21 consecutive days. Thereafter, the rats were injected carnosol or vehicle for 21 consecutive days. At the end of experiment, all the rats were subjected to his open field test and forced swimming test. Afterwards, the rats were sacrificed for measuring their oxidative stress parameters. To measure the modifications in the biochemical aspects after the experiment, the activities of malondialdehyde (MDA), reduced glutathione (GSH), as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were evaluated in the whole brain. Our data showed that the animals received chronic stress had a raised immobility time versus the non-stressed animals (p < 0.01). Furthermore, chronic stress diminished the number of crossing in the animals that were subjected to the chronic stress versus the non-stressed rats (p < 0.01). Carnosol ameliorated this alteration versus the non-treated rats (p < 0.05). In the vehicle treated rats that submitted to the stress, the level of MDA levels was significantly increased (P < 0.001), and the levels of GSH and antioxidant enzymes were significantly decreased versus the non-stressed animals (P < 0.001). Carnosol treatment reduced the modifications in the stressed animals as compared with the control groups (P < 0.001). All of these carnosol effects were nearly similar to those observed with fluoxetine. The current research shows that the protective effects of carnosol may be accompanied with enhanced antioxidant defenses and decreased oxidative injury.

Glymphatic clearance controls state-dependent changes in brain lactate concentration

DEFF Research Database (Denmark)

Lundgaard, Iben; Lu, Minh Lon; Yang, Ezra

2017-01-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lacta......-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.......Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate...... concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished...

Parameters influencing SPET regional brain uptake of technetium-99m hexamethylpropylene amine oxime measured by calibrated point sources as an external standard

International Nuclear Information System (INIS)

Dierckx, R.A.; Dobbeleir, A.; Maes, M.; Pickut, B.A.; Vervaet, A.; Deyn, P.P. de

1994-01-01

Using calibrated point sources as an external standard to convert SPET brain counts into absolute values of regional brain uptake (rBU) of technetium-99m hexamethylpropylene amine oxime (HMPAO), the relative contribution of different parameters to interindividual variability of cerebellar rBU was examined in 33 healthy volunteers. Stepwise regression analysis identified body surface as the most important factor underlying interindividual variability, when compared with brain volume. In the normal volunteer population presented, age decrement of rBU corrected for body surface and brain volume equalled 60.5-0.20xage. Based on the data of eight normal volunteers, including four test-retest studies with heart rate (HR) differences greater than 5 units and four test-stress studies with doubling of heart rate after bicycle exercise, influence of heart rate may be expressed by the equation ΔrBU = 0.35 ΔHR. Clinically, estimation of the relative influence of different factors allows normalization and extension of the applicability of the rBU quantification method used from longitudinal studies to group comparisons. Interestingly, results of the Daily Stress Inventory Scale and a subjective rating scale suggest the absence of a significant influence of minor stress on rBU. When using one vial per patient, chromatography may be omitted in clinical routine practice and lipophilicity may be estimated as 90% of the injected dose, if administered within 10 min after preparation. Finally, sensitivity of the quantification method was tested in eight volunteers using acetazolamide brain activation and showed a mean increase in cerebellar rBU of 30.2%, varying between 14.1% and 75.9%. (orig./MG)

Impacts of stress and sex hormones on dopamine neurotransmission in the adolescent brain.

Science.gov (United States)

Sinclair, Duncan; Purves-Tyson, Tertia D; Allen, Katherine M; Weickert, Cynthia Shannon

2014-04-01

Adolescence is a developmental period of complex neurobiological change and heightened vulnerability to psychiatric illness. As a result, understanding factors such as sex and stress hormones which drive brain changes in adolescence, and how these factors may influence key neurotransmitter systems implicated in psychiatric illness, is paramount. In this review, we outline the impact of sex and stress hormones at adolescence on dopamine neurotransmission, a signaling pathway which is critical to healthy brain function and has been implicated in psychiatric illness. We review normative developmental changes in dopamine, sex hormone, and stress hormone signaling during adolescence and throughout postnatal life, then highlight the interaction of sex and stress hormones and review their impacts on dopamine neurotransmission in the adolescent brain. Adolescence is a time of increased responsiveness to sex and stress hormones, during which the maturing dopaminergic neural circuitry is profoundly influenced by these factors. Testosterone, estrogen, and glucocorticoids interact with each other and have distinct, brain region-specific impacts on dopamine neurotransmission in the adolescent brain, shaping brain maturation and cognitive function in adolescence and adulthood. Some effects of stress/sex hormones on cortical and subcortical dopamine parameters bear similarities with dopaminergic abnormalities seen in schizophrenia, suggesting a possible role for sex/stress hormones at adolescence in influencing risk for psychiatric illness via modulation of dopamine neurotransmission. Stress and sex hormones may prove useful targets in future strategies for modifying risk for psychiatric illness.

Binary and ternary cocrystals of sulfa drug acetazolamide with pyridine carboxamides and cyclic amides

OpenAIRE

Bolla, Geetha; Nangia, Ashwini

2016-01-01

A novel design strategy for cocrystals of a sulfonamide drug with pyridine carboxamides and cyclic amides is developed based on synthon identification as well as size and shape match of coformers. Binary adducts of acetazolamide (ACZ) with lactams (valerolactam and caprolactam, VLM, CPR), cyclic amides (2-pyridone, labeled as 2HP and its derivatives MeHP, OMeHP) and pyridine amides (nicotinamide and picolinamide, NAM, PAM) were obtained by manual grinding, and their single crystals by solutio...

Glymphatic clearance controls state-dependent changes in brain lactate concentration.

Science.gov (United States)

Lundgaard, Iben; Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2017-06-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.

Cognitive benefit and cost of acute stress is differentially modulated by individual brain state.

Science.gov (United States)

Kohn, Nils; Hermans, Erno J; Fernández, Guillén

2017-07-01

Acute stress is associated with beneficial as well as detrimental effects on cognition in different individuals. However, it is not yet known how stress can have such opposing effects. Stroop-like tasks typically show this dissociation: stress diminishes speed, but improves accuracy. We investigated accuracy and speed during a stroop-like task of 120 healthy male subjects after an experimental stress induction or control condition in a randomized, counter-balanced cross-over design; we assessed brain-behavior associations and determined the influence of individual brain connectivity patterns on these associations, which may moderate the effect and help identify stress resilience factors. In the mean, stress was associated to increase in accuracy, but decrease in speed. Accuracy was associated to brain activation in a distributed set of brain regions overlapping with the executive control network (ECN) and speed to temporo-parietal activation. In line with a stress-related large-scale network reconfiguration, individuals showing an upregulation of the salience and down-regulation of the executive-control network under stress displayed increased speed, but decreased performance. In contrast, individuals who upregulate their ECN under stress show improved performance. Our results indicate that the individual large-scale brain network balance under acute stress moderates cognitive consequences of threat. © The Author (2017). Published by Oxford University Press.

Acetazolamide stimulation test in patients with unilateral internal carotid artery stenosis using Tc-99m HMPAO SPECT and transcranial doppler sonography

Energy Technology Data Exchange (ETDEWEB)

Hyun, I. Y.; Na, J. H. [Inha University Hospital, Incheon (Korea, Republic of)

2007-07-01

We compared perfusion reserve by acetazolamide (ACZ) challenged brain perfusion SPECT and cerebral vasoreactivity (CVR) by transcranial Doppler sonography (TCD) in patients with unilateral internal carotid artery stenosis. This study was conducted prospectively in 37 consecutive patients with angiographically proven unilateral internal carotid artery stenosis (stenosis> 50%). We estimated % CVR (100? {l_brace}post-ACZ mean velocity (cm/sec) - Pre-ACZ mean velocity (cm/sec){r_brace} / pre-ACZ mean velocity) by TCD. The % CVR was compared with perfusion reserve of SPECT. The % CVR of MCA and ICA was significantly decreased in the ipsilateral side to the carotid stenosis (p<0.05). The CVR impairment was more severe when cerebral infarct is already developed (p<0.01). There was a significant correlation between the degree of carotid stenosis and the CVR (p<0.01). In the area of impaired perfusion reserve on the SPECT, the estimated CVR by TCD was significantly lower (p<0.05), even to the negative value, implying that there is actually steal phenomenon in that area. ACZ challenge can actually decrease cerebral blood flow in the area of impaired perfusion reserve on brain SPECT. So we should be very cautiously performing in ACZ challenge especially when there is a severe carotid stenosis because there is a possibility of developing hemodynamic stroke.

Brain-derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress.

Science.gov (United States)

Dretsch, Michael N; Williams, Kathy; Emmerich, Tanja; Crynen, Gogce; Ait-Ghezala, Ghania; Chaytow, Helena; Mathura, Venkat; Crawford, Fiona C; Iverson, Grant L

2016-01-01

In addition to experiencing traumatic events while deployed in a combat environment, there are other factors that contribute to the development of posttraumatic stress disorder (PTSD) in military service members. This study explored the contribution of genetics, childhood environment, prior trauma, psychological, cognitive, and deployment factors to the development of traumatic stress following deployment. Both pre- and postdeployment data on 231 of 458 soldiers were analyzed. Postdeployment assessments occurred within 30 days from returning stateside and included a battery of psychological health, medical history, and demographic questionnaires; neurocognitive tests; and blood serum for the D2 dopamine receptor (DRD2), apolipoprotein E (APOE), and brain-derived neurotropic factor (BDNF) genes. Soldiers who screened positive for traumatic stress at postdeployment had significantly higher scores in depression (d = 1.91), anxiety (d = 1.61), poor sleep quality (d = 0.92), postconcussion symptoms (d = 2.21), alcohol use (d = 0.63), traumatic life events (d = 0.42), and combat exposure (d = 0.91). BDNF Val66 Met genotype was significantly associated with risk for sustaining a mild traumatic brain injury (mTBI) and screening positive for traumatic stress. Predeployment traumatic stress, greater combat exposure and sustaining an mTBI while deployed, and the BDNF Met/Met genotype accounted for 22% of the variance of postdeployment PTSD scores (R (2)  = 0.22, P PTSD scores. These findings suggest predeployment traumatic stress, genetic, and environmental factors have unique contributions to the development of combat-related traumatic stress in military service members.

Diamox-enhanced brain SPECT in cerebrovascular diseases

International Nuclear Information System (INIS)

Choi, Yun Young

2007-01-01

Acute event in cerebrovascular disease is the second most common cause of death in Korea following cancer, and it can also cause serious neurologic deficits. Understanding of perfusion status is important for clinical applications in management of patients with cerebrovascular diseases, and then the attacks of ischemic neurologic symptoms and the risk of acute events can be reduced. Therefore, the normal vascular anatomy of brain, various clinical applications of acetazolamide-enhanced brain perfusion SPECT, including meaning and role of assessment of vascular reserve in carotid stenosis before procedure, in pediatric Moyamoya disease before and after operation, in prediction of development of hyperperfusion syndrome before procedure, and in prediction of vasospasm and of prognosis in subarachnoid hemorrhage were reviewed in this paper

Monocyte Trafficking to the Brain with Stress and Inflammation: A Novel Axis of Immune-to-Brain Communication that Influences Mood and Behavior

Directory of Open Access Journals (Sweden)

Eric S Wohleb

2015-01-01

Full Text Available Psychological stressors cause physiological, immunological, and behavioral alterations in humans and rodents that can be maladaptive and negatively affect quality of life. Several lines of evidence indicate that psychological stress disrupts key functional interactions between the immune system and brain that ultimately affects mood and behavior. For example, activation of microglia, the resident innate immune cells of the brain, has been implicated as a key regulator of mood and behavior in the context of prolonged exposure to psychological stress. Emerging evidence implicates a novel neuroimmune circuit involving microglia activation and sympathetic outflow to the peripheral immune system that further reinforces stress-related behaviors by facilitating the recruitment of inflammatory monocytes to the brain. Evidence from various rodent models, including repeated social defeat (RSD, revealed that trafficking of monocytes to the brain promoted the establishment of anxiety-like behaviors following prolonged stress exposure. In addition, new evidence implicates monocyte trafficking from the spleen to the brain as key regulator of recurring anxiety following exposure to prolonged stress. The purpose of this review is to discuss mechanisms that cause stress-induced monocyte re-distribution in the brain and how dynamic interactions between microglia, endothelial cells, and brain macrophages lead to maladaptive behavioral responses.

Evaluation of cerebral vasoreactivity by SPECT and transcranial doppler sonography using the acetazolamide test

Energy Technology Data Exchange (ETDEWEB)

Pavics, L. [Dept. of Nuclear Medicine, Albert Szent-Gyoergyi Medical Univ., Szeged (Hungary); Gruenwald, F. [Bonn Univ. (Germany). Abt. fuer Nuklearmedizin; Barzo, P. [Dept. of Neurosurgery, Albert Szent-Gyoergyi Medical Univ., Szeged (Hungary); Ambrus, E. [Dept. of Nuclear Medicine, Albert Szent-Gyoergyi Medical Univ., Szeged (Hungary); Menzel, C. [Bonn Univ. (Germany). Abt. fuer Nuklearmedizin; Schomburg, A. [Bonn Univ. (Germany). Abt. fuer Nuklearmedizin; Borda, L. [Dept. of Neurosurgery, Albert Szent-Gyoergyi Medical Univ., Szeged (Hungary); Mate, E. [Laszlo Kalmar Kibernetic Lab., Attila Jozsef Univ., Szeged (Hungary); Bodosi, M. [Dept. of Neurosurgery, Albert Szent-Gyoergyi Medical Univ., Szeged (Hungary); Csernay, L. [Dept. of Nuclear Medicine, Albert Szent-Gyoergyi Medical Univ., Szeged (Hungary); Biersack, H.J. [Bonn Univ. (Germany). Abt. fuer Nuklearmedizin

1994-12-01

rCBF SPECT with {sup 99m}Tc-HMPAO was performed prospectively in 29 patients (3 controls and 26 stroke patients) as well as TCD studies in 20 patients (3 controls and 17 stroke patients) before and after 1 g i.v. acetazolamide. The sensitivity of rCBF SPECT increased from 62% to 77% after acetazolamide provocation in stroke patients. In patients with a reversible neurological deficit, the sensitivity under resting conditions was 50% which increased to 71%, while in cases with a permanent deficit it increased from 75% to 83%. In the evaluation of the cerebrovascular reserve capacity the results of rCBF SPECT and TCD coincided in 91% of the hemispheres. The correlation was statistically significant. (orig.) [Deutsch] Bei 29 Patienten (3 Kontrollpersonen, 26 Patienten mit zerebrovaskulaerer Erkrankung) wurde prospektiv die Hirn-SPECT mit {sup 99m}TC-HMPAO und bei 20 Patienten (3 Kontrollpersonen, 17 Patienten mit ZVK) die transkranielle Dopplersonographie (TCD) vor und nach i.v. Gabe von Azetazolamid durchgefuehrt. Die Sensitivitaet der Hirn-SPECT erhoehte sich mit Azetazolamid von 62% auf 77%. Bei Patienten mit reversiblem neurologischem Defizit wurde eine Verbesserung von 50% auf 71%, bei Patienten mit persistierendem Defizit von 75% auf 83% beobachtet. Die Ergebnisse der Hirn-SPECT und der TCD stimmten in der Beurteilung der zerebrovaskulaeren Reservekapazitaet in 91% der Hemisphaeren ueberein. Die Korrelation zwischen den beiden Methoden war statistisch signifikant. (orig.)

Autonomic and Brain Morphological Predictors of Stress Resilience

Directory of Open Access Journals (Sweden)

Luca Carnevali

2018-04-01

Full Text Available Stressful life events are an important cause of psychopathology. Humans exposed to aversive or stressful experiences show considerable inter-individual heterogeneity in their responses. However, the majority does not develop stress-related psychiatric disorders. The dynamic processes encompassing positive and functional adaptation in the face of significant adversity have been broadly defined as resilience. Traditionally, the assessment of resilience has been confined to self-report measures, both within the general community and putative high-risk populations. Although this approach has value, it is highly susceptible to subjective bias and may not capture the dynamic nature of resilience, as underlying construct. Recognizing the obvious benefits of more objective measures of resilience, research in the field has just started investigating the predictive value of several potential biological markers. This review provides an overview of theoretical views and empirical evidence suggesting that individual differences in heart rate variability (HRV, a surrogate index of resting cardiac vagal outflow, may underlie different levels of resilience toward the development of stress-related psychiatric disorders. Following this line of thought, recent studies describing associations between regional brain morphometric characteristics and resting state vagally-mediated HRV are summarized. Existing studies suggest that the structural morphology of the anterior cingulated cortex (ACC, particularly its cortical thickness, is implicated in the expression of individual differences in HRV. These findings are discussed in light of emerging structural neuroimaging research, linking morphological characteristics of the ACC to psychological traits ascribed to a high-resilient profile and abnormal structural integrity of the ACC to the psychophysiological expression of stress-related mental health consequences. We conclude that a multidisciplinary approach

The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity.

Science.gov (United States)

Lupien, Sonia J; Juster, Robert-Paul; Raymond, Catherine; Marin, Marie-France

2018-04-01

For the last five decades, science has managed to delineate the mechanisms by which stress hormones can impact on the human brain. Receptors for glucocorticoids are found in the hippocampus, amygdala and frontal cortex, three brain regions involved in memory processing and emotional regulation. Studies have shown that chronic exposure to stress is associated with reduced volume of the hippocampus and that chronic stress can modulate volumes of both the amygdala and frontal cortex, suggesting neurotoxic effects of stress hormones on the brain. Yet, other studies report that exposure to early adversity and/or familial/social stressors can increase vulnerability to stress in adulthood. Models have been recently developed to describe the roles that neurotoxic and vulnerability effects can have on the developing brain. These models suggest that developing early stress interventions could potentially counteract the effects of chronic stress on the brain and results going along with this hypothesis are summarized. Copyright © 2018 Elsevier Inc. All rights reserved.

Brain imaging for oxidative stress and mitochondrial dysfunction in neurodegenerative diseases

International Nuclear Information System (INIS)

Okazawa, H.; Tsujikawa, T.; Kiyono, Y.; Ikawa, M.; Yoneda, M.

2014-01-01

Oxidative stress, one of the most probable molecular mechanisms for neuronal impairment, is reported to occur in the affected brain regions of various neurodegenerative diseases. Recently, many studies showed evidence of a link between oxidative stress or mitochondrial damage and neuronal degeneration. Basic in vitro experiments and postmortem studies demonstrated that biomarkers for oxidative damage can be observed in the pathogenic regions of the brain and the affected neurons. Model animal studies also showed oxidative damage associated with neuronal degeneration. The molecular imaging method with positron emission tomography (PET) is expected to delineate oxidatively stressed microenvironments to elucidate pathophysiological changes of the in vivo brain; however, only a few studies have successfully demonstrated enhanced stress in patients. Radioisotope copper labeled diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) may be the most promising candidate for this oxidative stress imaging. The tracer is usually known as a hypoxic tissue imaging PET probe, but the accumulation mechanism is based on the electron rich environment induced by mitochondrial impairment and/or microsomal over-reduction, and thus it is considered to represent the oxidative stress state correlated with the degree of disease severity. In this review, Cu-ATSM PET is introduced in detail from the basics to practical methods in clinical studies, as well as recent clinical studies on cerebrovascular diseases and neurodegenerative diseases. Several other PET probes are also introduced from the point of view of neuronal oxidative stress imaging. These molecular imaging methods should be promising tools to reveal oxidative injuries in various brain diseases

Perfusion MRI before and after acetazolamide administration for assessment of cerebrovascular reserve capacity in patients with symptomatic internal carotid artery (ICA) occlusion: comparison with {sup 99m}Tc-ECD SPECT

Energy Technology Data Exchange (ETDEWEB)

Ma, J.; Holtmannspoetter, M.; Brueckmann, H. [University of Munich, Department of Neuroradiology, Klinikum Grosshadern, Munich (Germany); Mehrkens, J.H.; Schmid-Elsaesser, R. [University of Munich, Department of Neurosurgery, Klinikum Grosshadern, Munich (Germany); Linke, R. [University of Munich, Department of Nuclear Medicine, Klinikum Grosshadern, Munich (Germany); Steiger, H.J. [Heinrich-Heine University, Department of Neurosurgery, Duesseldorf (Germany); Bruening, R. [University of Munich, Department of Neuroradiology, Klinikum Grosshadern, Munich (Germany); Asklepios Klinik Barmbek, Department of Radiology, Hamburg (Germany)

2007-04-15

Impaired cerebral vascular reserve (CVR) in patients with symptomatic internal carotid artery (ICA) occlusion is regarded as a possible indication for performing extra-/intracranial (EC/IC) bypass surgery. As perfusion MR imaging (MRI) can demonstrate cerebral haemodynamics at capillary level, our hypothesis was that perfusion MRI could be used in these patients for the evaluation of CVR following acetazolamide challenge in a similar way to single photon emission CT (SPECT) and might provide additional information. Enrolled in the study were 12 patients (mean age 61.3 years; 11 male, 1 female) with symptomatic unilateral ICA occlusion proven by angiography. Both perfusion MRI and 99m-technetium-ethyl-cysteinate dimer ({sup 99m}Tc-ECD) SPECT were performed before and after injection of acetazolamide (Diamox,1000 mg i.v.). CVR parameters including regional cerebral blood flow (rCBF) and volume (rCBV), and mean transit times (MTT) were measured by perfusion MRI. The patients with impaired CVR proven by SPECT (n = 9) had a negative mean rCBF increment (-46.52%), negative rCBV increment (-13.5%) and delayed MTT (mean +2.98 s), respectively, on the occluded side (Student's t-test all P < 0.05). The patients with sufficient CVR (n = 3) had a mean rCBF increment of 1.2%, a decrement of rCBV of 10.46%, and a mean MTT shortening of 0.27 s following the acetazolamide injection. Perfusion MRI before and after acetazolamide administration compares favourably with {sup 99m}Tc-ECD SPECT for the detection of impaired CVR. The impact that perfusion MRI studies (before and after acetazolamide administration) might have on the treatment decision in patients with ICA occlusion has yet to be determined by a prospective study. (orig.)

Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury

Science.gov (United States)

Sturdivant, Nasya M.; Smith, Sean G.; Ali, Syed F.; Wolchok, Jeffrey C.; Balachandran, Kartik

2016-09-01

Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality.

Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response.

Science.gov (United States)

Stengel, Andreas; Taché, Yvette F

2017-01-01

Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates-in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis-other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake) and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

OpenAIRE

Andreas Stengel; Yvette F. Taché; Yvette F. Taché

2017-01-01

Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a br...

Oxidative stress and superoxide dismutase activity in brain of rats ...

African Journals Online (AJOL)

JTEkanem

effect of superoxide dismutase (SOD) activity in brain homogenates of Wistar rats. Oxidative stress measured as ..... on the brain and nervous system of humans as handlers and ... environment may be at higher health risk in that their internal ...

Social support, stress and the aging brain.

Science.gov (United States)

Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

2016-07-01

Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Cognitive benefit and cost of acute stress is differentially modulated by individual brain state

Science.gov (United States)

Hermans, Erno J.; Fernández, Guillén

2017-01-01

Abstract Acute stress is associated with beneficial as well as detrimental effects on cognition in different individuals. However, it is not yet known how stress can have such opposing effects. Stroop-like tasks typically show this dissociation: stress diminishes speed, but improves accuracy. We investigated accuracy and speed during a stroop-like task of 120 healthy male subjects after an experimental stress induction or control condition in a randomized, counter-balanced cross-over design; we assessed brain–behavior associations and determined the influence of individual brain connectivity patterns on these associations, which may moderate the effect and help identify stress resilience factors. In the mean, stress was associated to increase in accuracy, but decrease in speed. Accuracy was associated to brain activation in a distributed set of brain regions overlapping with the executive control network (ECN) and speed to temporo-parietal activation. In line with a stress-related large-scale network reconfiguration, individuals showing an upregulation of the salience and down-regulation of the executive-control network under stress displayed increased speed, but decreased performance. In contrast, individuals who upregulate their ECN under stress show improved performance. Our results indicate that the individual large-scale brain network balance under acute stress moderates cognitive consequences of threat. PMID:28402480

Does preoperative measurement of cerebral blood flow with acetazolamide challenge in addition to preoperative measurement of cerebral blood flow at the resting state increase the predictive accuracy of development of cerebral hyperperfusion after carotid endarterectomy? Results from 500 cases with brain perfusion single-photon emission computed tomography study.

Science.gov (United States)

Oshida, Sotaro; Ogasawara, Kuniaki; Saura, Hiroaki; Yoshida, Koji; Fujiwara, Shunro; Kojima, Daigo; Kobayashi, Masakazu; Yoshida, Kenji; Kubo, Yoshitaka; Ogawa, Akira

2015-01-01

The purpose of the present study was to determine whether preoperative measurement of cerebral blood flow (CBF) with acetazolamide in addition to preoperative measurement of CBF at the resting state increases the predictive accuracy of development of cerebral hyperperfusion after carotid endarterectomy (CEA). CBF at the resting state and cerebrovascular reactivity (CVR) to acetazolamide were quantitatively assessed using N-isopropyl-p-[(123)I]-iodoamphetamine (IMP)-autoradiography method with single-photon emission computed tomography (SPECT) before CEA in 500 patients with ipsilateral internal carotid artery stenosis (≥ 70%). CBF measurement using (123)I-IMP SPECT was also performed immediately and 3 days after CEA. A region of interest (ROI) was automatically placed in the middle cerebral artery territory in the affected cerebral hemisphere using a three-dimensional stereotactic ROI template. Preoperative decreases in CBF at the resting state [95% confidence intervals (CIs), 0.855 to 0.967; P = 0.0023] and preoperative decreases in CVR to acetazolamide (95% CIs, 0.844 to 0.912; P state (difference between areas, 0.173; P state (P state increases the predictive accuracy of the development of post-CEA hyperperfusion.

Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

Directory of Open Access Journals (Sweden)

Andreas Stengel

2017-04-01

Full Text Available Corticotropin-releasing factor (CRF is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

The stress-vulnerability model how does stress impact on mental illness at the level of the brain and what are the consequences?

Science.gov (United States)

Goh, Cindy; Agius, Mark

2010-06-01

The stress -vulnerability model (Zubin et al. 1977) is an extremely useful model for identifying and treating relapses of mental illness. We accept that human persons carry genetic and other predisposition to mental illness. However, the question arises as to how stress impacts on a person in order to cause mental illness to develop. Furthermore there arises the issue as to what other effects such stress has on the human body beyond the human brain. Our aim was to research and integrate the current literature in order to establish how stress impacts on the brain at the cellular level, and to establish whether there are other consequences for the human body brought about by the impact of stress on the human brain. Literature Search, using pubmed. We have identified much literature on how stress affects biological mechanisms within the brain, and how it relates to biological vulnerabilities carried by different individuals. We have identified communalities in how the interplay between stress and vulnerability occurs in different disease processes.

An experimental study on the mechanical properties of rat brain tissue using different stress-strain definitions.

Science.gov (United States)

Karimi, Alireza; Navidbakhsh, Mahdi

2014-07-01

There are different stress-strain definitions to measure the mechanical properties of the brain tissue. However, there is no agreement as to which stress-strain definition should be employed to measure the mechanical properties of the brain tissue at both the longitudinal and circumferential directions. It is worth knowing that an optimize stress-strain definition of the brain tissue at different loading directions may have implications for neuronavigation and surgery simulation through haptic devices. This study is aimed to conduct a comparative study on different results are given by the various definitions of stress-strain and to recommend a specific definition when testing brain tissues. Prepared cylindrical samples are excised from the parietal lobes of rats' brains and experimentally tested by applying load on both the longitudinal and circumferential directions. Three stress definitions (second Piola-Kichhoff stress, engineering stress, and true stress) and four strain definitions (Almansi-Hamel strain, Green-St. Venant strain, engineering strain, and true strain) are used to determine the elastic modulus, maximum stress and strain. The highest non-linear stress-strain relation is observed for the Almansi-Hamel strain definition and it may overestimate the elastic modulus at different stress definitions at both the longitudinal and circumferential directions. The Green-St. Venant strain definition fails to address the non-linear stress-strain relation using different definitions of stress and triggers an underestimation of the elastic modulus. The results suggest the application of the true stress-true strain definition for characterization of the brain tissues mechanics since it gives more accurate measurements of the tissue's response using the instantaneous values.

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.

Science.gov (United States)

Chen, Yuncai; Baram, Tallie Z

2016-01-01

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

Science.gov (United States)

Chen, Yuncai; Baram, Tallie Z

2016-01-01

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes ‘normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational

Effect of stress on structural brain asymmetry

Czech Academy of Sciences Publication Activity Database

Zach, P.; Valeš, Karel; Stuchlík, Aleš; Čermáková, P.; Mrzílková, J.; Koutella, A.; Kutová, M.

2016-01-01

Roč. 37, č. 4 (2016), s. 253-264 ISSN 0172-780X R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : laterality * asymmetry * brain * evolution * stress * neuropsychiatric disorders Subject RIV: FH - Neurology Impact factor: 0.918, year: 2016

Stress and the Adolescent Brain: Plasticity of Reproductive Behaviors in Female

Directory of Open Access Journals (Sweden)

Farideh Zafari Zangeneh

2009-03-01

Full Text Available Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging.  Much research attention has focused on the programming effects of the hypothalamus pituitary axis (HPA in early life and on understanding HPA function in response to stressors in adulthood. In comparison, there has been relatively little research on adolescence, a time of significant brain development particularly in the frontal lobe and a time which is of great importance for mental and physical health. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. During adolescence, HPA function is characterized by a prolonged activation in response to stressors compared to adulthood, which may render ongoing development of the brain vulnerable. Stress reactivity is markedly influenced by both the pubertal maturation and the experience of the individual. The frequency of the pulses is increased in chronic stress, since the neuroendocrine system is such a good candidate for mediators of many diseases linked to chronic stress. The activity of HPA axis  in life time of female,  sex maturity, pregnancy or lactation is a plasticity of the diurnal rhythm of pulse amplitude; chronic stress can change this program for   formation disorder in behavioral and physiological responses.

Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model

Directory of Open Access Journals (Sweden)

Gulay Hacioglu

2016-04-01

Full Text Available Objective(s: Exposing to stress may be associated with increased production of reactive oxygen species (ROS. Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. Materials and Methods: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT and superoxide dismutase (SOD enzymes, and the amount of malondialdehyde (MDA were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. Results: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. Conclusion: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain.

Acute iron overload and oxidative stress in brain

International Nuclear Information System (INIS)

Piloni, Natacha E.; Fermandez, Virginia; Videla, Luis A.; Puntarulo, Susana

2013-01-01

An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6 h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A·)/ascorbate (AH − ) ratio, taken as oxidative stress index, was assessed. The A·/AH − ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR·) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8 h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21 h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6 h after Fe administration. CAT activity was significantly increased after 8 h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR· generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR· generation rate after 6

Oxidative stress and superoxide dismutase activity in brain of rats ...

African Journals Online (AJOL)

The present study was envisaged to investigate the possible role of oxidative stress in permethrin neurotoxicity and to evaluate the protective effect of superoxide dismutase (SOD) activity in brain homogenates of Wistar rats. Oxidative stress measured as thiobarbituric acid reacting substances (TBARS) was found to ...

Effects of cryoprotectants on the structure and thermostability of the human carbonic anhydrase II–acetazolamide complex

International Nuclear Information System (INIS)

Aggarwal, Mayank; Boone, Christopher D.; Kondeti, Bhargav; Tu, Chingkuang; Silverman, David N.; McKenna, Robert

2013-01-01

Here, a case study of the effects of cryoprotectants on the kinetics of carbonic anhydrase II (CA II) and its inhibition by the clinically used inhibitor acetazolamide (AZM) is presented. Protein X-ray crystallography has seen a progressive shift from data collection at cool/room temperature (277–298 K) to data collection at cryotemperature (100 K) because of its ease of crystal preparation and the lessening of the detrimental effects of radiation-induced crystal damage, with 20–25%(v/v) glycerol (GOL) being the preferred choice of cryoprotectant. Here, a case study of the effects of cryoprotectants on the kinetics of carbonic anhydrase II (CA II) and its inhibition by the clinically used inhibitor acetazolamide (AZM) is presented. Comparative studies of crystal structure, kinetics, inhibition and thermostability were performed on CA II and its complex with AZM in the presence of either GOL or sucrose. These results suggest that even though the cryoprotectant GOL was previously shown to be directly bound in the active site and to interact with AZM, it affects neither the thermostability of CA II nor the binding of AZM in the crystal structure or in solution. However, addition of GOL does affect the kinetics of CA II, presumably as it displaces the water proton-transfer network in the active site

Effects of cryoprotectants on the structure and thermostability of the human carbonic anhydrase II–acetazolamide complex

Energy Technology Data Exchange (ETDEWEB)

Aggarwal, Mayank; Boone, Christopher D.; Kondeti, Bhargav; Tu, Chingkuang; Silverman, David N.; McKenna, Robert, E-mail: rmckenna@ufl.edu [University of Florida, 1600 SW Archer Road, PO Box 100245, Gainesville, FL 32610 (United States)

2013-05-01

Here, a case study of the effects of cryoprotectants on the kinetics of carbonic anhydrase II (CA II) and its inhibition by the clinically used inhibitor acetazolamide (AZM) is presented. Protein X-ray crystallography has seen a progressive shift from data collection at cool/room temperature (277–298 K) to data collection at cryotemperature (100 K) because of its ease of crystal preparation and the lessening of the detrimental effects of radiation-induced crystal damage, with 20–25%(v/v) glycerol (GOL) being the preferred choice of cryoprotectant. Here, a case study of the effects of cryoprotectants on the kinetics of carbonic anhydrase II (CA II) and its inhibition by the clinically used inhibitor acetazolamide (AZM) is presented. Comparative studies of crystal structure, kinetics, inhibition and thermostability were performed on CA II and its complex with AZM in the presence of either GOL or sucrose. These results suggest that even though the cryoprotectant GOL was previously shown to be directly bound in the active site and to interact with AZM, it affects neither the thermostability of CA II nor the binding of AZM in the crystal structure or in solution. However, addition of GOL does affect the kinetics of CA II, presumably as it displaces the water proton-transfer network in the active site.

Dynamics of intrarenal pressures and glomerular filtration rate after acetazolamide

DEFF Research Database (Denmark)

Leyssac, P P; Karlsen, F M; Skøtt, O

1991-01-01

-EDTA and lithium. Proximal tubular pressure (Pprox) increased initially by 1.7 +/- 0.1 mmHg after ACZ, causing a decrease in the hydrostatic pressure difference across the glomerular membrane (delta P). EDC increased, and then RBF, glomerular capillary pressure (Pgc), Pprox, and star vessel pressures (Psv) dropped......The dynamics of intrarenal pressures, early distal tubular fluid conductivity (EDC), and renal flood flow (RBF) were studied in rats given acetazolamide (ACZ), an inhibitor of proximal reabsorption. Glomerular filtration rate (GFR) and end-proximal flow were estimated by clearances of 51Cr...... as a result of afferent vasoconstriction. Pprox decreased less than Pgc, resulting in a further decrease in delta P, which after 25-30 s reached a constant level 3-4 mmHg below control. After a transient increase the pressures declined to a new steady state, in which Pprox was equal to control, Pgc...

Selective neuronal vulnerability to oxidative stress in the brain

Directory of Open Access Journals (Sweden)

Xinkun Wang

2010-03-01

Full Text Available Oxidative stress (OS, caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS, plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer’s disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.

Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model.

Science.gov (United States)

Son, Seung-Wan; Lee, Jin-Seok; Kim, Hyeong-Geug; Kim, Dong-Woon; Ahn, Yo-Chan; Son, Chang-Gue

2016-01-01

Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress-induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations

Chronic stress-induced effects of corticosterone on brain: direct and indirect

NARCIS (Netherlands)

Dallman, M. F.; Akana, S. F.; Strack, A. M.; Scribner, K. S.; Pecoraro, N.; La Fleur, S. E.; Houshyar, H.; Gomez, F.

2004-01-01

Acutely, glucocorticoids act to inhibit stress-induced corticotrophin-releasing factor (CRF) and adrenocorticotrophic hormone (ACTH) secretion through their actions in brain and anterior pituitary (canonical feedback). With chronic stress, glucocorticoid feedback inhibition of ACTH secretion changes

Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain

Directory of Open Access Journals (Sweden)

Debora Coimbra-Costa

2017-08-01

Full Text Available Acute hypoxia increases the formation of reactive oxygen species (ROS in the brain. However, the effect of reoxygenation, unavoidable to achieve full recovery of the hypoxic organ, has not been clearly established. The aim of the present study was to evaluate the effects of exposition to acute severe respiratory hypoxia followed by reoxygenation on the evolution of oxidative stress and apoptosis in the brain. We investigated the effect of in vivo acute severe normobaric hypoxia (rats exposed to 7% O2 for 6 h and reoxygenation in normoxia (21% O2 for 24 h or 48 h on oxidative stress markers, the antioxidant system and apoptosis in the brain. After respiratory hypoxia we found increased levels of HIF-1α expression, lipid peroxidation, protein oxidation and nitric oxide in brain extracts. Antioxidant defence systems such as superoxide dismutase (SOD, reduced glutathione (GSH and glutathione peroxidase (GPx and the reduced/oxidized glutathione (GSH/GSSG ratio were significantly decreased in the brain. After 24 h of reoxygenation, oxidative stress parameters and the anti-oxidant system returned to control values. Regarding the apoptosis parameters, acute hypoxia increased cytochrome c, AIF and caspase 3 activity in the brain. The apoptotic effect is greatest after 24 h of reoxygenation. Immunohistochemistry suggests that CA3 and dentate gyrus in the hippocampus seem more susceptible to hypoxia than the cortex. Severe acute hypoxia increases oxidative damage, which in turn could activate apoptotic mechanisms. Our work is the first to demonstrate that after 24 h of reoxygenation oxidative stress is attenuated, while apoptosis is maintained mainly in the hippocampus, which may, in fact, be the cause of impaired brain function. Keywords: Antioxidants, Apoptosis, Normobaric hypoxia, Oxidative stress, Reoxygenation

Brain and Serum Androsterone is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

Directory of Open Access Journals (Sweden)

Richard J Servatius

2016-08-01

Full Text Available Exposure to lateral fluid percussion (LFP injury consistent with mild traumatic brain injury (mTBI persistently attenuates acoustic startle responses (ASRs in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM. ASRs were measured post injury days (PIDs 1, 3, 7, 14, 21 and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34, PID 35 (S35, on both days (2S, or the experimental context (CON. Levels of the neurosteroids pregnenolone (PREG, allopregnanolone (ALLO, and androsterone (ANDRO were determined for the prefrontal cortex, hippocampus and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30 and 60 min post-stressor for determination of corticosterone (CORT levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner.

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Bollinger, Justin L; Collins, Kaitlyn E; Patel, Rushi; Wellman, Cara L

2017-01-01

Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress

Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner

Science.gov (United States)

Bollinger, Justin L.; Collins, Kaitlyn E.; Patel, Rushi

2017-01-01

Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress

Repeated swim stress alters brain benzodiazepine receptors measured in vivo

International Nuclear Information System (INIS)

Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

1989-01-01

The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of [ 3 H]Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in [14C]iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress [an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures], although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results

Repeated swim stress alters brain benzodiazepine receptors measured in vivo

Energy Technology Data Exchange (ETDEWEB)

Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

1989-06-01

The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

Stress and the psyche-brain-immune network in psychiatric diseases based on psychoneuroendocrineimmunology: a concise review.

Science.gov (United States)

Bottaccioli, Anna Giulia; Bottaccioli, Francesco; Minelli, Andrea

2018-05-15

In the last decades, psychoneuroendocrineimmunology research has made relevant contributions to the fields of neuroscience, psychobiology, epigenetics, molecular biology, and clinical research by studying the effect of stress on human health and highlighting the close interrelations between psyche, brain, and bodily systems. It is now well recognized that chronic stress can alter the physiological cross-talk between brain and biological systems, leading to long-lasting maladaptive effects (allostatic overload) on the nervous, immune, endocrine, and metabolic systems, which compromises stress resiliency and health. Stressful conditions in early life have been associated with profound alterations in cortical and subcortical brain regions involved in emotion regulation and the salience network, showing relevant overlap with different psychiatric conditions. This paper provides a summary of the available literature concerning the notable effects of stress on the brain and immune system. We highlight the role of epigenetics as a mechanistic pathway mediating the influences of the social and physical environment on brain structure and connectivity, the immune system, and psycho-physical health in psychiatric diseases. We also summarize the evidence regarding the effects of stress management techniques (mainly psychotherapy and meditation practice) on clinical outcomes, brain neurocircuitry, and immune-inflammatory network in major psychiatric diseases. © 2018 New York Academy of Sciences.

Hemodynamic evaluation in patients with superficial temporal artery-middle cerebral artery anastomosis; Stable xenon CT-CBF study and acetazolamide

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Touho, Hajime; Karasawa, Jun; Shishido, Hisashi; Morisako, Toshitaka; Yamada, Keisuke; Shibamoto, Keiji [Osaka Neurological Inst., Toyonaka (Japan)

1990-12-01

Sixteen patients with minor completed stroke in the chronic stage underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. The acetazolamide-activated regional cerebral blood flow (rCBF) was measured 20 minutes after the injection using inhalation of stable xenon and computed tomographic scanning (Xe{sup s} CT-CBF study) pre- and postoperatively. Eleven patients (Group 1) showed immediate improvement in neurological state within a few days of the operation, while five (Group 2) showed no improvements. Preoperative rCBF in the ischemic areas without infarction was 30.8+-3.0 ml/100 gm/min in Group 1 and 53.0+-5.2 ml/100 gm/min in Group 2. Preoperative vasodilatory capacity with acetazolamide in Group 1 was 5.7+-8.6 and significantly increased to 19.8+-4.9 after surgery. In Group 2, pre- and postoperative vasodilatory capacity was 12.7+-3.1 and 14.9+-2.9, respectively, and there was no significant change. These results suggested that minor stroke patients with moderate decrease of affected side rCBF (less than 40 ml/100 gm/min) and with hemodynamic impairment may have the surgical indication for STA-MCA anastomosis. (author).

Chronic vitamin C deficiency does not accelerate oxidative stress in ageing brains of guinea pigs

DEFF Research Database (Denmark)

Tveden-Nyborg, Pernille; Andersen, Stine Hasselholt; Miyashita, Namiyo

2012-01-01

  Increased oxidative stress in the brain has consistently been implied in ageing and in several degenerative brain disorders. Acting as a pivotal antioxidant in the brain, vitamin C is preferentially retained during deficiency and may play an essential role in neuroprotection during ageing. Thus......, a lack of vitamin C could be associated with an increase in redox imbalance in the ageing brain. The present study compared oxidative stress of ageing to that of a long-term non-scorbutic vitamin C deficiency in guinea pigs. Adults (3-9 months old) were compared to old (36-42 months old) animals during...... a six-month dietary intervention by assessing vitamin C transport and redox homeostasis in the brain. In contrast to our hypothesis, chronic vitamin C deficiency did not affect the measured markers of oxidative stress in the brains of adult and aged animals. However, aged animals generally showed...

Treatment of developmental stress disorder: mind, body and brain - analysis and pharmacology coupled.

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McFadden, Joseph

2017-11-01

The schism between psychiatry, psychology and analysis, while long present, has widened even more in the past half-century with the advances in psychopharmacology. With the advances in electronic brain imaging, particularly in developmental and post-traumatic stress disorders, there has emerged both an understanding of brain changes resulting from severe, chronic stress and an ability to target brain chemistry in ways that can relieve clinical symptomatology. The use of alpha-1 adrenergic brain receptor antagonists decreases many of the manifestations of PTSD. Additionally, this paper discusses the ways in which dreaming, thinking and the analytic process are facilitated with this concomitant treatment and hypervigilence and hyper-arousal states are signficiantly decreased. © 2017, The Society of Analytical Psychology.

Association Between Traumatic Brain Injury and Risk of Posttraumatic Stress Disorder in Active-Duty Marines

Science.gov (United States)

2013-01-01

traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder ( PTSD ) has been difficult to determine because of the prevalence of...Qualification Test; CAPS, Clinician-Administered PTSD Scale; PTSD , posttraumatic stress disorder ; TBI, traumatic brain injury. a For the zeromodel, base...New onset and persistent symptoms of post - traumatic stress disorder self reported after deployment and combat exposures. BMJ.

Possible effects of rosuvastatin on noise-induced oxidative stress in rat brain

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Alevtina Ersoy

2014-01-01

Full Text Available The problem of noise has recently gained more attention as it has become an integral part of our daily lives. However, its influence has yet to be fully elucidated. Other than being an unpleasant stimulus, noise may cause health disorders through annoyance and stress, including oxidative stress. Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, may possess antioxidant properties. Based on rat models, our project investigates the effect of rosuvastatin on noise-induced oxidative stress in the brain tissue. Thirty-two male Wistar albino rats were used. The rats were divided into four groups: Noise exposure plus rosuvastatin usage, only noise exposure, only rosuvastatin usage, and control. After the data had been collected, oxidant and antioxidant parameters were analyzed in the cerebral cortex, brain stem, and cerebellum. Results indicated that superoxide dismutase values were significantly decreased in the cerebral cortex, while malondialdehyde values in the brainstem and cerebellum were significantly increased in the group with only noise exposure. Superoxide dismutase values in the brainstem were significantly increased, but nitric oxide values in the cerebellum and brainstem and malondialdehyde values in the cerebellum and cerebral cortex were significantly decreased in the group where only rosuvastatin was used. During noise exposure, the use of rosuvastatin caused significantly increased superoxide dismutase values in the cerebral cortex and brainstem, but significantly reduced malondialdehyde values in the brain stem. Consequently, our data show that brain tissue was affected by oxidative stress due to continued exposure to noise. This noise-induced stress decreases with rosuvastatin therapy.

Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

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Haider Raza

2015-02-01

Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

A comparative study of simple methods to quantify cerebral blood flow with acetazolamide challenge by using iodine-123-IMP SPECT with one-point arterial sampling

Energy Technology Data Exchange (ETDEWEB)

Ohkubo, Masaki [Niigata Univ. (Japan). School of Health Sciences; Odano, Ikuo

2000-04-01

The aim of this study was to compare the accuracy of simplified methods for quantifying rCBF with acetazolamide challenge by using {sup 123}I-N-isopropyl-p-iodoamphetamine (IMP) and SPECT with one-point arterial sampling. After acetazolamide administration we quantified rCBF in 12 subjects by the following three methods: (a) the modified microsphere method, (b) the IMP-autoradiographic (ARG) method based on a two-compartment one-parameter model, and (c) the simplified method based on a two-compartment two-parameter model (functional IMP method). The accuracy of these methods was validated by comparing rCBF values with those obtained by the standard method: the super-early microsphere method with continuous withdrawal of arterial blood. On analyzing rCBF in each flow range (0-0.25, 0.25-0.5, 0.5-0.75 and more than 0.75 ml/g/min), rCBF values obtained by both methods (a) and (c) showed significant correlations (p<0.01) with those obtained by the standard method in every range, but rCBF values obtained by method (b) did not significantly correlated in the high flow range (0.5-0.75 and more than 0.75 ml/g/min). Method (c) was found to be the most accurate, even though it needs two serial SPECT scans. When requiring one SPECT scan, method (a) was considered to be superior to method (b) because of its accuracy, especially in high flow regions loaded with acetazolamide. (author)

Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognitive Functions

Science.gov (United States)

2017-05-14

the impact of oxidative stress on brain function, but also enable development of reliable screening tools for cognitive performance of individuals in...of Brain Oxidative Stress and its Correlation with Cognitive Functions Date 04/20/2017 PI information: Dr. Pravat K. Mandal,Ph.D Professor...relationship between the brain oxidative status and stress at a cellular, physiological as well as a psychological level. These stressors, in turn, have

Neurotherapy of Traumatic Brain Injury/Post-Traumatic Stress Symptoms in Vietnam Veterans.

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Nelson, David V; Esty, Mary Lee

2015-10-01

Previous report suggested the beneficial effects of an adaptation of the Flexyx Neurotherapy System (FNS) for the amelioration of mixed traumatic brain injury/post-traumatic stress symptoms in veterans of the Afghanistan and Iraq wars. As a novel variant of electroencephalograph biofeedback, FNS falls within the bioenergy domain of complementary and alternative medicine. Rather than learning voluntary control over the production/inhibition of brain wave patterns, FNS involves offsetting stimulation of brain wave activity by means of an external energy source, specifically, the conduction of electromagnetic energy stimulation via the connecting electroencephalograph cables. Essentially, these procedures subliminally induce strategic distortion of ongoing brain wave activity to presumably facilitate resetting of more adaptive patterns of activity. Reported herein are two cases of Vietnam veterans with mixed traumatic brain injury/post-traumatic stress symptoms, each treated with FNS for 25 sessions. Comparisons of pre- and post-treatment questionnaire assessments revealed notable decreases for all symptoms, suggesting improvements across the broad domains of cognition, pain, sleep, fatigue, and mood/emotion, including post-traumatic stress symptoms, as well as for overall activity levels. Findings suggest FNS treatment may be of potential benefit for the partial amelioration of symptoms, even in some individuals for whom symptoms have been present for decades. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Effects of acetazolamide on the micro- and macro-vascular cerebral hemodynamics: A diffuse optical and transcranial doppler ultrasound study

OpenAIRE

Zirak P.; Delgado-Mederos R.; Marti-Fabregas J.; Durduran T.

2010-01-01

Acetazolamide (ACZ) was used to stimulate the cerebral vasculature on ten healthy volunteers to assess the cerebral vasomotor reactivity (CVR). We have combined near infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS) and transcranial Doppler (TCD) technologies to non-invasively assess CVR in real-time by measuring oxy- and deoxy-hemoglobin concentrations, using NIRS, local cerebral blood flow (CBF), using DCS, and blood flow velocity (CBFV) in the middle cerebral artery, usi...

Soft-food diet induces oxidative stress in the rat brain.

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Yoshino, Fumihiko; Yoshida, Ayaka; Hori, Norio; Ono, Yumie; Kimoto, Katsuhiko; Onozuka, Minoru; Lee, Masaichi Chang-il

2012-02-02

Decreased dopamine (DA) release in the hippocampus may be caused by dysfunctional mastication, although the mechanisms involved remain unclear. The present study examined the effects of soft- and hard-food diets on oxidative stress in the brain, and the relationship between these effects and hippocampal DA levels. The present study showed that DA release in the hippocampus was decreased in rats fed a soft-food diet. Electron spin resonance studies using the nitroxyl spin probe 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl directly demonstrated a high level of oxidative stress in the rat brain due to soft-food diet feeding. In addition, we confirmed that DA directly react with reactive oxygen species such as hydroxyl radical and superoxide. These observations suggest that soft-food diet feeding enhances oxidative stress, which leads to oxidation and a decrease in the release of DA in the hippocampus of rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Programming of the Social Brain by Stress During Childhood and Adolescence: From Rodents to Humans.

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Tzanoulinou, Stamatina; Sandi, Carmen

2017-01-01

The quality and quantity of social experience is fundamental to an individual's health and well-being. Early life stress is known to be an important factor in the programming of the social brain that exerts detrimental effects on social behaviors. The peri-adolescent period, comprising late childhood and adolescence, represents a critical developmental window with regard to the programming effects of stress on the social brain. Here, we discuss social behavior and the physiological and neurobiological consequences of stress during peri-adolescence in the context of rodent paradigms that model human adversity, including social neglect and isolation, social abuse, and exposure to fearful experiences. Furthermore, we discuss peri-adolescent stress as a potent component that influences the social behaviors of individuals in close contact with stressed individuals and that can also influence future generations. We also discuss the temporal dynamics programmed by stress on the social brain and debate whether social behavior alterations are adaptive or maladaptive. By revising the existing literature and defining open questions, we aim to expand the framework in which interactions among peri-adolescent stress, the social brain, and behavior can be better conceptualized.

Brain prolactin is involved in stress-induced REM sleep rebound.

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Machado, Ricardo Borges; Rocha, Murilo Ramos; Suchecki, Deborah

2017-03-01

REM sleep rebound is a common behavioural response to some stressors and represents an adaptive coping strategy. Animals submitted to multiple, intermittent, footshock stress (FS) sessions during 96h of REM sleep deprivation (REMSD) display increased REM sleep rebound (when compared to the only REMSD ones, without FS), which is correlated to high plasma prolactin levels. To investigate whether brain prolactin plays a role in stress-induced REM sleep rebound two experiments were carried out. In experiment 1, rats were either not sleep-deprived (NSD) or submitted to 96h of REMSD associated or not to FS and brains were evaluated for PRL immunoreactivity (PRL-ir) and determination of PRL concentrations in the lateral hypothalamus and dorsal raphe nucleus. In experiment 2, rats were implanted with cannulas in the dorsal raphe nucleus for prolactin infusion and were sleep-recorded. REMSD associated with FS increased PRL-ir and content in the lateral hypothalamus and all manipulations increased prolactin content in the dorsal raphe nucleus compared to the NSD group. Prolactin infusion in the dorsal raphe nucleus increased the time and length of REM sleep episodes 3h after the infusion until the end of the light phase of the day cycle. Based on these results we concluded that brain prolactin is a major mediator of stress-induced REMS. The effect of PRL infusion in the dorsal raphe nucleus is discussed in light of the existence of a bidirectional relationship between this hormone and serotonin as regulators of stress-induced REM sleep rebound. Copyright © 2016 Elsevier Inc. All rights reserved.

Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat.

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Fujikawa, Takahiko; Soya, Hideaki; Tamashiro, Kellie L K; Sakai, Randall R; McEwen, Bruce S; Nakai, Naoya; Ogata, Masato; Suzuki, Ikukatsu; Nakashima, Kunio

2004-04-01

Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. We also show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

Exercise, learned helplessness, and the stress-resistant brain.

Science.gov (United States)

Greenwood, Benjamin N; Fleshner, Monika

2008-01-01

Exercise can prevent the development of stress-related mood disorders, such as depression and anxiety. The underlying neurobiological mechanisms of this effect, however, remain unknown. Recently, researchers have used animal models to begin to elucidate the potential mechanisms underlying the protective effects of physical activity. Using the behavioral consequences of uncontrollable stress or "learned helplessness" as an animal analog of depression- and anxiety-like behaviors in rats, we are investigating factors that could be important for the antidepressant and anxiolytic properties of exercise (i.e., wheel running). The current review focuses on the following: (1) the effect of exercise on the behavioral consequences of uncontrollable stress and the implications of these effects on the specificity of the "learned helplessness" animal model; (2) the neurocircuitry of learned helplessness and the role of serotonin; and (3) exercise-associated neural adaptations and neural plasticity that may contribute to the stress-resistant brain. Identifying the mechanisms by which exercise prevents learned helplessness could shed light on the complex neurobiology of depression and anxiety and potentially lead to novel strategies for the prevention of stress-related mood disorders.

Brain network reorganization differs in response to stress in rats genetically predisposed to depression and stress-resilient rats.

Science.gov (United States)

Gass, N; Becker, R; Schwarz, A J; Weber-Fahr, W; Clemm von Hohenberg, C; Vollmayr, B; Sartorius, A

2016-12-06

Treatment-resistant depression (TRD) remains a pressing clinical problem. Optimizing treatment requires better definition of the specificity of the involved brain circuits. The rat strain bred for negative cognitive state (NC) represents a genetic animal model of TRD with high face, construct and predictive validity. Vice versa, the positive cognitive state (PC) strain represents a stress-resilient phenotype. Although NC rats show depressive-like behavior, some symptoms such as anhedonia require an external trigger, i.e. a stressful event, which is similar to humans when stressful event induces a depressive episode in genetically predisposed individuals (gene-environment interaction). We aimed to distinguish neurobiological predisposition from the depressogenic pathology at the level of brain-network reorganization. For this purpose, resting-state functional magnetic resonance imaging time series were acquired at 9.4 Tesla scanner in NC (N=11) and PC (N=7) rats before and after stressful event. We used a graph theory analytical approach to calculate the brain-network global and local properties. There was no difference in the global characteristics between the strains. At the local level, the response in the risk strain was characterized with an increased internodal role and reduced local clustering and efficiency of the anterior cingulate cortex (ACC) and prelimbic cortex compared to the stress-resilient strain. We suggest that the increased internodal role of these prefrontal regions could be due to the enhancement of some of their long-range connections, given their connectivity with the amygdala and other default-mode-like network hubs, which could create a bias to attend to negative information characteristic for depression.

Dynamic regulation of NMDAR function in the adult brain by the stress hormone corticosterone

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Yiu Chung eTse

2012-03-01

Full Text Available Stress and corticosteroids dynamically modulate the expression of synaptic plasticity at glutamatergic synapses in the developed brain. Together with alpha-amino-3-hydroxy-methyl-4-isoxazole propionic acid receptors (AMPAR, N-methyl-D-aspartate receptors (NMDAR are critical mediators of synaptic function and are essential for the induction of many forms of synaptic plasticity. Regulation of NMDAR function by cortisol/corticosterone (CORT may be fundamental to the effects of stress on synaptic plasticity. Recent reports of the efficacy of NMDAR antagonists in treating certain stress-associated psychopathologies further highlight the importance of understanding the regulation of NMDAR function by CORT. Knowledge of how corticosteroids regulate NMDAR function within the adult brain is relatively sparse, perhaps due to a common belief that NMDAR function is relatively stable in the adult brain. We review recent results from our laboratory and others demonstrating dynamic regulation of NMDAR function by CORT in the adult brain. In addition, we consider the issue of how differences in the early life environment may program differential sensitivity to modulation of NMDAR function by CORT and how this may influence synaptic function during stress. Findings from these studies demonstrate that NMDAR function in the adult hippocampus remains sensitive to even brief exposures to CORT and that the capacity for modulation of NMDAR may be programmed, in part, by the early life environment. Modulation of NMDAR function may contribute to dynamic regulation of synaptic plasticity and adaptation in the face of stress, however enhanced NMDAR function may be implicated in mechanisms of stress related psychopathologies including depression.

Stress response in rat brain after different durations of noise exposure.

Science.gov (United States)

Samson, James; Sheeladevi, Rathinasamy; Ravindran, Rajan; Senthilvelan, Manohar

2007-01-01

The alteration in the levels of plasma corticosterone, brain norepinephrine (NE), and expression of brain heat shock proteins (Hsp70) after different durations of noise exposure (acute, 1 day; sub-acute, 15 days; chronic, 30 days) has been studied to analyze their role in combating time-dependent stress effects of noise. Broadband white noise (100dB) exposure to male Wistar albino rats significantly increased the levels of plasma corticosterone and NE in all three durations of noise exposure. The sustained increase observed in their levels in the chronic group suggests that animals are not getting adapted to noise even after 30 days of exposure. The important role of Hsp70 in combating noise induced stress is evident from the significant increase in its expression after chronic exposure, while there was a reciprocal decrease in the NE and corticosterone when compared with their levels after acute and sub-acute noise exposure. This clearly indicates that the time-dependent stress response to noise exposure is a complex mechanism involving highly interconnected systems such as hypothalamo-pituitary-adrenal (HPA) axis, heat shock proteins and may have serious implications in vital organs, particularly in the brain when there is a prolonged noise exposure.

Brain stimulation in posttraumatic stress disorder

Directory of Open Access Journals (Sweden)

Vladan Novakovic

2011-10-01

Full Text Available Posttraumatic stress disorder (PTSD is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT and Cranial electrotherapy stimulation (CES have both been in use for decades; transcranial magnetic stimulation (TMS, magnetic seizure therapy (MST, deep brain stimulation (DBS, transcranial Direct Current Stimulation (tDCS, and vagus nerve stimulation (VNS have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES, depression (ECT, CES, rTMS, VNS, DBS, obsessive-compulsive disorder (OCD (DBS, essential tremor, dystonia (DBS, epilepsy (DBS, VNS, Parkinson Disease (DBS, pain (CES, and insomnia (CES. To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in

The Role of the Brain's Endocannabinoid System in Pain and Its Modulation by Stress.

Science.gov (United States)

Corcoran, Louise; Roche, Michelle; Finn, David P

2015-01-01

Stress has a complex, bidirectional modulatory influence on pain. Stress may either reduce (stress-induced analgesia) or exacerbate (stress-induced hyperalgesia) pain depending on the nature, duration, and intensity of the stressor. The endogenous cannabinoid (endocannabinoid) system is present throughout the neuroanatomical pathways that mediate and modulate responses to painful stimuli. The specific role of the endocannabinoid system in the brain in pain and the modulation of pain by stress is reviewed herein. We first provide a brief overview of the endocannabinoid system, followed by a review of the evidence that the brain's endocannabinoid system modulates pain. We provide a comprehensive evaluation of the role of the endocannabinoid system supraspinally, and particularly in the rostral ventromedial medulla, periaqueductal gray, amygdala, and prefrontal cortex, in pain, stress-induced analgesia, and stress-induced hyperalgesia. Increased understanding of endocannabinoid-mediated regulation of pain and its modulation by stress will inform the development of novel therapeutic approaches for pain and its comorbidity with stress-related disorders. © 2015 Elsevier Inc. All rights reserved.

Cold stress-induced brain injury regulates TRPV1 channels and the PI3K/AKT signaling pathway.

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Liu, Ying; Liu, Yunen; Jin, Hongxu; Cong, Peifang; Zhang, Yubiao; Tong, Changci; Shi, Xiuyun; Liu, Xuelei; Tong, Zhou; Shi, Lin; Hou, Mingxiao

2017-09-01

Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel that interacts with several intracellular proteins in vivo, including calmodulin and Phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/Akt). TRPV1 activation has been reported to exert neuroprotective effects. The aim of this study was to examine the impact of cold stress on the mouse brain and the underlying mechanisms of TRPV1 involvement. Adult male C57BL/6 mice were subjected to cold stress (4°C for 8h per day for 2weeks). The behavioral deficits of the mice were then measured using the Morris water maze. Expression levels of brain injury-related proteins and mRNA were measured by western blot, immunofluorescence or RT-PCR analysis. The mice displayed behavioral deficits, inflammation and changes in brain injury markers following cold stress. As expected, upregulated TRPV1 expression levels and changes in PI3K/Akt expression were found. The TRPV1 inhibitor reduced the levels of brain injury-related proteins and inflammation. These data suggest that cold stress can induce brain injury, possibly through TRPV1 activation and the PI3K/Akt signaling pathway. Suppression of inflammation by inhibition of TRPV1 and the PI3K/Akt pathway may be helpful to prevent cold stress-induced brain injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain atrophy in the visual cortex and thalamus induced by severe stress in animal model.

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Yoshii, Takanobu; Oishi, Naoya; Ikoma, Kazuya; Nishimura, Isao; Sakai, Yuki; Matsuda, Kenichi; Yamada, Shunji; Tanaka, Masaki; Kawata, Mitsuhiro; Narumoto, Jin; Fukui, Kenji

2017-10-06

Psychological stress induces many diseases including post-traumatic stress disorder (PTSD); however, the causal relationship between stress and brain atrophy has not been clarified. Applying single-prolonged stress (SPS) to explore the global effect of severe stress, we performed brain magnetic resonance imaging (MRI) acquisition and Voxel-based morphometry (VBM). Significant atrophy was detected in the bilateral thalamus and right visual cortex. Fluorescent immunohistochemistry for Iba-1 as the marker of activated microglia indicates regional microglial activation as stress-reaction in these atrophic areas. These data certify the impact of severe psychological stress on the atrophy of the visual cortex and the thalamus. Unexpectedly, these results are similar to chronic neuropathic pain rather than PTSD clinical research. We believe that some sensitisation mechanism from severe stress-induced atrophy in the visual cortex and thalamus, and the functional defect of the visual system may be a potential therapeutic target for stress-related diseases.

Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor.

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Taliaz, Dekel; Loya, Assaf; Gersner, Roman; Haramati, Sharon; Chen, Alon; Zangen, Abraham

2011-03-23

Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.

Differential Effects of Voluntary and Forced Exercise on Stress Responses after Traumatic Brain Injury

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Griesbach, Grace S.; Tio, Delia L.; Vincelli, Jennifer; McArthur, David L.; Taylor, Anna N.

2012-01-01

Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) after traumatic brain injury (TBI) when it occurs during a delayed time window. In contrast, acute post-TBI exercise does not increase BDNF. It is well known that increases in glucocorticoids suppress levels of BDNF. Moreover, recent work from our laboratory showed that there is a heightened stress response after fluid percussion injury (FPI). In order to determine if a heightened stress response is also observed ...

ACTIONS OF PROLACTIN IN THE BRAIN: FROM PHYSIOLOGICAL ADAPTATIONS TO STRESS AND NEUROGENESIS TO PSYCHOPATHOLOGY

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Luz eTorner

2016-03-01

Full Text Available Prolactin is one of the most versatile hormones known. It is considered an adaptive hormone due to the key roles it plays in the modulation of the stress response and during pregnancy and lactation. Within the brain, prolactin acts as a neuropeptide to promote physiological responses related to reproduction, stress adaptation, neurogenesis, and neuroprotection. The action of prolactin on the nervous system contributes to the wide array of changes that occur in the female brain during pregnancy and result in the attenuation of the hypothalamic pituitary adrenal axis. Together, all these changes promote behavioral and physiological adaptations of the new mother to enable reproductive success. Brain adaptations driven by prolactin are also important for the regulation of maternal emotionality and wellbeing Prolactin also affects the male brain during the stress response but its effects have been less studied. Prolactin regulates neurogenesis both in the subventricular zone and in the hippocampus. Therefore, alterations in the prolactin system due to stress, or exposure to substances that reduce neurogenesis or other conditions, could contribute to maladaptive responses and pathological behavioral outcomes. Here we review the prolactin system and the role it plays in the modulation of stress response and emotion regulation. We discuss the effects of prolactin on neurogenesis and neuroprotection, the putative neuronal mechanisms underlying these effects, and their contribution to the onset of psychopathological states like depression.

Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

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Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

2015-01-01

Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

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C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

2014-12-01

3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

Postdeployment Symptom Changes and Traumatic Brain Injury and/or Posttraumatic Stress Disorder in Men

Science.gov (United States)

2012-01-01

Post - Deployment Health Assessment, according to traumatic brain injury (TBI) and posttraumatic stress disorder ( PTSD ...Key words: blasts, deployment, males, military, odds ratio, percent change, Post -Deployment Health Assessment, post - traumatic stress disorder ...Care Posttraumatic Stress Disorder Screen, PDHA = Post -Deployment Health Assessment, PDHRA = Post - Deployment Health Reassessment, PTSD =

Brain network disturbance related to posttraumatic stress and traumatic brain injury in veterans.

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Spielberg, Jeffrey M; McGlinchey, Regina E; Milberg, William P; Salat, David H

2015-08-01

Understanding the neural causes and consequences of posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) is a high research priority, given the high rates of associated disability and suicide. Despite remarkable progress in elucidating the brain mechanisms of PTSD and mTBI, a comprehensive understanding of these conditions at the level of brain networks has yet to be achieved. The present study sought to identify functional brain networks and topological properties (measures of network organization and function) related to current PTSD severity and mTBI. Graph theoretic tools were used to analyze resting-state functional magnetic resonance imaging data from 208 veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn, all of whom had experienced a traumatic event qualifying for PTSD criterion A. Analyses identified brain networks and topological network properties linked to current PTSD symptom severity, mTBI, and the interaction between PTSD and mTBI. Two brain networks were identified in which weaker connectivity was linked to higher PTSD re-experiencing symptoms, one of which was present only in veterans with comorbid mTBI. Re-experiencing was also linked to worse functional segregation (necessary for specialized processing) and diminished influence of key regions on the network, including the hippocampus. Findings of this study demonstrate that PTSD re-experiencing symptoms are linked to weakened connectivity in a network involved in providing contextual information. A similar relationship was found in a separate network typically engaged in the gating of working memory, but only in veterans with mTBI. Published by Elsevier Inc.

Quantitative assessment of blood flow reserve using {sup 99m}Tc-HMPAO in carotid stenosis

Energy Technology Data Exchange (ETDEWEB)

Garai, I.; Varga, J.; Galuska, L. [Department of Nuclear Medicine, University of Debrecen Medical and Health Centre, Debrecen (Hungary); Szomjak, E. [3. Department of Internal Medicine, University of Debrecen Medical and Health Centre, Debrecen (Hungary); Toth, C.; Olvaszto, S. [1. Department of Surgery, University of Debrecen Medical and Health Centre, Debrecen (Hungary); Bank, J. [Department of Neurology, Kenezy Hospital (Hungary); Ficzere, A. [Department of Neurology, University of Debrecen Medical and Health Centre, Debrecen (Hungary)

2002-02-01

Dynamic imaging of the inflow of technetium-99m hexamethylpropylene amine oxime (HMPAO) to the brain has been proved to allow estimation of the hemispherical cerebral blood flow (CBF) using the Patlak plot. In this study, we compared the hemispherical CBF (in ml/min/100 g) of different patient groups. A total of 25 patients (comprising 13 with migraine and 12 scheduled for endarterectomy owing to angiographically confirmed severe stenosis of the internal carotid artery on at least one side) underwent baseline and acetazolamide {sup 99m}Tc-HMPAO brain perfusion studies. In addition, acetazolamide {sup 99m}Tc-HMPAO studies were performed in 12 healthy subjects (no baseline study was performed for ethical reasons.) Dynamic studies were acquired by means of a dual-detector gamma camera with a large field of view (HELIX, Elscint). Special difference images were created to make definition of the aortic arch and hemispherical brain regions easier and more reproducible. A semi-automatic method was developed to determine the transit time from the aorta to the brain, making the generation of the Patlak plot even more robust. The baseline CBF values did not significantly depend on the disease (P>0.1), whereas the CBF values obtained after acetazolamide provocation did do so (ANOVA, P<0.001). Patients suffering from migraine showed a significant increase in global CBF values after acetazolamide provocation (paired t test, P<0.05), but we could not find any effect of the provocation in patients awaiting carotid endarterectomy, indicating a lack of cerebrovascular reserve capacity. Comparison of the results of the acetazolamide study in patients and the control group revealed the CBF values to be significantly lower in patients with carotid stenosis (two-sample t-test, P<0.001), but not in those with migraine (P>0.1). In summary, using quantitative analysis of {sup 99m}Tc-HMPAO brain studies we could objectively compare the CBF of patients suffering from different diseases

Development of quantification analysis software for measuring regional cerebral blood flow by the modified split-dose method with 123I-IMP before and after acetazolamide loading

International Nuclear Information System (INIS)

Nagaki, Akio; Kobara, Kouichi; Matsutomo, Norikazu

2003-01-01

We developed a quantification analysis software program for measuring regional cerebral blood flow (rCBF) at rest and under acetazolamide (ACZ) stress by the modified split-dose (MSD) method with iodine-123 N-isopropyl-p-iodoamphetamine (IMP) and compared the rCBF values measured by the MSD method and by the split dose 123 I-IMP SPECT (SD) method requiring one continuous withdrawal of arterial blood. Since the MSD method allows the input of two arterial blood sampling parameter values, the background subtraction procedure for obtaining ACZ-induced images in the MSD method is not identical to the procedure in the SD method. With our software program for rCBF quantification, the resting rCBF values determined by the MSD method were closely correlated with the values measured by the SD method (r=0.94), and there was also a good correlation between the ACZ-induced rCBF values obtained by the MSD method and by the SD method (r=0.81). The increase in rCBF under ACZ stress was estimated to be approximately 26% by the SD method and 38% by the MSD method, suggesting that the MSD method tends to overestimate the increase in rCBF under ACZ stress in comparison with the SD method, but the variability of the rCBF values at rest and during ACZ stress analyzed by the MSD method was smaller than the variability with the SD method. Further clinical studies are required to validate our rCBF quantification analysis program for the MSD method. (author)

The effect of L-Arginine on the brain tissue of stressed rats

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Batoul Ebadi

2010-01-01

Full Text Available Introduction: This study was conducted to determine the possible beneficial results of L-arginine on prefrontal cortex of rats which impressed by immobilization stress to define the synchronous impression of stress and nitric oxide (NO on evolution of prefrontal cortex of rats after birth. Methods: Forty-eight one month, male Wistar rats were divided into two groups: stressed and non-stressed. L-Arginine (200 mg/kg as a NO synthase (NOS inducer and L-NAME (2O mg/kg were injected intraperitonealy (IP and 7- nitroindazde (25 mg/kg as non-specific was injected subcutaneously (S.C. for 4 weeks. The kind of stress was immobilization for 4 weeks, every other day. The brain was removed after this period and each brain divided into two parts in a coronal section manner. Anterior part used for histological studies with H&E staining and posterior part used for measurement of NO production using spectrophotometer at 540 nm wavelengh. Results: Statistical analysis of microscopic and light microscopic finding showed that thickness of prefrontal cortex and NO production were significantly decreased in stressed rats and especially in groups which received 7- nitroindazole and L-NAME and L-arginine could reverse these results. Discussion: According to this research, we could say that L-arginine decreases the cortical damages in stressed rats and 7-nitroindazole and L-NAME increase this damage in non-stressed group. Although in non stressed groups, L-arginine, L-NAME and 7- nitroindazole were all non-protective and damaging.

The effect of L-Arginine on the brain tissue of stressed rats

Directory of Open Access Journals (Sweden)

Batoul Ebadi

2010-01-01

Full Text Available   Abstract  Introduction: This study was conducted to determine the possible beneficial results of L-arginine on prefrontal cortex of rats which impressed by immobilization stress to define the synchronous impression of stress and nitric oxide (NO on evolution of prefrontal cortex of rats after birth. Methods: Forty-eight one month, male Wistar rats were divided into two groups: stressed and non-stressed. L-Arginine (200 mg/kg as a NO synthase (NOS inducer and L-NAME (2O mg/kg were injected intraperitonealy (IP and 7- nitroindazde (25 mg/kg as non-specific was injected subcutaneously (S.C. for 4 weeks. The kind of stress was immobilization for 4 weeks, every other day. The brain was removed after this period and each brain divided into two parts in a coronal section manner. Anterior part used for histological studies with H&E staining and posterior part used for measurement of NO production using spectrophotometer at 540 nm wavelengh. Results: Statistical analysis of microscopic and light microscopic finding showed that thickness of prefrontal cortex and NO production were significantly decreased in stressed rats and especially in groups which received 7- nitroindazole and L-NAME and L-arginine could reverse these results. Discussion: According to this research, we could say that L-arginine decreases the cortical damages in stressed rats and 7-nitroindazole and L-NAME increase this damage in non-stressed group. Although in non stressed groups, L-arginine, L-NAME and 7- nitroindazole were all non-protective and damaging.

Defense Health Care: Research on Hyperbaric Oxygen Therapy to Treat Traumatic Brain Injury and Post-Traumatic Stress Disorder

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2015-12-01

Traumatic Brain Injury and Post - Traumatic Stress Disorder Why GAO Did This Study TBI and PTSD are signature...injury (TBI) and post - traumatic stress disorder ( PTSD ), most of which were focused solely on TBI (29 articles). The 32 articles consisted of 7 case...Case Report Articles on Hyperbaric Oxygen Therapy to Treat Traumatic Brain Injury (TBI) or Post - Traumatic Stress Disorder ( PTSD ),

Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

Institute of Scientific and Technical Information of China (English)

De-guo Jiang; Shi-li Jin; Gong-ying Li; Qing-qing Li; Zhi-ruo Li; Hong-xia Ma; Chuan-jun Zhuo; Rong-huan Jiang; Min-jie Ye

2016-01-01

Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry andin situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no signiifcant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our ifndings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

Brain structure in post-traumatic stress disorder: A voxel-based morphometry analysis.

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Tan, Liwen; Zhang, Li; Qi, Rongfeng; Lu, Guangming; Li, Lingjiang; Liu, Jun; Li, Weihui

2013-09-15

This study compared the difference in brain structure in 12 mine disaster survivors with chronic post-traumatic stress disorder, 7 cases of improved post-traumatic stress disorder symptoms, and 14 controls who experienced the same mine disaster but did not suffer post-traumatic stress disorder, using the voxel-based morphometry method. The correlation between differences in brain structure and post-traumatic stress disorder symptoms was also investigated. Results showed that the gray matter volume was the highest in the trauma control group, followed by the symptoms-improved group, and the lowest in the chronic post-traumatic stress disorder group. Compared with the symptoms-improved group, the gray matter volume in the lingual gyrus of the right occipital lobe was reduced in the chronic post-traumatic stress disorder group. Compared with the trauma control group, the gray matter volume in the right middle occipital gyrus and left middle frontal gyrus was reduced in the symptoms-improved group. Compared with the trauma control group, the gray matter volume in the left superior parietal lobule and right superior frontal gyrus was reduced in the chronic post-traumatic stress disorder group. The gray matter volume in the left superior parietal lobule was significantly positively correlated with the State-Trait Anxiety Inventory subscale score in the symptoms-improved group and chronic post-traumatic stress disorder group (r = 0.477, P = 0.039). Our findings indicate that (1) chronic post-traumatic stress disorder patients have gray matter structural damage in the prefrontal lobe, occipital lobe, and parietal lobe, (2) after post-traumatic stress, the disorder symptoms are improved and gray matter structural damage is reduced, but cannot recover to the trauma-control level, and (3) the superior parietal lobule is possibly associated with chronic post-traumatic stress disorder. Post-traumatic stress disorder patients exhibit gray matter abnormalities.

Brain structure in post-traumatic stress disorder: A voxel-based morphometry analysis

Science.gov (United States)

Tan, Liwen; Zhang, Li; Qi, Rongfeng; Lu, Guangming; Li, Lingjiang; Liu, Jun; Li, Weihui

2013-01-01

This study compared the difference in brain structure in 12 mine disaster survivors with chronic post-traumatic stress disorder, 7 cases of improved post-traumatic stress disorder symptoms, and 14 controls who experienced the same mine disaster but did not suffer post-traumatic stress disorder, using the voxel-based morphometry method. The correlation between differences in brain structure and post-traumatic stress disorder symptoms was also investigated. Results showed that the gray matter volume was the highest in the trauma control group, followed by the symptoms-improved group, and the lowest in the chronic post-traumatic stress disorder group. Compared with the symptoms-improved group, the gray matter volume in the lingual gyrus of the right occipital lobe was reduced in the chronic post-traumatic stress disorder group. Compared with the trauma control group, the gray matter volume in the right middle occipital gyrus and left middle frontal gyrus was reduced in the symptoms-improved group. Compared with the trauma control group, the gray matter volume in the left superior parietal lobule and right superior frontal gyrus was reduced in the chronic post-traumatic stress disorder group. The gray matter volume in the left superior parietal lobule was significantly positively correlated with the State-Trait Anxiety Inventory subscale score in the symptoms-improved group and chronic post-traumatic stress disorder group (r = 0.477, P = 0.039). Our findings indicate that (1) chronic post-traumatic stress disorder patients have gray matter structural damage in the prefrontal lobe, occipital lobe, and parietal lobe, (2) after post-traumatic stress, the disorder symptoms are improved and gray matter structural damage is reduced, but cannot recover to the trauma-control level, and (3) the superior parietal lobule is possibly associated with chronic post-traumatic stress disorder. Post-traumatic stress disorder patients exhibit gray matter abnormalities. PMID:25206550

Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

Science.gov (United States)

2014-01-01

Background Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. Results Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. Conclusions Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models. PMID:24512669

Sub-acute nickel exposure impairs behavior, alters neuronal microarchitecture, and induces oxidative stress in rats' brain.

Science.gov (United States)

Ijomone, Omamuyovwi Meashack; Okori, Stephen Odey; Ijomone, Olayemi Kafilat; Ebokaiwe, Azubike Peter

2018-02-26

Nickel (Ni) is a heavy metal with wide industrial uses. Environmental and occupational exposures to Ni are potential risk factors for neurological symptoms in humans. The present study investigated the behavior and histomorphological alterations in brain of rats sub-acutely exposed to nickel chloride (NiCl 2 ) and the possible involvement of oxidative stress. Rats were administered with 5, 10 or 20 mg/kg NiCl 2 via intraperitoneal injections for 21 days. Neurobehavioral assessment was performed using the Y-maze and open field test (OFT). Histomorphological analyses of brain tissues, as well as biochemical determination of oxidative stress levels were performed. Results showed that Ni treatments significantly reduced body weight and food intake. Cognitive and motor behaviors on the Y-maze and OFT, respectively, were compromised following Ni treatments. Administration of Ni affected neuronal morphology in the brain and significantly reduced percentage of intact neurons in both hippocampus and striatum. Additionally, markers of oxidative stress levels and nitric oxide (NO) levels were significantly altered following Ni treatments. These data suggest that compromised behavior and brain histomorphology following Ni exposures is associated with increase in oxidative stress.

Effect of shear stress on iPSC-derived human brain microvascular endothelial cells (dhBMECs).

Science.gov (United States)

DeStefano, Jackson G; Xu, Zinnia S; Williams, Ashley J; Yimam, Nahom; Searson, Peter C

2017-08-04

The endothelial cells that form the lumen of capillaries and microvessels are an important component of the blood-brain barrier. Cell phenotype is regulated by transducing a range of biomechanical and biochemical signals in the local microenvironment. Here we report on the role of shear stress in modulating the morphology, motility, proliferation, apoptosis, and protein and gene expression, of confluent monolayers of human brain microvascular endothelial cells derived from induced pluripotent stem cells. To assess the response of derived human brain microvascular endothelial cells (dhBMECs) to shear stress, confluent monolayers were formed in a microfluidic device. Monolayers were subjected to a shear stress of 4 or 12 dyne cm -2 for 40 h. Static conditions were used as the control. Live cell imaging was used to assess cell morphology, cell speed, persistence, and the rates of proliferation and apoptosis as a function of time. In addition, immunofluorescence imaging and protein and gene expression analysis of key markers of the blood-brain barrier were performed. Human brain microvascular endothelial cells exhibit a unique phenotype in response to shear stress compared to static conditions: (1) they do not elongate and align, (2) the rates of proliferation and apoptosis decrease significantly, (3) the mean displacement of individual cells within the monolayer over time is significantly decreased, (4) there is no cytoskeletal reorganization or formation of stress fibers within the cell, and (5) there is no change in expression levels of key blood-brain barrier markers. The characteristic response of dhBMECs to shear stress is significantly different from human and animal-derived endothelial cells from other tissues, suggesting that this unique phenotype that may be important in maintenance of the blood-brain barrier. The implications of this work are that: (1) in confluent monolayers of dhBMECs, tight junctions are formed under static conditions, (2) the formation

Parent-child intervention decreases stress and increases maternal brain activity and connectivity during own baby-cry: An exploratory study.

Science.gov (United States)

Swain, James E; Ho, S Shaun; Rosenblum, Katherine L; Morelen, Diana; Dayton, Carolyn J; Muzik, Maria

2017-05-01

Parental responses to their children are crucially influenced by stress. However, brain-based mechanistic understanding of the adverse effects of parenting stress and benefits of therapeutic interventions is lacking. We studied maternal brain responses to salient child signals as a function of Mom Power (MP), an attachment-based parenting intervention established to decrease maternal distress. Twenty-nine mothers underwent two functional magnetic resonance imaging brain scans during a baby-cry task designed to solicit maternal responses to child's or self's distress signals. Between scans, mothers were pseudorandomly assigned to either MP (n = 14) or control (n = 15) with groups balanced for depression. Compared to control, MP decreased parenting stress and increased child-focused responses in social brain areas highlighted by the precuneus and its functional connectivity with subgenual anterior cingulate cortex, which are key components of reflective self-awareness and decision-making neurocircuitry. Furthermore, over 13 weeks, reduction in parenting stress was related to increasing child- versus self-focused baby-cry responses in amygdala-temporal pole functional connectivity, which may mediate maternal ability to take her child's perspective. Although replication in larger samples is needed, the results of this first parental-brain intervention study demonstrate robust stress-related brain circuits for maternal care that can be modulated by psychotherapy.

Noninvasive regional cerebral blood flow measurements at pre- and post-acetazolamide test using 99mTc-ECD

International Nuclear Information System (INIS)

Matsuda, Hiroshi; Nakano, Seigo; Tanaka, Masaaki.

1996-01-01

A technique for serial noninvasive cerebral blood flow measurements at pre- and post-acetazolamide (Diamox) test was newly developed using 99m Tc-ECD without blood sampling. Baseline mean cerebral blood flow (mCBF) was measured from graphical analysis of time activity curves for brain and aortic arch obtained from radionuclide angiography by injection of 370-555 MBq 99m Tc-ECD. The first SPECT study was performed immediately after intravenous administration of 1 g of Diamox, then baseline regional cerebral blood flow (rCBF) was calculated using Lassen's correction algorithm. Immediately after the stop of the first SPECT study, additional 555-740 MBq of 99m Tc-ECD was administered, thereafter the second SPECT study was started. Post-Diamox SPECT images were obtained by subtraction of the first baseline images from the second images. Using Lassen's algorithm, post-Diamox mCBF was estimated from the baseline mCBF, the baseline mean SPECT counts, and post-Diamox mean SPECT counts corrected for administered dose and imaging time. Post-Diamox rCBF was obtained from the post-Diamox mCBF and the post-Diamox mean SPECT counts using Lassen's algorithm. Coefficient variation was shown 2.7% and 3.5%: mCBF and rCBF, respectively in test-retest results in six patients without Diamox administration. Nine demented patients without vascular disorders showed significant mCBF increase of 35.7% on the average by post-Diamox. In conclusion, this simplified method is practically useful for measuring CBF at pre- and post-Diamox test within short period of time without any blood sample. (author)

Ex-vivo diffusion MRI reveals microstructural alterations in stress-sensitive brain regions: A chronic mild stress recovery study

DEFF Research Database (Denmark)

Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove

Depression is a leading cause of disability worldwide and causes significant microstructural alterations in stress-sensitive brain regions. However, the potential recovery of these microstructural alterations has not previously been investigated, which we, therefore, set out to do using diffusion...... MRI (d-MRI) in the chronic mild stress (CMS) rat model of depression. This study reveals significant microstructural alterations after 8 weeks of recovery, in the opposite direction to change induced by stress in the acute phase of the experiment. Such findings may be useful in the prognosis...... of depression or for monitoring treatment response....

Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress.

Science.gov (United States)

Ozel Turkcu, Ummuhani; Bilgihan, Ayşe; Biberoglu, Gursel; Mertoglu Caglar, Oznur

2010-06-01

Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.

Studies on the effects of aspartame on memory and oxidative stress in brain of mice.

Science.gov (United States)

Abdel-Salam, O M E; Salem, N A; El-Shamarka, M E S; Hussein, J S; Ahmed, N A S; El-Nagar, M E S

2012-12-01

The dipeptide aspartame (N-L-alpha-aspartyl-Lphenylalanine, 1-methyl ester; alpha-APM) is one of the most widely used artificial sweeteners. The present study aimed to investigate the effect of repeated administration of aspartame in the working memory version of Morris water maze test, on oxidative stress and brain monoamines in brain of mice. Aspartame (0.625, 1.875 or 5.625 mg/kg) was administered once daily subcutaneously for 2 weeks and mice were examined four times a week for their ability to locate a submerged plate. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide levels (the concentrations of nitrite/nitrate) and glucose were determined in brain. Only at the highest dose of 5.625 mg/kg, did aspartame significantly impaired water maze performance. The mean time taken to find the escape platform (latency) over 2 weeks was significantly delayed by aspartame 5.625 mg/kg, compared with the saline-treated control group. Significant differences occurred only on the first trial to find the escape platform. Significant increase in brain MDA by 16.5% and nitric oxide by 16.2% and a decrease in GSH by 25.1% and glucose by 22.5% occurred after treatment with aspartame at 1.875 mg/kg. Aspartame administered at 5.625 mg/kg significantly increased brain MDA by 43.8%, nitric oxide by 18.6% and decreased GSH by 32.7% and glucose by 25.8%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline and dopamine. These findings suggest impaired memory performance and increased brain oxidative stress by repeated aspartame administration. The impaired memory performance is likely to involve increased oxidative stress as well as decreased brain glucose availability.

The physiological role of the brain GLP-1 system in stress

OpenAIRE

Holt, M. K.; Trapp, S.

2016-01-01

Glucagon-like peptide-1 (GLP-1) within the brain is a potent regulator of food intake and most studies have investigated the anorexic effects of central GLP-1. A range of brain regions have now been found to be involved in GLP-1 mediated anorexia, including some which are not traditionally associated with appetite regulation. However, a change in food intake can be indicative of not only reduced energy demand, but also changes in the organism's motivation to eat following stressful stimuli. I...

[STUDYING THE ROLE OF BRAIN MELANOCORTIN RECEPTORS IN THE SUPPRESSING OF FOOD INTAKE UNDER ETHER STRESS IN MICE].

Science.gov (United States)

Bazhan, N M; Kulikova, E V; Makarova, E N; Yakovleva, T V; Kazantseva, A Yu

2015-12-01

Melanocortin (MC) system regulates food intake under the rest conditions. Stress inhibits food intake. It is not clear whether brain MC system is involved in stress-induced anorexia in mice. The aim of the work was to investigate the effect of pharmacological blockade and activation of brain MC receptors on food intake under stress. C57B1/6J male mice were subjected to ether stress (0.5 minute ether anesthesia) before the administration of saline solution or synthetic non-selective blocker (SHU9119) or agonist (Melanotan II) of MC receptors into the lateral brain ventricle. Food intake was pre-stimulated with 17 hours of fasting in all mice. Ether stress decreased food intake, increased the plasma corticosterone level and hypothalamic mRNA AgRP (natural MC receptor antagonist) level at 1 hour after the stress. Pharmacological blockade of the MC receptors weakened stress-induced anorexia and decreased mRNA AgRP level in the hypothalamus. Pharmacological stimulation of the MC receptors enhanced ether stress-induced anorexia and hypercortisolism. Thus, our data demonstrated that the central MC system was involved in the development of stress-induced anorexia in mice.

Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

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Li, Yong; Gonzalez, Pablo; Zhang, Lubo

2012-01-01

Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions.

Science.gov (United States)

Li, Yong; Gonzalez, Pablo; Zhang, Lubo

2012-08-01

Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin.

Science.gov (United States)

Huong, Nguyen Thi Thu; Murakami, Yukihisa; Tohda, Michihisa; Watanabe, Hiroshi; Matsumoto, Kinzo

2005-08-01

Stressors with a physical factor such as immobilization, electric foot shock, cold swim, etc., have been shown to produce oxidative damage to membrane lipids in the brain. In this study, we investigated the effect of protracted social isolation stress on lipid peroxidation activity in the mouse brain and elucidated the protective effect of majonoside-R2, a major saponin component of Vietnamese ginseng, in mice exposed to social isolation stress. Thiobarbituric acid reactive substance levels, one of the end products of lipid peroxidation reaction, were increased in the brains of mice subjected to 6-8 weeks of social isolation stress. Measurements of nitric oxide (NO) metabolites (NO(x)(-)) also revealed a significant increase of NO production in the brains of socially isolated mice. Moreover, the depletion of brain glutathione content, an endogenous antioxidant, in socially isolated animals occurred in association with the rise in lipid peroxidation. The intraperitoneal administration of majonoside-R2 (10-50 mg/kg) had no effect on thiobarbituric acid reactive substances (TBARS), NO, or glutathione levels in the brains of group-housed control mice but it significantly suppressed the increase in TBARS and NO levels and the decrease in glutathione levels caused by social isolation stress. These results suggest that mice subjected to 6-8 weeks of social isolation stress produces oxidative damage in the brain partly via enhancement of NO production, and that majonoside-R2 exerts a protective effect by modulating NO and glutathione systems in the brain.

Altitude Stress During Participation of Medical Congress

Science.gov (United States)

Kim, Soon Bae; Kim, Jong Sung; Kim, Sang Jun; Cho, Su Hee

2016-01-01

Medical congresses often held in highlands. We reviewed several medical issues associated with altitude stress especially while physicians have participated medical congress held in high altitude. Altitude stress, also known as an acute mountain sickness (AMS), is caused by acute exposure to low oxygen level at high altitude which is defined as elevations at or above 1,200 m and AMS commonly occurs above 2,500 m. Altitude stress with various symptoms including insomnia can also be experienced in airplane. AMS and drunken state share many common features in symptoms, neurologic manifestations and even show multiple microbleeds in corpus callosum and white matter on MRI. Children are more susceptible to altitude stress than adults. Gradual ascent is the best method for the prevention of altitude stress. Adequate nutrition (mainly carbohydrates) and hydration are recommended. Consumption of alcohol can exacerbate the altitude-induced impairments in judgment and the visual senses and promote psychomotor dysfunction. For prevention or treatment of altitude stress, acetazolamide, phosphodiesterase inhibitors, dexamethasone and erythropoietin are helpful. Altitude stress can be experienced relatively often during participation of medical congress. It is necessary to remind the harmful effect of AMS because it can cause serious permanent organ damage even though the symptoms are negligible in most cases. PMID:27621942

Non invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions

Science.gov (United States)

2017-05-14

relationship between the brain oxidative status and stress at a cellular, physiological as well as a psychological level. These stressors, in turn, have...neuropsychological tests: cognitive performance, perceptual reasoning , working memory, processing speed and perceived stress scale were performed. Brain...following tests for verbal compression, working memory, perceptual reasoning and processing speed paper pencil tests were conducted. Each subject took more

Reducing the harm of stress: medications to rescue the prefrontal cortex and overcome bad habits: the science of stress: focus on the brain, breaking bad habits, and chronic disease.

Science.gov (United States)

Jin, Lu E

2011-12-01

Our brain is sensitive to stress. Both acute and chronic stress cause cognitive deficits and induce chronic disorders such as drug addiction. In a June 2011 conference at Yale entitled "The Science of Stress: Focus on the Brain, Breaking Bad Habits, and Chronic Disease," Drs. Amy Arnsten and Sherry Mckee discussed the roles of prefrontal cortex in the treatment of stress impairments and addiction. Medications to strengthen the prefrontal function, such as prazosin and guanfacine, may reduce the harm of stress and help overcome smoking and alcohol abuse.

Hypoxia Stress Modifies Na/K-ATPase, H/K-ATPase, , and Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish

Directory of Open Access Journals (Sweden)

MC Subhash Peter

2017-11-01

Full Text Available Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA expression of α1-subunit isoforms of Na + /K + -ATPase (NKA in the brain segments, namely, prosencephalon (PC, mesencephalon (MC, and metencephalon (MeC in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water or challenged with zymosan treatment (25-200 ng g −1 for 24 hours or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H + /K + -ATPase (HKA, and Na + / NH 4 + - ATPase (NNA in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a , nkaα1b , and nkaα1c , in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na + , K + , H + , and NH 4 + ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform

Depression Anxiety Stress Scales (DASS-21): Factor Structure in Traumatic Brain Injury Rehabilitation.

Science.gov (United States)

Randall, Diane; Thomas, Matt; Whiting, Diane; McGrath, Andrew

To confirm the construct validity of the Depression Anxiety Stress Scales-21 (DASS-21) by investigating the fit of published factor structures in a sample of adults with moderate to severe traumatic brain injury (posttraumatic amnesia > 24 hours). Archival data from 504 patient records at the Brain Injury Rehabilitation Unit at Liverpool Hospital, Australia. Participants were aged between 16 and 71 years and were engaged in a specialist rehabilitation program. The DASS-21. Two of the 6 models had adequate fit using structural equation modeling. The data best fit Henry and Crawford's quadripartite model, which comprised a Depression, Anxiety and Stress factor, as well as a General Distress factor. The data also adequately fit Lovibond and Lovibond's original 3-factor model, and the internal consistencies of each factor were very good (α = 0.82-0.90). This study confirms the structure and construct validity of the DASS-21 and provides support for its use as a screening tool in traumatic brain injury rehabilitation.

Dissecting the Roles of Brain Injury and Combat-Related Stress in Post-Traumatic Headache

Science.gov (United States)

2015-10-01

Dissecting the Roles of Brain Injury and Combat-Related Stress in Post- Traumatic Headache 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0366 5c...consequences of TBI is post-traumatic headache (PTH). Because both TBI and stress could contribute to PTH, we examine them together and separately...significant stress . Both TBI and stress are risk factors for chronic headache . They may contribute separate or overlapping mechanisms, and treatment can be

Invisible Bleeding: The Command Team’s Role in the Identification, Understanding, and Treatment of Traumatic Brain Injury and Post Traumatic Stress Disorder

Science.gov (United States)

2013-04-11

Traumatic Brain Injury, Post Traumatic Stress Disorder , TBI, PTSD , Wounded...Brain Injury (TBI) and Post Traumatic Stress Disorder ( PTSD ). Command teams must leverage the existing programs and infrastructure while demonstrating a...subsequent struggle with Traumatic Brain Injury (TBI) and Post Traumatic Stress Disorder ( PTSD ) have given me the unique insight to tackle

Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain.

Science.gov (United States)

Pavlovsky, A A; Boehning, D; Li, D; Zhang, Y; Fan, X; Green, T A

2013-08-29

Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30 min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Early and Later Life Stress Alter Brain Activity and Sleep in Rats

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Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

2013-01-01

Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way. PMID:23922857

Uncertainty and stress: Why it causes diseases and how it is mastered by the brain.

Science.gov (United States)

Peters, Achim; McEwen, Bruce S; Friston, Karl

2017-09-01

The term 'stress' - coined in 1936 - has many definitions, but until now has lacked a theoretical foundation. Here we present an information-theoretic approach - based on the 'free energy principle' - defining the essence of stress; namely, uncertainty. We address three questions: What is uncertainty? What does it do to us? What are our resources to master it? Mathematically speaking, uncertainty is entropy or 'expected surprise'. The 'free energy principle' rests upon the fact that self-organizing biological agents resist a tendency to disorder and must therefore minimize the entropy of their sensory states. Applied to our everyday life, this means that we feel uncertain, when we anticipate that outcomes will turn out to be something other than expected - and that we are unable to avoid surprise. As all cognitive systems strive to reduce their uncertainty about future outcomes, they face a critical constraint: Reducing uncertainty requires cerebral energy. The characteristic of the vertebrate brain to prioritize its own high energy is captured by the notion of the 'selfish brain'. Accordingly, in times of uncertainty, the selfish brain demands extra energy from the body. If, despite all this, the brain cannot reduce uncertainty, a persistent cerebral energy crisis may develop, burdening the individual by 'allostatic load' that contributes to systemic and brain malfunction (impaired memory, atherogenesis, diabetes and subsequent cardio- and cerebrovascular events). Based on the basic tenet that stress originates from uncertainty, we discuss the strategies our brain uses to avoid surprise and thereby resolve uncertainty. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Inflammation and oxidative stress are elevated in the brain, blood, and adrenal glands during the progression of post-traumatic stress disorder in a predator exposure animal model.

Science.gov (United States)

Wilson, C Brad; McLaughlin, Leslie D; Nair, Anand; Ebenezer, Philip J; Dange, Rahul; Francis, Joseph

2013-01-01

This study sought to analyze specific pathophysiological mechanisms involved in the progression of post-traumatic stress disorder (PTSD) by utilizing an animal model. To examine PTSD pathophysiology, we measured damaging reactive oxygen species and inflammatory cytokines to determine if oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation were upregulated in response to constant stress. Pre-clinical PTSD was induced in naïve, male Sprague-Dawley rats via a predator exposure/psychosocial stress regimen. PTSD group rats were secured in Plexiglas cylinders and placed in a cage with a cat for one hour on days 1 and 11 of a 31-day stress regimen. In addition, PTSD group rats were subjected to psychosocial stress whereby their cage cohort was changed daily. This model has been shown to cause heightened anxiety, exaggerated startle response, impaired cognition, and increased cardiovascular reactivity, all of which are common symptoms seen in humans with PTSD. At the conclusion of the predator exposure/psychosocial stress regimen, the rats were euthanized and their brains were dissected to remove the hippocampus, amygdala, and pre-frontal cortex (PFC), the three areas commonly associated with PTSD development. The adrenal glands and whole blood were also collected to assess systemic oxidative stress. Analysis of the whole blood, adrenal glands, and brain regions revealed oxidative stress increased during PTSD progression. In addition, examination of pro-inflammatory cytokine (PIC) mRNA and protein demonstrated neurological inflammatory molecules were significantly upregulated in the PTSD group vs. controls. These results indicate oxidative stress and inflammation in the brain, adrenal glands, and systemic circulation may play a critical role in the development and further exacerbation of PTSD. Thus, PTSD may not be solely a neurological pathology but may progress as a systemic condition involving multiple organ systems.

Effects of acute restraint-induced stress on glucocorticoid receptors and brain-derived neurotrophic factor after mild traumatic brain injury.

Science.gov (United States)

Griesbach, G S; Vincelli, J; Tio, D L; Hovda, D A

2012-05-17

We have previously reported that experimental mild traumatic brain injury results in increased sensitivity to stressful events during the first post-injury weeks, as determined by analyzing the hypothalamic-pituitary-adrenal (HPA) axis regulation following restraint-induced stress. This is the same time period when rehabilitative exercise has proven to be ineffective after a mild fluid-percussion injury (FPI). Here we evaluated effects of stress on neuroplasticity. Adult male rats underwent either an FPI or sham injury. Additional rats were only exposed to anesthesia. Rats were exposed to 30 min of restraint stress, followed by tail vein blood collection at post-injury days (PID) 1, 7, and 14. The response to dexamethasone (DEX) was also evaluated. Hippocampal tissue was collected 120 min after stress onset. Brain-derived neurotrophic factor (BDNF) along with glucocorticoid (GR) and mineralocorticoid (MR) receptors was determined by Western blot analysis. Results indicated injury-dependent changes in glucocorticoid and mineralocorticoid receptors that were influenced by the presence of dexamethasone. Control and FPI rats responded differentially to DEX in that GR increases after receiving the lower dose of DEX were longer lasting in the FPI group. A suppression of MR was found at PID 1 in vehicle-treated FPI and Sham groups. Decreases in the precursor form of BDNF were observed in different FPI groups at PIDs 7 and 14. These findings suggest that the increased sensitivity to stressful events during the first post-injury weeks, after a mild FPI, has an impact on hippocampal neuroplasticity. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Prolonged effect of stress at weaning on the brain serotonin metabolism and sexuality of female rats.

Science.gov (United States)

Tekes, K; Hantos, M; Gyenge, M; Karabélyos, Cs; Csaba, G

2006-12-01

Weanling female rats were stressed (by water and food deprivation for two days) and three months later the following indexes were studied: 5-HT and 5-HIAA levels in five brain regions, blood plasma and cerebrospinal fluid (CSF), sexual activity and nocistatin level of the plasma and CSF. The 5-HIAA content of hypothalamus and brainstem was significantly decreased (in the brainstem with one third) and in the striatum significantly increased. Plasma nocistatin level was significantly increased. Meyerson index and lordosis quotient were similar to control, but the estrus frequency almost doubled in the stressed animals. Much more defense reactions were observed in the stressed females during trials of mating. The results demonstrate that, 1) the perinatal period is not only sensitive to the remote-effects of stress but later could also be stress-sensitive critical periods, and 2) the continuously differentiating (e.g. bone marrow) cells are sensitive to late imprinting by stress, as well as to the brain and the sexual system.

The influence of stress on neuroinflammation and alterations in brain structure and function in major depressive disorder.

Science.gov (United States)

Kim, Yong-Ku; Won, Eunsoo

2017-06-30

Major depressive disorder (MDD) is a condition which has often been associated with chronic stress. The sympathetic nervous system is continuously activated without the normal counteraction of the parasympathetic nervous system under the influence of chronic stress. As a result, epinephrine and norepinephrine levels are increased, and acetylcholine levels are decreased, which in turn can increase the levels of pro-inflammatory cytokines. Peripheral inflammatory responses can access the brain, with neuroinflammation contributing to the increase in neurotoxic kynurenine pathway metabolites such as 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid, and decrease in neuroprotective metabolites such as kynurenic acid. Pro-inflammatory cytokines can also exert direct neurotoxic effects on specific brain regions. Previous imaging studies have reported associations between pro-inflammatory states and alterations in brain regions involved in emotional regulation, including the hippocampus, amygdala and anterior cingulate cortex. Alterations in structure and function of such brain areas due to the neurotoxic effects of increased inflammation may be associated with the pathophysiology of depression. This review focuses the influence of stress on neuroinflammation which may cause alterations in brain structure and function in MDD. Copyright © 2017. Published by Elsevier B.V.

Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

Science.gov (United States)

Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

2012-09-01

This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

Science.gov (United States)

Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

2015-01-01

In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

Brain susceptibility to oxidative stress in the perinatal period.

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Perrone, Serafina; Tataranno, Luisa M; Stazzoni, Gemma; Ramenghi, Luca; Buonocore, Giuseppe

2015-11-01

Oxidative stress (OS) occurs at birth in all newborns as a consequence of the hyperoxic challenge due to the transition from the hypoxic intrauterine environment to extrauterine life. Free radical (FRs) sources such as inflammation, hyperoxia, hypoxia, ischaemia-reperfusion, neutrophil and macrophage activation, glutamate and free iron release, all increases the OS during the perinatal period. Newborns, and particularly preterm infants, have reduced antioxidant defences and are not able to counteract the harmful effects of FRs. Energy metabolism is central to life because cells cannot exist without an adequate supply of ATP. Due to its growth, the mammalian brain can be considered as a steady-state system in which ATP production matches ATP utilisation. The developing brain is particularly sensitive to any disturbances in energy generation, and even a short-term interruption can lead to long-lasting and irreversible damage. Whenever energy failure develops, brain damage can occur. Accumulating evidence indicates that OS is implicated in the pathogenesis of many neurological diseases, such as intraventricular haemorrhage, hypoxic-ischaemic encephalopathy and epilepsy.

Up-regulation of Kir2.1 by ER stress facilitates cell death of brain capillary endothelial cells

International Nuclear Information System (INIS)

Kito, Hiroaki; Yamazaki, Daiju; Ohya, Susumu; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

2011-01-01

Highlights: → We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. → The ER stress facilitated the expression of inward rectifier K + channel (K ir 2.1) and induced sustained membrane hyperpolarization. → The membrane hyperpolarization induced sustained Ca 2+ entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. → The K ir 2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K + channel (K ir 2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K ir channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca 2+ concentration due to Ca 2+ influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K ir 2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.

Brain plasticity of rats exposed to prenatal immobilization stress

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Badalyan B. Yu.

2011-10-01

Full Text Available Aim. This histochemical and immunohistochemical study was aimed at examining the brain cellular structures of newborn rats exposed to prenatal immobilization (IMO stress. Methods. Histochemical method on detection of Ca2+-dependent acid phosphatase activity and ABC immunohistochemical technique. Results. Cell structures with radial astrocytes marker GFAP, neuroepithelial stem cell marker gene nestin, stem-cells marker and the hypothalamic neuroprotective proline-rich polypeptide PRP-1 (Galarmin, a natural cytokine of a common precursor to neurophysin vasopressin associated glycoprotein have been revealed in several brain regions. Conclusions. Our findings indicate the process of generation of new neurons in response to IMO and PRP-1 involvement in this recovery mechanism, as PRP-1-Ir was detected in the above mentioned cell structures, as well as in the neurons and nerve fibers.

Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats

NARCIS (Netherlands)

Lin, Yanhua; Ter Horst, Gert J.; Wichmann, Romy; Bakker, Petra; Liu, Aihua; Li, Xuejun; Westenbroek, Christel

Studies show that sex plays a role in stress-related depression, with women experiencing a higher vulnerability to its effect. Two major targets of antidepressants are brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element-binding protein (CREB). The aim of this

Differential targeting of brain stress circuits with a selective glucocorticoid receptor modulator

NARCIS (Netherlands)

Zalachoras, I.; Houtman, R.; Atucha, E.; Devos, R.; Tijssen, A.M.I.; Hu, P.; Lockey, P.M.; Datson, N.A.; Belanoff, J.K.; Lucassen, P.J.; Joëls, M.; de Kloet, E.R.; Roozendaal, B.; Hunt, H.; Meijer, O.C.

2013-01-01

Glucocorticoid receptor (GR) antagonism may be of considerable therapeutic value in stress-related psychopathology such as depression. However, blockade of all GR-dependent processes in the brain will lead to unnecessary and even counteractive effects, such as elevated endogenous cortisol levels.

Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice.

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Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Morsy, Safaa M Youssef; Omara, Enayat A; Sleem, Amany A

2014-05-01

Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

Differential changes of metabolic brain activity and interregional functional coupling in prefronto-limbic pathways during different stress conditions: Functional imaging in freely behaving rodent pups

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Joerg eBock

2012-05-01

Full Text Available The trumpet-tailed rat or degu (Octodon degus is an established model to investigate the consequences of early stress on the development of emotional brain circuits and behaviour. The aim of this study was to identify brain circuits, that respond to different stress conditions and to test if acute stress alters functional coupling of brain activity among prefrontal and limbic regions. Using functional imaging (2-Fluoro-deoxyglucose method in 8 day old male degu pups the following stress conditions were compared: (A pups together with parents and siblings (control, (B separation of the litter from the parents, (C individual separation from parents and siblings, (D individual separation and presentation of maternal calls. Condition (B significantly downregulated brain activity in the prefrontal cortex, hippocampus, nucleus accumbens and sensory areas compared to controls. Activity decrease was even more pronounced during condition (C, where, in contrast to all other regions, activity in the PAG was increased. Interestingly, brain activity in stress-associated brain regions such as the amygdala and habenula was not affected. In condition (D maternal vocalizations reactivated brain activity in the cingulate and precentral medial cortex, nucleus accumbens and striatum and in sensory areas. In contrast, reduced activity was measured in the prelimbic and infralimbic cortex and in the hippocampus and amygdala. Correlation analysis revealed complex, region- and situation-specific changes of interregional functional coupling among prefrontal and limbic brain regions during stress exposure. We show here for the first time that early life stress results in a widespread reduction of brain activity in the infant brain and changes interregional functional coupling. Moreover, maternal vocalizations can partly buffer stress-induced decrease in brain activity in some regions and evoked very different functional coupling patterns compared to the three other

Brain, lung, and heart oxidative stress assessment of an over-the ...

African Journals Online (AJOL)

We evaluated the brain, lung, and heart oxidative stress in rats exposed to aerosol of an over-thecounter pyrethroid insecticide product in Nigeria. The experimental animals were randomly divided into four groups: group I (control) was not exposed to the insecticide aerosol, while groups II, III, and IV were exposed to 6.0 mL ...

Interactions Between Stress and Sex in Microbial Responses Within the Microbiota-Gut-Brain Axis in a Mouse Model.

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Tsilimigras, Matthew C B; Gharaibeh, Raad Z; Sioda, Michael; Gray, Laura; Fodor, Anthony A; Lyte, Mark

2018-05-01

Animal models are frequently used to examine stress response, but experiments seldom include females. The connection between the microbiota-gut-brain axis and behavioral stress response is investigated here using a mixed-sex mouse cohort. CF-1 mice underwent alternating days of restraint and forced swim for 19 days (male n = 8, female n = 8) with matching numbers of control animals at which point the 16S rRNA genes of gut microbiota were sequenced. Mixed linear models accounting for stress status and sex with individuals nested in cage to control for cage effects evaluated these data. Murine behaviors in elevated plus-maze, open-field, and light/dark box were investigated. Community-level associations with sex, stress, and their interaction were significant. Males had higher microbial diversity than females (p = .025). Of the 638 operational taxonomic units detected in at least 25% of samples, 94 operational taxonomic units were significant: 31 (stress), 61 (sex), and 34 (sex-stress interaction). Twenty of the 39 behavioral measures were significant for stress, 3 for sex, and 6 for sex-stress. However, no significant associations between behavioral measures and specific microbes were detected. These data suggest sex influences stress response and the microbiota-gut-brain axis and that studies of behavior and the microbiome therefore benefit from consideration of how sex differences drive behavior and microbial community structure. Host stress resilience and absence of associations between stress-induced behaviors with specific microbes suggests that hypothalamic-pituitary-adrenal axis activation represents a threshold for microbial influence on host behavior. Future studies are needed in examining the intersection of sex, stress response, and the microbiota-gut-brain axis.

Intrauterine Exposure to Maternal Stress Alters Bdnf IV DNA Methylation and Telomere Length in the Brain of Adult Rat Offspring

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Blaze, Jennifer; Asok, Arun; Borrelli, Kristyn; Tulbert, Christine; Bollinger, Justin; Ronca Finco, April E.; Roth, Tania L.

2017-01-01

DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavioral outcomes. Here, we measured methylation of Brain-derived neurotrophic factor (Bdnf), a gene important in development and plasticity, and telomere length in the brains of adult rat male and female offspring whose mothers were exposed to unpredictable and variable stressors throughout gestation. Males exposed to prenatal stress had greater methylation (Bdnf IV) in the medial prefrontal cortex (mPFC) compared to non-stressed controls. Further, prenatally-stressed males had shorter telomeres than controls in the mPFC. This study provides the first evidence in a rodent model of an association between prenatal stress exposure and subsequent shorter brain telomere length. Together findings indicate a long-term impact of prenatal stress on DNA methylation and telomere biology with relevance for behavioral and health outcomes, and contribute to a growing literature linking stress to intergenerational epigenetic alterations and changes in telomere length.

Time Course of Cerebrovascular Reactivity in Patients Treated for Unruptured Intracranial Aneurysms: A One-Year Transcranial Doppler and Acetazolamide Follow-Up Study

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Marianne Lundervik Bøthun

2018-01-01

Full Text Available Background. Cerebrovascular reactivity (CVR is often impaired in the early phase after aneurysmal subarachnoid hemorrhage. There is, however, little knowledge about the time course of CVR in patients treated for unruptured intracranial aneurysms (UIA. Methods. CVR, assessed by transcranial Doppler and acetazolamide test, was examined within the first postoperative week after treatment for UIA and reexamined one year later. Results. Of 37 patients initially assessed, 34 were reexamined after one year. Bilaterally, baseline and acetazolamide-induced blood flow velocities were higher in the postoperative week compared with one year later (p<0.001. CVR on the ipsilateral side of treatment was lower in the initial examination compared with follow-up (58.9% versus 66.1%, p=0.04. There was no difference in CVR over time on the contralateral side (63.4% versus 65.0%, p=0.65. When mean values of right and left sides were considered there was no difference in CVR between exams. Larger aneurysm size was associated with increased change in CVR (p=0.04, and treatment with clipping was associated with 13.8%-point increased change in CVR compared with coiling (p=0.03. Conclusion. Patients with UIA may have a temporary reduction in CVR on the ipsilateral side after aneurysm treatment. The change in CVR appears more pronounced for larger-sized aneurysms and in patients treated with clipping. We recommend that ipsilateral and contralateral CVR should be assessed separately, as mean values can conceal side-differences.

Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome.

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Moloney, Rachel D; Johnson, Anthony C; O'Mahony, Siobhain M; Dinan, Timothy G; Greenwood-Van Meerveld, Beverley; Cryan, John F

2016-02-01

Visceral pain is a global term used to describe pain originating from the internal organs of the body, which affects a significant proportion of the population and is a common feature of functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience comorbid behavioral disorders, such as anxiety or depression; thus, IBS is described as a disorder of the gut-brain axis. Stress is implicated in the development and exacerbation of visceral pain disorders. Chronic stress can modify central pain circuitry, as well as change motility and permeability throughout the gastrointestinal (GI) tract. More recently, the role of the gut microbiota in the bidirectional communication along the gut-brain axis, and subsequent changes in behavior, has emerged. Thus, stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviors. This review will highlight the evidence by which stress and the gut microbiota interact in the regulation of visceral nociception. We will focus on the influence of stress on the microbiota and the mechanisms by which microbiota can affect the stress response and behavioral outcomes with an emphasis on visceral pain. © 2015 John Wiley & Sons Ltd.

Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses.

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Low, Lucie A; Bauer, Lucy C; Pitcher, Mark H; Bushnell, M Catherine

2016-08-01

With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the "nociceptive" central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli.

AGE-INDEPENDENT, GREY-MATTER-LOCALIZED, BRAIN ENHANCED OXIDATIVE STRESS IN MALE FISCHER 344 RATS,1,2

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While studies showed that aging is accompanied by increased exposure of the brain to oxidative stress, others have not detected any age-correlated differences in levels of markers of oxidative stress. Use of conventional markers of oxidative damage in vivo, which may be formed ex...

Brain aluminium accumulation and oxidative stress in the presence of calcium silicate dental cements.

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Demirkaya, K; Demirdöğen, B Can; Torun, Z Öncel; Erdem, O; Çırak, E; Tunca, Y M

2017-10-01

Mineral trioxide aggregate (MTA) is a calcium silicate dental cement used for various applications in dentistry. This study was undertaken to test whether the presence of three commercial brands of calcium silicate dental cements in the dental extraction socket of rats would affect the brain aluminium (Al) levels and oxidative stress parameters. Right upper incisor was extracted and polyethylene tubes filled with MTA Angelus, MTA Fillapex or Theracal LC, or left empty for the control group, were inserted into the extraction socket. Rats were killed 7, 30 or 60 days after operation. Brain tissues were obtained before killing. Al levels were measured by atomic absorption spectrometry. Thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined using spectrophotometry. A transient peak was observed in brain Al level of MTA Angelus group on day 7, while MTA Fillapex and Theracal LC groups reached highest brain Al level on day 60. Brain TBARS level, CAT, SOD and GPx activities transiently increased on day 7 and then returned to almost normal levels. This in vivo study for the first time indicated that initial washout may have occurred in MTA Angelus, while element leaching after the setting is complete may have taken place for MTA Fillapex and Theracal LC. Moreover, oxidative stress was induced and antioxidant enzymes were transiently upregulated. Further studies to search for oxidative neuronal damage should be done to completely understand the possible toxic effects of calcium silicate cements on the brain.

ESR imaging for estimation oxidative stress in the brain of rats

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Yokoyama, Hidekatsu; Itoh, Osam; Aoyama, Masaaki; Obara, Heitaro; Ohya, Hiroaki; Kamada, Hitoshi [Inst. for Life Support Technology, Matsuei, Yamagata (Japan)

2002-04-01

ESR imaging for estimating intracerebral oxidative stress of rats was performed. An acyl-protected hydroxylamine, 1-acetoxy-3-carbamoyl-2,2,5,5-tetramethylpyrrolidine (ACP), is a very stable non-radical compound outside cells, however, within cells, it is easily deprotected with esterase to yield 1-hydroxy-3-carbamoyl-2,2,5,5-tetramethylpyrrolidine, which is oxidized by oxidative stress to yield an ESR-detectable stable nitroxide radical, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl. Thus signal intensity in the ESR image reflects the strength of intracellular oxidative stress. From in vivo ESR image data of the brain of rats that received ACP, the average values of ESR signal intensity from the hippocampus, striatum, and cerebral cortex were computed. This imaging technique was applied to an epileptic seizure model. As a result, it was found that following a kainic acid-induced seizure, the oxidative stress in the hippocampus and striatum is enhanced, but not so in the cerebral cortex. (author)

Inflammatory cause of metabolic syndrome via brain stress and NF-κB

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Cai, Dongsheng; Liu, Tiewen

2012-01-01

Metabolic syndrome, a network of medical disorders that greatly increase the risk for developing metabolic and cardiovascular diseases, has reached epidemic levels in many areas of today's world. Despite this alarming medicare situation, scientific understandings on the root mechanisms of metabolic syndrome are still limited, and such insufficient knowledge contributes to the relative lack of effective treatments or preventions for related diseases. Recent interdisciplinary studies from neuroendocrinology and neuroimmunology fields have revealed that overnutrition can trigger intracellular stresses to cause inflammatory changes mediated by molecules that control innate immunity. This type of nutrition-related molecular inflammation in the central nervous system, particularly in the hypothalamus, can form a common pathogenic basis for the induction of various metabolic syndrome components such as obesity, insulin resistance, and hypertension. Proinflammatory NF-κB pathway has been revealed as a key molecular system for pathologic induction of brain inflammation, which translates overnutrition and resulting intracellular stresses into central neuroendocrine and neural dysregulations of energy, glucose, and cardiovascular homeostasis, collectively leading to metabolic syndrome. This article reviews recent research advances in the neural mechanisms of metabolic syndrome and related diseases from the perspective of pathogenic induction by intracellular stresses and NF-κB pathway of the brain. PMID:22328600

Mineralocorticoid receptor blockade prevents stress-induced modulation of multiple memory systems in the human brain.

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Schwabe, Lars; Tegenthoff, Martin; Höffken, Oliver; Wolf, Oliver T

2013-12-01

Accumulating evidence suggests that stress may orchestrate the engagement of multiple memory systems in the brain. In particular, stress is thought to favor dorsal striatum-dependent procedural over hippocampus-dependent declarative memory. However, the neuroendocrine mechanisms underlying these modulatory effects of stress remain elusive, especially in humans. Here, we targeted the role of the mineralocorticoid receptor (MR) in the stress-induced modulation of dorsal striatal and hippocampal memory systems in the human brain using a combination of event-related functional magnetic resonance imaging and pharmacologic blockade of the MR. Eighty healthy participants received the MR antagonist spironolactone (300 mg) or a placebo and underwent a stressor or control manipulation before they performed, in the scanner, a classification task that can be supported by the hippocampus and the dorsal striatum. Stress after placebo did not affect learning performance but reduced explicit task knowledge and led to a relative increase in the use of more procedural learning strategies. At the neural level, stress promoted striatum-based learning at the expense of hippocampus-based learning. Functional connectivity analyses showed that this shift was associated with altered coupling of the amygdala with the hippocampus and dorsal striatum. Mineralocorticoid receptor blockade before stress prevented the stress-induced shift toward dorsal striatal procedural learning, same as the stress-induced alterations of amygdala connectivity with hippocampus and dorsal striatum, but resulted in significantly impaired performance. Our findings indicate that the stress-induced shift from hippocampal to dorsal striatal memory systems is mediated by the amygdala, required to preserve performance after stress, and dependent on the MR. © 2013 Society of Biological Psychiatry.

Brain Transcriptome Profiling Analysis of Nile Tilapia (Oreochromis niloticus Under Long-Term Hypersaline Stress

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Yan Liu

2018-03-01

Full Text Available The fish brain plays an important role in controlling growth, development, reproduction, and adaptation to environmental change. However, few studies stem from the perspective of whole transcriptome change in a fish brain and its response to long-term hypersaline stress. This study compares the differential transcriptomic responses of juvenile Nile tilapia (Oreochromis niloticus maintained for 8 weeks in brackish water (16 practical salinity units, psu and in freshwater. Fish brains from each treatment were collected for RNA-seq analysis to identify potential genes and pathways responding to hypersaline stress. A total of 27,089 genes were annotated, and 391 genes were expressed differently in the salinity treatment. Ten pathways containing 40 differentially expressed genes were identified in the tilapia brain. Antigen processing and presentation and phagosome were the two principally affected pathways in the immune system. Thirty-one of 40 genes were involved in various expressions associated with environmental information processing pathways such as neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, the Jak-STAT signaling pathway, cell adhesion molecules (CAMs, and the PI3K-Akt signaling pathway, which are the upstream pathways for modulation of immunity and osmoregulation. The most-changed genes (>5-fold were all down-regulated, including four growth hormone/prolactin gene families, i.e., prolactin precursor (−10.62, prolactin-1 (−11, somatotropin (−10.15, somatolactin-like (−6.18, and two other genes [thyrotropin subunit beta (−7.73 and gonadotropin subunit beta-2 (−5.06] that stimulated prolactin release in tilapia. The downregulation pattern of these genes corroborates the decrease in tilapia immunity with increasing salinity and reveals an adaptive mechanism of tilapia to long-term hypersaline stress. Ovarian steroidogenesis, isoquinoline alkaloid biosynthesis, and phenylalanine metabolism are the

Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions

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Salvadore Christopher

2004-09-01

Full Text Available Abstract Background The mitogen-activated protein kinases (MAPKs have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2 has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6, were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE binding (CREB protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined. Results A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3 were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold. Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex areas. Conclusions Swim stress specifically and markedly

Glucose metabolism in different regions of the rat brain under hypokinetic stress influence

Science.gov (United States)

Konitzer, K.; Voigt, S.

1980-01-01

Glucose metabolism in rats kept under long term hypokinetic stress was studied in 7 brain regions. Determination was made of the regional levels of glucose, lactate, glutamate, glutamine, aspartate, gamma-aminobutyrate and the incorporation of C-14 from plasma glucose into these metabolites, in glycogen and protein. From the content and activity data the regional glucose flux was approximated quantitatively. Under normal conditions the activity gradient cortex and frontal pole cerebellum, thalamus and mesencephalon, hypothalamus and pons and medulla is identical with that of the regional blood supply (measured with I131 serum albumin as the blood marker). Within the first days of immobilization a functional hypoxia occurred in all brain regions and the utilization of cycle amino acids for protein synthesis was strongly diminished. After the first week of stress the capillary volumes of all regions increased, aerobic glucose metabolism was enhanced (factors 1.3 - 2.0) and the incorporation of glucose C-14 via cycle amino acids into protein was considerably potentiated. The metabolic parameters normalized between the 7th and 11th week of stress. Blood supply and metabolic rate increased most in the hypothalamus.

Social information changes stress hormone receptor expression in the songbird brain.

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Cornelius, Jamie M; Perreau, Gillian; Bishop, Valerie R; Krause, Jesse S; Smith, Rachael; Hahn, Thomas P; Meddle, Simone L

2018-01-01

Social information is used by many vertebrate taxa to inform decision-making, including resource-mediated movements, yet the mechanisms whereby social information is integrated physiologically to affect such decisions remain unknown. Social information is known to influence the physiological response to food reduction in captive songbirds. Red crossbills (Loxia curvirostra) that were food reduced for several days showed significant elevations in circulating corticosterone (a "stress" hormone often responsive to food limitation) only if their neighbors were similarly food restricted. Physiological responses to glucocorticoid hormones are enacted through two receptors that may be expressed differentially in target tissues. Therefore, we investigated the influence of social information on the expression of the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA in captive red crossbill brains. Although the role of MR and GR in the response to social information may be highly complex, we specifically predicted social information from food-restricted individuals would reduce MR and GR expression in two brain regions known to regulate hypothalamic-pituitary-adrenal (HPA) activity - given that reduced receptor expression may lessen the efficacy of negative feedback and release inhibitory tone on the HPA. Our results support these predictions - offering one potential mechanism whereby social cues could increase or sustain HPA-activity during stress. The data further suggest different mechanisms by which metabolic stress versus social information influence HPA activity and behavioral outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A study of acetazolamide-induced changes in cerebral blood flow using {sup 99m}Tc HMPAO SPECT in patients with cerebrovascular disease

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Asenbaum, S. [Neurological Clinic, Univ. Vienna (Austria); Reinprecht, A. [Neurosurgical Clinic, Univ. Vienna (Austria); Bruecke, T. [Neurological Clinic, Univ. Vienna (Austria); Wenger, S. [Neurological Clinic, Univ. Vienna (Austria); Podreka, I. [Neurological Clinic, Univ. Vienna (Austria); Deecke, L. [Neurological Clinic, Univ. Vienna (Austria)

1995-01-01

For semiquantification of SPECT studies we tried to calculate cerebral {sup 99m}Tc-HMPAO uptake related to injected dose and estimated brain volume. The method was applied to SPECT investigations of 27 patients who had a least one ischaemic attack and a confirmed 80-100% stenosis of the corresponding internal carotid artery (ICA). Vascular reactivity was tested by parenteral administration of acetazolamide (AZ). Increase in HMPAO uptake after AZ was evident in both hemispheres, although the increase (AZ effect) was significantly lower in the affected hemisphere (+24% versus +28%). No interhemispheric uptake differences were seen in patients with largely normal SPECT studies, although local asymmetries in HMPAO deposition were visible. Patients with low density lesions on CT and with a well-demarcated lesion in the same location on SPECT revealed interhemispheric uptake differences, with lower uptake on the affected side. This was not due solely to alterations in the lesion, but also to reduced HMPAO uptake and AZ effect in the surrounding area. The AZ effect showed no correlation with angiographic findings, indicating no major haemodynamic influence of the ICA stenosis on cerebral hemisphere perfusion. Calculated cerebral HMPAO uptake changes after AZ administration were in good accordance with absolute cerebral blood flow measurements, and made interindividual comparisons possible. However, as changes in the area around an infarct or local reduction in vascular reserve may not be reproduced adequately by uptake calculations, visual inspection is still necessary. (orig.)

Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells

International Nuclear Information System (INIS)

Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

2016-01-01

The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4–5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba 2+ -sensitive inward rectifier K + current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca 2+ imaging study revealed that the hypoxic stress enhanced store-operated Ca 2+ (SOC) entry, which was significantly reduced in the presence of 100 μM Ba 2+ . On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba 2+ . We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca 2+ entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. -- Highlights: •Hypoxic culture of brain endothelial cells (BEC) caused membrane hyperpolarization. •This hyperpolarization was due to the increased expression of Kir2.1 channels. •Hypoxia enhanced store-operated Ca 2+ (SOC) entry via Kir2.1 up-regulation. •Expression levels of putative SOC channels were not affected by hypoxia. �

Endoplasmic reticulum stress in the brain subfornical organ contributes to sex differences in angiotensin-dependent hypertension in rats.

Science.gov (United States)

Dai, S-Y; Fan, J; Shen, Y; He, J-J; Peng, W

2016-05-01

Endoplasmic reticulum (ER) stress in the brain subfornical organ (SFO), a key cardiovascular regulatory centre, has been implicated in angiotensin (ANG) II-induced hypertension in males; however, the contribution of ER stress to ANG II-induced hypertension in females is unknown. Female hormones have been shown to prevent ER stress in the periphery. We tested the hypothesis that females are less susceptible to ANG II-induced SFO ER stress than males, leading to sex differences in hypertension. Male, intact and ovariectomized (OVX) female rats received a continuous 2-week subcutaneous infusion of ANG II or saline. Additional male, intact and OVX female rats received intracerebroventricular (ICV) injection of ER stress inducer tunicamycin. ANG II, but not saline, increased blood pressure (BP) in both males and females, but intact females exhibited smaller increase in BP and less depressor response to ganglionic blockade compared with males or OVX females. Molecular studies revealed that ANG II elevated expression of ER stress biomarkers and Fra-like activity in the SFO in both males and females; however, elevations in these parameters were less in intact females than in males or OVX females. Moreover, ICV tunicamycin induced smaller elevation in BP and less increase in expression of ER stress biomarkers in the SFO in intact females compared with males or OVX females. The results suggest that differences in ANG II-induced brain ER stress between males and females contribute to sex differences in ANG II-mediated hypertension and that oestrogen protects females against ANG II-induced brain ER stress. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Pro-oxidant effects in the brain of rats concurrently exposed to uranium and stress

International Nuclear Information System (INIS)

Linares, Victoria; Sanchez, Domenec J.; Belles, Montserrat; Albina, Luisa; Gomez, Mercedes; Domingo, Jose L.

2007-01-01

Metal toxicity may be associated with increased rates of reactive oxygen species (ROS) generation within the central nervous system (CNS). Although the kidney is the main target organ for uranium (U) toxicity, this metal can also accumulate in brain. In this study, we investigated the modifications on endogenous antioxidant capacity and oxidative damage in several areas of the brain of U-exposed rats. Eight groups of adult male rats received uranyl acetate dihydrate (UAD) in the drinking water at 0, 10, 20, and 40 mg/kg/day for 3 months. Animals in four groups were concurrently subjected to restraint stress during 2 h/day throughout the study. At the end of the experimental period, cortex, hippocampus and cerebellum were removed and processed to examine the following stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as U concentrations. The results show that U significantly accumulated in hippocampus, cerebellum and cortex after 3 months of exposure. Moreover, UAD exposure promoted oxidative stress in these cerebral tissues. In cortex and cerebellum, TBARS levels were positively correlated with the U content, while in cerebellum GSSG and GSH levels were positively and negatively correlated, respectively, with U concentrations. In hippocampus, CAT and SOD activities were positively correlated with U concentration. The present results suggest that chronic oral exposure to UAD can cause progressive perturbations on physiological brain levels of oxidative stress markers. Although at the current UAD doses restraint scarcely showed additional adverse effects, its potential influence should not be underrated

Assessment of the hemodynamic changes after EDAS combined with bifrontal EGS in pediatric patients with moyamoya disease

Energy Technology Data Exchange (ETDEWEB)

Song, Yoo Sung; Kim, Yu Kyeong; Lee, Jae Sung; Kim, Seung Ki; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

2007-07-01

To assess the effect of encephaloduroarteriosynangiosis (EDAS) with or without bifrontal encephalogaleosynangiosis (EGS) in children with moyamoya disease, we evaluated cerebral hemodynamic changes using brain Tc-99m HMPAO SPECT. Total 34 pediatric patients (M: F=12:22, mean age;93 yrs) enrolled. Bypass surgery for both hemispheres (EDAS with EGS on one side, and EDAS on the other side) in 25 patients, unilateral EDAS with EGS in 7, and unilateral EDAS only in 2 were underwent. Perfusion SPECT before surgery, and 4 to 18 months after final surgery were done. The vascular territories for ICA, MCA and the brain regions for the frontal, parietal, temporal, and the occipital cortices were determined using standard ROls based on K-SPAM. Additionally, medial frontal cortex was selected to assess the effect of EGS. Basal/acetazolamide challenged cerebral blood flow (CBF), and cerebral vascular index (CVRI) were determined using normalized regional brain uptake to the cerebellum. 24 patients became symptom free, and 6 were improved but having some residual symptoms at the last follow up period. The other 3 were worsened after operation. Overall basal/acetazolamide stress CBF and CVRI for each brain region after surgery were increased, however, only the changes of CVRI were significant. Meanwhile, the improvement of CBF or CVRI in the brain regions ipsilateral to the hemisphere having EDAS with EGS was not significantly different when compared with those for the brain regions with EDAS only. Also, the hemodynamic improvement for the mesial frontal cortex in patients after EDAS with EGS was not significant, and showed no difference with those in patient with EDAS only. Quantitative perfusion SPECT demonstrated the hemodynamic improvement after EDAS with or without EGS in pediatric moyamoya disease. Cerebrovascular reserve showed meaningful improvement after surgery, implicating the effect of vascular anastomosis in ischemic areas.

Assessment of the hemodynamic changes after EDAS combined with bifrontal EGS in pediatric patients with moyamoya disease

International Nuclear Information System (INIS)

Song, Yoo Sung; Kim, Yu Kyeong; Lee, Jae Sung; Kim, Seung Ki; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul

2007-01-01

To assess the effect of encephaloduroarteriosynangiosis (EDAS) with or without bifrontal encephalogaleosynangiosis (EGS) in children with moyamoya disease, we evaluated cerebral hemodynamic changes using brain Tc-99m HMPAO SPECT. Total 34 pediatric patients (M: F=12:22, mean age;93 yrs) enrolled. Bypass surgery for both hemispheres (EDAS with EGS on one side, and EDAS on the other side) in 25 patients, unilateral EDAS with EGS in 7, and unilateral EDAS only in 2 were underwent. Perfusion SPECT before surgery, and 4 to 18 months after final surgery were done. The vascular territories for ICA, MCA and the brain regions for the frontal, parietal, temporal, and the occipital cortices were determined using standard ROls based on K-SPAM. Additionally, medial frontal cortex was selected to assess the effect of EGS. Basal/acetazolamide challenged cerebral blood flow (CBF), and cerebral vascular index (CVRI) were determined using normalized regional brain uptake to the cerebellum. 24 patients became symptom free, and 6 were improved but having some residual symptoms at the last follow up period. The other 3 were worsened after operation. Overall basal/acetazolamide stress CBF and CVRI for each brain region after surgery were increased, however, only the changes of CVRI were significant. Meanwhile, the improvement of CBF or CVRI in the brain regions ipsilateral to the hemisphere having EDAS with EGS was not significantly different when compared with those for the brain regions with EDAS only. Also, the hemodynamic improvement for the mesial frontal cortex in patients after EDAS with EGS was not significant, and showed no difference with those in patient with EDAS only. Quantitative perfusion SPECT demonstrated the hemodynamic improvement after EDAS with or without EGS in pediatric moyamoya disease. Cerebrovascular reserve showed meaningful improvement after surgery, implicating the effect of vascular anastomosis in ischemic areas

Activation of stress signaling molecules in bat brain during arousal from hibernation.

Science.gov (United States)

Lee, Moonyong; Choi, Inho; Park, Kyoungsook

2002-08-01

Induction of glucose-regulated proteins (GRPs) is a ubiquitous intracellular response to stresses such as hypoxia, glucose starvation and acidosis. The induction of GRPs offers some protection against these stresses in vitro, but the specific role of GRPs in vivo remains unclear. Hibernating bats present a good in vivo model to address this question. The bats must overcome local high oxygen demand in tissue by severe metabolic stress during arousal thermogenesis. We used brain tissue of a temperate bat Rhinolopus ferrumequinum to investigate GRP induction by high metabolic oxygen demand and to identify associated signaling molecules. We found that during 30 min of arousal, oxygen consumption increased from nearly zero to 11.9/kg/h, which was about 8.7-fold higher than its active resting metabolic rate. During this time, body temperature rose from 7 degrees C to 35 degrees C, and levels of TNF-alpha and lactate in brain tissue increased 2-2.5-fold, indicating a high risk of oxygen shortage. Concomitantly, levels of GRP75, GRP78 and GRP94 increased 1.5-1.7-fold. At the same time, c-Jun N-terminal protein kinase (JNK) activity increased 6.4-fold, and extracellular signal-regulated protein kinase (ERK) activity decreased to a similar degree (6.1-fold). p38 MAPK activity was very low and remained unchanged during arousal. In addition, survival signaling molecules protein kinase B (Akt) and protein kinase C (PKC) were activated 3- and 5-fold, respectively, during arousal. Taken together, our results showed that bat brain undergoes high oxygen demand during arousal from hibernation. Up-regulation of GRP proteins and activation of JNK, PKCgamma and Akt may be critical for neuroprotection and the survival of bats during the repeated process.

Estrogen, stress and the brain: progress toward unraveling gender discrepancies in major depressive disorder.

Science.gov (United States)

Shansky, Rebecca M

2009-07-01

Women are twice as likely as men to develop major depressive disorder (MDD) and, while the neurobiological factors underlying this discrepancy are yet to be identified, estrogen almost certainly plays a role. MDD can be precipitated or exacerbated by exposure to stress and there is substantial evidence to suggest that estrogen can interact with stress systems to produce unique stress effects in females. This review integrates current research in animal models regarding estrogen-stress interactions in three areas of the brain known to be relevant to MDD: the hippocampus, the amygdala and the prefrontal cortex. The results from these studies are discussed in the context of MDD, and their implications for future treatment of MDD in women are explored.

Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.

Science.gov (United States)

Beitnere, Ulrika; Dzirkale, Zane; Isajevs, Sergejs; Rumaks, Juris; Svirskis, Simons; Klusa, Vija

2014-12-15

The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol. Copyright © 2014 Elsevier B.V. All rights reserved.

Stress-Induced Recruitment of Bone Marrow-Derived Monocytes to the Brain Promotes Anxiety-Like Behavior

Science.gov (United States)

Wohleb, Eric S.; Powell, Nicole D.

2013-01-01

Social stress is associated with altered immunity and higher incidence of anxiety-related disorders. Repeated social defeat (RSD) is a murine stressor that primes peripheral myeloid cells, activates microglia, and induces anxiety-like behavior. Here we show that RSD-induced anxiety-like behavior corresponded with an exposure-dependent increase in circulating monocytes (CD11b+/SSClo/Ly6Chi) and brain macrophages (CD11b+/SSClo/CD45hi). Moreover, RSD-induced anxiety-like behavior corresponded with brain region-dependent cytokine and chemokine responses involved with myeloid cell recruitment. Next, LysM-GFP+ and GFP+ bone marrow (BM)-chimeric mice were used to determine the neuroanatomical distribution of peripheral myeloid cells recruited to the brain during RSD. LysM-GFP+ mice showed that RSD increased recruitment of GFP+ macrophages to the brain and increased their presence within the perivascular space (PVS). In addition, RSD promoted recruitment of GFP+ macrophages into the PVS and parenchyma of the prefrontal cortex, amygdala, and hippocampus of GFP+ BM-chimeric mice. Furthermore, mice deficient in chemokine receptors associated with monocyte trafficking [chemokine receptor-2 knockout (CCR2KO) or fractalkine receptor knockout (CX3CR1KO)] failed to recruit macrophages to the brain and did not develop anxiety-like behavior following RSD. Last, RSD-induced macrophage trafficking was prevented in BM-chimeric mice generated with CCR2KO or CX3CR1KO donor cells. These findings indicate that monocyte recruitment to the brain in response to social stress represents a novel cellular mechanism that contributes to the development of anxiety. PMID:23966702

From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth.

Science.gov (United States)

Fumagalli, Monica; Provenzi, Livio; De Carli, Pietro; Dessimone, Francesca; Sirgiovanni, Ida; Giorda, Roberto; Cinnante, Claudia; Squarcina, Letizia; Pozzoli, Uberto; Triulzi, Fabio; Brambilla, Paolo; Borgatti, Renato; Mosca, Fabio; Montirosso, Rosario

2018-01-01

Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (SLC6A4). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and SLC6A4 methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. SLC6A4 methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of SLC6A4 methylation at NICU discharge. Moreover, higher SLC6A4 discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in SLC6A4 methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain.

Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Kito, Hiroaki [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Yamazaki, Daiju [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Ohya, Susumu; Yamamura, Hisao [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp [Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan)

2011-07-29

Highlights: {yields} We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. {yields} The ER stress facilitated the expression of inward rectifier K{sup +} channel (K{sub ir}2.1) and induced sustained membrane hyperpolarization. {yields} The membrane hyperpolarization induced sustained Ca{sup 2+} entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. {yields} The K{sub ir}2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K{sup +} channel (K{sub ir}2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K{sub ir} channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca{sup 2+} concentration due to Ca{sup 2+} influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K{sub ir}2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.

Evaluation of successive Tc-99m brain angiography and vasoactive drugs on occlusive cerebrovascular disease

International Nuclear Information System (INIS)

Shimamura, Osamu

1986-01-01

Cerebral circulation in the patients with unilateral occlusive cerebrovascular disease (CVD) in chronic stage was evaluated by radionuclide angiography (RNA) using Tc-99m pertechnetate. RNA (each Tc-99m dose = 20 mCi) was repeated in short time interval. Employed parameters were as follows; appearance to peak time (APT), brain transit time (BTT), peak count (PC) and up slope (US). These parameters were calculated from time activity curve (TAC) of ''region of interest'' on each hemisphere and the values obtained in affected side were compared with those of normal side and control hemisphere. Reproducibility of these values were satisfactory in PC and US. The results obtained were as follows: In affected hemisphere, PC and US were significantly reduced, while APT and BTT were not significantly affected. The ratio of PC and US between left and right hemispheres increased in the patients with CVD and the latter was particularly significant to detect the abnormality. Effect of vasoactive drugs such as papaverine, acetazolamide, angiotensin II or methoxamine on these parameters was studied in 24 patients with CVD and 16 patients without CVD. Papaverine and acetazolamide increased significantly PC and US in normal hemisphere of patients without CVD and US in normal hemisphere of patients with CVD, while US in these hemispheres were decreased under high blood pressure induced by angiotensin II and methoxamine. These responses, however, were mild or not detected in the affected hemispheres. (J.P.N.)

Dietary l-tryptophan leaves a lasting impression on the brain and the stress response

DEFF Research Database (Denmark)

Höglund, Erik; Øverli, Øyvind; Åberg Andersson, Madelene

2017-01-01

Comparative models suggest that effects of dietary tryptophan (Trp) on brain serotonin (5-hydroxytryptamine; 5-HT) neurochemistry and stress responsiveness are present throughout the vertebrate lineage. Moreover, hypothalamic 5-HT seems to play a central role in control of the neuroendocrine stre...

Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao [Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp [Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan)

2016-08-05

The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4–5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba{sup 2+}-sensitive inward rectifier K{sup +} current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca{sup 2+} imaging study revealed that the hypoxic stress enhanced store-operated Ca{sup 2+} (SOC) entry, which was significantly reduced in the presence of 100 μM Ba{sup 2+}. On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba{sup 2+}. We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca{sup 2+} entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. -- Highlights: •Hypoxic culture of brain endothelial cells (BEC) caused membrane hyperpolarization. •This hyperpolarization was due to the increased expression of Kir2.1 channels. •Hypoxia enhanced store-operated Ca{sup 2+} (SOC) entry via Kir2.1 up-regulation. •Expression levels of putative SOC

Stress hormonal changes in the brain and plasma after acute noise exposure in mice.

Science.gov (United States)

Jin, Sang Gyun; Kim, Min Jung; Park, So Young; Park, Shi Nae

2017-06-01

To investigate the effects of acute noise stress on two amine stress hormones, norepinephrine (NE) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain and plasma of mice after noise exposure. Mice were grouped into the control and noise groups. Mice in the noise group were exposed to white noise of 110dB sound pressure level for 60min. Auditory brainstem response thresholds, distortion product otoacoustic emissions, the organ of Corti grading scores, western blots of NE/5-HIAA in the whole brain and hippocampus, and the plasma levels of NE/5-HIAA were compared between the two groups. Significant hearing loss and cochlear damage were demonstrated in the noise group. NE and 5-HIAA in the hippocampus were elevated in the noise group (p=0.019/0.022 for NE/5-HIAA vs. the control). Plasma levels of NE and 5-HIAA were not statistically different between the groups (p=0.052/0.671 for NE/5-HIAA). Hearing loss with outer hair cell dysfunction and morphological changes of the organ of Corti after noise exposure in C57BL/6 mice proved the reliability of our animal model as an acute noise stress model. NE and 5-HIAA are suggested to be the potential biomarkers for acute noise stress in the hippocampus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans.

Science.gov (United States)

Frodl, Thomas; O'Keane, Veronica

2013-04-01

There is evidence that excessive stress exposure of the brain, mediated through the neurotoxic effects of cortisol and possibly neuroinflammation, causes damage to brain structure and function: the glucocorticoid cascade hypothesis. Functional changes of hypothalamic-pituitary-adrenal (HPA) axis as well as alterations in brain structures like the hippocampus have been consistently reported in major depression. However, there has not been a lot of emphasis on bringing findings from studies on early childhood stress, HPA axis functioning and hippocampal imaging together. This is the subject for this systematic review of the literature on how developmental stress, specifically childhood maltreatment, may impact on HPA axis function and hippocampal structure. We will also review the literature on the relationship between HPA axis function and hippocampal volume in healthy, depressed and other disease states. There is evidence that prenatal stress and childhood maltreatment is associated with an abnormally developing HPA system, as well as hippocampal volume reduction. Smaller hippocampal volumes are associated with increased cortisol secretion during the day. We conclude that a model integrating childhood maltreatment, cortisol abnormalities and hippocampal volume may need to take other factors into account, such as temperament, genetics or the presence of depression; to provide a cohesive explanation of all the findings. Finally, we have to conclude that the cascade hypothesis, mainly based on preclinical studies, has not been translated enough into humans. While there is evidence that early life maltreatment results in structural hippocampal changes and these are in turn more prominent in subjects with higher continuous cortisol secretion it is less clear which role early life maltreatment plays in HPA axis alteration. Copyright © 2012 Elsevier Inc. All rights reserved.

An Unusual Transudative Pleural Effusion Succeeded by Pulmonary and Brain Edema and Death

Directory of Open Access Journals (Sweden)

Sayyed Gholam Reza Mortazavimoghaddam

2012-01-01

Full Text Available Here we report a 22-year old woman with massive and bilateral transudative effusion succeeded by pulmonary edema and brain edema and death. Investigations for systemic disorders were negative. Exacerbation of dyspnea after intravenous fluid infusion was a main problem. As effusion was refractory to medical treatment, the patient was referred for surgical pleurodesis and bilateral surgical pleurodesis were done separately. Postsurgically, dyspnea exacerbation occurred after each common cold infection. Vertigo and high intracranial pressure were also a problem postsurgically. CSF pressure was 225 mm/H2O. Therapeutic lumbar puncture was done in two sequential weeks, and the patient was on acetazolamide 250 mg/trivise a day. Despite the medical treatment, progressive dyspnea, headache, and high intracranial pressure followed by death nine months after pleurodesis. As there is a gradient of pressure between pleura and CSF, after pleurodesis brain edema must be a consequence of inversing this gradient. In conclusion, when there are any abnormalities about fluid volume or pressure in any of these cavities, we have to study other cavities.

Effect of atorvastatin on hyperglycemia-induced brain oxidative stress and neuropathy induced by diabetes

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Nastaran Faghihi

2015-04-01

Conclusion: The findings of the present study reveal that atorvastatin is able to prevent hyperglycemia-induced diabetic neuropathy and inhibit brain oxidative stress during diabetes. It is probable that reduction of urea is one of the reasons for atorvastatin prevention of hyperglycemia-induced neuropathy.

Effects of Pre-Encoding Stress on Brain Correlates Associated with the Long-Term Memory for Emotional Scenes

Science.gov (United States)

Wirkner, Janine; Weymar, Mathias; Löw, Andreas; Hamm, Alfons O.

2013-01-01

Recent animal and human research indicates that stress around the time of encoding enhances long-term memory for emotionally arousing events but neural evidence remains unclear. In the present study we used the ERP old/new effect to investigate brain dynamics underlying the long-term effects of acute pre-encoding stress on memory for emotional and neutral scenes. Participants were exposed either to the Socially Evaluated Cold Pressure Test (SECPT) or a warm water control procedure before viewing 30 unpleasant, 30 neutral and 30 pleasant pictures. Two weeks after encoding, recognition memory was tested using 90 old and 90 new pictures. Emotional pictures were better recognized than neutral pictures in both groups and related to an enhanced centro-parietal ERP old/new difference (400–800 ms) during recognition, which suggests better recollection. Most interestingly, pre-encoding stress exposure specifically increased the ERP old/new-effect for emotional (unpleasant) pictures, but not for neutral pictures. These enhanced ERP/old new differences for emotional (unpleasant) scenes were particularly pronounced for those participants who reported high levels of stress during the SECPT. The results suggest that acute pre-encoding stress specifically strengthens brain signals of emotional memories, substantiating a facilitating role of stress on memory for emotional scenes. PMID:24039697

Effects of pre-encoding stress on brain correlates associated with the long-term memory for emotional scenes.

Directory of Open Access Journals (Sweden)

Janine Wirkner

Full Text Available Recent animal and human research indicates that stress around the time of encoding enhances long-term memory for emotionally arousing events but neural evidence remains unclear. In the present study we used the ERP old/new effect to investigate brain dynamics underlying the long-term effects of acute pre-encoding stress on memory for emotional and neutral scenes. Participants were exposed either to the Socially Evaluated Cold Pressure Test (SECPT or a warm water control procedure before viewing 30 unpleasant, 30 neutral and 30 pleasant pictures. Two weeks after encoding, recognition memory was tested using 90 old and 90 new pictures. Emotional pictures were better recognized than neutral pictures in both groups and related to an enhanced centro-parietal ERP old/new difference (400-800 ms during recognition, which suggests better recollection. Most interestingly, pre-encoding stress exposure specifically increased the ERP old/new-effect for emotional (unpleasant pictures, but not for neutral pictures. These enhanced ERP/old new differences for emotional (unpleasant scenes were particularly pronounced for those participants who reported high levels of stress during the SECPT. The results suggest that acute pre-encoding stress specifically strengthens brain signals of emotional memories, substantiating a facilitating role of stress on memory for emotional scenes.

Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites

Directory of Open Access Journals (Sweden)

Darin J. Knapp

2016-07-01

Full Text Available Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C–C motif ligand 2 (CCL2, interleukin-1-beta (IL-1β, tumor necrosis factor alpha (TNFα and toll-like receptor 4 (TLR4 mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally—based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1 receptor inhibition in blocking WCE-induced cytokine mRNAs—the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals

Coping changes the brain

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Jordan M. Nechvatal

2013-02-01

Full Text Available One of the earliest and most consistent findings in behavioral neuroscience research is that learning changes the brain. Here we consider how learning as an aspect of coping in the context of stress exposure induces neuroadaptations that enhance emotion regulation and resilience. A systematic review of the literature identified 15 brain imaging studies in which humans with specific phobias or posttraumatic stress disorder were randomized to stress exposure therapies that diminished subsequent indications of anxiety. Most of these studies focused on functional changes in the amygdala and anterior corticolimbic brain circuits that control cognitive, motivational, and emotional aspects of physiology and behavior. Corresponding structural brain changes and the timing, frequency, and duration of stress exposure required to modify brain functions remain to be elucidated in future research. These studies will advance our understanding of coping as a learning process and provide mechanistic insights for the development of new interventions that promote stress coping skills.

Risky choice and brain CRF after adolescent ethanol vapor exposure and social stress in adulthood.

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Boutros, Nathalie; Der-Avakian, Andre; Semenova, Svetlana; Lee, Soon; Markou, Athina

2016-09-15

Adolescent ethanol exposure increases risky choice and alters corticotropin releasing factor (CRF) systems in adulthood. The impact of stress on risky choice after adolescent intermittent ethanol (AIE) exposure is not known. We investigated time-specific effects of AIE vapor exposure during early adolescence on risky choice after stress or no stress in adulthood. Male Wistar rats were exposed to air or AIE vapor on postnatal days 28-42 (adolescence) and were exposed to 10days of social defeat or no stress on postnatal days 172-181 (adulthood). Risky choice was assessed in the probability discounting task under baseline conditions and after days 1 and 10 of social defeat. CRF and CRF receptor 1 (CRFR1) mRNA levels were assessed in the prefrontal cortex (PFC) and the central nucleus of the amygdala (CeA) 24h post-stress to evaluate persistent effects of stress on the brain. AIE exposure had no effect on risky choice either at baseline or after social defeat. Additionally, neither acute nor chronic social defeat affected risky choice in air-exposed rats. In the PFC, chronic social defeat selectively decreased CRF mRNA levels in air-exposed rats and increased CRFR1 mRNA levels in all rats. AIE exposure increased CRF mRNA levels in the CeA with no effect of social stress. Our results indicate no effect of ethanol exposure via vapor during early adolescence on risky choice, while our previous findings indicated that AIE exposure via gavage affected risky choice. Both AIE exposure and social defeat altered CRF and CRFR1 mRNA levels in the brain. Copyright © 2016 Elsevier B.V. All rights reserved.

The whole brain diffusion tensor imaging study on acute phase of the posttraumatic stress disorder resulting from the single-prolonged stress based on tract based spatial statistics

International Nuclear Information System (INIS)

Xi Yibin; Liu Kang; Zhe Xia; Mu Yunfeng; Yin Hong; Huan Yi; Yang Xiaobin; Du Ping

2013-01-01

Objective: To study the changes of the brain white matter microstructure at the acute stage of posttraumatic stress disorder (PTSD) resulting from a single-prolonged stress. Methods: DTI scans were performed on 17 survivors buried more than 190 h in Shanxi Wangjialing mine disaster and 17 cases of normal controls using Siemens 3.0 T MR. The differences of the FA values measured from the whole brain DTI between the two groups were analyzed based on tract based spatial statistics (TBSS). FA data were statistically compared between the two groups based on nonparametric random permutation test (RPT), and the brain areas of the PTSD patients with abnormal FA were defined. Results: Compared with control group, FA values in the PTSD (at acute stage) group decreased in genu, rostral body of corpus callosum, and increased in the left thalamic and corticospinal tract region of bilateral corona radiata and the posterior limb of the left internal capsule, the left cerebral peduncle. The differences were statistically significant (P < 0.01 TFCE-corrected). Conclusions: TBSS is a comprehensive and accurate method for evaluating the changes of whole brain DTI in PTSD cases. The fiber structural abnormalities in the genu, rostral body of bilateral corpus callosum, anterior radiation of left thalamic may be due to stress. TBSS can provide a more objective basis for the early diagnosis and intervention of PTSD. (authors)

Altered oscillatory brain dynamics after repeated traumatic stress

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Ruf Martina

2007-10-01

Full Text Available Abstract Background Repeated traumatic experiences, e.g. torture and war, lead to functional and structural cerebral changes, which should be detectable in cortical dynamics. Abnormal slow waves produced within circumscribed brain regions during a resting state have been associated with lesioned neural circuitry in neurological disorders and more recently also in mental illness. Methods Using magnetoencephalographic (MEG-based source imaging, we mapped abnormal distributions of generators of slow waves in 97 survivors of torture and war with posttraumatic stress disorder (PTSD in comparison to 97 controls. Results PTSD patients showed elevated production of focally generated slow waves (1–4 Hz, particularly in left temporal brain regions, with peak activities in the region of the insula. Furthermore, differential slow wave activity in right frontal areas was found in PTSD patients compared to controls. Conclusion The insula, as a site of multimodal convergence, could play a key role in understanding the pathophysiology of PTSD, possibly accounting for what has been called posttraumatic alexithymia, i.e., reduced ability to identify, express and regulate emotional responses to reminders of traumatic events. Differences in activity in right frontal areas may indicate a dysfunctional PFC, which may lead to diminished extinction of conditioned fear and reduced inhibition of the amygdala.

Tianeptine, olanzapine and fluoxetine show similar restoring effects on stress induced molecular changes in mice brain: An FT-IR study

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Türker-Kaya, Sevgi; Mutlu, Oğuz; Çelikyurt, İpek K.; Akar, Furuzan; Ulak, Güner

2016-05-01

Chronic stress which can cause a variety of disorders and illness ranging from metabolic and cardiovascular to mental leads to alterations in content, structure and dynamics of biomolecules in brain. The determination of stress-induced changes along with the effects of antidepressant treatment on these parameters might bring about more effective therapeutic strategies. In the present study, we investigated unpredictable chronic mild stress (UCMS)-induced changes in biomolecules in mouse brain and the restoring effects of tianeptine (TIA), olanzapine (OLZ) and fluoxetine (FLX) on these variations, by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that chronic stress causes different membrane packing and an increase in lipid peroxidation, membrane fluidity. A significant increment for lipid/protein, Cdbnd O/lipid, CH3/lipid, CH2/lipid, PO-2/lipid, COO-/lipid and RNA/protein ratios but a significant decrease for lipid/protein ratios were also obtained. Additionally, altered protein secondary structure components were estimated, such as increment in random coils and beta structures. The administration of TIA, OLZ and FLX drugs restored these stress-induced variations except for alterations in protein structure and RNA/protein ratio. This may suggest that these drugs have similar restoring effects on the consequences of stress activity in brain, in spite of the differences in their action mechanisms. All findings might have importance in understanding molecular mechanisms underlying chronic stress and contribute to studies aimed for drug development.

Aging rather than stress strongly influences amino acid metabolisms in the brain and genital organs of female mice.

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Kodaira, Momoko; Nagasawa, Mao; Yamaguchi, Takeshi; Ikeda, Hiromi; Minaminaka, Kimie; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

2017-03-01

Aging and stress affect quality of life, and proper nourishment is one of means of preventing this effect. Today, there is a focus on the amount of protein consumed by elderly people; however, changes in the amino acid metabolism of individuals have not been fully considered. In addition, the difference between average life span and healthy life years is larger in females than it is in males. To prolong the healthy life years of females, in the present study we evaluated the influence of stress and aging on metabolism and emotional behavior by comparing young and middle-aged female mice. After 28 consecutive days of immobilization stress, behavioral tests were conducted and tissue sampling was performed. The results showed that the body weight of middle-aged mice was severely lowered by stress, but emotional behaviors were hardly influenced by either aging or stress. Aging influenced changes in amino acid metabolism in the brain and increased various amino acid levels in the uterus and ovary. In conclusion, we found that aged mice were more susceptible to stress in terms of body-weight reduction, and that amino acid metabolisms in the brain and genital organs were largely influenced by aging rather than by stress. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hypoxia Stress Modifies Na+/K+-ATPase, H+/K+-ATPase, [Formula: see text], and nkaα1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish.

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Peter, Mc Subhash; Simi, Satheesan

2017-01-01

Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na + /K + -ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g -1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H + /K + -ATPase (HKA), and [Formula: see text] (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a , nkaα1b , and nkaα1c , in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na + , K + , H + , and [Formula: see text] ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform

Brain Tissue Oxygen: In Vivo Monitoring with Carbon Paste Electrodes

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John P. Lowry

2005-11-01

Full Text Available In this communication we review selected experiments involving the use ofcarbon paste electrodes (CPEs to monitor and measure brain tissue O2 levels in awakefreely-moving animals. Simultaneous measurements of rCBF were performed using the H2clearance technique. Voltammetric techniques used include both differential pulse (O2 andconstant potential amperometry (rCBF. Mild hypoxia and hyperoxia produced rapidchanges (decrease and increase respectively in the in vivo O2 signal. Neuronal activation(tail pinch and stimulated grooming produced similar increases in both O2 and rCBFindicating that CPE O2 currents provide an index of increases in rCBF when such increasesexceed O2 utilization. Saline injection produced a transient increase in the O2 signal whilechloral hydrate produced slower more long-lasting changes that accompanied the behavioralchanges associated with anaesthesia. Acetazolamide increased O2 levels through an increasein rCBF.

Long-term occupational stress is associated with regional reductions in brain tissue volumes.

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Eva Blix

Full Text Available There are increasing reports of cognitive and psychological declines related to occupational stress in subjects without psychiatric premorbidity or major life trauma. The underlying neurobiology is unknown, and many question the notion that the described disabilities represent a medical condition. Using PET we recently found that persons suffering from chronic occupational stress had limbic reductions in the 5-HT1A receptor binding potential. Here we examine whether chronic work-related stress is also associated with changes in brain structure. We performed MRI-based voxel-based morphometry and structural volumetry in stressed subjects and unstressed controls focusing on gray (GM and white matter (WM volumes, and the volumes of hippocampus, caudate, and putamen - structures known to be susceptible to neurotoxic changes. Stressed subjects exhibited significant reductions in the GM volumes of the anterior cingulate cortex and the dorsolateral prefrontal cortex. Furthermore, their caudate and putamen volumes were reduced, and the volumes correlated inversely to the degree of perceived stress. Our results add to previous data on chronic psychosocial stress, and indicate a morphological involvement of the frontostriatal circuits. The present findings of morphological changes in these regions confirm our previous conclusion that symptoms from occupational stress merit careful investigations and targeted treatment.

Long-Term Occupational Stress Is Associated with Regional Reductions in Brain Tissue Volumes

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Blix, Eva; Perski, Aleksander; Berglund, Hans; Savic, Ivanka

2013-01-01

There are increasing reports of cognitive and psychological declines related to occupational stress in subjects without psychiatric premorbidity or major life trauma. The underlying neurobiology is unknown, and many question the notion that the described disabilities represent a medical condition. Using PET we recently found that persons suffering from chronic occupational stress had limbic reductions in the 5-HT1A receptor binding potential. Here we examine whether chronic work-related stress is also associated with changes in brain structure. We performed MRI-based voxel-based morphometry and structural volumetry in stressed subjects and unstressed controls focusing on gray (GM) and white matter (WM) volumes, and the volumes of hippocampus, caudate, and putamen – structures known to be susceptible to neurotoxic changes. Stressed subjects exhibited significant reductions in the GM volumes of the anterior cingulate cortex and the dorsolateral prefrontal cortex. Furthermore, their caudate and putamen volumes were reduced, and the volumes correlated inversely to the degree of perceived stress. Our results add to previous data on chronic psychosocial stress, and indicate a morphological involvement of the frontostriatal circuits. The present findings of morphological changes in these regions confirm our previous conclusion that symptoms from occupational stress merit careful investigations and targeted treatment. PMID:23776438

The interaction between stress and exercise, and its impact on brain function.

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Russell, Vivienne A; Zigmond, Michael J; Dimatelis, Jacqueline J; Daniels, William M U; Mabandla, Musa V

2014-06-01

In response to acute adversity, emotional signals shift the body into a state that permits rapid detection, identification, and appropriate response to a potential threat. The stress response involves the release of a variety of substances, including neurotransmitters, neurotrophic factors, hormones, and cytokines, that enable the body to deal with the challenges of daily life. The subsequent activation of various physiological systems can be both protective and damaging to the individual, depending on timing, intensity, and duration of the stressor. Successful recovery from stressful challenges during early life leads to strengthening of synaptic connections in health-promoting neural networks and reduced vulnerability to subsequent stressors that can be protective in later life. In contrast, chronic intense uncontrollable stress can be pathogenic and lead to disorders such as depression, anxiety, hypertension, Alzheimer's disease, Parkinson's disease, and an increased toxic response to additional stressors such as traumatic brain injury and stroke. This review briefly explores the interaction between stress experienced at different stages of development and exercise later in life.

Effect of thermal stress and water deprivation on the acetylcholinesterase activity of the pig brain and hypophyses

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Adejumo, D. O.; Egbunike, G. N.

1988-06-01

The effects of direct exposure of boars to thermal stress for 1 h daily for 5 days and to acute water deprivation for 24 or 48 h were studied on the acetylcholinesterase (AChE) activity of porcine brain and hypophysial regions. Mean ambient temperatures, respiratory rates and rectal temperatures in the open were significantly higher than inside the pen. Heat stress induced a rise in AChE activities in the pons, cerebellum, amygdala, hippocampus, hypothalamus, mid-brain and medulla oblongata. However, no significant changes were observed in the cerebral cortex, adenohypophysis and neurohypophysis. Water deprivation significantly ( Pmedulla oblongata were comparable to the amygdala in this respect. The adenohypophysis and neurohypophysis were relatively unaffected.

Social stress during adolescence in Wistar rats induces social anxiety in adulthood without affecting brain monoaminergic content and activity

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Vidal, Jose; de Bie, Josien; Granneman, Ramon A.; Wallinga, Alinde E.; Koolhaas, Jaap M.; Buwalda, Bauke

2007-01-01

Adolescence has been described as an important period to acquire social competences required for adult life. It has been suggested that early stress experiences could affect the development of the brain at different levels. These changes in the brain during adolescence may be related with the

Differential effects of voluntary and forced exercise on stress responses after traumatic brain injury.

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Griesbach, Grace S; Tio, Delia L; Vincelli, Jennifer; McArthur, David L; Taylor, Anna N

2012-05-01

Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) after traumatic brain injury (TBI) when it occurs during a delayed time window. In contrast, acute post-TBI exercise does not increase BDNF. It is well known that increases in glucocorticoids suppress levels of BDNF. Moreover, recent work from our laboratory showed that there is a heightened stress response after fluid percussion injury (FPI). In order to determine if a heightened stress response is also observed with acute exercise, at post-injury days 0-4 and 7-11, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) release were measured in rats running voluntarily or exposed to two daily 20-min periods of forced running wheel exercise. Forced, but not voluntary exercise, continuously elevated CORT. ACTH levels were initially elevated with forced exercise, but decreased by post-injury day 7 in the control, but not the FPI animals. As previously reported, voluntary exercise did not increase BDNF in the FPI group as it did in the control animals. Forced exercise did not increase levels of BDNF in any group. It did, however, decrease hippocampal glucocorticoid receptors in the control group. The results suggest that exercise regimens with strong stress responses may not be beneficial during the early post-injury period.

A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice.

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Nandar, Wint; Neely, Elizabeth B; Unger, Erica; Connor, James R

2013-06-01

Because of the increasing evidence that H63D HFE polymorphism appears in higher frequency in neurodegenerative diseases, we evaluated the neurological consequences of H63D HFE in vivo using mice that carry H67D HFE (homologous to human H63D). Although total brain iron concentration did not change significantly in the H67D mice, brain iron management proteins expressions were altered significantly. The 6-month-old H67D mice had increased HFE and H-ferritin expression. At 12 months, H67D mice had increased H- and L-ferritin but decreased transferrin expression suggesting increased iron storage and decreased iron mobilization. Increased L-ferritin positive microglia in H67D mice suggests that microglia increase iron storage to maintain brain iron homeostasis. The 6-month-old H67D mice had increased levels of GFAP, increased oxidatively modified protein levels, and increased cystine/glutamate antiporter (xCT) and hemeoxygenase-1 (HO-1) expression indicating increased metabolic and oxidative stress. By 12 months, there was no longer increased astrogliosis or oxidative stress. The decrease in oxidative stress at 12 months could be related to an adaptive response by nuclear factor E2-related factor 2 (Nrf2) that regulates antioxidant enzymes expression and is increased in the H67D mice. These findings demonstrate that the H63D HFE impacts brain iron homeostasis, and promotes an environment of oxidative stress and induction of adaptive mechanisms. These data, along with literature reports on humans with HFE mutations provide the evidence to overturn the traditional paradigm that the brain is protected from HFE mutations. The H67D knock-in mouse can be used as a model to evaluate how the H63D HFE mutation contributes to neurodegenerative diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Insulin Protects against Brain Oxidative Stress with an Apparent Effect on Episodic Memory in Doxorubicin-Induced Cognitive Dysfunction in Wistar Rats.

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Ramalingayya, Grandhi Venkata; Sonawane, Vishwajeet; Cheruku, Sri Pragnya; Kishore, Anoop; Nayak, Pawan G; Kumar, Nitesh; Shenoy, Rekha S; Nandakumar, Krishnadas

2017-01-01

The present study was aimed at assessing the protective effect of insulin against doxorubicin (DOX)-induced cognitive dysfunction in Wistar rats. Cognitive function for episodic memory was assessed by a novel object recognition task (NORT) in male Wistar rats. Oxidative stress markers-SOD, catalase, glutathione, and lipid peroxidation-in the hippocampus and frontal cortex were assessed using colorimetric methods. Doxorubicin treatment (2.5 mg/kg, i.p., every 5 days for 50 days) reduced recognition and discriminative indices in NORT with increased oxidative stress in the brain. A nonhypoglycemic dose of insulin (0.5 IU/kg, i.p.) significantly reduced brain oxidative stress (MDA) induced by doxorubicin with an increase in the antioxidant defense systems (SOD, catalase, and GSH). Rats treated with combined insulin and DOX spent comparatively more time with the novel object when compared to the non-novel objects; however, the observed difference was not statistically significant. An apparent improvement (p insulin reduces brain oxidative stress and apparently improves doxorubicin-induced cognitive dysfunction in Wistar rats.

Classroom Strategies for Teaching Veterans with Post-Traumatic Stress Disorder and Traumatic Brain Injury

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Sinski, Jennifer Blevins

2012-01-01

Postsecondary institutions currently face the largest influx of veteran students since World War II. As the number of veteran students who may experience learning problems caused by Post-Traumatic Stress Disorder and/or Traumatic Brain Injury continues to rise, the need for instructional strategies that address their needs increases. Educators may…

Structural and functional brain changes in posttraumatic stress disorder.

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Nutt, David J; Malizia, Andrea L

2004-01-01

Posttraumatic stress disorder (PTSD) is a highly disabling condition that is associated with intrusive recollections of a traumatic event, hyperarousal, avoidance of clues associated with the trauma, and psychological numbing. The field of neuroimaging has made tremendous advances in the past decade and has contributed greatly to our understanding of the physiology of fear and the pathophysiology of PTSD. Neuroimaging studies have demonstrated significant neurobiologic changes in PTSD. There appear to be 3 areas of the brain that are different in patients with PTSD compared with those in control subjects: the hippocampus, the amygdala, and the medial frontal cortex. The amygdala appears to be hyperreactive to trauma-related stimuli. The hallmark symptoms of PTSD, including exaggerated startle response and flashbacks, may be related to a failure of higher brain regions (i.e., the hippocampus and the medial frontal cortex) to dampen the exaggerated symptoms of arousal and distress that are mediated through the amygdala in response to reminders of the traumatic event. The findings of structural and functional neuroimaging studies of PTSD are reviewed as they relate to our current understanding of the pathophysiology of this disorder.

Role of Stress-Related Brain-Derived Neurotrophic Factor (BDNF) in the Rat Submandibular Gland

International Nuclear Information System (INIS)

Tsukinoki, Keiichi; Saruta, Juri

2012-01-01

The nerve growth factor (NGF) family comprises NGF, brain-derived neurotrophic factor (BDNF) and neurotrophins (NTs)-3, -4/5, -6 and -7, all of which are collectively referred to as neurotrophins. However, the expression of neurotrophins other than NGF in the salivary gland has not been described in detail. Through interaction with the TrkB receptor, BDNF plays an important role in long-term potentiation. We found that BDNF expression increased within submandibular gland tissue in response to stress, suggesting that the salivary glands are sensitive to stress. In addition, stress caused increases in plasma BDNF derived from the submandibular gland and in TrkB receptor mRNA in the adrenal medulla. Plasma BDNF might activate TrkB receptors in the adrenal medulla during acute stress. The salivary glands are likely to influence not only oral health, but also systemic organs. This review addressed the relationship between hormone-like effects and stress-related BDNF expression in the rat submandibular gland

Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain.

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Jašarević, Eldin; Howerton, Christopher L; Howard, Christopher D; Bale, Tracy L

2015-09-01

The neonate is exposed to the maternal vaginal microbiota during parturition, providing the primary source for normal gut colonization, host immune maturation, and metabolism. These early interactions between the host and microbiota occur during a critical window of neurodevelopment, suggesting early life as an important period of cross talk between the developing gut and brain. Because perturbations in the prenatal environment such as maternal stress increase neurodevelopmental disease risk, disruptions to the vaginal ecosystem could be a contributing factor in significant and long-term consequences for the offspring. Therefore, to examine the hypothesis that changes in the vaginal microbiome are associated with effects on the offspring gut microbiota and on the developing brain, we used genomic, proteomic and metabolomic technologies to examine outcomes in our mouse model of early prenatal stress. Multivariate modeling identified broad proteomic changes to the maternal vaginal environment that influence offspring microbiota composition and metabolic processes essential for normal neurodevelopment. Maternal stress altered proteins related to vaginal immunity and abundance of Lactobacillus, the prominent taxa in the maternal vagina. Loss of maternal vaginal Lactobacillus resulted in decreased transmission of this bacterium to offspring. Further, altered microbiota composition in the neonate gut corresponded with changes in metabolite profiles involved in energy balance, and with region- and sex-specific disruptions of amino acid profiles in the developing brain. Taken together, these results identify the vaginal microbiota as a novel factor by which maternal stress may contribute to reprogramming of the developing brain that may predispose individuals to neurodevelopmental disorders.

Hypoxia Stress Modifies Na+/K+-ATPase, H+/K+-ATPase, Na+/NH4+-ATPase, and nkaα1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish

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Peter, MC Subhash; Simi, Satheesan

2017-01-01

Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na+/K+-ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g−1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H+/K+-ATPase (HKA), and Na+/NH4+-ATPase (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a, nkaα1b, and nkaα1c, in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na+, K+, H+, and NH4+ ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform regulation. PMID:29238219

Chronic stress exposure may affect the brain's response to high calorie food cues and predispose to obesogenic eating habits.

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Tryon, Matthew S; Carter, Cameron S; Decant, Rashel; Laugero, Kevin D

2013-08-15

Exaggerated reactivity to food cues involving calorically-dense foods may significantly contribute to food consumption beyond caloric need. Chronic stress, which can induce palatable "comfort" food consumption, may trigger or reinforce neural pathways leading to stronger reactions to highly rewarding foods. We implemented functional magnetic resonance imaging (fMRI) to assess whether chronic stress influences activation in reward, motivation and executive brain regions in response to pictures of high calorie and low calorie foods in thirty women. On separate lab visits, we also assessed food intake from a snack food buffet and circulating cortisol. In women reporting higher chronic stress (HCS), pictures of high calorie foods elicited exaggerated activity in regions of the brain involving reward, motivation, and habitual decision-making. In response to pictures of high calorie food, higher chronic stress was also associated with significant deactivation in frontal regions (BA10; BA46) linked to strategic planning and emotional control. In functional connectivity analysis, HCS strengthened connectivity between amygdala and the putamen, while LCS enhanced connectivity between amygdala and the anterior cingulate and anterior prefrontal cortex (BA10). A hypocortisolemic signature and more consumption of high calorie foods from the snack buffet were observed in the HCS group. These results suggest that persistent stress exposure may alter the brain's response to food in ways that predispose individuals to poor eating habits which, if sustained, may increase risk for obesity. © 2013.

Behavioral and molecular processing of visceral pain in the brain of mice: impact of colitis and psychological stress

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Piyush eJain

2015-07-01

Full Text Available Gastrointestinal disorders with abdominal pain are associated with central sensitization and psychopathologies that are often exacerbated by stress. Here we investigated the impact of colitis induced by dextran sulfate sodium (DSS and repeated water avoidance stress (WAS on spontaneous and nociception-related behavior and molecular signaling in the mouse brain. DSS increased the mechanical pain sensitivity of the abdominal skin while both WAS and DSS enhanced the mechanical and thermal pain sensitivity of the plantar skin. These manifestations of central sensitization were associated with augmented c-Fos expression in spinal cord, thalamus, hypothalamus, amygdala and prefrontal cortex. While WAS stimulated phosphorylation of mitogen-activated protein kinase (MAPK p42/44, DSS activated another signaling pathway, both of which converged on c-Fos. The DSS- and WAS-induced hyperalgesia in the abdominal and plantar skin and c-Fos expression in the brain disappeared when the mice were subjected to WAS+DSS treatment. Intrarectal allyl isothiocyanate (AITC evoked aversive behavior (freezing, reduction of locomotion and exploration in association with p42/44 MAPK and c-Fos activation in spinal cord and brain. These effects were inhibited by morphine, which attests to their relationship with nociception. DSS and WAS exerted opposite effects on AITC-evoked p42/44 MAPK and c-Fos activation, which indicates that these transduction pathways subserve different aspects of visceral pain processing in the brain. In summary, behavioral perturbations caused by colitis and psychological stress are associated with distinct alterations in cerebral signaling. These findings provide novel perspectives on central sensitization and the sensory and emotional processing of visceral pain stimuli in the brain.

The military's approach to traumatic brain injury and post-traumatic stress disorder

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Ling, Geoffrey S. F.; Grimes, Jamie; Ecklund, James M.

2014-06-01

Traumatic brain injury (TBI) and Post Traumatic Stress Disorder (PTSD) are common conditions. In Iraq and Afghanistan, explosive blast related TBI became prominent among US service members but the vast majority of TBI was still due to typical causes such as falls and sporting events. PTS has long been a focus of the US military mental health providers. Combat Stress Teams have been integral to forward deployed units since the beginning of the Global War on Terror. Military medical management of disease and injury follows standard of care clinical practice guidelines (CPG) established by civilian counterparts. However, when civilian CPGs do not exist or are not applicable to the military environment, new practice standards are created. Such is the case for mild TBI. In 2009, the VA-DoD CPG for management of mild TBI/concussion was published and a system-wide clinical care program for mild TBI/concussion was introduced. This was the first large scale effort on an entire medical care system to address all severities of TBI in a comprehensive organized way. In 2010, the VA-DoD CPG for management of PTSD was published. Nevertheless, both TBI and PTS are still incompletely understood. Investment in terms of money and effort has been committed by the DoD to their study. The Defense and Veterans Brain Injury Center, National Intrepid Center of Excellence and the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury are prominent examples of this effort. These are just beginnings, a work in progress ready to leverage advances made scientifically and always striving to provide the very best care to its military beneficiaries.

Rapid stress-induced transcriptomic changes in the brain depend on beta-adrenergic signaling.

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Roszkowski, Martin; Manuella, Francesca; von Ziegler, Lukas; Durán-Pacheco, Gonzalo; Moreau, Jean-Luc; Mansuy, Isabelle M; Bohacek, Johannes

2016-08-01

Acute exposure to stressful experiences can rapidly increase anxiety and cause neuropsychiatric disorders. The effects of stress result in part from the release of neurotransmitters and hormones, which regulate gene expression in different brain regions. The fast neuroendocrine response to stress is largely mediated by norepinephrine (NE) and corticotropin releasing hormone (CRH), followed by a slower and more sustained release of corticosterone. While corticosterone is an important regulator of gene expression, it is not clear which stress-signals contribute to the rapid regulation of gene expression observed immediately after stress exposure. Here, we demonstrate in mice that 45 min after an acute swim stress challenge, large changes in gene expression occur across the transcriptome in the hippocampus, a region sensitive to the effects of stress. We identify multiple candidate genes that are rapidly and transiently altered in both males and females. Using a pharmacological approach, we show that most of these rapidly induced genes are regulated by NE through β-adrenergic receptor signaling. We find that CRH and corticosterone can also contribute to rapid changes in gene expression, although these effects appear to be restricted to fewer genes. These results newly reveal a widespread impact of NE on the transcriptome and identify novel genes associated with stress and adrenergic signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

The diagnostic value of 13N-ammonia PET in ischemic cerebrovascular disorders

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Qiao Shuixian; Tang Anwu; Wang Lijuan; Liu Xintong; Yuan Yanbo; Chen Liguang; Luo Yaowu; Zhang Xiangsong; Wang Shuxia; Liu Bin; Xu Weiping

2002-01-01

Objective: To evaluate the feasibility of 13 N-ammonia PET in diagnosing ischemic cerebrovascular disorders. Methods: A total of 25 subjects were investigated. Five healthy volunteers served as normal control. Twenty patients included 13 with transient ischemic attack (TIA), 6 with brain infarction and 1 with moyamoya disease. 740-925 MBq of 13 N-ammonia was injected intravenously, 3-5 min later, PET imaging was performed with T + E 2D acquisition with Siemens ECAT EXACT HR + PET scanner. Image analysis was done by visual and semiquantitative estimating. Standardized uptake value (SUV) was measured in mirror regions of cerebrum with autocopy methods. Nine patients underwent drug stress with oral acetazolamide (ACZ). Images were compared before and after oral ACZ intervention. Results: Physiological brain uptake with SUV ratio of 0.99 +- 0.15 (n=5, left/right) was observed in healthy volunteers. L/N 13 N-ammonia as radioactive tracer was a safe and noninvasive, sensitive and accurate functional imaging modality for brain perfusion. The oral ACZ stress is a safe, simple and reliable diagnostic method for ischemic cerebrovascular disorders. It is of important uses in detecting the potential reserve of cerebral blood flow

A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations.

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Zaidan, Hiba; Ramaswami, Gokul; Golumbic, Yaela N; Sher, Noa; Malik, Assaf; Barak, Michal; Galiani, Dalia; Dekel, Nava; Li, Jin B; Gaisler-Salomon, Inna

2018-01-08

Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the effects of development and environmental stress on A-to-I editing at 146 pre-selected, conserved sites in the rat prefrontal cortex and amygdala. Furthermore, we asked whether changes in editing can be observed in offspring of stress-exposed rats. In parallel, we assessed changes in ADARs expression levels. In agreement with previous studies, we found editing to be generally higher in adult compared to neonatal rat brain. At birth, editing was generally lower in prefrontal cortex than in amygdala. Stress affected editing at the serotonin receptor 2c (Htr2c), and editing at this site was significantly altered in offspring of rats exposed to prereproductive stress across two generations. Stress-induced changes in Htr2c editing measured with mmPCR-seq were comparable to changes measured with Sanger and Illumina sequencing. Developmental and stress-induced changes in Adar and Adarb1 mRNA expression were observed but did not correlate with editing changes. Our findings indicate that mmPCR-seq can accurately detect A-to-I RNA editing in rat brain samples, and confirm previous accounts of a developmental increase in RNA editing rates. Our findings also point to stress in adolescence as an environmental factor that alters RNA editing patterns several generations forward, joining a growing body of literature describing the transgenerational effects of stress.

Post-traumatic stress disorder risk and brain-derived neurotrophic factor Val66Met

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Zhang, Lei; Li, Xiao-Xia; Hu, Xian-Zhang

2016-01-01

Brain-derived neurotrophic factor (BDNF), which regulates neuronal survival, growth differentiation, and synapse formation, is known to be associated with depression and post-traumatic stress disorder (PTSD). However, the molecular mechanism for those mental disorders remains unknown. Studies have shown that BDNF is associated with PTSD risk and exaggerated startle reaction (a major arousal manifestation of PTSD) in United States military service members who were deployed during the wars in Iraq and Afghanistan. The frequency of the Met/Met in BDNF gene was greater among those with PTSD than those without PTSD. Among individuals who experienced fewer lifetime stressful events, the Met carriers have significantly higher total and startle scores on the PTSD Checklist than the Val/Val carriers. In addition, subjects with PTSD showed higher levels of BDNF in their peripheral blood plasma than the non-probable-PTSD controls. Increased BDNF levels and startle response were observed in both blood plasma and brain hippocampus by inescapable tail shock in rats. In this paper, we reviewed these data to discuss BDNF as a potential biomarker for PTSD risk and its possible roles in the onset of PTSD. PMID:27014593

The inhibitory effect of manganese on acetylcholinesterase activity enhances oxidative stress and neuroinflammation in the rat brain

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Santos, Dinamene; Milatovic, Dejan; Andrade, Vanda; Batoreu, M. Camila; Aschner, Michael; Marreilha dos Santos, A.P.

2012-01-01

Highlights: ► Acetylcholinesterase (AChE) is a target of Mn in the central nervous system. ► Mn inhibits AChE, representing a novel mechanistic finding for its mode of action. ► AChE inhibition may trigger or contribute to the development of oxidative stress. ► Excess Mn can trigger the release of inflammatory mediators. ► AChE activity may serve as an early biomarker of Mn neurotoxicity. -- Abstract: Background: Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated, at least in part, by oxidative stress. Objectives: The present study was undertaken to test the hypothesis that a decrease in acetylcholinesterase (AChE) activity mediates Mn-induced neurotoxicity. Methods: Groups of 6 rats received 4 or 8 intraperitoneal (i.p.) injections of 25 mg MnCl 2 /kg/day, every 48 h. Twenty-four hours after the last injection, brain AChE activity and the levels of F 2 -isoprostanes (F 2 -IsoPs) and F 4 -neuroprostanes (F 4 -NPs) (biomarkers of oxidative stress), as well as prostaglandin E 2 (PGE 2 ) (biomarker of neuroinflammation) were analyzed. Results: The results showed that after either 4 or 8 Mn doses, brain AChE activity was significantly decreased (p 2 -IsoPs and PGE 2 levels, but only after 8 doses. In rats treated with 4 Mn doses, a significant increase (p 4 -NPs levels was found. To evaluate cellular responses to oxidative stress, we assessed brain nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and Mn-superoxide dismutase (Mn-SOD, SOD2) protein expression levels. A significant increase in Mn-SOD protein expression (p < 0.05) and a trend towards increased Nrf2 protein expression was noted in rat brains after 4 Mn doses vs. the control group, but the expression of these proteins was decreased after 8 Mn

Therapeutic effects of L-Cysteine in newborn mice subjected to hypoxia-ischemia brain injury via the CBS/H2S system: Role of oxidative stress and endoplasmic reticulum stress.

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Liu, Song; Xin, Danqing; Wang, Lingxiao; Zhang, Tiantian; Bai, Xuemei; Li, Tong; Xie, Yunkai; Xue, Hao; Bo, Shishi; Liu, Dexiang; Wang, Zhen

2017-10-01

Neonatal hypoxic-ischemic (HI) injury is a major cause of neonatal death and neurological dysfunction. H 2 S has been shown to protect against hypoxia-induced injury and apoptosis of neurons. L-Cysteine is catalyzed by cystathionine-β-synthase (CBS) in the brain and sequentially produces endogenous H 2 S. The present study was designed to investigate whether L-Cysteine could attenuate the acute brain injury and improve neurobehavioral outcomes following HI brain injury in neonatal mice by releasing endogenous H 2 S. L-Cysteine treatment significantly attenuated brain edema and decreased infarct volume and neuronal cell death, as shown by a decrease in the Bax/Bcl-2 ratio, suppression of caspase-3 activation, and reduced phosphorylation of Akt and ERK at 72h after HI. Additionally, L-Cysteine substantially up-regulated NF-E2-related factor 2 and heme oxygenase-1 expression. L-Cysteine also decreased endoplasmic reticulum (ER) stress-associated pro-apoptotic protein expression. Furthermore, L-Cysteine had long-term effects by protecting against the loss of ipsilateral brain tissue and improving neurobehavioral outcomes. Importantly, pre-treatment with a CBS inhibitor significantly attenuated the neuroprotection of L-Cysteine on HI insult. Thus, L-Cysteine exerts neuroprotection against HI-induced injury in neonates via the CBS/H 2 S pathway, mediated in part by anti-apoptotic effects and reduced oxidative stress and ER stress. Thus, L-Cysteine may be a promising treatment for HI. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The correlation of insulin resistance with the cerebral injury and stress reaction in patients with traumatic brain injury

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Zhan Lan

2017-04-01

Full Text Available Objective: To study the correlation of insulin resistance with the cerebral injury and stress reaction in patients with traumatic brain injury (TBI. Methods: 78 patients who were diagnosed with acute traumatic brain injury in our hospital between May 2014 and August 2016 were selected as the TBI group, and 90 healthy volunteers who received physical examination during the same period were selected as the control group. The peripheral blood was collected to detect glucose, insulin and nerve injury marker molecules, stress hormones as well as oxidative stress reaction products, and the insulin resistance index (HOMA-IR was calculated. Results: The HOMA-IR index of TBI group was significantly higher than that of control group (P<0.05; serum neuron-specific enolase (NSE, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1, S100β, myelin basic protein (MBP, glucagon, growth hormone, cortisol, malondialdehyde (MDA and 8-hydroxy-deoxyguanosine (8-OHdGlevels of TBI group were significantly higher than those of control group (P<0.05; serum NSE, UCH-L1, S100β, MBP, glucagon, growth hormone, cortisol, MDA and 8-OHdG levels of patients with high HOMA-IR were significantly higher than those of patients with low HOMA-IR (P<0.05. Conclusion: The insulin resistance increases significantly in patients with traumatic brain injury, and is closely related to the degree of cerebral injury and stress reaction.

A Pilot Study of the Effects of Mindfulness-Based Stress Reduction on Post-traumatic Stress Disorder Symptoms and Brain Response to Traumatic Reminders of Combat in Operation Enduring Freedom/Operation Iraqi Freedom Combat Veterans with Post-traumatic Stress Disorder.

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Bremner, James Douglas; Mishra, Sanskriti; Campanella, Carolina; Shah, Majid; Kasher, Nicole; Evans, Sarah; Fani, Negar; Shah, Amit Jasvant; Reiff, Collin; Davis, Lori L; Vaccarino, Viola; Carmody, James

2017-01-01

Brain imaging studies in patients with post-traumatic stress disorder (PTSD) have implicated a circuitry of brain regions including the medial prefrontal cortex, amygdala, hippocampus, parietal cortex, and insula. Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders. Mindfulness-based stress reduction (MBSR) is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders. The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography (PET) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) combat veterans with PTSD. We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD. Twenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block randomized to receive eight sessions of MBSR or present-centered group therapy (PCGT). PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale (CAPS), mindfulness with the Five Factor Mindfulness Questionnaire (FFMQ) and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment. Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures. Post-traumatic stress disorder patients treated with MBSR (but not PCGT) had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment. MBSR also resulted in an increase in mindfulness measured with the FFMQ. MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group. This study shows that MBSR is a safe and effective treatment for PTSD. Furthermore, MBSR treatment is associated with

A Pilot Study of the Effects of Mindfulness-Based Stress Reduction on Post-traumatic Stress Disorder Symptoms and Brain Response to Traumatic Reminders of Combat in Operation Enduring Freedom/Operation Iraqi Freedom Combat Veterans with Post-traumatic Stress Disorder

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James Douglas Bremner

2017-08-01

Full Text Available ObjectiveBrain imaging studies in patients with post-traumatic stress disorder (PTSD have implicated a circuitry of brain regions including the medial prefrontal cortex, amygdala, hippocampus, parietal cortex, and insula. Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders. Mindfulness-based stress reduction (MBSR is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders. The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography (PET in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF combat veterans with PTSD. We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD.MethodTwenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block randomized to receive eight sessions of MBSR or present-centered group therapy (PCGT. PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale (CAPS, mindfulness with the Five Factor Mindfulness Questionnaire (FFMQ and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment. Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures.ResultsPost-traumatic stress disorder patients treated with MBSR (but not PCGT had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment. MBSR also resulted in an increase in mindfulness measured with the FFMQ. MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group.ConclusionThis study shows that MBSR is a safe and effective treatment for PTSD

Effect of Exercise Intensity on Neurotrophic Factors and Blood-Brain Barrier Permeability Induced by Oxidative-Nitrosative Stress in Male College Students.

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Roh, Hee-Tae; Cho, Su-Youn; Yoon, Hyung-Gi; So, Wi-Young

2017-06-01

We investigated the effects of aerobic exercise intensity on oxidative-nitrosative stress, neurotrophic factor expression, and blood-brain barrier (BBB) permeability. Fifteen healthy men performed treadmill running under low-intensity (LI), moderate-intensity (MI), and high-intensity (HI) conditions. Blood samples were collected immediately before exercise (IBE), immediately after exercise (IAE), and 60 min after exercise (60MAE) to examine oxidative-nitrosative stress (reactive oxygen species [ROS]; nitric oxide [NO]), neurotrophic factors (brain-derived neurotrophic factor [BDNF]; nerve growth factor [NGF]), and blood-brain barrier (BBB) permeability (S-100β; neuron-specific enolase). ROS concentration significantly increased IAE and following HI (4.9 ± 1.7 mM) compared with that after LI (2.8 ± 1.4 mM) exercise (p exercise (p exercise (p exercise (p exercise (p .05). Moderate- and/or high-intensity exercise may induce higher oxidative-nitrosative stress than may low-intensity exercise, which can increase peripheral neurotrophic factor levels by increasing BBB permeability.

Microwave assisted synthesis of some novel acetazolamide cyclocondensed 1,2,3,4-tetrahydropyrimidines as a potent antimicrobial and cytotoxic agents

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Karthikeyan Elumalai

2014-03-01

Full Text Available A new series of some novel acetazolamide cyclocondensed 1,2,3,4-tetrahydropyrimidines was prepared by reacting of N-{[5-(acetylamino-1,3,4-thiadiazol-2-yl]sulfonyl}-3-oxobutanamide with urea/thiourea and appropriate aldehyde in the presence of catalytic amount of laboratory made p-toluenesulfonic acid as an efficient catalyst. Confirmation of the chemical structure of the synthesized compounds (12a–n was substantiated by TLC, different spectral data IR, 1H NMR, Mass spectra and elemental analysis were done. The synthesized compounds were evaluated for in-vitro antimicrobial and cytotoxicity against Bacillus subtilis, Escherichia coli and Vero cells. The titled compounds exhibited weak, moderate, or high in-vitro antimicrobial and cytotoxicity. Compounds 12c, 12d, 12g and 12h, exhibited potential antimicrobial and in-vitro cytotoxicity.

Assessing emotional status following acquired brain injury: the clinical potential of the depression, anxiety and stress scales.

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Ownsworth, Tamara; Little, Trudi; Turner, Ben; Hawkes, Anna; Shum, David

2008-10-01

To investigate the clinical potential of the Depression, Anxiety and Stress Scales (DASS 42) and its shorter version (DASS 21) for assessing emotional status following acquired brain injury. Participants included 23 individuals with traumatic brain injury (TBI), 25 individuals with brain tumour and 29 non-clinical controls. Investigations of internal consistency, test-re-test reliability, theory-consistent differences, sensitivity to change and concurrent validity were conducted. Internal consistency of the DASS was generally acceptable (r > 0.70), with the exception of the anxiety scale for the TBI sample. Test-re-test reliability (1-3 weeks) was sound for the depression scale (r > 0.75) and significant but comparatively lower for other scales (r = 0.60-0.73, p scale (p DASS in the context of hospital discharge was demonstrated for depression and stress (p 0.05). Concurrent validity with the Hospital Anxiety and Depression Scale was significant for all scales of the DASS (p DASS following ABI, further research examining the factor structure of existing and modified versions of the DASS is recommended.

Interoception and Stress

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André eSchulz

2015-07-01

Full Text Available Afferent neural signals are continuously transmitted from visceral organs to the brain. Interoception refers to the processing of visceral-afferent neural signals by the central nervous system, which can finally result in the conscious perception of bodily processes. Interoception can, therefore, be described as a prominent example of information processing on the ascending branch of the brain-body axis. Stress responses involve a complex neuro-behavioral cascade, which is elicited when the organism is confronted with a potentially harmful stimulus. As this stress cascade comprises a range of neural and endocrine pathways, stress can be conceptualized as a communication process on the descending branch of the brain-body axis. Interoception and stress are, therefore, associated via the bi-directional transmission of information on the brain-body axis. It could be argued that excessive and/or enduring activation (e.g. by acute or chronic stress of neural circuits, which are responsible for successful communication on the brain-body axis, induces malfunction and dysregulation of these information processes. As a consequence, interoceptive signal processing may be altered, resulting in physical symptoms contributing to the development and/or maintenance of body-related mental disorders, which are associated with stress. In the current paper, we summarize findings on psychobiological processes underlying acute and chronic stress and their interaction with interoception. While focusing on the role of the physiological stress axes (HPA axis and autonomic nervous system, psychological factors in acute and chronic stress are also discussed. We propose a feed-forward model involving stress (in particular early life or chronic stress, as well as major adverse events, the dysregulation of physiological stress axes, altered perception of bodily sensations, and the generation of physical symptoms, which may in turn facilitate stress.

ω-3 and folic acid act against depressive-like behavior and oxidative damage in the brain of rats subjected to early- or late-life stress.

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Réus, Gislaine Z; Maciel, Amanda L; Abelaira, Helena M; de Moura, Airam B; de Souza, Thays G; Dos Santos, Thais R; Darabas, Ana Caroline; Parzianello, Murilo; Matos, Danyela; Abatti, Mariane; Vieira, Ana Carolina; Fucillini, Vanessa; Michels, Monique; Dal-Pizzol, Felipe; Quevedo, João

2018-03-30

To investigate the antidepressant and antioxidant effects of omega-3, folic acid and n-acetylcysteine (NAC) in rats which were subjected to early or late life stress. Early stress was induced through maternal deprivation (MD), while late life stress was induced using the chronic mild stress (CMS) protocol. Young rats which were subjected to MD and the adult rats which were subjected to CMS were treated with omega-3 fatty acids (0.72 g/kg), NAC (20 mg/kg) or folic acid (50 mg/kg) once/day, for a period of 20 days. Then, the animals' immobility times were evaluated using the forced swimming test. Oxidative stress parameters were evaluated in the brain. Depressive-like behavior induced by CMS was prevented by NAC and folic acid, and depressive-like behavior induced by MD was prevented by NAC, folic acid and omega-3. NAC, folic acid and omega-3 were able to exert antioxidant effects in the brain of rats subjected to CMS or MD. These preventive treatments decreased the levels of protein carbonylation and lipid peroxidation, and also decreased the concentrations of nitrite/nitrate and reduced the activity of myeloperoxidase activity in the rat brain which was induced by CMS or MD. NAC, folic acid and omega-3 increased superoxide dismutase and catalase activities in the rat brain subjected to early or late life stress. NAC, omega-3 and folic acid may present interesting lines of treatment based on their antioxidant properties, which cause an inhibition of behavioral and brain changes that occur from stressful life events. Copyright © 2018 Elsevier Inc. All rights reserved.

Aging Brain: Prevention of Oxidative Stress by Vitamin E and Exercise

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Sambe Asha Devi

2009-01-01

Full Text Available With aging, the brain undergoes neuronal loss in many areas. Although the loss of cells in the cerebral cortex, in particular the frontal cortex, has been recognized with aging, the influence of synaptic losses has a larger impact on cognitive decline. Much of the recent research on animals, as well as humans, has been aimed at slowing the cognitive decline through enrichment, and it has been found that the key factors are antioxidants and exercise. Several reports support the concept that regular supplementation of vitamin E and physical activity from as early as middle age can slow the cognitive decline observed during the later years. A few studies have also suggested that exercise is analogous to acetylcholine esterase inhibitors that are also used extensively to treat cognitive impairment and dementia in Alzheimer's disease. In addition, reports also support that vitamin E and exercise may act synergistically to overcome free radical injury and oxidative stress in the aging brain.

Correlation of serum GFAP, S100B and NSE contents with posttraumatic oxidative stress response and insulin resistance in patients with traumatic brain injury

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Bing-Feng Tian

2018-07-01

Full Text Available Objective: To study the correlation of serum GFAP, S100B and NSE contents with posttraumatic oxidative stress response and insulin resistance in patients with traumatic brain injury. Methods: A total of 110 patients with traumatic brain injury who were treated in our hospital between January 2015 and December 2016 were collected as the observation group, and 60 healthy subjects who received physical examination in our hospital during the same period were collected as normal control group. Serum GFAP, S100B and NSE levels as well as oxidative stress index and insulin resistance index levels of two groups of subjects were detected, and Pearson test was used to further evaluate the correlation of serum GFAP, S100B and NSE contents with oxidative stress response and insulin resistance in patients with traumatic brain injury. Results: Serum GFAP, S100B and NSE contents of observation group were significantly higher than those of normal control group; serum oxidative stress indexes MDA, MPO and LPO contents were higher than those of normal control group while SOD and TAC contents were lower than those of normal control group; serum insulin resistance indexes GLU, INS and HOMA-IR levels were higher than those of control group. Pearson test showed that serum GFAP, S100B and NSE contents in patients with traumatic brain injury were directly correlated with post-traumatic oxidative stress and insulin resistance. Conclusion: The serum GFAP, S100B and NSE contents increase in patients with traumatic brain injury, and the increase is directly correlated with the oxidative stress and insulin resistance.

Manganese-enhanced magnetic resonance imaging (MEMRI) reveals brain circuitry involved in responding to an acute novel stress in rats with a history of repeated social stress.

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Bangasser, Debra A; Lee, Catherine S; Cook, Philip A; Gee, James C; Bhatnagar, Seema; Valentino, Rita J

2013-10-02

Responses to acute stressors are determined in part by stress history. For example, a history of chronic stress results in facilitated responses to a novel stressor and this facilitation is considered to be adaptive. We previously demonstrated that repeated exposure of rats to the resident-intruder model of social stress results in the emergence of two subpopulations that are characterized by different coping responses to stress. The submissive subpopulation failed to show facilitation to a novel stressor and developed a passive strategy in the Porsolt forced swim test. Because a passive stress coping response has been implicated in the propensity to develop certain psychiatric disorders, understanding the unique circuitry engaged by exposure to a novel stressor in these subpopulations would advance our understanding of the etiology of stress-related pathology. An ex vivo functional imaging technique, manganese-enhanced magnetic resonance imaging (MEMRI), was used to identify and distinguish brain regions that are differentially activated by an acute swim stress (15 min) in rats with a history of social stress compared to controls. Specifically, Mn(2+) was administered intracerebroventricularly prior to swim stress and brains were later imaged ex vivo to reveal activated structures. When compared to controls, all rats with a history of social stress showed greater activation in specific striatal, hippocampal, hypothalamic, and midbrain regions. The submissive subpopulation of rats was further distinguished by significantly greater activation in amygdala, bed nucleus of the stria terminalis, and septum, suggesting that these regions may form a circuit mediating responses to novel stress in individuals that adopt passive coping strategies. The finding that different circuits are engaged by a novel stressor in the two subpopulations of rats exposed to social stress implicates a role for these circuits in determining individual strategies for responding to stressors

Effect of bypass on the motor activation SPECT compared to the acetazolamide SPECT

International Nuclear Information System (INIS)

Kawaguchi, Shoichiro; Iwahashi, Hideaki; Sakaki, Toshisuke; Imai, Teruhiko; Ohishi, Hajime

2002-01-01

The authors evaluated and analyzed motor activation single photon emission computed tomography (M-SPECT) in ischemic cerebrovascular disease compared to resting and acetazolamide (ACZ) activated SPECT studies. Seventeen cases with STA-MCA bypass performed for ischemic cerebrovascular disease were examined. The SPECT studies consisting of resting, ACZ activation, and motor activation stages were performed before bypass, at 1 month, and 3 months after bypass. The result of the M-SPECT was expressed as negative or positive. Before bypass: In all 17 cases, SPECT studies of the affected side showed reduction of resting cerebral blood flow (CBF) and reduction of cerebrovascular reserve capacity (CVRC). Eight cases were positive in the M-SPECT study. One week after bypass: The resting CBF increased in seven cases. Four showed preoperative positive M-SPECT. Eight cases showed improvement of the CVRC. Twelve cases were positive in M-SPECT, and two were negative in the preoperative M-SPECT. Three months after bypass: Thirteen cases showed improvement in the resting CBF, and fourteen cases showed improvement of the CVRC. Fourteen cases were positive in the M-SPECT, and among these, 6 were negative in the preoperative M-SPECT. There was a discrepancy between the improvement in CVRC and M-SPECT. M-SPECT study can provide information about the degree of hemodynamic compromise and effect of bypass surgery. (author)

Effect of bypass on the motor activation SPECT compared to the acetazolamide SPECT

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Kawaguchi, Shoichiro; Iwahashi, Hideaki; Sakaki, Toshisuke; Imai, Teruhiko; Ohishi, Hajime [Nara Medical Univ., Kashihara (Japan)

2002-03-01

The authors evaluated and analyzed motor activation single photon emission computed tomography (M-SPECT) in ischemic cerebrovascular disease compared to resting and acetazolamide (ACZ) activated SPECT studies. Seventeen cases with STA-MCA bypass performed for ischemic cerebrovascular disease were examined. The SPECT studies consisting of resting, ACZ activation, and motor activation stages were performed before bypass, at 1 month, and 3 months after bypass. The result of the M-SPECT was expressed as negative or positive. Before bypass: In all 17 cases, SPECT studies of the affected side showed reduction of resting cerebral blood flow (CBF) and reduction of cerebrovascular reserve capacity (CVRC). Eight cases were positive in the M-SPECT study. One week after bypass: The resting CBF increased in seven cases. Four showed preoperative positive M-SPECT. Eight cases showed improvement of the CVRC. Twelve cases were positive in M-SPECT, and two were negative in the preoperative M-SPECT. Three months after bypass: Thirteen cases showed improvement in the resting CBF, and fourteen cases showed improvement of the CVRC. Fourteen cases were positive in the M-SPECT, and among these, 6 were negative in the preoperative M-SPECT. There was a discrepancy between the improvement in CVRC and M-SPECT. M-SPECT study can provide information about the degree of hemodynamic compromise and effect of bypass surgery. (author)

Formulation design of oral pediatric Acetazolamide suspension: dose uniformity and physico-chemical stability study.

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Santoveña, Ana; Suárez-González, Javier; Martín-Rodríguez, Cristina; Fariña, José B

2017-03-01

The formulation of an active pharmaceutical ingredient (API) as oral solution or suspension in pediatrics is a habitual practice, due to the non-existence of many commercialized medicines in pediatric doses. It is also the simplest way to prepare and administer them to this vulnerable population. The design of a formulation that assures the dose and the system stability depends on the physico-chemical properties of the API. In this study, we formulate a class IV API, Acetazolamide (AZM) as suspension for oral administration to pediatric population. The suspension must comply attributes of quality, safety and efficacy for this route of administration. We use simple compounding procedures, as well as fewer pure excipients, as recommended for children. Mass and uniformity content assays and physical and chemical stability studies were performed. To quantify the API an UPLC method was used. We verified the physico-chemical stability of the suspensions and that they passed the mass test of the European Pharmacopeia (EP), but not the dose uniformity test. This reveals that AZM must be formulated as liquid forms with a more complex system of excipients (not usually indicated in pediatrics), or otherwise solid forms capable of assuring uniformity of mass and dose for every dosage unit.

Activation of the endoplasmic reticulum stress response by the amyloid-beta 1-40 peptide in brain endothelial cells.

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Fonseca, Ana Catarina R G; Ferreiro, Elisabete; Oliveira, Catarina R; Cardoso, Sandra M; Pereira, Cláudia F

2013-12-01

Neurovascular dysfunction arising from endothelial cell damage is an early pathogenic event that contributes to the neurodegenerative process occurring in Alzheimer's disease (AD). Since the mechanisms underlying endothelial dysfunction are not fully elucidated, this study was aimed to explore the hypothesis that brain endothelial cell death is induced upon the sustained activation of the endoplasmic reticulum (ER) stress response by amyloid-beta (Aβ) peptide, which deposits in the cerebral vessels in many AD patients and transgenic mice. Incubation of rat brain endothelial cells (RBE4 cell line) with Aβ1-40 increased the levels of several markers of ER stress-induced unfolded protein response (UPR), in a time-dependent manner, and affected the Ca(2+) homeostasis due to the release of Ca(2+) from this intracellular store. Finally, Aβ1-40 was shown to activate both mitochondria-dependent and -independent apoptotic cell death pathways. Enhanced release of cytochrome c from mitochondria and activation of the downstream caspase-9 were observed in cells treated with Aβ1-40 concomitantly with caspase-12 activation. Furthermore, Aβ1-40 activated the apoptosis effectors' caspase-3 and promoted the translocation of apoptosis-inducing factor (AIF) to the nucleus demonstrating the involvement of caspase-dependent and -independent mechanisms during Aβ-induced endothelial cell death. In conclusion, our data demonstrate that ER stress plays a significant role in Aβ1-40-induced apoptotic cell death in brain endothelial cells suggesting that ER stress-targeted therapeutic strategies might be useful in AD to counteract vascular defects and ultimately neurodegeneration. © 2013.

Soluble (Prorenin Receptor and Obstructive Sleep Apnea Syndrome: Oxidative Stress in Brain?

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Kazuhiro Takahashi

2017-06-01

Full Text Available (Prorenin receptor ((PRR is a multi-functional molecule that is related to both the renin-angiotensin system (RAS and vacuolar H+-ATPase (v-ATPase, an ATP-dependent multi-subunit proton pump. Soluble (PRR (s(PRR, which consists of the extracellular domain of (PRR, is present in blood and urine. Elevated plasma s(PRR concentrations are reported in patients with chronic kidney disease and pregnant women with hypertension or diabetes mellitus. In addition, we have shown that plasma s(PRR concentrations are elevated in patients with obstructive sleep apnea syndrome (OSAS. Interestingly, the levels are elevated in parallel with the severity of OSAS, but are not related to the presence of hypertension or the status of the circulating RAS in OSAS. It is known that v-ATPase activity protects cells from endogenous oxidative stress, and loss of v-ATPase activity results in chronic oxidative stress. We hypothesize that hypoxia and subsequent oxidative stress, perhaps in the brain, may be one of the factors that elevate plasma s(PRR levels in OSAS.

Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat

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Han JH

2015-06-01

Full Text Available Jin-hong Han,1,2 Hong-zhao Tian,2 Yang-yang Lian,1 Yi Yu,1 Cheng-biao Lu,2 Xin-min Li,3 Rui-ling Zhang,1 Haiyun Xu4 1The Second Affiliated Hospital of Xinxiang Medical University, 2School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 3Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 4The Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Quetiapine, an atypical antipsychotic, has been employed to treat alcoholic patients with comorbid psychopathology. It was shown to scavenge hydroxyl radicals and to protect cultured cells from noxious effects of oxidative stress, a pathophysiological mechanism involved in the toxicity of alcohol. This study compared the redox status of the liver and the brain regions of prefrontal cortex, hippocampus, and cerebellum of rats treated with or without ethanol and quetiapine. Ethanol administration for 1 week induced oxidative stress in the liver and decreased the activity of glutathione peroxidase and total antioxidant capacity (TAC there. Coadministration of quetiapine did not protect glutathione peroxidase and TAC in the liver against the noxious effect of ethanol, thus was unable to mitigate the ethanol-induced oxidative stress there. The ethanol-induced alteration in the redox status in the prefrontal cortex is mild, whereas the hippocampus and cerebellum are more susceptible to ethanol intoxication. For all the examined brain regions, coadministration of quetiapine exerted effective protection on the antioxidants catalase and total superoxide dismutase and on the TAC, thus completely blocking the ethanol-induced oxidative stress in these brain regions. These protective effects may explain the clinical observations that quetiapine reduced psychiatric symptoms intensity and maintained a good level of tolerability in chronic alcoholism with

Left Brain/Right Brain Learning for Adult Education.

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Garvin, Barbara

1986-01-01

Contrasts and compares the theory and practice of adult education as it relates to the issue of right brain/left brain learning. The author stresses the need for a whole-brain approach to teaching and suggests that adult educators, given their philosophical directions, are the perfect potential users of this integrated system. (Editor/CT)

Protective effect of pineapple (Ananas cosmosus peel extract on alcohol-induced oxidative stress in brain tissues of male albino rats

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Ochuko L Erukainure

2011-03-01

Full Text Available Objective: To investigate the ability of pineapple peels to protect against alcohol-induced oxidative stress in brain tissues using male albino rat models. Methods: Response surface methodology (RSM was used to design a series of experiments to optimize treatment conditions with the aim of investigating the protective effect of pineapple peel extract on alcohol-induced oxidative stress in brain tissues. Oxidative stress was induced by oral administration of ethanol (20% w/v at a dosage of 5 mL/kg bw. The treatment lasted for 28 days. At the end of the treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Tissue homogenates were used for the assessment of protein concentration, reduced glutathione (GSH content, catalase, and SOD. Results: Alcohol administration caused a significant decrease (P>0.05 in GSH level in the group which was only fed alcohol. Treatment with pineapple peel extracts caused increase in GSH level in alcohol fed groups. No significant difference (P<0.05 was observed in SOD levels of the negative control and group fed on only pineapple peel extract. Elevated level of catalase was observed in the negative control but pineapple peel extract significantly reduced the levels. Conclusions: This study indicates the protective effect of pineapple peel against alcoholinduced oxidative stress in brain tissues.

Endogenous reward mechanisms and their importance in stress reduction, exercise and the brain.

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Esch, Tobias; Stefano, George B

2010-06-30

Stress can facilitate disease processes and causes strain on the health care budgets. It is responsible or involved in many human ailments of our time, such as cardiovascular illnesses, particularly related to the psychosocial stressors of daily life, including work. Besides pharmacological or clinical medical treatment options, behavioral stress reduction is much-needed. These latter approaches rely on an endogenous healing potential via life-style modification. Hence, research has suggested different ways and approaches to self-treat stress or buffer against stressors and their impacts. These self-care-centred approaches are sometimes referred to as mind-body medicine or multi-factorial stress management strategies. They consist of various cognitive behavioral techniques, as well as relaxation exercises and nutritional counselling. However, a critical and consistent element of modern effective stress reduction strategies are exercise practices. With regard to underlying neurobiological mechanisms of stress relief, reward and motivation circuitries that are imbedded in the limbic regions of the brain are responsible for the autoregulatory and endogenous processing of stress. Exercise techniques clearly have an impact upon these systems. Thereby, physical activities have a potential to increase mood, i.e., decrease psychological distress by pleasure induction. For doing so, neurobiological signalling molecules such as endogenous morphine and coupled nitric oxide pathways get activated and finely tuned. Evolutionarily, the various activities and autoregulatory pathways are linked together, which can also be demonstrated by the fact that dopamine is endogenously converted into morphine which itself leads to enhanced nitric oxide release by activation of constitutive nitric oxide synthase enzymes. These molecules and mechanisms are clearly stress-reducing.

Clarifying relations between dispositional aggression and brain potential response: overlapping and distinct contributions of impulsivity and stress reactivity.

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Venables, Noah C; Patrick, Christopher J; Hall, Jason R; Bernat, Edward M

2011-03-01

Impulsive-aggressive individuals exhibit deficits in amplitude of the P3 brain potential response, however, it remains unclear how separable dispositional traits account for this association. The current study sought to clarify the basis of this association by examining contributions of trait impulsiveness and stress reactivity to the observed relationship between dispositional aggression and amplitude of the P3 brain potential response in a visual novelty-oddball procedure. A significant negative association was found between aggressiveness and amplitude of P3 response to both target and novel stimuli over frontal-central scalp sites. Impulsivity showed a parallel inverse relationship with P3 amplitude, attributable to its overlap with dispositional aggression. In contrast, stress reactivity did not exhibit a zero-order association with P3 amplitude, but modestly predicted P3 in a positive direction after accounting for its overlap with aggression. Results are discussed in terms of their implications for individual difference variables and brain processes underlying impulsive-aggressive behavior. Copyright © 2011 Elsevier B.V. All rights reserved.

Fisetin alleviates oxidative stress after traumatic brain injury via the Nrf2-ARE pathway.

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Zhang, Li; Wang, Handong; Zhou, Yali; Zhu, Yihao; Fei, Maoxin

2018-05-22

Fisetin, a natural flavonoid, has neuroprotection properties in many brain injury models. However, its role in traumatic brain injury (TBI) has not been fully explained. In the present study, we aimed to explore the neuroprotective effects of fisetin in a mouse model of TBI. We found that fisetin improved neurological function, reduced cerebral edema, attenuated brain lesion and ameliorated blood-brain barrier (BBB) disruption after TBI. Moreover, the up-regulation of malondialdehyde (MDA) and the activity of glutathione peroxidase (GPx) were reversed by fisetin treatment. Furthermore, administration of fisetin suppressed neuron cell death and apoptosis, increased the expression of B-cell lymphoma 2 (Bcl-2), while decreased the expression of Bcl-2-associated X protein (Bax) and caspase-3 after TBI. In addition, fisetin activated the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway following TBI. However, fisetin only failed to suppress oxidative stress in Nrf2 -/- mice. In conclusion, our data provided the first evidence that fisetin played a critical role in neuroprotection after TBI partly through the activation of the Nrf2-ARE pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ethanolic extract of Astragali radix and Salviae radix prohibits oxidative brain injury by psycho-emotional stress in whisker removal rat model.

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Hyeong-Geug Kim

Full Text Available Myelophil, an ethanolic extract of Astragali Radix and Salviae Radix, has been clinically used to treat chronic fatigue and stress related disorders in South Korea. In this study, we investigated the protective effects of Myelophil on a whisker removal-induced psycho-emotional stress model. SD rats were subjected to whisker removal after oral administration of Myelophil or ascorbic acid for consecutive 4 days. Whisker removal considerably increased total reactive oxygen species in serum levels as well as cerebral cortex and hippocampal regions in brain tissues. Lipidperoxidation levels were also increased in the cerebral cortex, hippocampus regions, and brain tissue injuries as shown in histopathology and immunohistochemistry. However, Myelophil significantly ameliorated these alterations, and depletion of glutathione contents in both cerebral cortex and hippocampus regions respectively. Serum levels of corticosterone and adrenaline were notably altered after whisker removal stress, whereas these abnormalities were significantly normalized by pre-treatment with Myelophil. The NF-κB was notably activated in both cerebral cortex and hippocampus after whisker removal stress, while it was efficiently blocked by pre-treatment with Myelophil. Myelophil also significantly normalizes alterations of tumor necrosis factor-α, interleukin (IL-1β, IL-6 and interferon-γ in both gene expressions and protein levels. These results suggest that Myelophil has protective effects on brain damages in psycho-emotional stress, and the underlying mechanisms involve regulation of inflammatory proteins, especially NF-κB modulation.

Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species

Czech Academy of Sciences Publication Activity Database

Wilhelm, Jiří; Vytášek, Richard; Uhlík, Jiří; Vajner, Luděk

2016-01-01

Roč. 2016, č. 2016 (2016), č. článku 5057610. ISSN 1942-0900 R&D Projects: GA ČR(CZ) GAP303/11/0298 Institutional support: RVO:67985823 Keywords : oxidative stress * developing rat brain * lipid peroxidation Subject RIV: ED - Physiology Impact factor: 4.593, year: 2016

Mdivi-1 ameliorates early brain injury after subarachnoid hemorrhage via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis.

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Fan, Lin-Feng; He, Ping-You; Peng, Yu-Cong; Du, Qing-Hua; Ma, Yi-Jun; Jin, Jian-Xiang; Xu, Hang-Zhe; Li, Jian-Ru; Wang, Zhi-Jiang; Cao, Sheng-Long; Li, Tao; Yan, Feng; Gu, Chi; Wang, Lin; Chen, Gao

2017-11-01

Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms. The endovascular perforation model of SAH was performed in adult male Sprague Dawley rats. The results indicated Mdivi-1(a selective Drp1 inhibitor) reversed the morphologic changes of mitochondria and Drp1 translocation, reduced ROS levels, ameliorated the BBB disruption and brain edema remarkably, decreased the expression of MMP-9 and prevented degradation of tight junction proteins-occludin, claudin-5 and ZO-1. Mdivi-1 administration also inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB), leading to decreased expressions of TNF-ɑ, IL-6 and IL-1ß. Moreover, Mdivi-1 treatment attenuated neuronal cell death and improved neurological outcome. To investigate the underlying mechanisms further, we determined that Mdivi-1 reduced p-PERK, p-eIF2α, CHOP, cleaved caspase-3 and Bax expression as well as increased Bcl-2 expression. Rotenone (a selective inhibitor of mitochondrial complexes I) abolished both the anti-BBB disruption and anti-apoptosis effects of Mdivi-1. In conclusion, these data implied that excessive mitochondrial fission might inhibit mitochondrial complex I to become a cause of oxidative stress in SAH, and the inhibition of Drp1 by Mdivi-1 attenuated early brain injury after SAH probably via the suppression

Acute stress evokes sexually dimorphic, stressor-specific patterns of neural activation across multiple limbic brain regions in adult rats.

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Sood, Ankit; Chaudhari, Karina; Vaidya, Vidita A

2018-03-01

Stress enhances the risk for psychiatric disorders such as anxiety and depression. Stress responses vary across sex and may underlie the heightened vulnerability to psychopathology in females. Here, we examined the influence of acute immobilization stress (AIS) and a two-day short-term forced swim stress (FS) on neural activation in multiple cortical and subcortical brain regions, implicated as targets of stress and in the regulation of neuroendocrine stress responses, in male and female rats using Fos as a neural activity marker. AIS evoked a sex-dependent pattern of neural activation within the cingulate and infralimbic subdivisions of the medial prefrontal cortex (mPFC), lateral septum (LS), habenula, and hippocampal subfields. The degree of neural activation in the mPFC, LS, and habenula was higher in males. Female rats exhibited reduced Fos positive cell numbers in the dentate gyrus hippocampal subfield, an effect not observed in males. We addressed whether the sexually dimorphic neural activation pattern noted following AIS was also observed with the short-term stress of FS. In the paraventricular nucleus of the hypothalamus and the amygdala, FS similar to AIS resulted in robust increases in neural activation in both sexes. The pattern of neural activation evoked by FS was distinct across sexes, with a heightened neural activation noted in the prelimbic mPFC subdivision and hippocampal subfields in females and differed from the pattern noted with AIS. This indicates that the sex differences in neural activation patterns observed within stress-responsive brain regions are dependent on the nature of stressor experience.

Effect of chronic forced swimming stress on whole brain radiation induced cognitive dysfunction and related mechanism

International Nuclear Information System (INIS)

Zhang Yuan; Sun Rui; Zhu Yaqun; Zhang Liyuan; Ji Jianfeng; Li Kun; Tian Ye

2014-01-01

Objective: To explore whether chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction and possible mechanism. Methods: Thirty-nine one month old male Sprague-Dawley rats were randomized into sham control group(C), swimming group(C-S), radiation group(R), and radiation plus swimming group(R-S). Radiation groups were given a single dose of 20 Gy on whole-brain. Rats in the swimming groups were trained with swimming of 15 min/d, 5 d/w. Rat behavior was performed 3 months after radiation in an order of free activity in an open field and the Morris water maze test including the place navigation and spatial probe tests. Then, the protein expressions of BDNF, P-ERK, T-ERK, P-CREB and T-CREB in the rat hippocampus tissue were assayed by Western blot. Results: On the day 2, in the place navigation test of Morris water maze, the latency of swimming group was significantly shorter than that of sham group, the latency of sham group was significantly shorter than that of radiation group, and the latency of radiation swimming group was significantly shorter than that of radiation group(P 0.05). Western blot assay showed that the expressions of BDNF and its downstream signals including P-ERK and P-CREB were markedly reduced by radiation (P < 0.05), but this reduction was attenuated by the chronic forced swimming stress. Conclusion: The chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction by up-regulating the expressions of BDNF and its downstream signal molecules of P-ERK and P-CREB in hippocampus. (authors)

Near-infrared transillumination back scattering sounding--new method to assess brain microcirculation in patients with chronic carotid artery stenosis.

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Andrzej F Frydrychowski

Full Text Available PURPOSE: The purpose of the study was to assess the responses of pial artery pulsation (cc-TQ and subarachnoid width (sas-TQ to acetazolamide challenge in patients with chronic carotid artery stenosis and relate these responses to changes in peak systolic velocity (PSV, cerebral blood flow (CBF, cerebral blood volume (CBV, mean transit time (MTT and time to peak response (TTP. METHODS: Fifteen patients with carotid artery stenosis ≥ 90% on the ipsilateral side and <50% on the contralateral side were enrolled into the study. PSV was assessed using colour-coded duplex sonography, CBF, CBV, MTT and TTP with perfusion computed tomography, cc-TQ and sas-TQ with near-infrared transillumination/backscattering sounding (NIR-T/BSS. RESULTS: Based on the ipsilateral/contralateral cc-TQ ratio after acetazolamide challenge two groups of patients were distinguished: the first group with a ratio ≥ 1 and the second with a ratio <1. In the second group increases in CBF and CBV after the acetazolamide test were significantly higher in both hemispheres (ipsilateral: +33.0% ± 8.1% vs. +15.3% ± 4.4% and +26.3% ± 6.6% vs. +14.3% ± 5.1%; contralateral: +26.8% ± 7.0% vs. +17.6% ± 5.6% and +20.0% ± 7.3% vs. +10.0% ± 3.7%, respectively, cc-TQ was significantly higher only on the ipsilateral side (+37.3% ± 9.3% vs. +26.6% ± 8.6% and the decrease in sas-TQ was less pronounced on the ipsilateral side (-0.7% ± 1.5% vs. -10.2% ± 1.5%, in comparison with the first group. The changes in sas-TQ following the acetazolamide test were consistent with the changes in TTP. CONCLUSIONS: The ipsilateral/contralateral cc-TQ ratio following acetazolamide challenge may be used to distinguish patient groups characterized by different haemodynamic parameters. Further research on a larger group of patients is warranted.

Neuroprotective effect of Quince leaf hydroalcoholic extract on intracerebroventricular streptozotocin-induced oxidative stress in cortical tissue of rat brain

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A Hajizadeh Moghaddam

2015-12-01

Full Text Available Background & aim: Oxidative stress is a result of the imbalance between free radicals and the antioxidant system of the body. Increased oxidative stress in brain causes dysfunction of brain activities, destruction of neurons, and disease such as Alzheimer. Antioxidants, for example vitamins, phenolic compounds and flavonoids have been extensively investigated as potential therapeutic agents in vitro and in vivo for prevention of neurodegenerative diseases. In the present experimental study, the neuro-protective effect of quince leaf hydroalcoholic extract (QLHE on intracerebroventricular streptozotocin (icv-STZ-induced oxidative stress in cortical tissue of rat brain was examined. Methods: In the present experimental research, forty-two Wistar rats were randomly divided into control, sham, icv-STZ and icv-STZ treated with QLHE groups. The ICV-STZ group rats were injected unilaterally with ICV-STZ (3 mg/kg using a stereotactic device and QLHE (50, 100 and 150 mg/kg/day were administered for 6 weeks starting from 3 weeks before of ICV-STZ injection. The rats were killed at the end of the study and their brain cortical tissue superoxide dismutase and catalase activity were measured. The assay of catalase and superoxide dismutase was performed by following the Genet method. The amount of protein was determined according to the Bradford method.The statistical analysis was performed using one way ANOVA. Data were expressed as mean±SD and  P<0.05 was considered significant. Results: The present study indicated that in the ICV-STZ group showed significant decrease (P<0.001 in enzymatic antioxidants superoxide dismutase and catalase in the cortical tissue of the brain. Treatment of different doses of QLHE significantly increased superoxide dismutase and catalase activity compared to icv-STZ group (P<0.001 in cortical tissue of the brain. Conclusion: The study demonstrated the effectiveness of quince leaf hydroalcoholic extract as a powerful antioxidant

Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impairment and oxidative stress in rat brain.

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Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Ataee, Ramin; Moghaddam, Shiva Nasiraei

2010-08-01

Aging is the major risk factor for neurodegenerative diseases and oxidative stress and is involved in their pathophysiology. Oxidative stress can induce neuronal damage and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study we investigated the neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (5, 15, or 45 mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intracerebroventricular injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests, were evaluated 24 hours after the last injection of curcumin or vehicle. Results indicated that Hcy induces lipid peroxidation and increases malondialdehyde (MDA) and superoxide anion (SOA) levels in whole rat brain. In addition, Hcy impaired memory retention in the passive avoidance learning test. However, curcumin treatment significantly decreased MDA and SOA levels and improved learning and memory in rats. These results suggest that Hcy may induce lipid peroxidation in rat brain and that polyphenol treatment (curcumin) improves learning and memory deficits by protecting the nervous system against oxidative stress.

Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience.

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Yang, Bangkun; Yang, Chun; Ren, Qian; Zhang, Ji-Chun; Chen, Qian-Xue; Shirayama, Yukihiko; Hashimoto, Kenji

2016-12-01

Using learned helplessness (LH) model of depression, we measured protein expression of brain-derived neurotrophic factor (BDNF) pro-peptide, BDNF precursors (proBDNF and preproBDNF) in the brain regions of LH (susceptible) and non-LH rats (resilience). Expression of preproBDNF, proBDNF and BDNF pro-peptide in the medial prefrontal cortex of LH rats, but not non-LH rats, was significantly higher than control rats, although expression of these proteins in the nucleus accumbens of LH rats was significantly lower than control rats. This study suggests that regional differences in conversion of BDNF precursors into BDNF and BDNF pro-peptide by proteolytic cleavage may contribute to stress resilience.

The Serial Change of Cerebral Hemodynamics by Vascular Territory after Extracranial-Intracranial Bypass Surgery in Patients with Atherosclerosis of Cerebral Arteries

International Nuclear Information System (INIS)

Hong, Il Ki; Kim, Jae Seung; Ahn, Jae Sung; Kwon, Sun Uck; Im, Ki Chun; Lee, Jai Hyuen; Moon, Dae Hyuk

2008-01-01

To assess the effect of extracranial-intracranial (EC-IC) bypass surgery on hemodynamic improvement, we evaluated serial regional cerebral hemodynamic change of the middle cerebral artery (MCA) in symptomatic patients with atherosclerotic occlusion of the internal carotid artery (ICA) or MCA using 99m Tc-ECD acetazolamide stress brain perfusion SPECT (Acetazolamide SPECT). The patients who had suffered a recent stroke with atherosclerotic ICA or MCA occlusion underwent EC-IC bypass surgery and Acetazolamide SPECT at 1 week before and three to six months after surgery. For image analysis, attenuation corrected images were spatially normalized to SPECT templates with SPM2. Anatomical automated labeling was applied to calculate mean counts of each Volume-Of-Interest (VOI). Seven VOIs of bilateral frontal, parietal, temporal regions of the MCA territory and the ipsilateral cerebellum were defined. Using mean counts of 7 VOIs, cerebral perfusion index and perfusion reserve index were calculated. Seventeen patients (M:F=12:5, mean age: 53±2yr) were finally included in the analysis. The cerebral blood flow of the parietal region increased at 1 week (p=0.003) and decreased to the preoperative level at 3-6 months (p=0.003). The cerebrovascular reserve of the frontal and parietal regions increased significantly at 1 week after surgery (p<0.01) and improved further at 3-6 months. Cerebrovascular reserve of the MCA territory was significantly improved at early postoperative period after EC-IC bypass and kept improved state during long-term follow-up, although cerebral blood flow did not significantly improved. Therefore, cerebrovascular reserve may be a good indicator of postoperative hemodynamic improvement resulted from bypass effect

The Serial Change of Cerebral Hemodynamics by Vascular Territory after Extracranial-Intracranial Bypass Surgery in Patients with Atherosclerosis of Cerebral Arteries

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Hong, Il Ki; Kim, Jae Seung; Ahn, Jae Sung; Kwon, Sun Uck; Im, Ki Chun; Lee, Jai Hyuen; Moon, Dae Hyuk [Asan Medial Center, Ulsan University School of Medicine, Seoul (Korea, Republic of)

2008-02-15

To assess the effect of extracranial-intracranial (EC-IC) bypass surgery on hemodynamic improvement, we evaluated serial regional cerebral hemodynamic change of the middle cerebral artery (MCA) in symptomatic patients with atherosclerotic occlusion of the internal carotid artery (ICA) or MCA using {sup 99m}Tc-ECD acetazolamide stress brain perfusion SPECT (Acetazolamide SPECT). The patients who had suffered a recent stroke with atherosclerotic ICA or MCA occlusion underwent EC-IC bypass surgery and Acetazolamide SPECT at 1 week before and three to six months after surgery. For image analysis, attenuation corrected images were spatially normalized to SPECT templates with SPM2. Anatomical automated labeling was applied to calculate mean counts of each Volume-Of-Interest (VOI). Seven VOIs of bilateral frontal, parietal, temporal regions of the MCA territory and the ipsilateral cerebellum were defined. Using mean counts of 7 VOIs, cerebral perfusion index and perfusion reserve index were calculated. Seventeen patients (M:F=12:5, mean age: 53{+-}2yr) were finally included in the analysis. The cerebral blood flow of the parietal region increased at 1 week (p=0.003) and decreased to the preoperative level at 3-6 months (p=0.003). The cerebrovascular reserve of the frontal and parietal regions increased significantly at 1 week after surgery (p<0.01) and improved further at 3-6 months. Cerebrovascular reserve of the MCA territory was significantly improved at early postoperative period after EC-IC bypass and kept improved state during long-term follow-up, although cerebral blood flow did not significantly improved. Therefore, cerebrovascular reserve may be a good indicator of postoperative hemodynamic improvement resulted from bypass effect.

Early Life Stress-Related Elevations in Reaction Time Variability Are Associated with Brain Volume Reductions in HIV+ Adults

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Uraina S. Clark

2018-01-01

Full Text Available There is burgeoning evidence that, among HIV+ adults, exposure to high levels of early life stress (ELS is associated with increased cognitive impairment as well as brain volume abnormalities and elevated neuropsychiatric symptoms. Currently, we have a limited understanding of the degree to which cognitive difficulties observed in HIV+ High-ELS samples reflect underlying neural abnormalities rather than increases in neuropsychiatric symptoms. Here, we utilized a behavioral marker of cognitive function, reaction time intra-individual variability (RT-IIV, which is sensitive to both brain volume reductions and neuropsychiatric symptoms, to elucidate the unique contributions of brain volume abnormalities and neuropsychiatric symptoms to cognitive difficulties in HIV+ High-ELS adults. We assessed the relation of RT-IIV to neuropsychiatric symptom levels and total gray and white matter volumes in 44 HIV+ adults (26 with high ELS. RT-IIV was examined during a working memory task. Self-report measures assessed current neuropsychiatric symptoms (depression, stress, post-traumatic stress disorder. Magnetic resonance imaging was used to quantify total gray and white matter volumes. Compared to Low-ELS participants, High-ELS participants exhibited elevated RT-IIV, elevated neuropsychiatric symptoms, and reduced gray and white matter volumes. Across the entire sample, RT-IIV was significantly associated with gray and white matter volumes, whereas significant associations with neuropsychiatric symptoms were not observed. In the High-ELS group, despite the presence of elevated neuropsychiatric symptom levels, brain volume reductions explained more than 13% of the variance in RT-IIV, whereas neuropsychiatric symptoms explained less than 1%. Collectively, these data provide evidence that, in HIV+ High-ELS adults, ELS-related cognitive difficulties (as indexed by RT-IIV exhibit strong associations with global brain volumes, whereas ELS-related elevations in

The effects of poverty on childhood brain development: the mediating effect of caregiving and stressful life events.

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Luby, Joan; Belden, Andy; Botteron, Kelly; Marrus, Natasha; Harms, Michael P; Babb, Casey; Nishino, Tomoyuki; Barch, Deanna

2013-12-01

IMPORTANCE The study provides novel data to inform the mechanisms by which poverty negatively impacts childhood brain development. OBJECTIVE To investigate whether the income-to-needs ratio experienced in early childhood impacts brain development at school age and to explore the mediators of this effect. DESIGN, SETTING, AND PARTICIPANTS This study was conducted at an academic research unit at the Washington University School of Medicine in St Louis. Data from a prospective longitudinal study of emotion development in preschool children who participated in neuroimaging at school age were used to investigate the effects of poverty on brain development. Children were assessed annually for 3 to 6 years prior to the time of a magnetic resonance imaging scan, during which they were evaluated on psychosocial, behavioral, and other developmental dimensions. Preschoolers included in the study were 3 to 6 years of age and were recruited from primary care and day care sites in the St Louis metropolitan area; they were annually assessed behaviorally for 5 to 10 years. Healthy preschoolers and those with clinical symptoms of depression participated in neuroimaging at school age/early adolescence. EXPOSURE Household poverty as measured by the income-to-needs ratio. MAIN OUTCOMES AND MEASURES Brain volumes of children's white matter and cortical gray matter, as well as hippocampus and amygdala volumes, obtained using magnetic resonance imaging. Mediators of interest were caregiver support/hostility measured observationally during the preschool period and stressful life events measured prospectively. RESULTS Poverty was associated with smaller white and cortical gray matter and hippocampal and amygdala volumes. The effects of poverty on hippocampal volume were mediated by caregiving support/hostility on the left and right, as well as stressful life events on the left. CONCLUSIONS AND RELEVANCE The finding that exposure to poverty in early childhood materially impacts brain

Attenuating brain edema, hippocampal oxidative stress, and cognitive dysfunction in rats using hyperbaric oxygen preconditioning during simulated high-altitude exposure.

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Lin, Hung; Chang, Ching-Ping; Lin, Hung-Jung; Lin, Mao-Tsun; Tsai, Cheng-Chia

2012-05-01

We assessed whether hyperbaric oxygen preconditioning (HBO2P) in rats induced heat shock protein (HSP)-70 and whether HSP-70 antibody (Ab) preconditioning attenuates high altitude exposure (HAE)-induced brain edema, hippocampal oxidative stress, and cognitive dysfunction. Rats were randomly divided into five groups: the non-HBO2P + non-HAE group, the HBO2P + non-HAE group, the non-HBO2P + HAE group, the HBO2P + HAE group, and the HBO2P + HSP-70 Abs + HAE group. The HBO2P groups were given 100% O2 at 2.0 absolute atmospheres for 1 hour per day for 5 consecutive days. The HAE groups were exposed to simulated HAE (9.7% O2 at 0.47 absolute atmospheres of 6,000 m) in a hypobaric chamber for 3 days. Polyclonal rabbit anti-mouse HSP-70-neutralizing Abs were intravenously injected 24 hours before the HAE experiments. Immediately after returning to normal atmosphere, the rats were given cognitive performance tests, overdosed with a general anesthetic, and then their brains were excised en bloc for water content measurements and biochemical evaluation and analysis. Non-HBO2P group rats displayed cognitive deficits, brain edema, and hippocampal oxidative stress (evidenced by increased toxic oxidizing radicals [e.g., nitric oxide metabolites and hydroxyl radicals], increased pro-oxidant enzymes [e.g., malondialdehyde and oxidized glutathione] but decreased antioxidant enzymes [e.g., reduced glutathione, glutathione peroxide, glutathione reductase, and superoxide dismutase]) in HAE. HBO2P induced HSP-70 overexpression in the hippocampus and significantly attenuated HAE-induced brain edema, cognitive deficits, and hippocampal oxidative stress. The beneficial effects of HBO2P were significantly reduced by HSP-70 Ab preconditioning. Our results suggest that high-altitude cerebral edema, cognitive deficit, and hippocampal oxidative stress can be prevented by HSP-70-mediated HBO2P in rats.

Effects of noise pollution stress during pregnancy on anatomical and functional brain cortex development of the offsprings of NMRI mice

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Sara Bijani

2012-12-01

Full Text Available Introduction: Effects of stress on changes in neural system activity is well defined, which might be because of the changes in brain cortex architecture. In the present study, the effects of maternal noise stress on the morphological and functional changes in brain cortex of off springs of NMRI mice were examined.Materials and Methods: Female pregnant mice divided into two groups. Control group was maintained in their home cages without any invasion but the experimental group was exposed to the noise stress (80 db for 5 min/day from day zero of pregnancy to day 14 (i.e. 15 days. After delivery, six pups from each group were killed and their brains were fixed, sectioned and stained in H&E. These sections were investigated by MOTIC software for both control and experimental groups. Other pups were nursed by their mothers until their adolescence (22 g-8 weeks old. Then they were examined for behavioral side-biased and locomotor activity tests.Results: Decrease in cortex diameter and diameter of each layer for the experimental group was observed. In addition, neuron counting in each layer indicated that the number of the neurons in the middle and outer layers of cortex for the experimental group was reduced than the control group. In contrast, the number of the neurons in the inner layer of the experimental group was increased. From the functional view, in experimental group increases in left-handness especially in female off springs were observed. Furthermore, spontaneous locomotor activity in the new environment was increased in the experimental group.Conclusion: These results indicated that neuronal immigration and network connections in the inner layer of cortex through the middle and outer layers in the experimental group were inhibited. In other word, noise stress was able to inhibit brain cortex development in next generation

Acetazolamide Inhibits the Level of Tyrosinase and Melanin: An Enzyme Kinetic, In Vitro, In Vivo, and In Silico Studies.

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Abbas, Qamar; Raza, Hussain; Hassan, Mubashir; Phull, Abdul Rehman; Kim, Song Ja; Seo, Sung-Yum

2017-09-01

Melanin is the major factor that determines skin color and protects from ultraviolet radiation. In present study we evaluated the anti-melanogenesis effect of acetazolamide (ACZ) using four different approaches: enzyme kinetic, in vitro, in vivo and in silico. ACZ demonstrated significant inhibitory activity (IC 50 7.895 ± 0.24 μm) against tyrosinase as compared to the standard drug kojic acid (IC 50 16.84 ± 0.64 μm) and kinetic analyses showed that ACZ is a non-competitive inhibitor without cytotoxic effect. In in vitro experiments, A375 human melanoma cells were treated with 20 or 40 μm of ACZ with or without 50 μm of l-DOPA. Western blot results showed that ACZ significantly (P melanin and it could be used as a lead for developing the drugs for hyperpigmentary disorders and skin whitening. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Effects of acetazolamide on the micro- and macro-vascular cerebral hemodynamics: a diffuse optical and transcranial doppler ultrasound study.

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Zirak, Peyman; Delgado-Mederos, Raquel; Martí-Fàbregas, Joan; Durduran, Turgut

2010-11-19

Acetazolamide (ACZ) was used to stimulate the cerebral vasculature on ten healthy volunteers to assess the cerebral vasomotor reactivity (CVR). We have combined near infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS) and transcranial Doppler (TCD) technologies to non-invasively assess CVR in real-time by measuring oxy- and deoxy-hemoglobin concentrations, using NIRS, local cerebral blood flow (CBF), using DCS, and blood flow velocity (CBFV) in the middle cerebral artery, using TCD. Robust and persistent increases in oxy-hemoglobin concentration, CBF and CBFV were observed. A significant agreement was found between macro-vascular (TCD) and micro-vascular (DCS) hemodynamics, between the NIRS and TCD data, and also within NIRS and DCS results. The relative cerebral metabolic rate of oxygen, rCMRO(2), was also determined, and no significant change was observed. Our results showed that the combined diffuse optics-ultrasound technique is viable to follow (CVR) and rCMRO(2) changes in adults, continuously, at the bed-side and in real time.

Effectiveness of acetazolamide for reversal of metabolic alkalosis in weaning COPD patients from mechanical ventilation.

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Faisy, Christophe; Mokline, Amel; Sanchez, Olivier; Tadié, Jean-Marc; Fagon, Jean-Yves

2010-05-01

To evaluate the effects of a single daily dose of acetazolamide (ACET) on metabolic alkalosis and respiratory parameters in weaning chronic obstructive pulmonary disease (COPD) patients from invasive mechanical ventilation. Case-control study. An 18-bed intensive care unit (ICU) in a university hospital. Twenty-six intubated COPD patients with mixed metabolic alkalosis (serum bicarbonate >26 mmol/l and arterial pH >or=7.38) were compared with a historical control group (n = 26) matched for serum bicarbonate, arterial pH, age, and severity of illness at admission to ICU. ACET administration (500 mg intravenously) was monitored daily according to arterial blood gas analysis from readiness to wean until extubation. ACET was administered 4 (1-11) days throughout the weaning period. Patients with ACET treatment significantly decreased their serum bicarbonate (p = 0.01 versus baseline) and arterial blood pH (p respiratory parameters except PaO(2)/FiO(2) ratio (p = 0.03). ACET patients and their matched controls had similar duration of weaning. Extubation success rate was not significantly different between groups, and causes of reintubation were comparable. ACET used at the dosage of 500 mg per day reduces metabolic alkalosis but has no benefit in terms of improving PaCO(2) or respiratory parameters in weaning COPD patients from mechanical ventilation.

Therapeutic effect of methanolic extract of Laportea aestuans (L.) Chew, on oxidative stress in the brain of male Wistar rats

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Elizabeth, Omotosho Omolola; Olawumi, Ogunlade Oladipupo

2018-04-01

The aim of this study was to assess the effect of diclofenac-induced oxidative stress in the brain of Wistar rats. The experiment was carried out using thirty-six rats. Six groups contained six rats in each. The first group being the control group received 1ml of gum acacia which is the vehicle. Groups 2 to 6 were induced with oxidative stress by oral administration of 40 mg/kg body weight of diclofenac and pretreated as follows: group 2 received only diclofenac, group 3 with 200 mg/kg body weight of methanolic extract of Laportea aestuans (L.) Chew, group 4 with 400 mg/kg body weight of Laportea aestuans extract, group 5 with 800 mg/kg body weight of Laportea aestuans and group 6 with 50 mg/kg body weight of cimetidine. The pretreatment was carried out for a period of seven days after which oxidative stress was induced. The animals were thereafter sacrificed and brain was excised. Antioxidant enzymes and molecules such as superoxide dismutase, catalase, glutathione, levels of malondialdehyde and protein carbonyl were assayed by standard methods. The results showed significant increases in glutathione level and activities of catalase, superoxide dismutase and significant decrease in lipid peroxidation and protein carbonyl in groups 3 to 5 when compared to group 2. This shows that the methanolic extract of Laportea aestuans has a protective effect on the brain against oxidative stress.

Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

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Megha, Kanu; Deshmukh, Pravin Suryakantrao; Banerjee, Basu Dev; Tripathi, Ashok Kumar; Ahmed, Rafat; Abegaonkar, Mahesh Pandurang

2015-12-01

Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n=6 in each group): group I consisted of sham exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration. Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (pmicrowave exposed groups (pmicrowave exposed animal (pmicrowave exposed groups as compared to their corresponding values in sham exposed group (pmicrowave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect. The study also indicates that increased oxidative stress and inflammatory response might be the factors involved in DNA damage following low intensity microwave exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble[(3,5,5-Trimethylhexanoyl)ferrocene

DEFF Research Database (Denmark)

Lykkesfeldt, Jens; Morgan, Evan; Christen, Stephan

2007-01-01

Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month old rats following supplementationwith the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (......, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.......Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month old rats following supplementationwith the lipophilic iron derivative [(3,5,5-trimethylhexanoyl......)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of a- and ¿-tocopherols and glutathione (GSH) were also higher. In contrast, the brain...

Impact of Posttraumatic Stress Disorder and Injury Severity on Recovery in Children with Traumatic Brain Injury

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Kenardy, Justin; Le Brocque, Robyne; Hendrikz, Joan; Iselin, Greg; Anderson, Vicki; McKinlay, Lynne

2012-01-01

The adverse impact on recovery of posttraumatic stress disorder (PTSD) in mild traumatic brain injury (TBI) has been demonstrated in returned veterans. The study assessed this effect in children's health outcomes following TBI and extended previous work by including a full range of TBI severity, and improved assessment of PTSD within a…

Evidence for altered brain reactivity to norepinephrine in Veterans with a history of traumatic stress

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Rebecca C. Hendrickson

2018-02-01

Full Text Available Background: Increases in the quantity or impact of noradrenergic signaling have been implicated in the pathophysiology of posttraumatic stress disorder (PTSD. This increased signaling may result from increased norepinephrine (NE release, from altered brain responses to NE, or from a combination of both factors. Here, we tested the hypothesis that Veterans reporting a history of trauma exposure would show an increased association between brain NE and mental health symptoms commonly observed after trauma, as compared to Veterans who did not report a history of trauma exposure, consistent with the possibility of increased brain reactivity to NE after traumatic stress. Methods: Using a convenience sample of 69 male Veterans with a history of combat-theater deployment, we examined the relationship between trauma-related mental health symptoms and the concentration of NE in cerebrospinal fluid (CSF. CSF NE levels were measured by HPLC in CSF from morning lumbar puncture. Behavioral symptoms associated with diagnoses of PTSD, depression, insomnia, or post-concussive syndrome (PCS, which together cover a wide variety of symptoms associated with alterations in arousal systems, such as sleep, mood, concentration, and anxiety, were assessed via self-report (PTSD Checklist [PCL] for PTSD, Patient Health Questionnaire 9 [PHQ9] for depression, Pittsburgh Sleep Quality Index [PSQI] for sleep problems including insomnia, and Neurobehavioral Symptom Inventory [NSI] for PCS and structured clinical interview (Clinician-Administered PSTD Scale [CAPS]. Individuals meeting criterion A of the DSM-IV diagnostic criteria for PTSD were considered trauma-exposed. Linear regression models were used to quantify the association between CSF NE and symptom intensity in participants with and without a history of trauma exposure, as well as in participants with a history of trauma exposure who were currently taking the noradrenergic receptor antagonist prazosin. Results: Fifty

Posttraumatic Stress Disorder, Traumatic Brain Injury, and Suicide Attempt History among Veterans Receiving Mental Health Services

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Brenner, Lisa A.; Betthauser, Lisa M.; Homaifar, Beeta Y.; Villarreal, Edgar; Harwood, Jeri E. F.; Staves, Pamela J.; Huggins, Joseph A.

2011-01-01

History of posttraumatic stress disorder (PTSD) or traumatic brain injury (TBI) has been found to increase risk of suicidal behavior. The association between suicide attempt history among veterans with PTSD and/or TBI was explored. Cases (N = 81) and 2:1 matched controls (N = 160) were randomly selected from a Veterans Affairs Medical Center…

The brain-derived neurotrophic factor pathway, life stress, and chronic multi-site musculoskeletal pain.

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Generaal, Ellen; Milaneschi, Yuri; Jansen, Rick; Elzinga, Bernet M; Dekker, Joost; Penninx, Brenda W J H

2016-01-01

Brain-derived neurotrophic factor (BDNF) disturbances and life stress, both independently and in interaction, have been hypothesized to induce chronic pain. We examined whether (a) the BDNF pathway (val(66)met genotype, gene expression, and serum levels), (b) early and recent life stress, and (c) their interaction are associated with the presence and severity of chronic multi-site musculoskeletal pain. Cross-sectional data are from 1646 subjects of the Netherlands Study of Depression and Anxiety. The presence and severity of chronic multi-site musculoskeletal pain were determined using the Chronic Pain Grade (CPG) questionnaire. The BDNF val(66)met polymorphism, BDNF gene expression, and BDNF serum levels were measured. Early life stress before the age of 16 was assessed by calculating a childhood trauma index using the Childhood Trauma Interview. Recent life stress was assessed as the number of recent adverse life events using the List of Threatening Events Questionnaire. Compared to val(66)val, BDNF met carriers more often had chronic pain, whereas no differences were found for BDNF gene expression and serum levels. Higher levels of early and recent stress were both associated with the presence and severity of chronic pain (p stress in the associations with chronic pain presence and severity. This study suggests that the BDNF gene marks vulnerability for chronic pain. Although life stress did not alter the impact of BDNF on chronic pain, it seems an independent factor in the onset and persistence of chronic pain. © The Author(s) 2016.

Use of 123I-IMP brain SPET to predict outcome following STA-MCA bypass surgery: cerebral blood flow but not vasoreactivity is a predictive parameter

International Nuclear Information System (INIS)

Kume, Norihiko; Hayashida, Kohei; Iwama, Toru; Cho, I.; Matsunaga, N.

1998-01-01

Superficial temporal artery - middle cerebral artery (STA-MCA) bypass surgery might improve the cerebral blood flow (CBF) but fail to reduce the risk of post-surgical events such as ischaemic stroke. In this study, we studied retrospectively whether the risk of post-surgical events corresponded to the change in resting CBF and/or the change in vasoreactivity observed before and after STA-MCA surgery using N-isopropyl-I-123-p-iodoamphetamine ( 123 I-IMP) brain single-photon emission tomography (SPET). 123 I-IMP brain SPET images obtained at rest and following acetazolamide challenge both before and after STA-MCA surgery were studied in 30 patients. Resting CBF was estimated semiquantitatively using the resting count ratios of the middle cerebral artery (MCA) area to the cerebellum. Acetazolamide challenge was assumed to result in an average increase in flow of 40% in the cerebellum. The vasoreactive response was then estimated as the ratio of the change in counts (acetazolamide - rest) to the resting cerebellar counts multiplied by 1.4. We classified 14 patients (50.5±19.3 years) into group I, who had a change in their resting CBF from before to after surgery of >10%, and 16 patients (54.0±18.8 years) into group II, who had a change in their resting CBF from before to after surgery of ≤10%. Oxygen-15 positron emission tomography (PET) studies were performed in five patients from group I and five patients from group II. One post-surgical event occurred in group I while there were eight post-surgical events in group II (P<0.05). Resting CBF improved by 20.4%±7.5% in group I and by 0.9%±6.9% in group II patients after surgery (P<0.001). No significant difference in the improvement in vasoreactivity was observed between group I patients (32.6%±17.7%) and group II patients (24.6%±15.6%) following surgery. Patients in the group I PET subset showed normalization of oxygen extraction fraction (OEF) from 0.59±0.09 before surgery to 0.46±0.06 after surgery (P<0

Changes in brain amino acid content induced by hyposmolar stress and energy deprivation.

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Haugstad, T S; Valø, E T; Langmoen, I A

1995-12-01

The changes in endogenous amino acids in brain extracellular and intracellular compartments evoked by hyposmotic stress and energy deprivation were compared. Tissue content and release of ten amino acids were measured simultaneously in rat hippocampal slices by means of high performance liquid chromatography. Hyposmotic stress induced a large release of taurine (25568 pmol mg-1 protein), and a smaller release of glutamate, accompanied by an inverse change in tissue content. Adding mannitol to correct osmolarity, blocked these changes. Energy deprivation caused an increase in the release of all amino acids except glutamine. The release was particularly large for glutamate and GABA (31141 and 13282 pmol mg-1, respectively). The intracellular concentrations were generally reduced, but the total amount of the released amino acids increased In contrast to the effect seen during hyposmolar stress, mannitol enhanced the changes due to energy deprivation. The results show that hyposmolar stress and energy deprivation cause different content and release profiles, suggesting that the mechanisms involved in the two situations are either different or modulated in different ways. The intracellular amino acid depletion seen during energy deprivation shows that increased outward transport is probably a primary event, and increased amino acid formation likely secondary to this release.

Selol, an organic selenium donor, prevents lipopolysaccharide-induced oxidative stress and inflammatory reaction in the rat brain.

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Dominiak, Agnieszka; Wilkaniec, Anna; Jęśko, Henryk; Czapski, Grzegorz A; Lenkiewicz, Anna M; Kurek, Eliza; Wroczyński, Piotr; Adamczyk, Agata

2017-09-01

Neuroinflammation and oxidative stress are key intertwined pathological factors in many neurological, particularly neurodegenerative diseases, such as Alzheimer's and Parkinson's disorders as well as autism. The present study was conducted to evaluate the protective effects of Selol, an organic selenium donor, against lipopolysaccharide (LPS)-mediated inflammation in rat brain. The results demonstrated that the peripheral administration of LPS in a dose of 100 μg/kg b.w. evoked typical pathological reaction known as systemic inflammatory response. Moreover, we observed elevated blood levels of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress, as well as increased concentration of tumor necrosis factor-α (TNF-α) in LPS-treated animals. Selol significantly prevented these LPS-evoked changes. Subsequently, Selol protected against LPS-induced up-regulation of proinflammatory cytokines (Tnfa, Ifng, Il6) in rat brain cortex. The molecular mechanisms through which Selol prevented the neuroinflammation were associated with the inhibition of oxidized glutathione (GSSG) accumulation and with an increase of glutathione-associated enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR) as well as thioredoxin reductase (TrxR) activity and expression. Finally, we observed that Selol administration effectively protected against LPS-induced changes in the expression of brain-derived neurotrophic factor (Bdnf). In conclusion, our studies indicated that Selol effectively protects against LPS-induced neuroinflammation by inhibiting pro-inflammatory cytokine release, by boosting antioxidant systems, and by augmenting BDNF level. Therefore, Selol could be a multi-potent and effective drug useful in the treatment and prevention of brain disorders associated with neuroinflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats

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Pari, Leelavinothan; Murugavel, Ponnusamy

2007-01-01

Cadmium (Cd) is a neurotoxic metal, which induces oxidative stress and membrane disturbances in nerve system. The garlic compound diallyl tetrasulfide (DTS) has the cytoprotective and antioxidant activity against Cd induced toxicity. The present study was carried out to investigate the efficacy of DTS in protecting the Cd induced changes in the activity of acetylcholinesterase (AChE), membrane bound enzymes, lipid peroxidation (LPO) and antioxidant status in the brain of rats. In rats exposed to Cd (3 mg/kg/day subcutaneously) for 3 weeks, a significant (P + K + -ATPase, Mg 2+ -ATPase and Ca 2+ -ATPase) were observed in brain tissue. Oral administration of DTS (40 mg/kg/day) with Cd significantly (P < 0.05) diminished the levels of LPO and protein carbonyls and significantly (P < 0.05) increased the activities of ATPases, antioxidant enzymes, GSH and TSH in brain. These results indicate that DTS attenuate the LPO and alteration of antioxidant and membrane bound enzymes in Cd exposed rats, which suggest that DTS protects the brain function from toxic effects of Cd

Oxidative stress in the developing brain: effects of postnatal glucocorticoid therapy and antioxidants in the rat.

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Emily J Camm

Full Text Available In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on long-term neurological function. Glucocorticoid excess promotes free radical overproduction. We hypothesised that the adverse effects of postnatal glucocorticoid therapy on the developing brain are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects. Male rat pups received a clinically-relevant tapering course of dexamethasone (DEX; 0.5, 0.3, and 0.1 mg x kg(-1 x day(-1, with or without antioxidant vitamins C and E (DEXCE; 200 mg x kg(-1 x day(-1 and 100 mg x kg(-1 x day(-1, respectively, on postnatal days 1-6 (P1-6. Controls received saline or saline with vitamins. At weaning, relative to controls, DEX decreased total brain volume (704.4±34.7 mm(3 vs. 564.0±20.0 mm(3, the soma volume of neurons in the CA1 (1172.6±30.4 µm(3 vs. 1002.4±11.8 µm(3 and in the dentate gyrus (525.9±27.2 µm(3 vs. 421.5±24.6 µm(3 of the hippocampus, and induced oxidative stress in the cortex (protein expression: heat shock protein 70 [Hsp70]: +68%; 4-hydroxynonenal [4-HNE]: +118% and nitrotyrosine [NT]: +20%. Dexamethasone in combination with vitamins resulted in improvements in total brain volume (637.5±43.1 mm(3, and soma volume of neurons in the CA1 (1157.5±42.4 µm(3 and the dentate gyrus (536.1±27.2 µm(3. Hsp70 protein expression was unaltered in the cortex (+9%, however, 4-HNE (+95% and NT (+24% protein expression remained upregulated. Treatment of neonates with vitamins alone induced oxidative stress in the cortex (Hsp70: +67%; 4-HNE: +73%; NT: +22% and in the hippocampus (NT: +35%. Combined glucocorticoid and antioxidant therapy in premature infants may be safer for the developing brain than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended.

Oxidative stress response of Forster's terns (Sterna forsteri) and Caspian terns (Hydroprogne caspia) to mercury and selenium bioaccumulation in liver, kidney, and brain

Science.gov (United States)

Hoffman, David J.; Eagles-Smith, Collin A.; Ackerman, Joshua T.; Adelsbach, Terrence L.; Stebbins, Katherine R.

2011-01-01

Bioindicators of oxidative stress were examined in prebreeding and breeding adult and chick Forster's terns (Sterna forsteri) and in prebreeding adult Caspian terns (Hydroprogne caspia) in San Francisco Bay, California. Highest total mercury (THg) concentrations (mean±standard error;μg/g dry wt) in liver (17.7±1.7), kidney (20.5±1.9), and brain (3.0±0.3) occurred in breeding adult Forster's terns. The THg concentrations in liver were significantly correlated with hepatic depletion of reduced glutathione (GSH), increased oxidized glutathione (GSSG):GSH ratio, and decreased hepatic gamma-glutamyl transferase (GGT) activity in adults of both tern species. Prefledging Forster's tern chicks with one-fourth the hepatic THg concentration of breeding adults exhibited effects similar to adults. Total mercury-related renal GSSG increased in adults and chicks. In brains of prebreeding adults, THg was correlated with a small increase in glucose-6-phosphate dehydrogenase (G-6-PDH) activity, suggestive of a compensatory response. Brain THg concentrations were highest in breeding adult Forster's terns and brain tissue exhibited increased lipid peroxidation as thiobarbituric acid-reactive substances, loss of protein bound thiols (PBSH), and decreased activity of antioxidant enzymes, GSSG reductase (GSSGrd), and G-6-PDH. In brains of Forster's tern chicks there was a decrease in total reduced thiols and PBSH. Multiple indicator responses also pointed to greater oxidative stress in breeding Forster's terns relative to prebreeding terns, attributable to the physiological stress of reproduction. Some biondicators also were related to age and species, including thiol concentrations. Enzymes GGT, G-6-PDH, and GSSGred activities were related to species. Our results indicate that THg concentrations induced oxidative stress in terns, and suggest that histopathological, immunological, and behavioral effects may occur in terns as reported in other species.

Effects of Fat and Sugar, Either Consumed or Infused toward the Brain, on Hypothalamic ER Stress Markers

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Evita Belegri

2017-05-01

Full Text Available Protein-folding stress at the Endoplasmic Reticulum (ER occurs in the hypothalamus during diet-induced obesity (DIO and is linked to metabolic disease development. ER stress is buffered by the activation of the unfolded protein response (UPR, a controlled network of pathways inducing a set of genes that recovers ER function. However, it is unclear whether hypothalamic ER stress during DIO results from obesity related changes or from direct nutrient effects in the brain. We here investigated mRNA expression of UPR markers in the hypothalamus of rats that were exposed to a free choice high-fat high-sugar (fcHFHS diet for 1 week and then overnight fed ad libitum, or fasted, or fat/sugar deprived (i.e., switched from obesogenic diet to chow. In addition, we determined the direct effects of fat/sugar on mRNA expression of hypothalamus UPR markers by intracarotic infusions of intralipids and/or glucose in chow-fed rats that were fasted overnight. Short term (1 week exposure to fcHFHS diet increased adiposity compared to chow-feeding. Short term exposure to a fcHFHS diet, followed by mild food restriction overnight, induced hypothalamic ER stress in rats as characterized by an increase in spliced to unspliced X-box binding protein 1 mRNA ratio in hypothalamus of fcHFHS fed rats compared to chow fed rats. Moreover, infused lipids toward the brain of overnight fasted rats, were able to induce a similar response. Non-restricted ad libitum fcHFHS-diet fed or totally fasted rats did not show altered ratios. We also observed a clear increase in hypothalamic activating transcription factor 4 mRNA in rats on the fcHFHS diet while being ad libitum fed or when infused with intralipid via the carotic artery compared to vehicle infusions. However, we did not observe induction of downstream targets implying that this effect is a more general stress response and not related to ER stress. Overall, we conclude that the hypothalamic stress response might be a sensitive

Effect of acetazolamide on post-NIV metabolic alkalosis in acute exacerbated COPD patients.

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Fontana, V; Santinelli, S; Internullo, M; Marinelli, P; Sardo, L; Alessandrini, G; Borgognoni, L; Ferrazza, A M; Bonini, M; Palange, P

2016-01-01

Non-invasive ventilation (NIV) is an effective treatment in patients with acute exacerbation of COPD (AECOPD). However, it may induce post-hypercapnic metabolic alkalosis (MA). This study aims to evaluate the effect of acetazolamide (ACET) in AECOPD patients treated with NIV. Eleven AECOPD patients, with hypercapnic respiratory failure and MA following NIV, were treated with ACET 500 mg for two consecutive days and compared to a matched control group. Patients and controls were non invasively ventilated in a bilevel positive airway pressure (BiPAP) mode to a standard maximal pressure target of 15-20 cmH2O. ACET intra-group analysis showed a significant improvement for PaCO2 (63.9 ± 9.8 vs. 54.9 ± 8.3 mmHg), HCO3- (43.5 ± 5.9 vs. 36.1 ± 5.4 mmol/L) and both arterial pH (7.46 ± 0.06 vs. 7.41 ± 0.06) and urinary pH (6.94 ± 0.77 vs 5.80 ± 0.82), already at day 1. No significant changes in endpoints considered were observed in the control group at any time-point. Inter-group analysis showed significant differences between changes in PaCO2 and HCO3- (delta), both at day 1 and 2. Furthermore, the length of NIV treatment was significantly reduced in the ACET group compared to controls (6 ± 8 vs. 19 ± 19 days). No adverse events were recorded in the ACET and control groups. ACET appears to be effective and safe in AECOPD patients with post-NIV MA.

Stress and brain functional changes in patients with Crohn's disease: A functional magnetic resonance imaging study.

Science.gov (United States)

Agostini, A; Ballotta, D; Righi, S; Moretti, M; Bertani, A; Scarcelli, A; Sartini, A; Ercolani, M; Nichelli, P; Campieri, M; Benuzzi, F

2017-10-01

In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). The MCC integrate "high" emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity. © 2017 John Wiley & Sons Ltd.

The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val(66)Met

NARCIS (Netherlands)

Elzinga, Bernet M.; Molendijk, Marc L.; Voshaar, Richard C. Oude; Bus, Boudewijn A. A.; Prickaerts, Jos; Spinhoven, Philip; Penninx, Brenda J. W. H.

Recent findings show lowered brain-derived neurotrophic factor (BDNF) levels in major depressive disorder (MDD). Exposure to stressful life events may (partly) underlie these BDNF reductions, but little is known about the effects of early or recent life stress on BDNF levels. Moreover, the effects

The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val(66)Met

NARCIS (Netherlands)

Elzinga, B.M.; Molendijk, M.L.; Voshaar, R.C.O.; Bus, B.A.A.; Prickaerts, J.; Spinhoven, P.; Penninx, B.W.J.H.

2011-01-01

Rationale: Recent findings show lowered brain-derived neurotrophic factor (BDNF) levels in major depressive disorder (MDD). Exposure to stressful life events may (partly) underlie these BDNF reductions, but little is known about the effects of early or recent life stress on BDNF levels. Moreover,

The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met

NARCIS (Netherlands)

Elzinga, B.M.; Molendijk, M.L.; Oude Voshaar, R.C.; Bus, B.A.A.; Prickaerts, J.; Spinhoven, P.; Penninx, B.J.

2011-01-01

RATIONALE: Recent findings show lowered brain-derived neurotrophic factor (BDNF) levels in major depressive disorder (MDD). Exposure to stressful life events may (partly) underlie these BDNF reductions, but little is known about the effects of early or recent life stress on BDNF levels. Moreover,

Chernobyl birds have smaller brains.

Directory of Open Access Journals (Sweden)

Anders Pape Møller

2011-02-01

Full Text Available Animals living in areas contaminated by radioactive material from Chernobyl suffer from increased oxidative stress and low levels of antioxidants. Therefore, normal development of the nervous system is jeopardized as reflected by high frequencies of developmental errors, reduced brain size and impaired cognitive abilities in humans. Alternatively, associations between psychological effects and radiation have been attributed to post-traumatic stress in humans.Here we used an extensive sample of 550 birds belonging to 48 species to test the prediction that even in the absence of post-traumatic stress, there is a negative association between relative brain size and level of background radiation. We found a negative association between brain size as reflected by external head volume and level of background radiation, independent of structural body size and body mass. The observed reduction in brain size in relation to background radiation amounted to 5% across the range of almost a factor 5,000 in radiation level. Species differed significantly in reduction in brain size with increasing background radiation, and brain size was the only morphological character that showed a negative relationship with radiation. Brain size was significantly smaller in yearlings than in older individuals.Low dose radiation can have significant effects on normal brain development as reflected by brain size and therefore potentially cognitive ability. The fact that brain size was smaller in yearlings than in older individuals implies that there was significant directional selection on brain size with individuals with larger brains experiencing a viability advantage.

Beneficial Effects of Tianeptine on Hippocampus-Dependent Long-Term Memory and Stress-Induced Alterations of Brain Structure and Function

Science.gov (United States)

Zoladz, Phillip R.; Muñoz, Carmen; Diamond, David M.

2010-01-01

Tianeptine is a well-described antidepressant which has been shown to prevent stress from producing deleterious effects on brain structure and function. Preclinical studies have shown that tianeptine blocks stress-induced alterations of neuronal morphology and synaptic plasticity. Moreover, tianeptine prevents stress from impairing learning and memory, and, importantly, demonstrates memory-enhancing properties in the absence of stress. Recent research has indicated that tianeptine works by normalizing glutamatergic neurotransmission, a mechanism of action that may underlie its effectiveness as an antidepressant. These findings emphasize the value in focusing on the mechanisms of action of tianeptine, and specifically, the glutamatergic system, in the development of novel pharmacotherapeutic strategies in the treatment of depression.

Beneficial Effects of Tianeptine on Hippocampus-Dependent Long-Term Memory and Stress-Induced Alterations of Brain Structure and Function

Directory of Open Access Journals (Sweden)

Carmen Muñoz

2010-10-01

Full Text Available Tianeptine is a well-described antidepressant which has been shown to prevent stress from producing deleterious effects on brain structure and function. Preclinical studies have shown that tianeptine blocks stress-induced alterations of neuronal morphology and synaptic plasticity. Moreover, tianeptine prevents stress from impairing learning and memory, and, importantly, demonstrates memory-enhancing properties in the absence of stress. Recent research has indicated that tianeptine works by normalizing glutamatergic neurotransmission, a mechanism of action that may underlie its effectiveness as an antidepressant. These findings emphasize the value in focusing on the mechanisms of action of tianeptine, and specifically, the glutamatergic system, in the development of novel pharmacotherapeutic strategies in the treatment of depression.

A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment.

Science.gov (United States)

Xie, Long; Dolui, Sudipto; Das, Sandhitsu R; Stockbower, Grace E; Daffner, Molly; Rao, Hengyi; Yushkevich, Paul A; Detre, John A; Wolk, David A

2016-01-01

Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease.

Concepts and strategies for clinical management of blast-induced traumatic brain injury and posttraumatic stress disorder.

Science.gov (United States)

Chen, Yun; Huang, Wei; Constantini, Shlomi

2013-01-01

After exposure of the human body to blast, kinetic energy of the blast shock waves might be transferred into hydraulic energy in the cardiovascular system to cause a rapid physical movement or displacement of blood (a volumetric blood surge). The volumetric blood surge moves through blood vessels from the high-pressure body cavity to the low-pressure cranial cavity, causing damage to tiny cerebral blood vessels and the blood-brain barrier (BBB). Large-scale cerebrovascular insults and BBB damage that occur globally throughout the brain may be the main causes of non-impact, blast-induced brain injuries, including the spectrum of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). The volumetric blood surge may be a major contributor not only to blast-induced brain injuries resulting from physical trauma, but may also be the trigger to psychiatric disorders resulting from emotional and psychological trauma. Clinical imaging technologies, which are able to detect tiny cerebrovascular insults, changes in blood flow, and cerebral edema, may help diagnose both TBI and PTSD in the victims exposed to blasts. Potentially, prompt medical treatment aiming at prevention of secondary neuronal damage may slow down or even block the cascade of events that lead to progressive neuronal damage and subsequent long-term neurological and psychiatric impairment.

Two-day fasting evokes stress, but does not affect mood, brain activity, cognitive, psychomotor, and motor performance in overweight women.

Science.gov (United States)

Solianik, Rima; Sujeta, Artūras

2018-02-15

The physiological, cognitive state, and motor behavior changes that occur during acute fasting are not completely understood. Thus, the aim of this study was to estimate the effect of 2-day total fasting on evoked stress, mood, brain activity, and cognitive, psychomotor, and motor function in overweight women. Eleven overweight women (body mass index above 25kg/m 2 ) aged 20-30 years were tested under two conditions allocated randomly: 2-day zero-calorie diet with water provided ad libitum and 2-day usual diet. One week before the experiment, aerobic fitness was evaluated. Subjective stress ratings in relation to the diet, autonomic function, prefrontal cortex activity, cognitive performance, psychomotor coordination, and grip strength were evaluated before and after each diet. The study demonstrated that fasting decreased log-transformed high-frequency (HF) power, without affecting heart rate. The relative maximum oxygen uptake was negatively correlated with subjective stress rating and changes in log-transformed HF. Fasting did not affect mood, brain activity, and cognitive, motor, and psychomotor performance. Thus, 2-day total fasting evoked moderate stress with a shift of the autonomic nervous system balance toward sympathetic activity in overweight women. Better aerobic endurance is likely to facilitate the capacity for dealing with acute fasting. Regardless of the evoked stress, cognitive state and motor behavior remained intact. Copyright © 2017 Elsevier B.V. All rights reserved.

The joint power of sex and stress to modulate brain-gut-microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome.

Science.gov (United States)

Pigrau, M; Rodiño-Janeiro, B K; Casado-Bedmar, M; Lobo, B; Vicario, M; Santos, J; Alonso-Cotoner, C

2016-04-01

Intestinal homeostasis is a dynamic process that takes place at the interface between the lumen and the mucosa of the gastrointestinal tract, where a constant scrutiny for antigens and toxins derived from food and microorganisms is carried out by the vast gut-associated immune system. Intestinal homeostasis is preserved by the ability of the mucus layer and the mucosal barrier to keep the passage of small-sized and antigenic molecules across the epithelium highly selective. When combined and preserved, immune surveillance and barrier's selective permeability, the host capacity of preventing the development of intestinal inflammation is optimized, and viceversa. In addition, the brain-gut-microbiome axis, a multidirectional communication system that integrates distant and local regulatory networks through neural, immunological, metabolic, and hormonal signaling pathways, also regulates intestinal function. Dysfunction of the brain-gut-microbiome axis may induce the loss of gut mucosal homeostasis, leading to uncontrolled permeation of toxins and immunogenic particles, increasing the risk of appearance of intestinal inflammation, mucosal damage, and gut disorders. Irritable bowel syndrome is prevalent stress-sensitive gastrointestinal disorder that shows a female predominance. Interestingly, the role of stress, sex and gonadal hormones in the regulation of intestinal mucosal and the brain-gut-microbiome axis functioning is being increasingly recognized. We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain-gut-microbiome axis dysfunction and the implications for irritable bowel syndrome. © 2015 John Wiley & Sons Ltd.

Oxidative stress induces the decline of brain EPO expression in aging rats.

Science.gov (United States)

Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

2016-10-01

Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (paging rats, the expressions of EPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (paging could result in the decline of EPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability. Copyright © 2016 Elsevier Inc. All rights reserved.

Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress.

Science.gov (United States)

Chen, Guotao; Yang, Baibing; Chen, Jianhuai; Zhu, Leilei; Jiang, Hesong; Yu, Wen; Zang, Fengchao; Chen, Yun; Dai, Yutian

2018-02-01

Non-organic erectile dysfunction (noED) at functional imaging has been related to abnormal brain activity and requires animal models for further research on the associated molecular mechanisms. To develop a noED animal model based on chronic mild stress and investigate brain activity changes. We used 6 weeks of chronic mild stress to induce depression. The sucrose consumption test was used to assess the hedonic state. The apomorphine test and sexual behavior test were used to select male rats with ED. Rats with depression and ED were considered to have noED. Blood oxygen level-dependent-based resting-state functional magnetic resonance imaging (fMRI) studies were conducted on these rats, and the amplitude of low-frequency fluctuations and functional connectivity were analyzed to determine brain activity changes. The sexual behavior test and resting-state fMRI were used for outcome measures. The induction of depression was confirmed by the sucrose consumption test. A low intromission ratio and increased mount and intromission latencies were observed in male rats with depression. No erection was observed in male rats with depression during the apomorphine test. Male rats with depression and ED were considered to have noED. The possible central pathologic mechanism shown by fMRI involved the amygdaloid body, dorsal thalamus, hypothalamus, caudate-putamen, cingulate gyrus, insular cortex, visual cortex, sensory cortex, motor cortex, and cerebellum. Similar findings have been found in humans. The present study provided a novel noED rat model for further research on the central mechanism of noED. The present study developed a novel noED rat model and analyzed brain activity changes based at fMRI. The observed brain activity alterations might not extend to humans. The present study developed a novel noED rat model with brain activity alterations related to sexual arousal and erection, which will be helpful for further research involving the central mechanism of noED. Chen

Cancer: brain-regulated biphasic stress response induces cell growth or cell death to adapt to psychological stressors.

Science.gov (United States)

Thomas, Charles; Bhatia, Shruti

2014-01-01

According to Indian Vedic philosophy, a human being contains 3 major bodies: (1) the matter body--brain, organs, and senses; (2) the mental body--mind, individual consciousness, intellect, and ego; and (3) the soul or causal body--universal consciousness. The third, which is located in the heart according to all spiritual traditions and recent scientific literature, can be seen as the information body that contains all memories. The mental body, which can interface with the matter and information bodies, can be seen as a field of immaterial energy that can carry, regulate, and strengthen all information (eg, thoughts or emotions) both positively and negatively. This body of information may store ancestral and/or autobiographical memories: unconscious memories from inner traumas--inner information (Ii) or samskaras in Vedic philosophy--and conscious memories from outer traumas--outer information (Io). These conscious and unconscious memories can be seen as potential psychological stressors. Resonance between Ii and Io may induce active conflicts if resistance occurs in the mental body; this conflict may cause specific metabolic activity in the brain and a stress response in the physical body, which permits adjustment to psychological stressors. The brainregulated stress response may be biphasic: cell death or growth induced by adrenergic molecular pathways during the conflict's unresolved phase and reversion to cell growth or death induced by cholinergic molecular pathways during the conflict's resolved phase. Case studies and data mining from PubMed suggest that this concept complies with the principles of holistic medicine and the scientific literature supporting its benefits. We suggest that the evolution of cancer can be seen as a biphasic stress response regulated by the brain to adapt to psychological stressors, which produce imbalance among the physical, mental, and information bodies.

Neuronal pH regulation

DEFF Research Database (Denmark)

Vorstrup, S; Jensen, K E; Thomsen, C

1989-01-01

The intracellular pH in the brain was studied in six healthy volunteers before and immediately after the administration of 2 g of acetazolamide. Phosphorus-31 nuclear magnetic resonance spectroscopy by a 1.5 tesla whole-body scanner was used. The chemical shift between the inorganic phosphate...

Diagnosis of ischemic cerebrovascular diseases with 99mTc-HMPAO brain SPECT using upright stress test

International Nuclear Information System (INIS)

Chen Shaoliang; Xiu Yan; Sun Xiaoguang

1998-01-01

Purpose: To evaluate the value of upright brain SPECT stress test, the authors performed 99m Tc-HMPAO brain SPECT in association with measurement of blood pressure in both upright and supine positions. Methods: The authors studied 5 patients with unilateral stenosis occlusion of the internal carotid (Group A), 8 patients with orthostatic hypotension (group B) and 7 normal controls. 370 MBq 99m Tc-HMPAO was injected immediately after uprighting from a supine position. then the first SPECT scan were performed. After the first SPECT, another 555 MBq of 99m Tc-HMPAO were administered while the patients remained on original supine position. Results: Semiquantitive analysis showed that the asymmetric ratios between upright and supine positions in group A changed significantly. In group B, showed postural cerebral hypoperfusion in the bilateral frontal areas, the mean count ratio of the frontal to cerebellar area between the upright and supine positions also significantly changed. In the normal group, there were no significantly changes during the upright test. Conclusions: The upright stress test is useful for detecting not only silent cerebral hypoperfusion, but also orthostatic hypoperfusion

Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative stress in hippocampus, cerebellum, and brainstem

International Nuclear Information System (INIS)

Zhong, Yanjun; Dong, Guicheng; Luo, Haiguang; Cao, Jie; Wang, Chang; Wu, Jianyuan; Feng, Yu-Qi; Yue, Jiang

2012-01-01

Ethanol is one of the most commonly abused substances, and oxidative stress is an important causative factor in ethanol-induced neurotoxicity. Cytochrome P450 2E1 (CYP2E1) is involved in ethanol metabolism in the brain. This study investigates the role of brain CYP2E1 in the susceptibility of certain brain regions to ethanol neurotoxicity. Male Wistar rats were intragastrically treated with ethanol (3.0 g/kg, 30 days). CYP2E1 protein, mRNA expression, and catalytic activity in various brain regions were respectively assessed by immunoblotting, quantitative quantum dot immunohistochemistry, real-time RT-PCR, and LC–MS. The generation of reactive oxygen species (ROS) was analyzed using a laser confocal scanning microscope. The hippocampus, cerebellum, and brainstem were selectively damaged after ethanol treatment, indicated by both lactate dehydrogenase (LDH) activity and histopathological analysis. Ethanol markedly increased the levels of CYP2E1 protein, mRNA expression, and activity in the hippocampus and cerebellum. CYP2E1 protein and activity were significantly increased by ethanol in the brainstem, with no change in mRNA expression. ROS levels induced by ethanol paralleled the enhanced CYP2E1 proteins in the hippocampus, granular layer and white matter of cerebellum as well as brainstem. Brain CYP2E1 activity was positively correlated with the damage to the hippocampus, cerebellum, and brainstem. These results suggest that the selective sensitivity of brain regions to ethanol neurodegeneration may be attributed to the regional and cellular-specific induction of CYP2E1 by ethanol. The inhibition of CYP2E1 levels may attenuate ethanol-induced oxidative stress via ROS generation.

The Stressed Female Brain: Neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress

Directory of Open Access Journals (Sweden)

Lisa Y. Maeng

2013-12-01

Full Text Available Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD, indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL and infralimbic (IL subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. 24h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similar to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful

The Effect of Oral Feeding of Tribulus Terrestris Fruit on Some Markers of Oxidative Stress in the Brain of Diabetic Rats

Directory of Open Access Journals (Sweden)

M Roghani

2013-06-01

Full Text Available Introduction: Chronic diabetes mellitus in the long run accompanies enhanced oxidative stress burden and decreases activity of antioxidant defense system. Due to significant role of these factors in development of some neurological disorders and with regard to antidiabetic and antioxidant effect of Tribulus terrestris (TT, this study was conducted to evaluate the effect of its oral administration on brain tissue level of some markers of lipid peroxidation and oxidative stress in diabetic rats. Methods: In this experimental study, rats were divided into 4 groups, i.e. control, TT-treated control, diabetic, and TT-treated diabetic groups. For induction of diabetes, streptozotcin (STZ was intraperitoneally administered (60mg/Kg. In addition, TT-treated groups received TT mixed with standard pelleted food at a weight ratio of 3% for 5 weeks. Level of malondialdehyde (MDA and nitrite as well as activity of superoxide dismutase (SOD in brain tissue were measured at the end of the study. Results: Diabetic rats showed a significant increase in tissue level of MDA (p<0.01 and nitrite (p<0.01 and a non-significant reduction of SOD activity. Furthermore, TT treatment significantly reduced level of MDA p<0.01 and nitrite (p<0.05. Also, SOD activity in treated-diabetic group was non-significantly higher as compared to diabetics. Conclusion: Chronic oral treatment with TT could attenuate some markers of lipid peroxidation and oxidative stress in brain tissue in diabetic rats which this could possibly prevent some neurological disorders due to enhanced oxidative stress.

Antidepressant Effects of Pharmacopuncture on Behavior and Brain-Derived Neurotrophic Factor (BDNF Expression in Chronic Stress Model of Mice

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Yunna Kim

2017-12-01

Conclusion: HJ11 improves depressive-like behaviors in the stress-induced mouse model of depression, and the results indicate that the neuroprotective effect of HJ11, identified by brain-derived neurotrophic factor expression, may play a critical role in its antidepressant effect.

Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats.

Science.gov (United States)

El-Terras, Adel; Soliman, Mohamed Mohamed; Alkhedaide, Adel; Attia, Hossam Fouad; Alharthy, Abdullah; Banaja, Abdel Elah

2016-04-01

In Saudi Arabia, the consumption of carbonated soft drinks is common and often occurs with each meal. Carbonated soft drink consumption has been shown to exhibit effects on the liver, kidney and bone. However, the effects of these soft drinks on brain activity have not been widely examined, particularly at the gene level. Therefore, the current study was conducted with the aim of evaluating the effects of chronic carbonated soft drink consumption on oxidative stress, brain gene biomarkers associated with aggression and brain histology. In total, 40 male Wistar rats were divided into four groups: Group 1 served as a control and was provided access to food and water ad libitum; and groups 2‑4 were given free access to food and carbonated soft drinks only (Cola for group 2, Pepsi for group 3 and 7‑UP for group 4). Animals were maintained on these diets for 3 consecutive months. Upon completion of the experimental period, animals were sacrificed and serological and histopathological analyses were performed on blood and tissues samples. Reverse transcription‑polymerase chain reaction was used to analyze alterations in gene expression levels. Results revealed that carbonated soft drinks increased the serum levels of malondialdehyde (MDA). Carbonated soft drinks were also observed to downregulate the expression of antioxidants glutathione reductase (GR), catalase and glutathione peroxidase (GPx) in the brain when compared with that in the control rats. Rats administered carbonated soft drinks also exhibited decreased monoamine oxidase A (MAO‑A) and acetylcholine esterase (AChE) serum and mRNA levels in the brain. In addition, soft drink consumption upregulated mRNA expression of dopamine D2 receptor (DD2R), while 5-hydroxytryptamine transporter (5‑HTT) expression was decreased. However, following histological examination, all rats had a normal brain structure. The results of this study demonstrated that that carbonated soft drinks induced oxidative stress and

Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit.

Science.gov (United States)

Banks, William A; Gray, Alicia M; Erickson, Michelle A; Salameh, Therese S; Damodarasamy, Mamatha; Sheibani, Nader; Meabon, James S; Wing, Emily E; Morofuji, Yoichi; Cook, David G; Reed, May J

2015-11-25

Disruption of the blood-brain barrier (BBB) occurs in many diseases and is often mediated by inflammatory and neuroimmune mechanisms. Inflammation is well established as a cause of BBB disruption, but many mechanistic questions remain. We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in mice. BBB disruption was measured using (14)C-sucrose and radioactively labeled albumin. Brain cytokine responses were measured using multiplex technology and dependence on cyclooxygenase (COX) and oxidative stress determined by treatments with indomethacin and N-acetylcysteine. Astrocyte and microglia/macrophage responses were measured using brain immunohistochemistry. In vitro studies used Transwell cultures of primary brain endothelial cells co- or tri-cultured with astrocytes and pericytes to measure effects of LPS on transendothelial electrical resistance (TEER), cellular distribution of tight junction proteins, and permeability to (14)C-sucrose and radioactive albumin. In comparison to LPS-induced weight loss, the BBB was relatively resistant to LPS-induced disruption. Disruption occurred only with the highest dose of LPS and was most evident in the frontal cortex, thalamus, pons-medulla, and cerebellum with no disruption in the hypothalamus. The in vitro and in vivo patterns of LPS-induced disruption as measured with (14)C-sucrose, radioactive albumin, and TEER suggested involvement of both paracellular and transcytotic pathways. Disruption as measured with albumin and (14)C-sucrose, but not TEER, was blocked by indomethacin. N-acetylcysteine did not affect disruption. In vivo, the measures of neuroinflammation induced by LPS were mainly not reversed by indomethacin. In vitro, the effects on LPS and indomethacin were not altered when brain endothelial cells (BECs) were cultured with astrocytes or pericytes. The BBB is relatively resistant to LPS-induced disruption with some brain regions more vulnerable than others. LPS-induced disruption appears is

The impact of developmental timing for stress and recovery

Directory of Open Access Journals (Sweden)

Dylan G. Gee

2015-01-01

Full Text Available Stress can have lasting effects on the brain and behavior. Delineating the impact of stress on the developing brain is fundamental for understanding mechanisms through which stress induces persistent effects on behavior that can lead to psychopathology. The growing field of translational developmental neuroscience has revealed a significant role of the timing of stress on risk, resilience, and neuroplasticity. Studies of stress across species have provided essential insight into the mechanisms by which the brain changes and the timing of those changes on outcome. In this article, we review the neurobiological effects of stress and propose a model by which sensitive periods of neural development interact with stressful life events to affect plasticity and the effects of stress on functional outcomes. We then highlight how early-life stress can alter the course of brain development. Finally, we examine mechanisms of buffering against early-life stress that may promote resilience and positive outcomes. The findings are discussed in the context of implications for early identification of risk and resilience factors and development of novel interventions that target the biological state of the developing brain to ultimately ameliorate the adverse consequences of stress during childhood and adolescence.

Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models.

Science.gov (United States)

Takada, M; Nishida, K; Kataoka-Kato, A; Gondo, Y; Ishikawa, H; Suda, K; Kawai, M; Hoshi, R; Watanabe, O; Igarashi, T; Kuwano, Y; Miyazaki, K; Rokutan, K

2016-07-01

This study aimed to examine the effects of Lactobacillus casei strain Shirota (LcS) on gut-brain interactions under stressful conditions. Three double-blind, placebo-controlled trials were conducted to examine the effects of LcS on psychological and physiological stress responses in healthy medical students under academic examination stress. Subjects received LcS-fermented milk or placebo daily for 8 weeks prior to taking a national standardized examination. Subjective anxiety scores, salivary cortisol levels, and the presence of physical symptoms during the intervention were pooled and analyzed. In the animal study, rats were given feed with or without LcS for 2 weeks, then submitted to water avoidance stress (WAS). Plasma corticosterone concentration and the expression of cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured immediately after WAS. In an electrophysiological study, gastric vagal afferent nerve activity was monitored after intragastric administration of LcS to urethane-anesthetized rats. Academic stress-induced increases in salivary cortisol levels and the incidence rate of physical symptoms were significantly suppressed in the LcS group compared with the placebo group. In rats pretreated with LcS, WAS-induced increases in plasma corticosterone were significantly suppressed, and the number of CRF-expressing cells in the PVN was reduced. Intragastric administration of LcS stimulated gastric vagal afferent activity in a dose-dependent manner. These findings suggest that LcS may prevent hypersecretion of cortisol and physical symptoms under stressful conditions, possibly through vagal afferent signaling to the brain and reduced stress reactivity in the PVN. © 2016 John Wiley & Sons Ltd.

Neuro emotional technique effects on brain physiology in cancer patients with traumatic stress symptoms: preliminary findings.

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Monti, Daniel A; Tobia, Anna; Stoner, Marie; Wintering, Nancy; Matthews, Michael; He, Xiao-Song; Doucet, Gaelle; Chervoneva, Inna; Tracy, Joseph I; Newberg, Andrew B

2017-08-01

The purpose of this study was to characterize the neurophysiological and clinical effects that may result from the neuro emotional technique (NET) in patients with traumatic stress symptoms associated with a cancer-related event. We hypothesized that self-regulatory processing of traumatic memories would be observable as physiological changes in key brain areas after undergoing the NET intervention and that these changes would be associated with improvement of traumatic stress symptoms. We enrolled 23 participants with a prior cancer diagnosis who expressed a distressing cancer-related memory that was associated with traumatic stress symptoms of at least 6 months in duration. Participants were randomized to either the NET intervention or a waitlist control condition. To evaluate the primary outcome of neurophysiological effects, all participants received functional magnetic resonance imaging (fMRI) during the auditory presentation of both a neutral stimulus and a description of the specific traumatic event. Pre/post-comparisons were performed between the traumatic and neutral condition, within and between groups. Psychological measures included the Impact of Event Scale (IES), State Trait Anxiety Index (STAI), Brief Symptom Inventory (BSI)-18, and Posttraumatic Cognitions Inventory (PTCI). The initial fMRI scans in both groups showed significant increases in the bilateral parahippocampus and brainstem. After NET, reactivity in the parahippocampus, brainstem, anterior cingulate, and insula was significantly decreased during the traumatic stimulus. Likewise, participants receiving the NET intervention had significant reductions (p stress as measured by the IES and PTCI. This study is an initial step towards understanding mechanistic features of the NET intervention. Specifically, brain regions involved with traumatic memories and distress such as the brainstem, insula, anterior cingulate gyrus, and parahippocampus had significantly reduced activity after the NET

The protective effect of N-acetylcysteine on oxidative stress in the brain caused by the long-term intake of aspartame by rats.

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Finamor, Isabela A; Ourique, Giovana M; Pês, Tanise S; Saccol, Etiane M H; Bressan, Caroline A; Scheid, Taína; Baldisserotto, Bernardo; Llesuy, Susana F; Partata, Wânia A; Pavanato, Maria A

2014-09-01

Long-term intake of aspartame at the acceptable daily dose causes oxidative stress in rodent brain mainly due to the dysregulation of glutathione (GSH) homeostasis. N-Acetylcysteine provides the cysteine that is required for the production of GSH, being effective in treating disorders associated with oxidative stress. We investigated the effects of N-acetylcysteine treatment (150 mg kg(-1), i.p.) on oxidative stress biomarkers in rat brain after chronic aspartame administration by gavage (40 mg kg(-1)). N-Acetylcysteine led to a reduction in the thiobarbituric acid reactive substances, lipid hydroperoxides, and carbonyl protein levels, which were increased due to aspartame administration. N-Acetylcysteine also resulted in an elevation of superoxide dismutase, glutathione peroxidase, glutathione reductase activities, as well as non-protein thiols, and total reactive antioxidant potential levels, which were decreased after aspartame exposure. However, N-acetylcysteine was unable to reduce serum glucose levels, which were increased as a result of aspartame administration. Furthermore, catalase and glutathione S-transferase, whose activities were reduced due to aspartame treatment, remained decreased even after N-acetylcysteine exposure. In conclusion, N-acetylcysteine treatment may exert a protective effect against the oxidative damage in the brain, which was caused by the long-term consumption of the acceptable daily dose of aspartame by rats.

Anti-oxidative effects of Rooibos tea (Aspalathus linearis on immobilization-induced oxidative stress in rat brain.

Directory of Open Access Journals (Sweden)

In-Sun Hong

Full Text Available Exposure to chronic psychological stress may be related to increased reactive oxygen species (ROS or free radicals, and thus, long-term exposure to high levels of oxidative stress may cause the accumulation of oxidative damage and eventually lead to many neurodegenerative diseases. Compared with other organs, the brain appears especially susceptible to excessive oxidative stress due to its high demand for oxygen. In the case of excessive ROS production, endogenous defense mechanisms against ROS may not be sufficient to suppress ROS-associated oxidative damage. Dietary antioxidants have been shown to protect neurons against a variety of experimental neurodegenerative conditions. In particular, Rooibos tea might be a good source of antioxidants due to its larger proportion of polyphenolic compounds. An optimal animal model for stress should show the features of a stress response and should be able to mimic natural stress progression. However, most animal models of stress, such as cold-restraint, electric foot shock, and burn shock, usually involve physical abuse in addition to the psychological aspects of stress. Animals subjected to chronic restraint or immobilization are widely believed to be a convenient and reliable model to mimic psychological stress. Therefore, in the present study, we propose that immobilization-induced oxidative stress was significantly attenuated by treatment with Rooibos tea. This conclusion is demonstrated by Rooibos tea's ability to (i reverse the increase in stress-related metabolites (5-HIAA and FFA, (ii prevent lipid peroxidation (LPO, (iii restore stress-induced protein degradation (PD, (iv regulate glutathione metabolism (GSH and GSH/GSSG ratio, and (v modulate changes in the activities of antioxidant enzymes (SOD and CAT.

Lifetime stress cumulatively programs brain transcriptome and impedes stroke recovery: benefit of sensory stimulation.

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Fabíola C R Zucchi

Full Text Available Prenatal stress (PS represents a critical variable affecting lifetime health trajectories, metabolic and vascular functions. Beneficial experiences may attenuate the effects of PS and its programming of health outcomes in later life. Here we investigated in a rat model (1 if PS modulates recovery following cortical ischemia in adulthood; (2 if a second hit by adult stress (AS exaggerates stress responses and ischemic damage; and (3 if tactile stimulation (TS attenuates the cumulative effects of PS and AS. Prenatally stressed and non-stressed adult male rats underwent focal ischemic motor cortex lesion and were tested in skilled reaching and skilled walking tasks. Two groups of rats experienced recurrent restraint stress in adulthood and one of these groups also underwent daily TS therapy. Animals that experienced both PS and AS displayed the most severe motor disabilities after lesion. By contrast, TS promoted recovery from ischemic lesion and reduced hypothalamic-pituitary-adrenal axis activity. The data also showed that cumulative effects of adverse and beneficial lifespan experiences interact with disease outcomes and brain plasticity through the modulation of gene expression. Microarray analysis of the lesion motor cortex revealed that cumulative PS and AS interact with genes related to growth factors and transcription factors, which were not affected by PS or lesion alone. TS in PS+AS animals reverted these changes, suggesting a critical role for these factors in activity-dependent motor cortical reorganization after ischemic lesion. These findings suggest that beneficial experience later in life can moderate adverse consequences of early programming to improve cerebrovascular health.

Protective effect of Allium sativum (garlic) aqueous extract against lead-induced oxidative stress in the rat brain, liver, and kidney.

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Manoj Kumar, V; Henley, A K; Nelson, C J; Indumati, O; Prabhakara Rao, Y; Rajanna, S; Rajanna, B

2017-01-01

The present investigation was undertaken to evaluate the ameliorative activity of Allium sativum against lead-induced oxidative stress in the brain, liver, and kidney of male rats. Four groups of male Wistar strain rats (100-120 g) were taken: group 1 received 1000 mg/L sodium acetate and group 2 was given 1000 mg/L lead acetate through drinking water for 2 weeks. Group 3 and 4 were treated with 250 mg/kg body weight/day of A. sativum and 500 mg/kg body weight/day of A. sativum, respectively, by oral intubation for a period of 2 weeks along with lead acetate. The rats were sacrificed after treatment and the brain, liver, and kidney were isolated on ice. In the brain, four important regions namely the hippocampus, cerebellum, cerebral cortex, and brain stem were separated and used for the present investigation. Blood was also drawn by cardiac puncture and preserved in heparinized vials at 4 °C for estimation of delta-aminolevulinic acid dehydratase (ALAD) activity. The results showed a significant (p sativum resulted in tissue-specific recovery of oxidative stress parameters namely ROS, LPP, and TPCC. A. sativum treatment also restored the blood delta-ALAD activity back to control. Overall, our results indicate that A. sativum administration could be an effective antioxidant treatment strategy for lead-induced oxidative insult.

Brain angiotensin-(1-7)/Mas axis: A new target to reduce the cardiovascular risk to emotional stress.

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Fontes, Marco Antônio Peliky; Martins Lima, Augusto; Santos, Robson Augusto Souza dos

2016-04-01

Emotional stress is now considered a risk factor for several diseases including cardiac arrhythmias and hypertension. It is well known that the activation of neuroendocrine and autonomic mechanisms features the response to emotional stress. However, its link to cardiovascular diseases and the regulatory mechanisms involved remain to be further comprehended. The renin-angiotensin system (RAS) plays an important role in homeostasis on all body systems. Specifically in the brain, the RAS regulates a number of physiological aspects. Recent data indicate that the activation of angiotensin-converting enzyme/angiotensin II/AT1 receptor axis facilitates the emotional stress responses. On the other hand, growing evidence indicates that its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/(Ang)iotensin-(1-7)/Mas axis, reduces anxiety and attenuates the physiological responses to emotional stress. The present review focuses on angiotensin-(1-7)/Mas axis as a promising target to attenuate the physiological response to emotional stress reducing the risk of cardiovascular diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of cerebral metabolism in patients with unilateral carotid stenosis by proton MR spectroscopy: a correlative study with cerebral hemodynamics by acetazolamide stress brain perfusion SPECT (acz-SPECT)

International Nuclear Information System (INIS)

Kim, Jae Seung; Kim, Geun Eun; Lee, Jeong Hee; Kim, Do Gyun; Kim, Sang Tae; Lee, Hee Kyung

2001-01-01

Carotid stenosis may lead not only to cerebral hemodynamic compromise but also cerebral metabolic changes without overt infarction. To investigate the brain metabolic changes as a result of hemodynamic compromise in pts with carotid stenosis, we compared the changes in metabolism of the gray and white matter detected by proton MRS with cortical hemodynamics measured by Acz-SPECT. We prospectively studied symptomatic 18 pts (M/F=15/3, mean ages: 64.4y) with unilateral carotid stenosis. All pts underwent Acz-SPECT and MRS with 3 days. rCBF and rCVR of MCA territory were assessed by Acz-SPECT. Hemodynamic compromise was graded as stage 0 (normal rCBF and rCVR), stage 1 (normal rCBF and reduced rCVR), and stage 2( reduced rCBF and rCVR). Brain metabolism was assessed by measuring the peaks of N-acetyl aspartate (NAA), choline (Cho), and the sum of creatine and phosphocreatine (Cr) from noninfarcted white matter in the both centrum semiovales and gray matter in both MCA territories. On Acz-SPECT, 7 pts showed stage 2 were significantly lower than in pts with stage 0 (p<0.01). The asymmetric ratio of NAA/Cr in pts with state 2 was also significantly lower than in pts with stage 1(p<0.05). The asymmetric ratio of Cho/Cr was increased as hemodynamic stage increased but the differences were not statistically significant among 3 stages. In cortical gray matter, the asymmetric ratios of NAA/Cho and NAA/Cr were decreased statistically significant among 3 stages. In cortical gray matter, the asymmetric ratios of NAA/Cho and NAA/Cr were decreased and that of Cho/Cr was increased as hemodynamic stage increased. However, these differences were not statistically significant among 3 stages. The asymmetric ratios of NAA/Cho of centrum semiovale in pts with reduced rCBF and/or reduced rCVR were lower than in pts with normal perfusion. Our results indicate the metabolic changes detected by proton MRS in patients with carotid stenosis reflect a hemodynamic compromised state

Stress-sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation.

Science.gov (United States)

Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel, A L; Akulov, A E

2017-05-01

What is the central question of this study? Stress-sensitive arterial hypertension is considered to be controlled by changes in central and peripheral sympathetic regulating mechanisms, which eventually result in haemodynamic alterations and blood pressure elevation. Therefore, study of the early stages of development of hypertension is of particular interest, because it helps in understanding the aetiology of the disease. What is the main finding and its importance? Non-invasive in vivo investigation in ISIAH rats demonstrated that establishment of sustainable stress-sensitive hypertension is accompanied by a decrease in prefrontal cortex activity and mobilization of hypothalamic processes, with considerable correlations between haemodynamic parameters and individual metabolite ratios. The study of early development of arterial hypertension in association with emotional stress is of great importance for better understanding of the aetiology and pathogenesis of the hypertensive disease. Magnetic resonance imaging (MRI) was applied to evaluate the changes in haemodynamics and brain metabolites in 1- and 3-month-old inherited stress-induced arterial hypertension (ISIAH) rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive Wistar Albino Glaxo (WAG) rats (eight male rats). In the 3-month-old ISIAH rats, the age-dependent increase in blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of the abdominal aorta. The renal vascular resistance in the ISIAH rats decreased during ageing, although at both ages it remained higher than the renal vascular resistance in WAG rats. An integral metabolome portrait demonstrated that development of hypertension in the ISIAH rats was associated with an attenuation of the excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats the opposite age-dependent changes were observed. In contrast, in the

Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain

DEFF Research Database (Denmark)

Lykkesfeldt, Jens; Trueba, Gilberto Perez; Poulsen, Henrik E

2007-01-01

Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency...... incision repair (P = 0.014) were all increased, while protein oxidation decreased (P = 0.003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may...

Differences in frontal and limbic brain activation in a small sample of monozygotic twin pairs discordant for severe stressful life events

Directory of Open Access Journals (Sweden)

Detre A. Godinez

2016-12-01

Full Text Available Monozygotic twin pairs provide a valuable opportunity to control for genetic and shared environmental influences while studying the effects of nonshared environmental influences. The question we address with this design is whether monozygotic twins selected for discordance in exposure to severe stressful life events during development (before age 18 demonstrate differences in brain activation during performance of an emotional word-face Stroop task. In this study, functional magnetic resonance imaging was used to assess brain activation in eighteen young adult twins who were discordant in exposure to severe stress such that one twin had two or more severe events compared to their control co-twin who had no severe events. Twins who experienced higher levels of stress during development, compared to their control co-twins with lower stress, exhibited significant clusters of greater activation in the ventrolateral and medial prefrontal cortex, basal ganglia, and limbic regions. The control co-twins showed only the more typical recruitment of frontoparietal regions thought to be important for executive control of attention and maintenance of task goals. Behavioral performance was not significantly different between twins within pairs, suggesting the twins with stress recruited additional neural resources associated with affective processing and updating working memory when performing at the same level. This study provides a powerful glimpse at the potential effects of stress during development while accounting for shared genetic and environmental influences.

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

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Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V.; Balsevich, Georgia; Schmidt, Mathias V.; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E.; Conley, Emily Drabant; Ripke, Stephan; Wray, Naomi R.; Lewis, Cathryn M.; Hamilton, Steven P.; Weissman, Myrna M.; Breen, Gerome; Byrne, Enda M.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Cichon, Sven; Heath, Andrew C.; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A.F.; Martin, Nicholas G.; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M.; Penninx, Brenda P.; Pergadia, Michele L.; Potash, James B.; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J.; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H.; Preisig, Martin; Smoller, Jordan W.; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E.; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R.; Bettecken, Thomas; Binder, Elisabeth B.; Breuer, René; Castro, Victor M.; Churchill, Susanne E.; Coryell, William H.; Craddock, Nick; Craig, Ian W.; Czamara, Darina; De Geus, Eco J.; Degenhardt, Franziska; Farmer, Anne E.; Fava, Maurizio; Frank, Josef; Gainer, Vivian S.; Gallagher, Patience J.; Gordon, Scott D.; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V.; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A.; Kohane, Isaac S.; Kohli, Martin A.; Korszun, Ania; Landen, Mikael; Lawson, William B.; Lewis, Glyn; MacIntyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Middleton, Lefkos; Montgomery, Grant M.; Murphy, Shawn N.; Nauck, Matthias; Nolen, Willem A.; Nyholt, Dale R.; O’Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A.; Schulz, Andrea; Schulze, Thomas G.; Shyn, Stanley I.; Sigurdsson, Engilbert; Slager, Susan L.; Smit, Johannes H.; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B.; Willemsen, Gonneke; Zitman, Frans G.; Neale, Benjamin; Daly, Mark; Levinson, Douglas F.; Sullivan, Patrick F.; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R.; Binder, Elisabeth B.

2015-01-01

Summary Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. Video Abstract PMID:26050039

Structural brain aberrations associated with the dissociative subtype of post-traumatic stress disorder.

Science.gov (United States)

Daniels, J K; Frewen, P; Theberge, J; Lanius, R A

2016-03-01

One factor potentially contributing to the heterogeneity of previous results on structural grey matter alterations in adult participants suffering from post-traumatic stress disorder (PTSD) is the varying levels of dissociative symptomatology. The aim of this study was therefore to test whether the recently defined dissociative subtype of PTSD characterized by symptoms of depersonalization and derealization is characterized by specific differences in volumetric brain morphology. Whole-brain MRI data were acquired for 59 patients with PTSD. Voxel-based morphometry was carried out to test for group differences between patients classified as belonging (n = 15) vs. not belonging (n = 44) to the dissociative subtype of PTSD. The correlation between dissociation (depersonalization/derealization) severity and grey matter volume was computed. Patients with PTSD classified as belonging to the dissociative subtype exhibited greater grey matter volume in the right precentral and fusiform gyri as well as less volume in the right inferior temporal gyrus. Greater dissociation severity was associated with greater volume in the right middle frontal gyrus. The results of this first whole-brain investigation of specific grey matter volume in dissociative subtype PTSD indentified structural aberrations in regions subserving the processing and regulation of emotional arousal. These might constitute characteristic biomarkers for the dissociative subtype PTSD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Investigations of oxidative stress effects and their mechanisms in rat brain after systemic administration of ceria engineered nanomaterials

Science.gov (United States)

Hardas, Sarita S.

Advancing applications of engineered nanomaterials (ENM) in various fields create the opportunity for intended (e.g. drug and gene delivery) or unintended (e.g. occupational and environmental) exposure to ENM. However, the knowledge of ENM-toxicity is lagging behind their application development. Understanding the ENM hazard can help us to avoid potential human health problems associated with ENM applications as well as to increase their public acceptance. Ceria (cerium [Ce] oxide) ENM have many current and potential commercial applications. Beyond the traditional use of ceria as an abrasive, the scope of ceria ENM applications now extends into fuel cell manufacturing, diesel fuel additives and for therapeutic intervention as a putative antioxidant. However, the biological effects of ceria ENM exposure have yet to be fully defined. Both pro-and anti-oxidative effects of ceria ENM exposure are repeatedly reported in literature. EPA, NIEHS and OECD organizations have nominated ceria for its toxicological evaluation. All these together gave us the impetus to examine the oxidative stress effects of ceria ENM after systemic administration. Induction of oxidative stress is one of the primary mechanisms of ENM toxicity. Oxidative stress plays an important role in maintaining the redox homeostasis in the biological system. Increased oxidative stress, due to depletion of antioxidant enzymes or molecules and / or due to increased production of reactive oxygen (ROS) or nitrogen (RNS) species may lead to protein oxidation, lipid peroxidation and/or DNA damage. Increased protein oxidation or lipid peroxidation together with antioxidant protein levels and activity can serve as markers of oxidative stress. To investigate the oxidative stress effects and the mechanisms of ceria-ENM toxicity, fully characterized ceria ENM of different sizes (˜ 5nm, 15nm, 30nm, 55nm and nanorods) were systematically injected into rats intravenously in separate experiments. Three brain regions

Early-life stress induces persistent alterationsin 5-HT1Areceptor and serotonin transporter mRNA expression in the adultrat brain.

Directory of Open Access Journals (Sweden)

Javier A. Bravo

2014-04-01

Full Text Available Early-life experience plays a major role in the stress response throughout life. Neonatal maternal separation (MS is an animal model of depression with an altered serotonergic response. We hypothesize that this alteration may be caused by differences in 5-HT1A receptor and serotonin transporter (SERT mRNA expression in brain areas involved in the control of emotions, memory and fear as well as in regions controlling the central serotonergic tone.To test this, Sprague-Dawley rats were subjected to MS for 3h daily during post-natal days 2-12. As control, age matched rats were not separated (NS from their dams. When animals reached adulthood (11-13 weeks brain was extracted and mRNA expression of 5-HT1A receptor in amygdala, hippocampus and dorsal raphé nucleus (DRN and SERT in the DRN was analyzed through in-situ hybridisation.Densitometric analysis revealed that MS increased 5-HT1A receptor mRNA expression in the amygdala, and reduced its expression in the DRN, but no changes were observed in the hippocampus in comparison to NS controls. Also, MS reduced SERT mRNA expression in the DRN when compared to NS rats.These results suggest that early-life stress induces persistent changes in 5-HT1A receptor and SERT mRNA expression in key brain regions involved in the development of stress-related psychiatric disorders. The reduction in SERT mRNA indicates an alteration that is in line with clinical findings such as polymorphic variants in individuals with higher risk of depression. These data may help to understand how early-life stress contributes to the development of mood disorders in adulthood.

Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder from Traumatic Brain Injury in Focused and Large Community Datasets

OpenAIRE

Amen, Daniel G.; Raji, Cyrus A.; Willeumier, Kristen; Taylor, Derek; Tarzwell, Robert; Newberg, Andrew; Henderson, Theodore A.

2015-01-01

Background Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing challenges in reliable classification and treatment. Single photon emission computed tomography (SPECT) may be advantageous in the diagnostic separation of these disorders when comorbid or clinically indistinct. Methods Subjects were selected from a multisite database, where rest and on-task SPECT scans were obtained on a large gr...

Sumoylation of IkB attenuates NF-kB-induced nitrosative stress at rostral ventrolateral medulla and cardiovascular depression in experimental brain death.

Science.gov (United States)

Tsai, Ching-Yi; Li, Faith C H; Wu, Carol H Y; Chang, Alice Y W; Chan, Samuel H H

2016-09-22

Small ubiquitin-related modifier (SUMO) is a group of proteins that participates in post-translational modifications. One known SUMO target is the transcription factor nuclear factor-kB (NF-kB) that plays a pivotal role in many disease processes; sumoylation inactivates NF-kB by conjugation with inhibitors of NF-kB (IkB). Our laboratory demonstrated previously that transcriptional upregulation of nitric oxide synthase II (NOS II) by NF-kB, leading to nitrosative stress by the formation of peroxynitrite in the rostral ventrolateral medulla (RVLM), underpins the defunct brain stem cardiovascular regulation that precedes brain death. Based on an experimental endotoxemia model, this study evaluated the hypothesis that sumoylation plays a pro-life role in brain death by interacting with the NF-kB/NOS II/peroxynitrite signaling pathway in the RVLM. In Sprague-Dawley rats, intravenous administration of Escherichia coli lipopolysaccharide (LPS; 10 mg kg -1 ) elicited an augmentation of SUMO-1 and ubiquitin-conjugase 9 (Ubc9) mRNA or protein levels, alongside SUMO-1-conjugated proteins in the RVLM. Immunoneutralization of SUMO-1 or Ubc9 in the RVLM significantly potentiated the already diminished sumoylation of IkBα and intensified NF-kB activation and NOS II/peroxynitrite expression in this brain stem substrate, together with exacerbated fatality, cardiovascular depression and reduction of an experimental index of a life-and-death signal detected from arterial pressure that disappears in comatose patients signifying failure of brain stem cardiovascular regulation before brain death. We conclude that sumoylation of IkB in the RVLM ameliorates the defunct brain stem cardiovascular regulation that underpins brain death in our experimental endotoxemia modal by reducing nitrosative stress via inhibition of IkB degradation that diminishes the induction of the NF-kB/NOS II/peroxynitrite signaling cascade.

Brain SPECT analysis using statistical parametric mapping in patients with posttraumatic stress disorder

Energy Technology Data Exchange (ETDEWEB)

Kim, Euy Neyng; Sohn, Hyung Sun; Kim, Sung Hoon; Chung, Soo Kyo; Yang, Dong Won [College of Medicine, The Catholic Univ. of Korea, Seoul (Korea, Republic of)

2001-07-01

This study investigated alterations in regional cerebral blood flow (rCBF) in patients with posttraumatic stress disorder (PTSD) using statistical parametric mapping (SPM99). Noninvasive rCBF measurements using {sup 99m}Tc-ethyl cysteinate dimer (ECD) SPECT were performed on 23 patients with PTSD and 21 age matched normal controls without re-exposure to accident-related stimuli. The relative rCBF maps in patients with PTSD and controls were compared. In patients with PTSD, significant increased rCBF was found along the limbic system in the brain. There were a few foci of decreased rCBF in the superior frontal gyrus, parietal and temporal region. PTSD is associated with increased rCBF in limbic areas compared with age-matched normal controls. These findings implicate regions of the limbic brain, which may mediate the response to aversive stimuli in healthy individuals, play on important role in patients suffering from PTSD and suggest that ongoing hyperfunction of 'overlearned survival response' or flashbacks response in these regions after painful, life threatening, or horrifying events without re-exposure to same traumatic stimulus.

Brain SPECT analysis using statistical parametric mapping in patients with posttraumatic stress disorder

International Nuclear Information System (INIS)

Kim, Euy Neyng; Sohn, Hyung Sun; Kim, Sung Hoon; Chung, Soo Kyo; Yang, Dong Won

2001-01-01

This study investigated alterations in regional cerebral blood flow (rCBF) in patients with posttraumatic stress disorder (PTSD) using statistical parametric mapping (SPM99). Noninvasive rCBF measurements using 99m Tc-ethyl cysteinate dimer (ECD) SPECT were performed on 23 patients with PTSD and 21 age matched normal controls without re-exposure to accident-related stimuli. The relative rCBF maps in patients with PTSD and controls were compared. In patients with PTSD, significant increased rCBF was found along the limbic system in the brain. There were a few foci of decreased rCBF in the superior frontal gyrus, parietal and temporal region. PTSD is associated with increased rCBF in limbic areas compared with age-matched normal controls. These findings implicate regions of the limbic brain, which may mediate the response to aversive stimuli in healthy individuals, play on important role in patients suffering from PTSD and suggest that ongoing hyperfunction of 'overlearned survival response' or flashbacks response in these regions after painful, life threatening, or horrifying events without re-exposure to same traumatic stimulus

Usefulness of rate of increase in SPECT counts in one-day method of N-isopropyl-4-iodoamphetamine [123I] SPECT studies at rest and after acetazolamide challenge using a method for estimating time-dependent distribution at rest

International Nuclear Information System (INIS)

Kawamura, Yoshifumi; Ashizaki, Michio; Saida, Shoko; Sugimoto, Hideharu

2008-01-01

When N-isopropyl-4-iodoamphetamine ( 123 I-IMP) single-photon emission computed tomography (SPECT) studies at rest and after acetazolamide (ACZ) challenge are conducted in a day, the time-dependent change in IMP in the brain at rest should be estimated accurately. We devised the method and investigated whether our one-day method for measuring the rate of increase in SPECT counts allowed reduction in the acquisition time. Sequential, 5-min SPECT scans were performed. We estimated the time-dependent change in the brain using the change in slopes of two linear equations derived from the first three SPECT counts. For the one-day method, ACZ was administered 15 min or 20 min after IMP administration. The second IMP was administered 10 min after ACZ administration. Time-dependent changes in the brain were classified into 13 patterns when estimation was started at 5 min after IMP administration and 6 patterns when estimation was started at 10 min, and fitting coefficients were determined. The correlation between actual measurements at 37.5 min and estimates was high with a correlation coefficient of 0.99 or greater. Rates of increase obtained from 20-min data were highly correlated with those obtained from 15-min or 10-min data (r=0.97 or greater). In patients with unilateral cerebrovascular disease, the rate of increase on the unaffected side was 44.4±10.9% when ACZ was administered 15 min later and 48.0±16.0% when ACZ was administered 20 min later, and the rates of increase with different timings of administration were not significantly different. The examination time may be reduced from 50 min to 45 min or 40 min as needed. The rate of increase was not influenced by the time frame for determination or the timing of ACZ administration. These findings suggest that our estimation method is accurate and versatile. (author)

How does the brain affect cardiovascular health?

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Vitaliy Bezsheiko

2017-08-01

Full Text Available In the article the mechanisms of stress response regulation by the brain are reviewed, as well as the data from a new study in this area, which was focused on a detailed analysis of brain activity changes in people with excessive cardiovascular stress response.

Liver antioxidant stores protect the brain from electromagnetic radiation (900 and 1800 MHz)-induced oxidative stress in rats during pregnancy and the development of offspring.

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Çetin, Hasan; Nazıroğlu, Mustafa; Çelik, Ömer; Yüksel, Murat; Pastacı, Nural; Özkaya, Mehmet Okan

2014-12-01

The present study determined the effects of mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) exposure on oxidative stress in the brain and liver as well as the element levels in growing rats from pregnancy to 6 weeks of age. Thirty-two rats and their offspring were equally divided into three different groups: the control, 900 MHz, and 1800 MHz groups. The 900 MHz and 1800 MHz groups were exposed to EMR for 60 min/d during pregnancy and neonatal development. At the 4th, 5th, and 6th weeks of the experiment, brain samples were obtained. Brain and liver glutathione peroxidase activities, as well as liver vitamin A and β-carotene concentrations decreased in the EMR groups, although brain iron, vitamin A, and β-carotene concentrations increased in the EMR groups. In the 6th week, selenium concentrations in the brain decreased in the EMR groups. There were no statistically significant differences in glutathione, vitamin E, chromium, copper, magnesium, manganese, and zinc concentrations between the three groups. EMR-induced oxidative stress in the brain and liver was reduced during the development of offspring. Mobile phone-induced EMR could be considered as a cause of oxidative brain and liver injury in growing rats.

Stress-induced brain histone H3 phosphorylation: contribution of the intensity of stressors and length of exposure.

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Rotllant, David; Pastor-Ciurana, Jordi; Armario, Antonio

2013-05-01

Expression of c-fos is used for the characterization of brain areas activated by stressors. Recently, some epigenetic markers associated with enhanced transcription have been identified that may be also useful to detect neuronal populations important for the processing of stressors: phosphorylation of histone H3 in serine 10 or 28 (pH3S₁₀ or pH3S₂₈). Then, we compared in rats the response to stress of c-fos and these epigenetic changes. More specifically, we studied the influence of the type of stressor (novel environment vs. immobilization, IMO) and the dynamics of the response to IMO. Stress increased pH3S₁₀ positive neurons, with a more restricted pattern than that of c-fos, both in terms of brain areas activated and number of positive neurons. Changes in pH3S₁₀ showed a maximum at 30 min, then progressively declining in most areas in spite of the persistence of IMO. Moreover, the decline was in general more sensitive than c-fos to the termination of IMO. The pattern of pH3S₂₈ was even more restricted that of pH3S₁₀, but they showed co-localization. The present data demonstrate a more selective pattern of stress-induced histone H3 phosphorylation than c-fos. The factors determining such a selectivity and its biological meaning remain to be studied. © 2013 International Society for Neurochemistry.

Effects on pig immunophysiology, PBMC proteome and brain neurotransmitters caused by group mixing stress and human-animal relationship

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Valent, Daniel; Arroyo, Laura; Peña, Raquel; Yu, Kuai; Carreras, Ricard; Mainau, Eva; Velarde, Antonio

2017-01-01

Peripheral blood mononuclear cells (PBMC) are an interesting sample for searching for biomarkers with proteomic techniques because they are easy to obtain and do not contain highly abundant, potentially masking proteins. Two groups of pigs (n = 56) were subjected to mixing under farm conditions and afterwards subjected to different management treatments: negative handling (NH) and positive handling (PH). Serum and PBMC samples were collected at the beginning of the experiment one week after mixing (t0) and after two months of different handling (t2). Brain areas were collected after slaughter and neurotransmitters quantified by HPLC. Hair cortisol and serum acute phase proteins decreased and serum glutathione peroxidase increased at t2, indicating a lower degree of stress at t2 after adaptation to the farm. Differential gel electrophoresis (DIGE) was applied to study the effects of time and treatment on the PBMC proteome. A total of 54 differentially expressed proteins were identified, which were involved in immune system modulation, cell adhesion and motility, gene expression, splicing and translation, protein degradation and folding, oxidative stress and metabolism. Thirty-seven protein spots were up-regulated at t2 versus t0 whereas 27 were down-regulated. Many of the identified proteins share the characteristic of being potentially up or down-regulated by cortisol, indicating that changes in protein abundance between t0 and t2 are, at least in part, consequence of lower stress upon adaptation to the farm conditions after group mixing. Only slight changes in brain neurotransmitters and PBMC oxidative stress markers were observed. In conclusion, the variation in hair cortisol and serum APPs as well as the careful analysis of the identified proteins indicate that changes in protein composition in PBMC throughout time is mainly due to a decrease in the stress status of the individuals, following accommodation to the farm and the new group. PMID:28475627

Effects on pig immunophysiology, PBMC proteome and brain neurotransmitters caused by group mixing stress and human-animal relationship.

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Valent, Daniel; Arroyo, Laura; Peña, Raquel; Yu, Kuai; Carreras, Ricard; Mainau, Eva; Velarde, Antonio; Bassols, Anna

2017-01-01

Peripheral blood mononuclear cells (PBMC) are an interesting sample for searching for biomarkers with proteomic techniques because they are easy to obtain and do not contain highly abundant, potentially masking proteins. Two groups of pigs (n = 56) were subjected to mixing under farm conditions and afterwards subjected to different management treatments: negative handling (NH) and positive handling (PH). Serum and PBMC samples were collected at the beginning of the experiment one week after mixing (t0) and after two months of different handling (t2). Brain areas were collected after slaughter and neurotransmitters quantified by HPLC. Hair cortisol and serum acute phase proteins decreased and serum glutathione peroxidase increased at t2, indicating a lower degree of stress at t2 after adaptation to the farm. Differential gel electrophoresis (DIGE) was applied to study the effects of time and treatment on the PBMC proteome. A total of 54 differentially expressed proteins were identified, which were involved in immune system modulation, cell adhesion and motility, gene expression, splicing and translation, protein degradation and folding, oxidative stress and metabolism. Thirty-seven protein spots were up-regulated at t2 versus t0 whereas 27 were down-regulated. Many of the identified proteins share the characteristic of being potentially up or down-regulated by cortisol, indicating that changes in protein abundance between t0 and t2 are, at least in part, consequence of lower stress upon adaptation to the farm conditions after group mixing. Only slight changes in brain neurotransmitters and PBMC oxidative stress markers were observed. In conclusion, the variation in hair cortisol and serum APPs as well as the careful analysis of the identified proteins indicate that changes in protein composition in PBMC throughout time is mainly due to a decrease in the stress status of the individuals, following accommodation to the farm and the new group.

Thiamine and benfotiamine prevent stress-induced suppression of hippocampal neurogenesis in mice exposed to predation without affecting brain thiamine diphosphate levels.

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Vignisse, Julie; Sambon, Margaux; Gorlova, Anna; Pavlov, Dmitrii; Caron, Nicolas; Malgrange, Brigitte; Shevtsova, Elena; Svistunov, Andrey; Anthony, Daniel C; Markova, Natalyia; Bazhenova, Natalyia; Coumans, Bernard; Lakaye, Bernard; Wins, Pierre; Strekalova, Tatyana; Bettendorff, Lucien

2017-07-01

Thiamine is essential for normal brain function and its deficiency causes metabolic impairment, specific lesions, oxidative damage and reduced adult hippocampal neurogenesis (AHN). Thiamine precursors with increased bioavailability, especially benfotiamine, exert neuroprotective effects not only for thiamine deficiency (TD), but also in mouse models of neurodegeneration. As it is known that AHN is impaired by stress in rodents, we exposed C57BL6/J mice to predator stress for 5 consecutive nights and studied the proliferation (number of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn immature neurons in the subgranular zone of the dentate gyrus. In stressed mice, the number of Ki67- and BrdU-positive cells was reduced compared to non-stressed animals. This reduction was prevented when the mice were treated (200mg/kg/day in drinking water for 20days) with thiamine or benfotiamine, that were recently found to prevent stress-induced behavioral changes and glycogen synthase kinase-3β (GSK-3β) upregulation in the CNS. Moreover, we show that thiamine and benfotiamine counteract stress-induced bodyweight loss and suppress stress-induced anxiety-like behavior. Both treatments induced a modest increase in the brain content of free thiamine while the level of thiamine diphosphate (ThDP) remained unchanged, suggesting that the beneficial effects observed are not linked to the role of this coenzyme in energy metabolism. Predator stress increased hippocampal protein carbonylation, an indicator of oxidative stress. This effect was antagonized by both thiamine and benfotiamine. Moreover, using cultured mouse neuroblastoma cells, we show that in particular benfotiamine protects against paraquat-induced oxidative stress. We therefore hypothesize that thiamine compounds may act by boosting anti-oxidant cellular defenses, by a mechanism that still remains to be unveiled. Our study demonstrates, for the first time, that thiamine and benfotiamine prevent

Specificity protein 1-zinc finger protein 179 pathway is involved in the attenuation of oxidative stress following brain injury

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Jian-Ying Chuang

2017-04-01

Full Text Available After sudden traumatic brain injuries, secondary injuries may occur during the following days or weeks, which leads to the accumulation of reactive oxygen species (ROS. Since ROS exacerbate brain damage, it is important to protect neurons against their activity. Zinc finger protein 179 (Znf179 was shown to act as a neuroprotective factor, but the regulation of gene expression under oxidative stress remains unknown. In this study, we demonstrated an increase in Znf179 protein levels in both in vitro model of hydrogen peroxide (H2O2-induced ROS accumulation and animal models of traumatic brain injury. Additionally, we examined the sub-cellular localization of Znf179, and demonstrated that oxidative stress increases Znf179 nuclear shuttling and its interaction with specificity protein 1 (Sp1. Subsequently, the positive autoregulation of Znf179 expression, which is Sp1-dependent, was further demonstrated using luciferase reporter assay and green fluorescent protein (GFP-Znf179-expressing cells and transgenic mice. The upregulation of Sp1 transcriptional activity induced by the treatment with nerve growth factor (NGF led to an increase in Znf179 levels, which further protected cells against H2O2-induced damage. However, Sp1 inhibitor, mithramycin A, was shown to inhibit NGF effects, leading to a decrease in Znf179 expression and lower cellular protection. In conclusion, the results obtained in this study show that Znf179 autoregulation through Sp1-dependent mechanism plays an important role in neuroprotection, and NGF-induced Sp1 signaling may help attenuate more extensive (ROS-induced damage following brain injury.

The Mancozeb-containing carbamate fungicide tattoo induces mild oxidative stress in goldfish brain, liver, and kidney.

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Atamaniuk, Tetiana M; Kubrak, Olga I; Husak, Viktor V; Storey, Kenneth B; Lushchak, Volodymyr I

2014-11-01

Tattoo belongs to the group of carbamate fungicides and contains Mancozeb (ethylene(bis)dithiocarbamate) as its main constituent. The toxicity of Mancozeb to living organisms, particularly fish, is not resolved. This work investigated the effects of 96 h of exposure to 3, 5, or 10 mg L(-1) of Tattoo (corresponding to 0.9, 1.5, or 3 mg L(-1) of Mancozeb) on the levels of oxidative stress markers and the antioxidant enzyme system of brain, liver, and kidney of goldfish, Carassius auratus). In liver, Tattoo exposure resulted in increased activities of superoxide dismutase (SOD) by 70%-79%, catalase by 23%-52% and glutathione peroxidase (GPx) by 49%. The content of protein carbonyls (CP) in liver was also enhanced by 92%-125% indicating extensive damage to proteins. Similar increases in CP levels (by 98%-111%) accompanied by reduced glucose-6-phosphate dehydrogenase activity (by 13%-15%) was observed in kidney of fish exposed to Tattoo; however, SOD activity increased by 37% in this tissue after treatment with 10 mg L(-1) Tattoo. In brain, a rise in lipid peroxide level (by 29%) took place after exposure to 10 mg L(-1) Tattoo and was accompanied by elevation of high-molecular mass thiols (by 14%). Tattoo exposure also resulted in a concentration-dependent decrease in glutathione reductase activity (by 26%-37%) in brain. The data collectively show that exposure of goldfish to 3-10 mg L(-1) of the carbamate fungicide Tattoo resulted in the development of mild oxidative stress and activation of antioxidant defense systems in goldfish tissues. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

Differential effects of stress and amphetamine administration on Fos-like protein expression in corticotropin releasing factor-neurons of the rat brain.

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Rotllant, David; Nadal, Roser; Armario, Antonio

2007-05-01

Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine.

Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury Post-Concussion Syndrome (PCS) and Post Traumatic Stress Disorder (PTSD)

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2017-10-01

Post-Concussion Syndrome (PCS) and Post Traumatic Stress Disorder (PTSD) PRINCIPAL INVESTIGATOR: Paul G. Harch, M.D. CONTRACTING ORGANIZATION...Traumatic Brain Injury Post-Concussion Syndrome (PCS) and Post Traumatic Stress Disorder (PTSD) 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...injury (TBI) and post-traumatic stress disorder (PTSD) affect 11-28% and 13-17%, respectively, of U.S. combat troops returning from Iraq and

Opposing effects of traumatic brain injury on excitatory synaptic function in the lateral amygdala in the absence and presence of preinjury stress.

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Klein, Rebecca C; Acheson, Shawn K; Qadri, Laura H; Dawson, Alina A; Rodriguiz, Ramona M; Wetsel, William C; Moore, Scott D; Laskowitz, Daniel T; Dawson, Hana N

2016-06-01

Traumatic brain injury (TBI) is a leading cause of death and disability among young adults and is highly prevalent among recently deployed military personnel. Survivors of TBI often experience cognitive and emotional deficits, suggesting that long-term effects of injury may disrupt neuronal function in critical brain regions, including the amygdala, which is involved in emotion and fear memory. Amygdala hyperexcitability has been reported in both TBI and posttraumatic stress disorder patients, yet little is known regarding the effects of combined stress and TBI on amygdala structure and function at the neuronal level. The present study seeks to determine how the long-term effects of preinjury foot-shock stress and TBI interact to influence synaptic plasticity in the lateral amygdala (LA) of adult male C57BL/6J mice by using whole-cell patch clamp electrophysiology 2-3 months postinjury. In the absence of stress, TBI resulted in a significant increase in membrane excitability and spontaneous excitatory postsynaptic currents (sEPSCs) in LA pyramidal-like neurons. Foot-shock stress in the absence of TBI also resulted in increased sEPSC activity. In contrast, when preinjury stress and TBI occurred in combination, sEPSC activity was significantly decreased compared with either condition alone. There were no significant differences in inhibitory activity or total dendritic length among any of the treatment groups. These results demonstrate that stress and TBI may be contributing to amygdala hyperexcitability via different mechanisms and that these pathways may counterbalance each other with respect to long-term pathophysiology in the LA. © 2015 Wiley Periodicals, Inc.

Neuroprotection via Reduction in Stress: Altered Menstrual Patterns as a Marker for Stress and Implications for Long-Term Neurologic Health in Women

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David Prokai

2016-12-01

Full Text Available Individuals under chronic psychological stress can be difficult to identify clinically. There is often no outwardly visible phenotype. Chronic stress of sufficient magnitude not only impacts reproductive function, but also concomitantly elicits a constellation of neuroendocrine changes that may accelerate aging in general and brain aging in particular. Functional hypothalamic amenorrhea, a phenotypically recognizable form of stress, is due to stress-induced suppression of endogenous gonadotropin-releasing hormone secretion. Reversal of functional hypothalamic amenorrhea includes restoration of ovulatory ovarian function and fertility and amelioration of hypercortisolism and hypothyroidism. Taken together, recovery from functional hypothalamic amenorrhea putatively offers neuroprotection and ameliorates stress-induced premature brain aging and possibly syndromic Alzheimer’s disease. Amenorrhea may be viewed as a sentinel indicator of stress. Hypothalamic hypogonadism is less clinically evident in men and the diagnosis is difficult to establish. Whether there are other sex differences in the impact of stress on brain aging remains to be better investigated, but it is likely that both low estradiol from stress-induced anovulation and low testosterone from stress-induced hypogonadism compromise brain health.

Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females.

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Gupta, Arpana; Labus, Jennifer; Kilpatrick, Lisa A; Bonyadi, Mariam; Ashe-McNalley, Cody; Heendeniya, Nuwanthi; Bradesi, Sylvie; Chang, Lin; Mayer, Emeran A

2016-04-01

Early adverse life events (EALs) have been associated with regional thinning of the subgenual cingulate cortex (sgACC), a brain region implicated in the development of disorders of mood and affect, and often comorbid functional pain disorders, such as irritable bowel syndrome (IBS). Regional neuroinflammation related to chronic stress system activation has been suggested as a possible mechanism underlying these neuroplastic changes. However, the interaction of genetic and environmental factors in these changes is poorly understood. The current study aimed to evaluate the interactions of EALs and candidate gene polymorphisms in influencing thickness of the sgACC. 210 female subjects (137 healthy controls; 73 IBS) were genotyped for stress and inflammation-related gene polymorphisms. Genetic variation with EALs, and diagnosis on sgACC thickness was examined, while controlling for race, age, and total brain volume. Compared to HCs, IBS had significantly reduced sgACC thickness (p = 0.03). Regardless of disease group (IBS vs. HC), thinning of the left sgACC was associated with a significant gene-gene environment interaction between the IL-1β genotype, the NR3C1 haplotype, and a history of EALs (p = 0.05). Reduced sgACC thickness in women with the minor IL-1β allele, was associated with EAL total scores regardless of NR3C1 haplotype status (p = 0.02). In subjects homozygous for the major IL-1β allele, reduced sgACC with increasing levels of EALs was seen only with the less common NR3C1 haplotype (p = 0.02). These findings support an interaction between polymorphisms related to stress and inflammation and early adverse life events in modulating a key region of the emotion arousal circuit.

Neurosignal record with a Brain-Computer interface to estimate the level of stress in a student during a class

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Luz Angela Moreno Cueva

2017-07-01

Full Text Available Introduction: This work shows an individual study of the capture, recording, and analysis of the level of stress of a university student during a class that involves an evaluation. The stress information was estimated using a commercial and low-cost computer-brain interface. This allows solving the problem of easily obtaining quantitative and not only qualitative measures. Objective: The aim of this article is to analyze the behavior of neural signals to estimate the level of stress in a student to some verbal and nonverbal events generated by a teacher. Methodology: An experimental design of individual character was developed taking as disturbances the level of stress, events such as questions, time limits, and gestures. Results: Some events that caused stress in students produced by the verbal and non-verbal language of the teacher when teaching the class were evidenced. Conclusions: Teachers are encouraged to moderate their body language during assessments by avoiding actions that emulate anxieties or pressures in unnecessary times.

Chlorella vulgaris reduces the impact of stress on hypothalamic-pituitary-adrenal axis and brain c-fos expression.

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Souza Queiroz, Julia; Marín Blasco, Ignacio; Gagliano, Humberto; Daviu, Nuria; Gómez Román, Almudena; Belda, Xavier; Carrasco, Javier; Rocha, Michelle C; Palermo Neto, João; Armario, Antonio

2016-03-01

Predominantly emotional stressors activate a wide range of brain areas, as revealed by the expression of immediate early genes, such as c-fos. Chlorella vulgaris (CV) is considered a biological response modifier, as demonstrated by its protective activities against infections, tumors and stress. We evaluated the effect of acute pretreatment with CV on the peripheral and central responses to forced swimming stress in adult male rats. Pretreatment with CV produced a significant reduction of stress-related hypothalamic-pituitary-adrenal activation, demonstrated by decreased corticotrophin releasing factor gene expression in the hypothalamic paraventricular nucleus (PVN) and lower ACTH response. Hyperglycemia induced by the stressor was similarly reduced. This attenuated neuroendocrine response to stress occurred in parallel with a diminished c-fos expression in most evaluated areas, including the PVN. The data presented in this study reinforce the usefulness of CV to diminish the impact of stressors, by reducing the HPA response. Although our results suggest a central effect of CV, further studies are necessary to understand the precise mechanisms underpinning this effect. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sodium butyrate has an antimanic effect and protects the brain against oxidative stress in an animal model of mania induced by ouabain.

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Valvassori, Samira S; Dal-Pont, Gustavo C; Steckert, Amanda V; Varela, Roger B; Lopes-Borges, Jéssica; Mariot, Edemilson; Resende, Wilson R; Arent, Camila O; Carvalho, André F; Quevedo, João

2016-01-30

Studies have consistently reported the participation of oxidative stress in bipolar disorder (BD). Evidence indicates that epigenetic regulations have been implicated in the pathophysiology of mood disorders. Considering these evidences, the present study aimed to investigate the effects of sodium butyrate (SB), a histone deacetylase (HDAC)inhibitor, on manic-like behavior and oxidative stress parameters (TBARS and protein carbonyl content and SOD and CAT activities) in frontal cortex and hippocampus of rats subjected to the animal model of mania induced by intracerebroventricular (ICV) ouabain administration.The results showed that SB reversed ouabain-induced hyperactivity, which represents a manic-like behavior in rats. In addition, the ouabain ICV administration induced oxidative damage to lipid and protein and alters antioxidant enzymes activity in all brain structures analyzed. The treatment with SB was able to reversesboth behavioral and oxidative stress parameters alteration induced by ouabain.In conclusion, we suggest that SB can be considered a potential new mood stabilizer by acts on manic-like behavior and regulatesthe antioxidant enzyme activities, protecting the brain against oxidative damage. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Principle of cerebral hemodynamic perfusion in SPECT and new evaluation method of hemodynamic reserve capacity using {sup 99m}Tc tracer

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Hashimoto, Masaaki; Mukai, Hironobu; Tada, Motoyuki; Miyazaki, Yoshiharu; Takimoto, Masamori; Shiozaki, Jun; Inoue, Hisashi [Noto General Hospital, Nanao, Ishikawa (Japan)

2002-07-01

We performed quantitative measurements of cerebral blood flow (CBF) using {sup 99m}Tc tracer by the Patlak Plot method with reference to normal aging and cerebrovascular reserve (CVR) capacity and then investigated a new evaluation method of CVR. Aging and decrease of ADL were significantly associated with reduction of the mean hemispheric CBF. In the acetazolamide (ACZ) stress test, these retrospective data showed some overlap in each ischemic grade on the relationship between rCBF and CVR response for the predictability of EC/IC bypass surgery. In these controversial problems, we must reconfirm the principle of cerebral hemodynamic perfusion in SPECT. First, retention tracer is distributed via the microcirculatory system to brain tissue. Second, therefore, we should understand not only the circulation of major vessels, but also the dynamics and rheology in parenchymal microcirculation to determine brain SPECT and CVR capacity. In the next step, we approached the new evaluation method of CVR capacity using {sup 99m}Tc tracer by a serial dynamic SPECT with a slip-ring rotational gamma camera. These preliminally findings suggest that a serial dynamic SPECT may be more useful for analyzing the pathophysiology on brain circulation and CVR than conventional approaches. (author)

Do glutathione levels decline in aging human brain?

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Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

2016-04-01

For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Epigenetic modulation of gene expression governs the brain's response to injury.

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Simon, Roger P

2016-06-20

Mild stress from ischemia, seizure, hypothermia, or infection can produce a transient neuroprotected state in the brain. In the neuroprotected state, the brain responds differently to a severe stress and sustains less injury. At the genomic level, the response of the neuroprotected brain to a severe stress is characterized by widespread differential regulation of genes with diverse functions. This reprogramming of gene expression observed in the neuroprotected brain in response to a stress is consistent with an epigenetic model of regulation mediated by changes in DNA methylation and histone modification. Here, we summarize our evolving understanding of the molecular basis for endogenous neuroprotection and review recent findings that implicate DNA methylation and protein mediators of histone modification as epigenetic regulators of the brain's response to injury. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of chronic acetazolamide administration on gas exchange and acid-base control in pulmonary circulation in exercising horses.

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Vengust, M; Stämpfli, H; De Moraes, A N; Teixeiro-Neto, F; Viel, L; Heigenhauser, G

2010-11-01

Carbonic anhydrase (CA) catalyses the hydration/dehydration reaction of CO(2) and increases the rate of Cl(-) and HCO(3)(-) exchange between the erythrocytes and plasma. Therefore, chronic inhibition of CA has a potential to attenuate CO(2) output and induce greater metabolic and respiratory acidosis in exercising horses. To determine the effects of Carbonic anhydrase inhibition on CO(2) output and ionic exchange between erythrocytes and plasma and their influence on acid-base balance in the pulmonary circulation (across the lung) in exercising horses with and without CA inhibition. Six horses were exercised to exhaustion on a treadmill without (Con) and with CA inhibition (AczTr). CA inhibition was achieved with administration of acetazolamide (10 mg/kg bwt t.i.d. for 3 days and 30 mg/kg bwt before exercise). Arterial, mixed venous blood and CO(2) output were sampled at rest and during exercise. An integrated physicochemical systems approach was used to describe acid base changes. AczTr decreased the duration of exercise by 45% (P changes across the lung with exception of lactate. CO(2) and chloride changes in erythrocytes across the lung seem to be the major contributors to acid-base and ions balance in pulmonary circulation in exercising horses. © 2010 EVJ Ltd.

Brain sites mediating corticosteroid feedback inhibition of stimulated ACTH secretion

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Jacobson, L.

1989-01-01

There is substantial evidence that the brain mediates stress-induced and circadian increases in ACTH secretion and that corticosteroid concentrations which normalize basal plasma ACTH are insufficient to normalize ACTH responses to circadian or stressful stimuli in adrenalectomized rats. To identify brain sites mediating corticosteroid inhibition of stimulated ACTH secretion, two approaches were used. The first compared brain [ 14 C]-2-deoxyglucose uptake in rats with differential ACTH responses to stress. Relative to sham-adrenalectomized (SHAM) rats, adrenalectomized rats replaced with low, constant corticosterone levels via a subcutaneous corticosterone pellet (B-PELLET) exhibited elevated and prolonged ACTH responses to a variety of stimuli. Adrenalectomized rate given a circadian corticosterone rhythm via corticosterone in their drinking water exhibited elevated ACTH levels immediately after stress, but unlike B-PELLET rats, terminated stress induced ACTH secretion normally relative to SHAMS. Therefore, the abnormal ACTH responses to stress in B-PELLET rats were due to the lack of both circadian variations and stress-induced increases in corticosterone. Hypoxia was selected as a standardized stimulus for correlating brain [ 14 C]-2-deoxyglucose uptake with ACTH secretion. In intact rats, increases in plasma ACTH and decreases in arterial PO 2 correlated with the severity of hypoxia at arterial PCO 2 below 60 mm Hg. Hypoxia PELLET vs. SHAM rats. However, in preliminary experiments, although hypoxia increased brain 2-deoxyglucose uptake in most brain regions, plasma ACTH correlated poorly with 2-deoxyglucose uptake at 12% and 10% O 2

Vulnerability imposed by diet and brain trauma for anxiety-like phenotype: implications for post-traumatic stress disorders.

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Tyagi, Ethika; Agrawal, Rahul; Zhuang, Yumei; Abad, Catalina; Waschek, James A; Gomez-Pinilla, Fernando

2013-01-01

Mild traumatic brain injury (mTBI, cerebral concussion) is a risk factor for the development of psychiatric illness such as posttraumatic stress disorder (PTSD). We sought to evaluate how omega-3 fatty acids during brain maturation can influence challenges incurred during adulthood (transitioning to unhealthy diet and mTBI) and predispose the brain to a PTSD-like pathobiology. Rats exposed to diets enriched or deficient in omega-3 fatty acids (n-3) during their brain maturation period, were transitioned to a western diet (WD) when becoming adult and then subjected to mTBI. TBI resulted in an increase in anxiety-like behavior and its molecular counterpart NPY1R, a hallmark of PTSD, but these effects were more pronounced in the animals exposed to n-3 deficient diet and switched to WD. The n-3 deficiency followed by WD disrupted BDNF signaling and the activation of elements of BDNF signaling pathway (TrkB, CaMKII, Akt and CREB) in frontal cortex. TBI worsened these effects and more prominently in combination with the n-3 deficiency condition. Moreover, the n-3 deficiency primed the immune system to the challenges imposed by the WD and brain trauma as evidenced by results showing that the WD or mTBI affected brain IL1β levels and peripheral Th17 and Treg subsets only in animals previously conditioned to the n-3 deficient diet. These results provide novel evidence for the capacity of maladaptive dietary habits to lower the threshold for neurological disorders in response to challenges.

Hypertonic saline solution reduces the oxidative stress responses in traumatic brain injury patients

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Mojtaba Mojtahedzadeh

2014-01-01

Full Text Available Background: Oxidative stress processes play an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI. Hypertonic saline (HTS has advantages as being preferred osmotic agent, but few studies investigated oxidant and antioxidant effects of HTS in TBI. This study was designed to compare two different regimens of HTS 5% with mannitol on TBI-induced oxidative stress. Materials and Methods: Thirty-three adult patients with TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 h as bolus, 500 cc of HTS 5%as infusion for 24 h or 1 g/kg mannitol of 20% as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 h based on patient′s response for 3 days. Serum total antioxidant power (TAP, reactive oxygen species (ROS and nitric oxide (NO were measured at baseline and daily for 3 days. Results: Initial serum ROS and NO levels in patients were higher than control(6.86± [3.2] vs. 1.57± [0.5] picoM, P = 0.001, 14.6± [1.6] vs. 7.8± [3.9] mM, P = 0.001, respectively. Levels of ROS have decreased for all patients, but reduction was significantly after HTS infusion and mannitol (3. 08 [±3.1] to 1.07 [±1.6], P = 0.001, 5.6 [±3.4] to 2.5 [±1.8], P = 0.003 respectively. During study, NO levels significantly decreased in HTS infusion but significantly increased in mannitol. TAP Levels had decreased in all patients during study especially in mannitol (P = 0.004. Conclusion: Hypertonic saline 5% has significant effects on the oxidant responses compared to mannitol following TBI that makes HTS as a perfect therapeutic intervention for reducing unfavorable outcomes in TBI patients.

Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

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Valérie Wolff

2015-01-01

Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

Explaining brain size variation: from social to cultural brain.

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van Schaik, Carel P; Isler, Karin; Burkart, Judith M

2012-05-01

Although the social brain hypothesis has found near-universal acceptance as the best explanation for the evolution of extensive variation in brain size among mammals, it faces two problems. First, it cannot account for grade shifts, where species or complete lineages have a very different brain size than expected based on their social organization. Second, it cannot account for the observation that species with high socio-cognitive abilities also excel in general cognition. These problems may be related. For birds and mammals, we propose to integrate the social brain hypothesis into a broader framework we call cultural intelligence, which stresses the importance of the high costs of brain tissue, general behavioral flexibility and the role of social learning in acquiring cognitive skills. Copyright © 2012 Elsevier Ltd. All rights reserved.

Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress.

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Yang, Hongying; Fan, Shourui; Song, Dianping; Wang, Zhuo; Ma, Shungao; Li, Shuqing; Li, Xiaohong; Xu, Mian; Xu, Min; Wang, Xianmo

2013-02-01

The aim of this study was to investigate pathophysiological alterations and oxidative stress in various stages of streptozotocin (STZ)‑induced diabetes mellitus (DM) in rats. Male Sprague-Dawley rats (120) were randomized into DM and control groups. Body mass, plasma glucose, glycated hemoglobin (HbA1c), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, as well as aldose reductase (AR) activities, in brain tissue and serum were determined. Electron microscopy was used to observe neuron and vessel changes in the brain. In STZ‑treated rats, blood glucose, low density lipoproteins, triglycerides and total cholesterol levels increased 1.43‑3.0‑fold and high density lipoprotein, HbA1c and insulin sensitivity index increased 1.1‑1.23‑fold compared with control. At week 16 following treatment, DM rat serum H2O2 concentration was increased, indicating oxidative stress and mRNA levels of GPx and SOD were 2‑fold higher than the control. Protein GPx and SOD levels were reduced (PNeuron cells and blood vessels in the DM rat brains became increasingly abnormal over time with altered Golgi bodies, mitochondria and endoplasmic reticulum cisterns, concurrent with SOD inactivation and AR protein accumulation. Disease progression in rats with STZ‑induced DM included brain pathologies with vascular and neuron cell abnormalities, associated with the reduction of SOD, CAT and GPx activities and also AR accumulation.

Endoplasmic reticulum stress increases brain MAPK signaling, inflammation and renin-angiotensin system activity and sympathetic nerve activity in heart failure.

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Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

2016-10-01

We previously reported that endoplasmic reticulum (ER) stress is induced in the subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN) of heart failure (HF) rats and is reduced by inhibition of mitogen-activated protein kinase (MAPK) signaling. The present study further examined the relationship between brain MAPK signaling, ER stress, and sympathetic excitation in HF. Sham-operated (Sham) and HF rats received a 4-wk intracerebroventricular (ICV) infusion of vehicle (Veh) or the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 10 μg/day). Lower mRNA levels of the ER stress biomarkers GRP78, ATF6, ATF4, and XBP-1s in the SFO and PVN of TUDCA-treated HF rats validated the efficacy of the TUDCA dose. The elevated levels of phosphorylated p44/42 and p38 MAPK in SFO and PVN of Veh-treated HF rats, compared with Sham rats, were significantly reduced in TUDCA-treated HF rats as shown by Western blot and immunofluorescent staining. Plasma norepinephrine levels were higher in Veh-treated HF rats, compared with Veh-treated Sham rats, and were significantly lower in the TUDCA-treated HF rats. TUDCA-treated HF rats also had lower mRNA levels for angiotensin converting enzyme, angiotensin II type 1 receptor, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and NF-κB p65, and a higher mRNA level of IκB-α, in the SFO and PVN than Veh-treated HF rats. These data suggest that ER stress contributes to the augmented sympathetic activity in HF by inducing MAPK signaling, thereby promoting inflammation and renin-angiotensin system activity in key cardiovascular regulatory regions of the brain.

Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio)

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Zheng, Jia-Lang, E-mail: zhengjialang@aliyun.com; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming

2016-11-15

Highlights: • Cd induced oxidative stress and immunotoxicity by the generation of ROS. • The toxic effects depended on exposure time and different tissues. • Nrf2 and NF-κB mediated antioxidant and inflammatory responses. • Gene changed at transcriptional, translational, post-translational levels. - Abstract: Cadmium (Cd) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. The mechanisms underlying Cd-induced oxidative stress and immunotoxicity in fish remain largely unknown. In this study, adult female zebrafish were exposed to 0 (control), 1 mg L{sup −1} Cd for 24 h and 96 h, and the oxidative stress and inflammatory responses induced by Cd were evaluated in the brain, liver and ovary. Reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) increased in a time-dependent manner after treatment with Cd in the brain and liver. The increase may result from the disturbance of genes including copper and zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), inducible nitric oxide synthase (iNOS), and ciclooxigenase-2 (COX-2) at mRNA, protein and activity levels. Although ROS, NO and MDA were not significantly affected by Cd in the ovary, the up-regulation of Cu/Zn-SOD, CAT, iNOS, and COX-2 was observed. Exposure to Cd induced a sharp increase in the protein levels of tumor necrosis factor alpha (TNF-α) in the brain, liver and ovary, possibly contributing to activate inflammatory responses. Furthermore, we also found a dramatic increase in mRNA levels of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor κB (NF-κB) at 24 h in the liver and ovary. The corresponding changes in the mRNA levels of Kelch-like-ECH-associated protein 1 (Keap1a and Keap1b) and the inhibitor of κBα (IκBαa and IκBαb) may contribute to regulate the transcriptional activity of Nrf2 and NF-κB, respectively. Contrarily, mRNA levels of Nrf2, NF-κB, Keap1, Keap1b, IκBαa and IκBαb remained

Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio)

International Nuclear Information System (INIS)

Zheng, Jia-Lang; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming

2016-01-01

Highlights: • Cd induced oxidative stress and immunotoxicity by the generation of ROS. • The toxic effects depended on exposure time and different tissues. • Nrf2 and NF-κB mediated antioxidant and inflammatory responses. • Gene changed at transcriptional, translational, post-translational levels. - Abstract: Cadmium (Cd) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. The mechanisms underlying Cd-induced oxidative stress and immunotoxicity in fish remain largely unknown. In this study, adult female zebrafish were exposed to 0 (control), 1 mg L"−"1 Cd for 24 h and 96 h, and the oxidative stress and inflammatory responses induced by Cd were evaluated in the brain, liver and ovary. Reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) increased in a time-dependent manner after treatment with Cd in the brain and liver. The increase may result from the disturbance of genes including copper and zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), inducible nitric oxide synthase (iNOS), and ciclooxigenase-2 (COX-2) at mRNA, protein and activity levels. Although ROS, NO and MDA were not significantly affected by Cd in the ovary, the up-regulation of Cu/Zn-SOD, CAT, iNOS, and COX-2 was observed. Exposure to Cd induced a sharp increase in the protein levels of tumor necrosis factor alpha (TNF-α) in the brain, liver and ovary, possibly contributing to activate inflammatory responses. Furthermore, we also found a dramatic increase in mRNA levels of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor κB (NF-κB) at 24 h in the liver and ovary. The corresponding changes in the mRNA levels of Kelch-like-ECH-associated protein 1 (Keap1a and Keap1b) and the inhibitor of κBα (IκBαa and IκBαb) may contribute to regulate the transcriptional activity of Nrf2 and NF-κB, respectively. Contrarily, mRNA levels of Nrf2, NF-κB, Keap1, Keap1b, IκBαa and IκBαb remained

Quantification of VGF- and pro-SAAS-derived peptides in endocrine tissues and the brain, and their regulation by diet and cold stress.

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Chakraborty, Tandra R; Tkalych, Oleg; Nanno, Daniela; Garcia, Angelo L; Devi, Lakshmi A; Salton, Stephen R J

2006-05-17

Two novel granin-like polypeptides, VGF and pro-SAAS, which are stored in and released from secretory vesicles and are expressed widely in nervous, endocrine, and neuroendocrine tissues, play roles in the regulation of body weight, feeding, and energy expenditure. Both VGF and pro-SAAS are cleaved into peptide fragments, several of which are biologically active. We utilized a highly sensitive and specific radioimmunoassay (RIA) to immunoreactive, pro-SAAS-derived PEN peptides, developed another against immunoreactive, VGF-derived AQEE30 peptides, and quantified these peptides in various mouse tissues and brain regions. Immunoreactive AQEE30 was most abundant in the pituitary, while brain levels were highest in hypothalamus, striatum, and frontal cortex. Immunoreactive PEN levels were highest in the pancreas and spinal cord, and in brain, PEN was most abundant in striatum, hippocampus, pons and medulla, and cortex. Since both peptides were expressed in hypothalamus, a region of the brain that controls feeding and energy expenditure, double label immunofluorescence studies were employed. These demonstrated that 42% of hypothalamic arcuate neurons coexpress VGF and SAAS peptides, and that the intracellular distributions of these peptides in arcuate neurons differed. By RIA, cold stress increased immunoreactive AQEE30 and PEN peptide levels in female but not male hypothalamus, while a high fat diet increased AQEE30 and PEN peptide levels in female but not male hippocampus. VGF and SAAS-derived peptides are therefore widely expressed in endocrine, neuroendocrine, and neural tissues, can be accurately quantified by RIA, and are differentially regulated in the brain by diet and cold stress.

A mathematical model of brain glucose homeostasis

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Kimura Hidenori

2009-11-01

Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation.

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Navjot Shah

Full Text Available Ashwagandha, a traditional Indian herb, has been known for its variety of therapeutic activities. We earlier demonstrated anticancer activities in the alcoholic and water extracts of the leaves that were mediated by activation of tumor suppressor functions and oxidative stress in cancer cells. Low doses of these extracts were shown to possess neuroprotective activities in vitro and in vivo assays.We used cultured glioblastoma and neuroblastoma cells to examine the effect of extracts (alcoholic and water as well as their bioactive components for neuroprotective activities against oxidative stress. Various biochemical and imaging assays on the marker proteins of glial and neuronal cells were performed along with their survival profiles in control, stressed and recovered conditions. We found that the extracts and one of the purified components, withanone, when used at a low dose, protected the glial and neuronal cells from oxidative as well as glutamate insult, and induced their differentiation per se. Furthermore, the combinations of extracts and active component were highly potent endorsing the therapeutic merit of the combinational approach.Ashwagandha leaf derived bioactive compounds have neuroprotective potential and may serve as supplement for brain health.

Huperzine A alleviates neuroinflammation, oxidative stress and improves cognitive function after repetitive traumatic brain injury.

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Mei, Zhengrong; Zheng, Peiying; Tan, Xiangping; Wang, Ying; Situ, Bing

2017-12-01

Traumatic brain injury (TBI) may trigger secondary injury cascades including endoplasmic reticulum stress, oxidative stress, and neuroinflammation. Unfortunately, there are no effective treatments targeting either primary or secondary injuries that result in long-term detrimental consequences. Huperzine A (HupA) is a potent acetylcholinesterase inhibitor (AChEI) that has been used treatment of Alzheimer's disease (AD). This study aimed to explore the neuroprotective effects of HupA in TBI and its possible mechanisms. Repetitive mild closed head injury (CHI) model was used to mimic concussive TBI. Mice were randomly assigned into three groups including sham, vehicle-treated and HupA-treated injured mice. The HupA was given at dose of 1.0 mg/kg/day and was initiated 30 min after the first injury, then administered daily for a total of 30 days. The neuronal functions including motor functions, emotion-like behaviors, learning and memory were tested. Axonal injury, reactive oxygen species (ROS), and neuroinflammation were examined as well. The results showed that injured mice treated with HupA had significant improvement in Morris water maze performance compared with vehicle-treated injured mice. HupA treatment significantly attenuated markers of neuroinflammation and oxidative stress in the injured mice. Taken together, HupA was effective in reducing neuroinflammation, oxidative stress and behavioral recovery after TBI. HupA is a promising candidate for treatment of TBI.

Do positive or negative stressful events predict the development of new brain lesions in people with Multiple Sclerosis?

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Burns, Michelle Nicole; Nawacki, Ewa; Kwasny, Mary J.; Pelletier, Daniel; Mohr, David C.

2014-01-01

Background Stressful life events have long been suspected to contribute to multiple sclerosis (MS) disease activity. The few studies examining the relationship between stressful events and neuroimaging markers have been small and inconsistent. This study examined whether different types of stressful events and perceived stress could predict development of brain lesions. Methods This was a secondary analysis of 121 patients with MS followed for 48 weeks during a randomized controlled trial comparing Stress Management Therapy for MS to a waitlist control. Patients underwent MRI’s every 8 weeks. Monthly, patients completed an interview measure assessing stressful life events, and self-report measures of perceived stress, anxiety, and depressive symptoms, which were used to predict the presence of gadolinium enhancing (Gd+) and T2 lesions on MRI’s 29–62 days later. Participants classified stressful events as positive or negative. Negative events were considered “major” if they involved physical threat or threat to the patient’s family structure, and “moderate” otherwise. Results Positive stressful events predicted decreased risk for subsequent Gd+ lesions in the control group (OR=.53 for each additional positive stressful event, 95% CI=.30–.91) and less risk for new or enlarging T2 lesions regardless of group assignment (OR=.74, 95% CI=.55–.99). Across groups, major negative stressful events predicted Gd+ lesions (OR=1.77, 95% CI=1.18–2.64) and new or enlarging T2 lesions (OR=1.57, 95% CI=1.11–2.23), while moderate negative stressful events, perceived stress, anxiety, and depressive symptoms did not. Conclusions Major negative stressful events predict increased risk for Gd+ and T2 lesions, while positive stressful events predict decreased risk. PMID:23680407

Stress and Fear Extinction

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Maren, Stephen; Holmes, Andrew

2016-01-01

Stress has a critical role in the development and expression of many psychiatric disorders, and is a defining feature of posttraumatic stress disorder (PTSD). Stress also limits the efficacy of behavioral therapies aimed at limiting pathological fear, such as exposure therapy. Here we examine emerging evidence that stress impairs recovery from trauma by impairing fear extinction, a form of learning thought to underlie the suppression of trauma-related fear memories. We describe the major structural and functional abnormalities in brain regions that are particularly vulnerable to stress, including the amygdala, prefrontal cortex, and hippocampus, which may underlie stress-induced impairments in extinction. We also discuss some of the stress-induced neurochemical and molecular alterations in these brain regions that are associated with extinction deficits, and the potential for targeting these changes to prevent or reverse impaired extinction. A better understanding of the neurobiological basis of stress effects on extinction promises to yield novel approaches to improving therapeutic outcomes for PTSD and other anxiety and trauma-related disorders. PMID:26105142

Estrogen restores brain insulin sensitivity in ovariectomized non-obese rats, but not in ovariectomized obese rats.

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Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2014-06-01

We previously demonstrated that obesity caused the reduction of peripheral and brain insulin sensitivity and that estrogen therapy improved these defects. However, the beneficial effect of estrogen on brain insulin sensitivity and oxidative stress in either ovariectomy alone or ovariectomy with obesity models has not been determined. We hypothesized that ovariectomy alone or ovariectomy with obesity reduces brain insulin sensitivity and increases brain oxidative stress, which are reversed by estrogen treatment. Thirty female rats were assigned as either sham-operated or ovariectomized. After the surgery, each group was fed either a normal diet or high-fat diet for 12 weeks. At week 13, rats in each group received either the vehicle or estradiol for 30 days. At week 16, blood and brain were collected for determining the peripheral and brain insulin sensitivity as well as brain oxidative stress. We found that ovariectomized rats and high-fat diet fed rats incurred obesity, reduced peripheral and brain insulin sensitivity, and increased brain oxidative stress. Estrogen ameliorated peripheral insulin sensitivity in these rats. However, the beneficial effect of estrogen on brain insulin sensitivity and brain oxidative stress was observed only in ovariectomized normal diet-fed rats, but not in ovariectomized high fat diet-fed rats. Our results suggested that reduced brain insulin sensitivity and increased brain oxidative stress occurred after either ovariectomy or obesity. However, the reduced brain insulin sensitivity and the increased brain oxidative stress in ovariectomy with obesity could not be ameliorated by estrogen treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Oxidative stress following traumatic brain injury: enhancement of ...

African Journals Online (AJOL)

neuronal loss following traumatic brain injury and presents experimental and clinical evidence of the role of exogenous antioxidants as neuroprotectants. Method: We reviewed published literature on reactive oxygen species and their role in experimental and clinical brain injuries in journals and the Internet using Yahoo ...

99mTc-ECD brain SPECT in patients with Moyamoya disease: a reflection of cerebral perfusion status at tissue level in the disease process

International Nuclear Information System (INIS)

Kashyap, Raghava; Mittal, Bhagwant Rai; Sunil, Hejjaji Venkataramarao; Bhattacharya, Anish; Singh, Baljinder; Mukherjee, Kanchan Kumar; Gupta, Sunil Kumar

2011-01-01

Moyamoya disease is a rare, progressive cerebrovascular disorder caused by intracranial stenosis of the circle of Willis, resulting in successive ischemic events. Computed tomography (CT) and magnetic resonance imaging (MRI) play a major role in diagnosis. The aim of the study was to describe the spectrum of findings on brain SPECT in patients with Moyamoya disease and to compare the findings with other investigations. 99m Tc-ECD SPECT scans of seventeen patients (7 children and 10 adults) were analysed to study the brain perfusion. Features of Moyamoya disease were detected on DSA in 11 patients, CTA in one, MR angiography in one patient. Brain perfusion SPECT analysis showed unilateral perfusion defects in 11 patients, normal perfusion in 2 and bilateral defects in 4 patients. No perfusion defects despite bilateral vascular changes were noted in one patient. Cerebral infarcts were detected on MRI unilaterally in three subjects while multiple infarcts were identified in one. 99m Tc-ECD Brain SPECT showed perfusion defects that were more extensive compared to those detected on MRI. Post acetazolamide studies for assessment of cerebrovascular reserve were done in three patients. Two of them showed good cerebrovascular reserve (>1). Follow-up studies post-surgical procedures (Myo-dura synangiosis) done in two patients showed partial resolution of perfusion defects in the involved areas. Brain perfusion scintigraphy is an important adjunct in evaluation of patients with Moyamoya disease yielding information about the direct end results of the pathology in the vessels and also prognostic information. (author)

Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

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Bock, J; Breuer, S; Poeggel, G; Braun, K

2017-03-01

In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

Upregulation of transcription factor NRF2-mediated oxidative stress response pathway in rat brain under short-term chronic hypobaric hypoxia.

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Sethy, Niroj Kumar; Singh, Manjulata; Kumar, Rajesh; Ilavazhagan, Govindasamy; Bhargava, Kalpana

2011-03-01

Exposure to high altitude (and thus hypobaric hypoxia) induces electrophysiological, metabolic, and morphological modifications in the brain leading to several neurological clinical syndromes. Despite the known fact that hypoxia episodes in brain are a common factor for many neuropathologies, limited information is available on the underlying cellular and molecular mechanisms. In this study, we investigated the temporal effect of short-term (0-12 h) chronic hypobaric hypoxia on global gene expression of rat brain followed by detailed canonical pathway analysis and regulatory network identification. Our analysis revealed significant alteration of 33, 17, 53, 81, and 296 genes (p stress response pathway and genes were detected at all time points suggesting activation of NRF2-ARE antioxidant defense system. The results were further validated by assessing the expression levels of selected genes in temporal as well as brain regions with quantitative RT-PCR and western blot. In conclusion, our whole brain approach with temporal monitoring of gene expression patterns during hypobaric hypoxia has resulted in (1) deciphering sequence of pathways and signaling networks activated during onset of hypoxia, and (2) elucidation of NRF2-orchestrated antioxidant response as a major intrinsic defense mechanism. The results of this study will aid in better understanding and management of hypoxia-induced brain pathologies.

mammalian brain system

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Alan Kania

2014-06-01

Full Text Available Relaxin-3, a member of the relaxin peptide family, was discovered in 2001 as a homologue of relaxin – a well-known reproductive hormone. However, it is the brain which turned out to be a major expression site of this newly discovered peptide. Both its molecular structure and expression pattern were shown to be very conserved among vertebrates. Extensive research carried out since the discovery of relaxin-3 contributed to the significant progress in our knowledge regarding this neuropeptide. The endogenous relaxin-3 receptor (RXFP3 was identified and the anatomy of the yet uncharacterized mammalian brain system was described, with nucleus incertus as the main center of relaxin-3 expression. Not only its diffusive projections throughout the whole brain, which reach various brain structures such as the hippocampus, septum, intergeniculate leaflet or amygdala, but also functional studies of the relaxin-3/RXFP3 signaling system, allowed this brain network to be classified as one of the ascending nonspecific brain systems. Thus far, research depicts the connection of relaxin-3 with phenomena such as feeding behavior, spatial memory, sleep/wake cycle or modulation of pituitary gland hormone secretion. Responsiveness of relaxin-3 neurons to stress factors and the strong orexigenic effect exerted by this peptide suggest its participation in modulation of feeding by stress, in particular of the chronic type. The discovery of relaxin-3 opened a new research field which will contribute to our better understanding of the neurobiological basis of feeding disorders.

Statistical image analysis of cerebral blood flow in moyamoya disease

International Nuclear Information System (INIS)

Yamada, Masaru; Yuzawa, Izumi; Suzuki, Sachio; Kurata, Akira; Fujii, Kiyotaka; Asano, Yuji

2007-01-01

The Summary of this study was to investigate pathophysiology of moyamoya disease, we analyzed brain single photon emission tomography (SPECT) images of patients with this disease by using interface software for a 3-dimensional (3D) data extraction format. Presenting symptoms were transient ischemic attack (TIA) in 21 patients and hemorrhage in 6 patients. All the patients underwent brain SPECT scan of 123 I-iofetamine (IMP) at rest and after acetazolamide challenge (17 mg/kg iv, 2-day method). Cerebral blood flow (CBF) was quantitatively measured using arterial blood sampling and an autoradiography model. The group of the patients who presented with TIAs showed decreased CBF in the frontal lobe at rest compared to that of patients with hemorrhage, but Z-score ((mean-patient data)/ standard deviation (SD)) did not reach statistical significance. Significant CBF decrease after acetazolamide challenge was observed in a wider cerebral cortical area in the TIA group than in the hemorrhagic group. The brain region of hemodynamic ischemia (stage II) correlated well with the responsible cortical area for clinical symptoms of TIA. A hemodynamic ischemia stage image clearly represented recovery of reserve capacity after bypass surgery. Statistical evaluation of SPECT may be useful to understand and clarify the pathophysiology of this disease. (author)

Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

International Nuclear Information System (INIS)

Kodavanti, Prasada Rao S.; Royland, Joyce E.; Richards, Judy E.; Besas, Jonathan; MacPhail, Robert C.

2011-01-01

The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), γ-glutamylcysteine synthetase (γ-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at − 80 °C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure resulted in oxidative

Silica nanoparticles mediated neuronal cell death in corpus striatum of rat brain: implication of mitochondrial, endoplasmic reticulum and oxidative stress

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Parveen, Arshiya; Rizvi, Syed Husain Mustafa; Mahdi, Farzana; Tripathi, Sandeep; Ahmad, Iqbal; Shukla, Rajendra K.; Khanna, Vinay K.; Singh, Ranjana; Patel, Devendra K.; Mahdi, Abbas Ali

2014-11-01

Extensive uses of silica nanoparticles (SiNPs) in biomedical and industrial fields have increased the risk of exposure, resulting concerns about their safety. We focussed on some of the safety aspects by studying neurobehavioural impairment, oxidative stress (OS), neurochemical and ultrastructural changes in corpus striatum (CS) of male Wistar rats exposed to 80-nm SiNPs. Moreover, its role in inducing mitochondrial and endoplasmic reticulum (ER) stress-mediated neuronal apoptosis was also investigated. The results demonstrated impairment in neurobehavioural indices, and a significant increase in lipid peroxide levels (LPO), hydrogen peroxide (H2O2), superoxide (O2 -) and protein carbonyl content, whereas there was a significant decrease in the activities of the enzymes, manganese superoxide dismutase (Mn SOD), glutathione peroxidase (GPx), catalase (CAT) and reduced glutathione (GSH) content, suggesting impaired antioxidant defence system. Protein (cytochrome c, Bcl-2, Bax, p53, caspase-3, caspase 12 and CHOP/Gadd153) and mRNA (Bcl-2, Bax, p53 and CHOP/Gadd153, cytochrome c) expression studies of mitochondrial and ER stress-related apoptotic factors suggested that both the cell organelles were involved in OS-mediated apoptosis in treated rat brain CS. Moreover, electron microscopic studies clearly showed mitochondrial and ER dysfunction. In conclusion, the result of the study suggested that subchronic SiNPs' exposure has the potential to alter the behavioural activity and also to bring about changes in biochemical, neurochemical and ultrastructural profiles in CS region of rat brain. Furthermore, we also report SiNPs-induced apoptosis in CS, through mitochondrial and ER stress-mediated signalling.

Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice.

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Burokas, Aurelijus; Arboleya, Silvia; Moloney, Rachel D; Peterson, Veronica L; Murphy, Kiera; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

2017-10-01

The realization that the microbiota-gut-brain axis plays a critical role in health and disease, including neuropsychiatric disorders, is rapidly advancing. Nurturing a beneficial gut microbiome with prebiotics, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), is an appealing but underinvestigated microbiota manipulation. Here we tested whether chronic prebiotic treatment modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior. C57BL/6J male mice were administered FOS, GOS, or a combination of FOS+GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS+GOS- or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed. Chronic prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic effects. Moreover, the administration of GOS and the FOS+GOS combination reduced stress-induced corticosterone release. Prebiotics modified specific gene expression in the hippocampus and hypothalamus. Regarding short-chain fatty acid concentrations, prebiotic administration increased cecal acetate and propionate and reduced isobutyrate concentrations, changes that correlated significantly with the positive effects seen on behavior. Moreover, FOS+GOS reduced chronic stress-induced elevations in corticosterone and proinflammatory cytokine levels and depression-like and anxiety-like behavior in addition to normalizing the effects of stress on the microbiota. Taken together, these data strongly suggest a beneficial role of prebiotic treatment for stress-related behaviors. These findings strengthen the evidence base supporting therapeutic targeting of the gut microbiota for brain-gut axis disorders, opening new avenues in the field of nutritional neuropsychopharmacology. Copyright © 2017 Society of Biological Psychiatry. Published by

How the selfish brain organizes its supply and demand.

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Hitze, Britta; Hubold, Christian; van Dyken, Regina; Schlichting, Kristin; Lehnert, Hendrik; Entringer, Sonja; Peters, Achim

2010-01-01

During acute mental stress, the energy supply to the human brain increases by 12%. To determine how the brain controls this demand for energy, 40 healthy young men participated in two sessions (stress induced by the Trier Social Stress Test and non-stress intervention). Subjects were randomly assigned to four different experimental groups according to the energy provided during or after stress intervention (rich buffet, meager salad, dextrose-infusion and lactate-infusion). Blood samples were frequently taken and subjects rated their autonomic and neuroglycopenic symptoms by standard questionnaires. We found that stress increased carbohydrate intake from a rich buffet by 34 g (from 149 +/- 13 g in the non-stress session to 183 +/- 16 g in the stress session; P 4.0 +/- 1.3 vs. 39.8 +/- 7.7 pmol/l; P supply (regardless of its character, i.e., rich buffet or energy infusions) was shown to counteract a neuroglycopenic state that developed during stress. Exogenous energy did not dampen the sympatho-adrenal stress-responses. We conclude that the brain under stressful conditions demands for energy from the body by using a mechanism, which we refer to as "cerebral insulin suppression" and in so doing it can satisfy its excessive needs.