Chronicle of a death foretold: a case of catastrophic vascular Behcet's disease.

PubMed

Planer, David; Leibowitz, David; Elitzur, Yair; Korach, Amit; Hiller, Nurith; Chajek-Shaul, Tova

2007-03-01

A 20-year-old man with Behcet's disease characterized by recurrent arterial aneurysms presented with a new aortic root aneurysm. This patient previously had aneurysms of the coronary arteries and vein, as well as ruptured renal artery aneurysm. Chronic maintenance immunosuppressive therapy was recommended due to the catastrophic nature of the disease, which the patient refused to take. The patient died shortly after admission. This case demonstrates the unique catastrophic natural history of vascular Behcet's disease with recurrent life-threatening arterial events, and this case stresses the therapeutic dilemma of maintenance immunosuppressive therapy in selected patients.

Surgical lung biopsy to diagnose Behcet's vasculitis with adult respiratory distress syndrome.

PubMed

Vydyula, Ravikanth; Allred, Charles; Huartado, Mariana; Mina, Bushra

2014-10-01

A 34-year-old female presented with fever and abdominal pain. Past medical history includes Crohn's and Behcet's disease. Examination revealed multiple skin ulcerations, oral aphthae, and bilateral coarse rales. She developed respiratory distress with diffuse bilateral alveolar infiltrates on chest radiograph requiring intubation. PaO2/FiO2 ratio was 132. The chest computed tomography revealed extensive nodular and patchy ground-glass opacities. Bronchoalveolar lavage demonstrated a predominance of neutrophils. Methylprednisolone 60 mg every 6 h and broad-spectrum antimicrobials were initiated. No infectious etiologies were identified. Surgical lung biopsy demonstrated diffuse alveolar damage (DAD) mixed with lymphocytic and necrotizing vasculitis with multiple small infarcts and thrombi consistent with Behcet's vasculitis. As she improved, steroids were tapered and discharged home on oral cyclophosphamide. Pulmonary involvement in Behcet's is unusual and commonly manifests as pulmonary artery aneurysms, thrombosis, infarction, and hemorrhage. Lung biopsy findings demonstrating DAD are consistent with the clinical diagnosis of adult respiratory distress syndrome. The additional findings of necrotizing vasculitis and infarcts may have led to DAD.

Validation and reliability of a Behcet's Syndrome Activity Scale in Korea.

PubMed

Choi, Hyo Jin; Seo, Mi Ryoung; Ryu, Hee Jung; Baek, Han Joo

2016-01-01

We prepared a cross-cultural adaptation of the Behcet's Syndrome Activity Scale (BSAS) and evaluated its reliability and validity in Korea. Fifty patients with Behcet's disease (BD) who attended the Rheumatology Clinic of Gachon University Gil Medical Center were included in this study. The first BSAS questionnaire was administered at each clinic visit, and the second questionnaire was completed at home within 24 hours of the visit. A Behcet's Disease Current Activity Form (BDCAF) and a Behcet's Disease Quality of Life (BDQOL) form were also given to patients. The test-retest reliability was analyzed by intraclass correlation coefficients (ICC). To assess the validity, the total BSAS score was compared with the BDCAF score, the patient/physician global assessment, and the BDQOL by Spearman rank correlation. Twelve males and 38 females were enrolled. The mean age was 48.5 years and the mean disease duration was 6.7 years. Thirty-eight patients (76.0%) returned the questionnaire by mail. For the test-retest reliability, the two assessments were significantly correlated on all 10 items of the BSAS questionnaire (p < 0.05) and the total BSAS score (ICC, 0.925; p < 0.001). The total BSAS score was statistically correlated with the BDQOL, BDCAF, and patient/physician global assessment (p < 0.01). The Korean version of BSAS is a reliable and valid instrument to measure BD activity.

Delayed habituation in Behcet's disease.

PubMed

Gulturk, Sefa; Akyol, Melih; Kececi, Hulusi; Ozcelik, Sedat; Cinar, Ziynet; Demirkazik, Ayse

2008-01-01

The autonomic nervous system in Behcet's patients may be affected due to various reasons. This entity may be detected with the measurement of the electrodermal activities, heart rate variability and pupillometric methods. Habituation is one of the implicit forms of learning and memory and the loss of habituation can reveal pathological changes in the synaptic regions. To determine whether there is a functional decrease in the synaptic effectiveness (habituation) of the pathways to sympathetic neurons that had been repeatedly activated in Behcet's. Twelve patients with Behcet's disease and 12 healthy controls were included in the study. Sympathetic skin potential (SSP) records were taken at normal room temperature in a quiet place within a Faraday cage. Sixteen square wave single shock impulses (duration: 1200 ms, strength: 5 mA) were applied on each case. After the 1st stimulus, the SSP amplitudes were lower in the patients compared to the controls (P<0.001, t value=7.69). There was no significant differences among the SSP amplitudes after the 13th impulse in the patients (P>0.05). Whereas there was no significant differences among the SSP amplitudes after the 9th impulse in the controls (P>0.05). The habituation rate of the SSP after consecutive impulses was slowest in the patients compared to controls (P<0.001, t value=12.39). There is a delayed habituation in Behcet's disease and that may due to pathologic changes with vasculitis through their peripheral nerves.

[Behcet syndrome: thirty comments with lung and vascular injury of peripheral vessels].

PubMed

Sekkach, Youssef; Elomri, Naoual; Jira, Mohamed; Elqatni, Mohamed; Fatihi, Jamal; Mekouar, Fadwa; Smaali, Jihane; Badaoui, Mohamed; Hammi, Salaheddine; Amezyane, Taoufik; Abouzahir, Ali; Khattabi, Abdessadek El; Ghafir, Driss

2012-02-01

Behcet's disease is a systematic vasculitis of unknown cause, characterized essentially by eye, cutaneous, articular, neurological and vascular manifestations. We retrospectively analysed the Behcet's disease cases that were followed up in our ward from January 2000 to January 2009. The inclusion criteria were those of International Study Group on Behçet's disease (aphthosis mouth was required). Data were retrieved and analysed with two softwares (Access(®) and Epi Info(®)). We observed 30 cases with vascular lesions on a series of 92 patients with Behcet's disease. Most patients were male, with an average age around 40. The venous manifestations, concerning essentially the lower limbs (deep and superficial thrombosis) were found at 27 patients (90 %), and the average of age during the appearance of the venous lesions was 40 years. Arterial lesions appear more late in 13 patients (43 %) (average of age 43 years). We noted, on the other hand, 11 cases of aneurysms and five cases of arterial thrombosis. The use of corticosteroids was necessary in all cases in association with the others drugs (anticoagulants, colchicine, immunosuppressors). Among the patients having had aneurysms, six were treated surgically. The outcome was favorable for most patients. Two patients had pulmonary embolism and two post-surgery complications. One patient died in the consequences of an intragastric break of an aneurysm of the abdominal aorta. The vascular involvement in Behcet's disease is manifested primarily by thrombophlebitis. Achieving blood pressure, less common, is problematic therapeutic because of the recurrent and life threatening. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Interferon alpha-2a treatment for refractory Behcet uveitis in Korean patients.

PubMed

Lee, Ji Hwan; Lee, Christopher Seungkyu; Lee, Sung Chul

2018-02-20

To evaluate therapeutic outcomes of interferon alpha-2a (IFNα2a) treatment in patients with Behcet's disease who were refractory to immunosuppressive agents. This retrospective case series reviewed the medical records of 5 patients with refractory Behcet uveitis from January 2011 to February 2017. IFNα2a was administered at a dose of 3 million IU 3 times per week. Clinical response, relapse rate, and change of visual acuity were evaluated. The mean age of patients was 39.60 ± 9.21 years, and the median treatment duration was 6 months. Four of the 5 patients (80%) presented with responses to IFNα2a without any uveitis attack during the treatment period. The mean number of uveitis attacks/year per patient during the treatment was 0.40 ± 0.89. The mean log of the Minimum Angle of Resolution visual acuity improved from 1.44 ± 0.38 at baseline to 1.02 ± 0.58 at the final follow up. IFNα2a is an effective therapy for Behcet uveitis refractory to conventional immunosuppressants in Korean patients.

Durability of aneurysm treatments in patients with active Behcet's disease.

PubMed

Elsharawy, Mohamed A; Elsaid, Aymen; Al-Dhafery, Bander; Alghnimi, Ibrahim; Almabyouq, Fatimah

2016-10-01

Aneurysms in Behcet's disease are rare, serious, and recurrent. To achieve durable treatment, patients should receive immunosuppressive therapy before intervention to induce remission. We present early and long-term results of emergency cases of active Behcet's disease, which did not permit waiting for suppressive treatment. The study was undertaken on all cases admitted to the vascular unit, King Fahd Hospital of University for aneurysm treatment in patients with active Behcet's disease over about 10 years. All patients had exclusion of the aneurysm either by open surgery or endovascular intervention. Morbidities and mortality were recorded within the hospital admission and on the follow-up. During the study period, three cases were included. All interventions were successful and lifesaving. However, two cases, treated with surgical interposition grafts, were blocked in the intermediate term follow-up (2-12 months) and one case, treated with endovascular treatment, complicated with pseudoaneurysm at femoral puncture site after six months. Although early results were good, intermediate ones were not satisfactory because of progressive graft thrombosis and formation of new aneurysms. Awareness of these rare cases help for early identification and proper immunosuppressive before emergency vascular intervention is warranted. © The Author(s) 2015.

Incidence of secondary glaucoma in behcet disease.

PubMed

Elgin, Ufuk; Berker, Nilufer; Batman, Aygen

2004-12-01

To determine the incidence of secondary glaucoma in Behcet disease. A total of 230 eyes of 129 patients with Behcet disease, were examined in uveitis and glaucoma clinics of Ankara Social Security Eye Hospital between January 1997 and September 2002. The data from all patients were investigated both retrospectively and prospectively. The mean age of 129 patients was 34.2 +/- 7.4 years (range, 18 to 55 years). In 22 patients (17%), the disease was diagnosed on the basis of the ocular findings, while in the remaining 107 patients (83%), the period between the diagnosis of Behcet disease and the onset of the ocular symptoms was 23.3 +/- 17 months (range, 1 month to 5.3 years); 122 eyes (53%) had the episodes of acute recurrent iridocyclitis, while 108 eyes (47%) developed chronic posterior uveitis, including vitreitis, retinitis, vasculitis, or optic nerve involvement. Secondary glaucoma was diagnosed in 25 eyes (10.9%); 11 eyes (44%) with steroid or inflammation induced open angle glaucoma, 6 eyes (24%) with partial angle-closure glaucoma and peripheral anterior synechiae, 5 eyes (20%) with angle closure glaucoma, peripheral anterior synechiae, and pupil block and 3 eyes (12%) with neovascular glaucoma. The treatments included YAG-laser iridotomy in 5 eyes, diode-laser cyclodestruction in 3 eyes, primary trabeculectomies with mitomycin-c in 4 eyes, secondary trabeculectomies with mitomycin-c in 2 eyes, Ahmed valve implantations in 2 eyes, and cyclocryotherapy in 3 eyes. We suggest that secondary glaucoma is a common and serious complication of Behcet disease. It develops as a result of multiple factors, generally triggered by recurrent intraocular inflammation. Early recognition and treatment of these factors have vital importance to avoid the visual morbidity.

Lipid Storage Myopathy in Behçet's Disease: A Rare Cause of Elevated Serum Creatine Kinases Levels

PubMed Central

Yilmaz, Sedat; Cinar, Muhammet; Karslioglu, Yıldırım; Simsek, Ismail; Erdem, Hakan; Pay, Salih; Dinc, Ayhan

2012-01-01

Muscular involvement in Behçet's disease is rare and there are only a few case reports in the literature. The causes of elevated muscle enzymes in a patient with Behcet's disease are many, including myositis, drug-induced myopathy, metabolic myopathy, and the disease itself. We herein have defined an algorithmic approach to a patient with Behcet's disease and elevated muscle enzymes and report a case of coexisting of lipid storage myopathy. PMID:22937450

Echocardiographic manifestations of Adamantiades-Behcet's disease.

PubMed

Leibowitz, David; Planer, David; Chajek-Shaul, Tova

2007-12-01

Adamantiades-Behcet disease (ABD) is a multisystemic, chronic inflammatory disorder of unknown etiology with diffuse clinical manifestations including those involving the cardiovascular system. While the disease is most prevalent in the Mediterranean region, the Middle East and the Far East, its prevalence is increasing in Western countries due to migration patterns. Cardiovascular involvement in ABD may include myocardial disease, venous disease and disease of the aorta and great vessels. Use of echocardiography in these patients is crucial to assess their pathology and in this article we review the spectrum of echocardiographic findings in patients with ABD.

Observational Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

ClinicalTrials.gov

2016-09-26

Other Specified Inflammatory Disorders of Skin or Subcutaneous Tissue; Pyoderma Gangrenosum; Erosive Pustular Dermatosis of the Scalp; Sweet's Syndrome; Behcet's Disease; Bowel-associated Dermatosis-arthritis Syndrome; Pustular Psoriasis; Acute Generalized Exanthematous Pustulosis; Keratoderma Blenorrhagicum; Sneddon-Wilkinson Disease; IgA Pemphigus; Amicrobial Pustulosis of the Folds; Infantile Acropustulosis; Transient Neonatal Pustulosis; Neutrophilic Eccrine Hidradenitis; Rheumatoid Neutrophilic Dermatitis; Neutrophilic Urticaria; Still's Disease; Erythema Marginatum; Unclassified Periodic Fever Syndromes / Autoinflammatory Syndromes; Dermatitis Herpetiformis; Linear IgA Bullous Dermatosis; Bullous Systemic Lupus Erythematosus; Inflammatory Epidermolysis Bullosa Aquisita; Neutrophilic Dermatosis of the Dorsal Hands (Pustular Vasculitis); Small Vessel Vasculitis Including Urticarial Vasculitis; Erythema Elevatum Diutinum; Medium Vessel Vasculitis

Cross-cultural adaptation and validation of the Behcet's Disease Current Activity Form in Korea.

PubMed

Choi, Hyo Jin; Seo, Mi Ryoung; Ryu, Hee Jung; Baek, Han Joo

2015-09-01

This study was undertaken to perform a cross-cultural adaptation of the Behcet's Disease Current Activity Form (BDCAF, version 2006) questionnaire to the Korean language and to evaluate its reliability and validity in a population of Korean patients with Behcet's disease (BD). A cross-cultural study was conducted among patients with BD who attended our rheumatology clinic between November 2012 and March 2013. There were 11 males and 35 females in the group. The mean age of the participants was 48.5 years and the mean disease duration was 6.4 years. The first BDCAF questionnaire was completed on arrival and the second assessment was performed 20 minutes later by a different physician. The test-retest reliability was analyzed by computing κ statistics. Kappa scores of > 0.6 indicated a good agreement. To assess the validity, we compared the total BDCAF score with the patient's/clinician's perception of disease activity and the Korean version of the Behcet's Disease Quality of Life (BDQOL). For the test-retest reliability, good agreements were achieved on items such as headache, oral/genital ulceration, erythema, skin pustules, arthralgia, nausea/vomiting/abdominal pain, and diarrhea with altered/frank blood per rectum. Moderate agreement was observed for eye and nervous system involvement. We achieved a fair agreement for arthritis and major vessel involvement. Significant correlations were obtained between the total BDCAF score with the BDQOL and the patient's/clinician's perception of disease activity p < 0.05). The Korean version of the BDCAF is a reliable and valid instrument for measuring current disease activity in Korean BD patients.

The Role of Th17 Cells in the Pathogenesis of Behcet's Disease.

PubMed

Nanke, Yuki; Yago, Toru; Kotake, Shigeru

2017-07-21

Behcet's disease (BD) is a polysymptomatic and recurrent systemic vasculitis with a chronic course and unknown cause. The pathogenesis of BD has not been fully elucidated; however, BD has been considered to be a typical Th1-mediated inflammatory disease, characterized by elevated levels of Th1 cytokines such as IFN-γ, IL-2, and TNF-α. Recently, some studies reported that Th17-associated cytokines were increased in BD; thus, Th17 cells and the IL17/IL23 pathway may play important roles in the pathogenesis of BD. In this chapter, we focus on the pathogenic role of Th17 cells in BD.

Diagnosis/Classification Criteria for Behcet's Disease

PubMed Central

Davatchi, Fereydoun

2012-01-01

Historical Background. The ISG criteria for Behcet's, created in 1990, have excellent specificity, but lack sensitivity. The International Criteria for Behcet's Disease (ICBD) was created in 2006, as replacement to ISG. The aim of this study was to compare their performance. ISG and ICBD Criteria. For ISG oral aphthosis is mandatory. The presence of any two of the following (genital aphthosis, skin lesions, eye lesions, and positive pathergy test) will diagnose/classify the patient as BD. For ICBD, vascular lesions were added, while oral aphthosis is no more mandatory. Getting 3 or more points diagnose/classify the patient as BD (genital aphthosis 2 points, eye lesions 2 points, and the remaining each one point). Performance and Comparison of ISG and ICBD. Their sensitivity, specificity, and accuracy (percent agreement), were tested in three independent cohort of patients from Far-East (China), Middle-East (Iran), and Europe (Germany). The sensitivity for ISG was respectively 65.4%, 78.1%, 83.7% and for ICBD 87%, 98.2%, and 96.5%. The specificity for ISG was 99.2%, 98.8%, 89.5% and for ICBD 94.1%, 95.6%, and 73.7%. The accuracy for ISG was 74.2%, 85.5%, 85.5% and for ICBD 88.9%, 97.3%, and 89.5%. Conclusion. ICBD has better sensitivity, and accuracy than ISG. PMID:21961081

Educational Needs of Patients With Systemic Vasculitis

ClinicalTrials.gov

2014-07-11

Behcet's Disease; Churg-Strauss Syndrome; Vasculitis, Central Nervous System; Giant Cell Arteritis; Wegener Granulomatosis; Henoch-Schoenlein Purpura; Microscopic Polyangiitis; Polyarteritis Nodosa; Takayasu's Arteritis

Behcet's Disease

MedlinePlus

... this research; and the dissemination of information on research progress in these diseases. Contact Us NIAMS Archive Viewers and Players Social Media Moderation Policy FOIA Privacy Statement Accessibility Disclaimer Digital Strategy ...

Impact of Vasculitis on Employment and Income

ClinicalTrials.gov

2016-01-26

Vasculitis; Systemic Vasculitis; Behcet's Disease; CNS Vasculitis; Cryoglobulinemic Vasculitis; Eosinophilic Granulomatosis; Temporal Arteritis; Wegener Granulomatosis; Henoch-Schoenlein Purpura; Microscopic Polyangiitis; Polyarteritis Nodosa (PAN); Takayasu's Arteritis; Urticarial Vasculitis

Thalidomide

MedlinePlus

... biology of immunomodulatory drugs (IMiDs) in cancer. Pharmacology & Therapeutics. 2012;136:56. Thalomid (prescribing information). Summit, N. ... Behcet disease. In: Treatment of Skin Disease: Comprehensive Therapeutic Strategies. 4th ed. Philadelphia, Pa.: Saunders Elsevier; 2014. ...

Reproductive Health in Men and Women With Vasculitis

ClinicalTrials.gov

2014-06-25

Giant Cell Arteritis; Takayasu's Arteritis; Polyarteritis Nodosa; Wegener's Granulomatosis; Microscopic Polyangiitis; Churg-Strauss Syndrome; Behcet's Disease; Kawasaki Disease; Henoch-schoenlein Purpura; Vasculitis, Central Nervous System; Drug-induced Necrotizing Vasculitis

Putative Role of Serum Amyloid-A and Proinflammatory Cytokines as Biomarkers for Behcet's Disease

PubMed Central

Lopalco, Giuseppe; Lucherini, Orso Maria; Vitale, Antonio; Talarico, Rosaria; Lopalco, Antonio; Galeazzi, Mauro; Lapadula, Giovanni; Cantarini, Luca; Iannone, Florenzo

2015-01-01

Abstract Behcet's disease (BD) is a multisystemic disorder of unknown etiology characterized by relapsing oral–genital ulcers, uveitis, and involvement of vascular, gastrointestinal, neurological, and musculoskeletal system. Although disease pathogenesis is still unclear, both innate and adaptive immunity have shown to play a pivotal role, and multiple proinflammatory cytokines seem to be involved in different pathogenic pathways that eventually lead to tissue damage. The aims of our study were to evaluate serum cytokines levels of IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, CXCL9, and SAA levels in patients with BD, in comparison to healthy controls (HC), and to correlate their levels to disease activity. We included 78 serum samples obtained from 58 BD patients and analyzed a set of proinflammatory cytokines including IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, and CXCL9 by multiplex bead analysis as well as SAA by enzyme-linked immunosorbent assay. Compared to HC, BD patients showed elevated cytokine levels of IL-8, IL-18, IFN-α2a, and IL-6, and low levels of CXCL11. BD patients with SAA serum levels >20 mg/L showed higher levels of proinflammatory markers than HC or group with SAA ≤20 mg/L. IL-18, IFN-α2a, and IL-6 were higher in BD group with SAA >20 mg/L than HC, while IL-8 and CXCL9 levels were higher than in patients with SAA ≤20 mg/L and HC. Active BD patients with SAA >20 mg/L exhibited elevated levels of inflammatory mediators, suggesting that may exist a relationship between SAA and proinflammatory cytokines in the intricate scenario of BD pathogenesis. PMID:26496336

Behcet's disease.

PubMed

Suzuki Kurokawa, M; Suzuki, N

2004-09-01

Behcet's disease (BD) is a systemic disorder of recurrent acute inflammation, characterized by major symptoms of oral aphthous ulcers, uveitis, skin lesions and genital ulcers. Involvement of intestines, vessels, and central nervous system (CNS) sometimes leads to a poor prognosis. Patients with BD are known to distribute along the ancient Silk Road. The incidence is relatively higher from eastern Asia to the Mediterranean area as roughly 1-10 patients in 10,000 people, whereas only 1-2 patients in 1,000,000 people in UK and North America. Although etiology of the disease is still unknown, high prevalence of HLA-B51, increased expression of heat shock protein 60 and Th1 dominant immune responses in the patients are considered important in its pathogenesis. Non-infectious neutrophil activation and infection with Streptococcus sanguis and herpes simplex virus would also be associated. Because BD lacks any pathognomonic symptoms and laboratory findings, the diagnosis relies largely upon the criteria proposed by the International Study Group for Behcet's disease in 1990. In Japan, the diagnosis was also made according to the Japanese criteria revised in 1987. Recently, the Behcet's Disease Research Committee of Japan again revised the Japanese criteria in 2003 to avoid overdiagnosis. The new Japanese criteria are introduced in this review. Differential diagnosis excluding Sweet's disease, pemphigus, erythema nodosum and Crohn's disease is important, and positive laboratory data for pathergy test, prick test for dead Streptococci and HLA-B51 are emphasized to make appropriate diagnosis in these criteria. Pathological findings of the disease-affected site such as erythematous nodosum is also stressed. Treatment for the disease has been chosen according to the clinical symptoms. Non-steroidal anti-inflammatory drugs, immunosuppressants, corticosteroids and colchicine are basically introduced. Recently, effects of interferon-alpha/beta, anti-tumor necrosis factor antibody and thalidomide are encouraging, specifically in treatment for the cases with poor prognosis including eye, intestine, vessel and CNS involvement. Low dose weekly administration of methotraxate looks effective for the cases with CNS involvement. Further studies for elucidation of the etiology, improvement of the diagnostic criteria and development of new therapy are needed to conquer the disease.

Behcet's Disease

MedlinePlus

... Old Silk Route,” which spans the region from Japan and China in the Far East to the ... the disease’s epidemiology is not well understood. In Japan, Behcet’s disease ranks as a leading cause of ...

Vasculitis Pregnancy Registry

ClinicalTrials.gov

2018-04-30

Vasculitis; Behcet's Disease; CNS Vasculitis; Cryoglobulinemic Vasculitis; Eosinophilic Granulomatosis With Polyangiitis (EGPA); Churg-Strauss Syndrome (CSS); Granulomatosis With Polyangiitis (GPA); Wegener's Granulomatosis; IgA Vasculitis; Henoch-Schoenlein Purpura (HSP); Microscopic Polyangiitis (MPA); Polyarteritis Nodosa (PAN); Takayasu Arteritis (TAK); Urticarial Vasculitis; Systemic Vasculitis

Endovascular Treatment of Veno-Occlusive Behcet's Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tekbas, Guven, E-mail: drgtekbas@gmail.com; Oguzkurt, Levent, E-mail: loguzkurt@yahoo.com; Gur, Serkan, E-mail: mserkangur@yahoo.com

Purpose: To retrospectively evaluate the outcome of endovascular treatments for patients with chronic veno-occlusive disease in different vascular beds secondary to Behcet's disease (BD). There are few case reports on the subject, and this is the largest study to date. Materials and Methods: From January 2001 through October 2009, chronic venous occlusions were treated in 10 patients (all male [age range 18-76 years]) with BD using percutaneous transluminal angioplasty and/or stent placement. All patients were symptomatic and had chronic iliofemoral deep venous thrombosis (DVT; n = 5), central venous occlusion (n = 3), or Budd-Chiari syndrome (BCS; n = 2).more » All patients met criteria of the International Study Group on Behcet's Disease. Results: Two of five patients with DVT had unsuccessful recanalization attempts. Three patients had successful recanalization with stent placement. All three veins were occluded within 1 month with unsuccessful reinterventions. Three patients with chronic central venous occlusion had successful recanalization with percutaneous transluminal angioplasty (n = 1) and stent placement (n = 2). Two patients had reocclusion with successful reintervention. Two BCS patients had successful treatment with stent placements. Overall technical success was 69%, and no procedural complications were encountered. None of the patients with chronic DVT had patent veins; however, all patients with central venous occlusion or BCS had patent veins on color Doppler ultrasonography at follow-up ranging from 3 to 48 months after intervention. Conclusion: Endovenous treatment for chronic iliofemoral DVT due to BD had a poor outcome. However, long-term outcome after endovenous treatment for upper-extremity central venous occlusion and BCS syndrome was good.« less

Journey of Patients With Vasculitis From First Symptom to Diagnosis

ClinicalTrials.gov

2018-06-05

Vasculitis; Systemic Vasculitis; Behcet's Disease; CNS Vasculitis; Cryoglobulinemic Vasculitis; Eosinophilic Granulomatous Vasculitis; Temporal Arteritis; Giant Cell Arteritis; Granulomatosis With Polyangiitis; Wegener Granulomatosis; Henoch Schonlein Purpura; IgA Vasculitis; Microscopic Polyangiitis; Polyarteritis Nodosa; Takayasu Arteritis; Urticarial Vasculitis

Induction of Regulatory t Cells by Low Dose il2 in Autoimmune and Inflammatory Diseases

ClinicalTrials.gov

2018-01-10

Rheumatoid Arthritis; Ankylosing Spondylitis; Systemic Lupus Erythematosus; Psoriasis; Behcet's Disease; Wegener's Granulomatosis; Takayasu's Disease; Crohn's Disease; Ulcerative Colitis; Autoimmune Hepatitis; Sclerosing Cholangitis; Gougerot-sjögren; Idiopathic Thrombocytopenic Purpura; Systemic Sclerosis

Biotherapies in inflammatory ocular disorders: Interferons, immunoglobulins, monoclonal antibodies.

PubMed

Saadoun, D; Bodaghi, B; Bienvenu, B; Wechsler, B; Sene, D; Trad, S; Abad, S; Cacoub, P; Kodjikian, L; Sève, P

2013-05-01

Biotherapies used in clinical practice for the treatment of ophthalmologic manifestations of systemic diseases include interferons (IFN), intravenous immunoglobulins (IVIG) and monoclonal antibodies (anti-TNF, anakinra, tocilizumab and rituximab). Several open prospective studies have shown the effectiveness of IFN-α (78 to 98% complete remission) for the treatment of severe uveitis in Behcet's disease. IFN is capable of inducing prolonged remission and continued after his arrest, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behcet's disease. They are almost always (>90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIG are used for the treatment of Kawasaki disease and Birdshot disease. Several open or retrospective studies showed their effectiveness for the treatment of severe and refractory cicatricial pemphigoid. Tolerance of IVIG is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection associated with this biotherapy limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1R) showed interesting results in terms of efficiency in one small open study in Behcet's disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis. Copyright © 2013 Elsevier B.V. All rights reserved.

Methotrexate in ocular manifestations of Behcet's disease: a longitudinal study up to 15 years.

PubMed

Davatchi, Fereydoun; Shams, Hormoz; Shahram, Farhad; Nadji, Abdolhadi; Chams-Davatchi, Cheyda; Sadeghi Abdollahi, Bahar; Faezi, Tahereh; Akhlaghi, Massoomeh; Ashofteh, Farimah

2013-10-01

Ocular manifestations of Behcet's disease (BD) need aggressive treatment to prevent severe loss of vision or blindness. Cytotoxic drugs are the main therapeutic agents and the first line treatment. Methotrexate is the least toxic, used mainly for posterior uveitis. We present here the outcome of eye lesions with methotrexate and prednisolone, in a longitudinal study of up to 15 years, on 682 patients (5447 eye-years of follow-up). Methotrexate was started at 7.5-15 mg/week. Prednisolone was added at 0.5 mg/kg/daily, then adjusted as needed. (i) fulfilling the International Criteria for Behcet's Disease; and (ii) having active posterior uveitis (PU). Visual acuity (VA) was calculated on a scale of 10. Activity indexes were calculated for PU and retinal vasculitis (RV) for each eye. Total Inflammatory Activity Index (TIAI) demonstrating the inflammatory index of both eyes of the patient, and Total Adjusted Disease Activity Index (TADAI) showing both TIAI + VA were also calculated. Overall results: the mean VA improvement was 0.4 (P < 001), PU 1.2 (P < 0.001) and RV 0.6 (P < 0.001). VA improved in 46.5%, PU in 75.4%, and RV in 53.7% of eyes. TIAI improved in 74% of patients and TADAI in 69.4%. VA was aggravated in 37.2%, PU in 11.1%, and RV in 30.3% of eyes. TIAI was aggravated in 17.4% and TADAI in 21.6% of the patients. The remaining kept their baseline values. All parameters improved, PU better than RV. Improvement of VA was the least, mainly due to secondary cataracts. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

DD genotype of ACE gene I/D polymorphism is associated with Behcet disease in a Turkish population.

PubMed

Yigit, Serbülent; Tural, Sengül; Rüstemoglu, Aydin; Inanir, Ahmet; Gul, Ulker; Kalkan, Goknur; Akkanet, Songul; Karakuş, Nevin; Ateş, Omer

2013-01-01

Behcet's disease (BD) is a chronic, multi-systemic and inflammatory disorder. The local renin-angiotensin system (RAS) in the vessel wall plays a role in the endothelial control and contributes to inflammatory processes. Angiotensin-converting enzyme (ACE) is the regulatory component of the RAS. This study was conducted in Turkish patients with BD to determine the frequency of I/D polymorphism genotypes of ACE gene. Genomic DNA obtained from 566 persons (266 patients with BD and 300 healthy controls). ACE gene I/D polymorphism genotypes were determined using polymerase chain reaction using I and D allele-specific primers. There was statistically significant difference between the groups with respect to genotype distribution (p < 0.001). This study is the largest study in Turkish population that ACE gene I/D polymorphism investigated in BD. As a result of this study, ACE gene I/D polymorphism DD genotype could be a genetic marker in BD in Turkish study population.

Role of Brain Perfusion SPECT with 99mTc HMPAO in the Assessment of Response to Drug Therapy in Patients with Autoimmune Vasculitis: A Prospective Study

PubMed Central

Mauro, Liberatore; Manuela, Morreale; Valentina, Megna; Sara, Collorone; Chondrogiannis, Sotirios; Maria, Drudi Francesco; Christos, Anagnostou; Liana, Civitelli; Ada, Francia; Maffione, Anna Margherita; Marzola, Maria Cristina; Rubello, Domenico

2015-01-01

Background: The diagnosis of vasculitis in the brain remains a quite difficult achievement. To the best of our knowledge, there is no imaging method reported in literature which is capable of reaching to a diagnosis of vasculitis with very high sensitivity. Aim: The aim of this study was to determine whether perfusion brain single photon emission computed tomography (SPECT) can be usefully employed in monitoring the treatment of vasculitis, allowing treating only potentially responder patients and avoiding the side effects on patients who do not respond. Materials and Methods: Twenty patients (two males and 18 females) suffering from systemic lupus erythematosus (SLE; n = 5), Behcet's disease (BD; n = 5), undifferentiated vasculitis (UV; n = 5), and Sjogren's syndrome (SS; n = 5) were included in the study. All patients underwent a wide neurological anamnestic investigation, a complete objective neurological examination and SPECT of the brain with 99mTc-hexamethyl-propylene-aminoxime (HMPAO). The brain SPECT was then repeated after appropriate medical treatment. The neurological and neuropsychiatric follow-up was performed at 6 months after the start of the treatment. Results: Overall, the differences between the scintigraphic results obtained after and before the medical treatment indicated a statistically significant increase of the cerebral perfusion (CP). In 19 out of 200 regions of interest (ROI) studied, the difference between pre- and post treatment percentages had negative sign, indicating a worsening of CP. This latter event has occurred six times (five in the same patients) in the UV, 10 times (eight in the same patients) in the SLE, never in BD, and three times (two in the same patient) in the SS. Conclusion: The reported results seem to indicate the possibility of identifying, by the means of a brain SPECT, responder and nonresponder (unchanged or worsened CP) patients, affected by autoimmune vasculitis, to the therapy. PMID:25973400

JAK2 (V617F) mutation is not associated with thrombosis in Behcet syndrome.

PubMed

Ar, M Cem; Hatemi, Gülen; Ekizoğlu, Seda; Bilgen, Hülya; Saçli, Sevgi; Buyru, A Nur; Soysal, Teoman; Ülkü, Birsen; Yazici, Hasan

2012-07-01

The Janus kinase 2(V617F) (JAK2 (V617F)) mutation is an acquired genetic defect that is considered to enhance thrombosis in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Thrombosis is also a well-defined component of Behcet syndrome (BS). The aim of this study was to determine the frequency of JAK2 ( V617F ) mutation in BS-associated thrombosis. A total of 152 patients with BS (62 with thrombosis and 90 without thrombosis) were enrolled. An additional 186 patients with MPNs and 107 healthy blood donors were included to serve as diseased and healthy controls, respectively. None of the patients with BS and healthy controls carried the JAK2 (V617F) mutation, whereas 67% of patients with MPNs were positive for JAK2 ( V617F ). The frequency of thrombosis in patients with MPNs was not statistically different between carriers and non-carriers of JAK2 ( V617F ) mutation. Our data suggest that JAK2 (V617F) is not directly related to thrombosis in MPNs and in other thrombotic entities, such as BS.

Patterns of uveitis in a tertiary eye care center in Iran.

PubMed

Soheilian, Masood; Heidari, Kumars; Yazdani, Shahin; Shahsavari, Mohsen; Ahmadieh, Hamid; Dehghan, Mohammad

2004-12-01

To identify the distribution and characteristics of new uveitis referrals to a tertiary eye care center in Tehran. A three-year prospective study was carried out to obtain information on 544 new patients referred with uveitis. A complete ophthalmologic examination was performed in all cases; a routine set of tests and an additional battery of directed workup were conducted when indicated. Mean age was 32.3 years. There was no significant sex predominance. The most common forms of uveitis were anterior (38.4%) vs. other anatomical forms, chronic (62.1%) vs. acute (28.3%), nongranulomatous (85.5%) vs. granulomatous (14.5%), and noninfectious (83.5%) vs. infectious (16.5%). With regard to etiology, 45.5% were idiopathic, 19.9% were due to specific ocular disease, and 37.3% were associated with systemic disorders. Behcet's disease was the most common noninfectious disease and toxoplasmosis the most common infectious entity. The most prevalent causes were idiopathic, Fuchs' heterochromic iridocylitis, and seronegative spondyloarthropathies in anterior uveitis; toxoplasmosis, Eales disease, and toxocariasis in posterior uveitis; idiopathic, sarcoidosis, and multiple sclerosis in intermediate uveitis; and, finally, Behcet's disease, idiopathic, and Vogt-Koyanagi-Harada syndrome in panuveitis. The most frequent cause in patients under 16 years of age was pars planitis. Over 80% of the patients belonged to middle-to-upper socioeconomic classes. Uveitis significantly affected patients' lives in 63.1% of the cases. Although the current study was performed at a referral center, it may reflect to some extent the different distribution of uveitis in Iran and probably other Middle Eastern countries. Some entities such as presumed ocular histoplasmosis were not found, cytomegalovirus retinitis and birdshot chorioretinopathy were extremely rare, and HLA-B27-associated iridocyclitis was less commonly observed. In contrast, Behcet's disease, Fuchs' heterochromic iridocyclitis, Eales disease, and toxocariasis were among the more prevalent entities.

A variant of CLEC16A gene confers protection for Vogt-Koyanagi-Harada syndrome but not for Behcet's disease in a Chinese Han population.

PubMed

Li, Ke; Hou, Shengping; Qi, Jian; Kijlstra, Aize; Yang, Peizeng

2015-03-01

Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) are two common form of uveitis in China. The aim of this study was to investigate the association of C-type lectin domain family 16, member A (CLEC16A) gene polymorphisms with Vogt-Koyanagi-Harada syndrome and Behcet's disease in a Chinese Han population. A two-stage association study was carried out in 988 VKH syndrome patients，400 BD patients and 976 healthy controls. Eight single nucleotide polymorphisms of CLEC16A gene were determined with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data were analyzed by χ(2) test or Fisher's exact test and corrected for multiple comparisons by the Bonferroni method. The first stage study showed that the frequency of the A allele of rs6498169 was significantly decreased in VKH syndrome patients (Pc = 1.1 × 10(-2), OR = 0.7, 95%CI = 0.6-0.9). No significant association was observed in the other 7 SNPs between VKH syndrome patients and controls. No association was found with BD for the 8 SNPs tested. We further confirmed the association of single nucleotide polymorphism rs6498169 with VKH syndrome in another cohort. Consistent with the first stage study, the combined study showed significantly lower frequencies of the AA genotype and the A allele of rs6498169 in VKH syndrome patients (Pc = 3.5 × 10(-4), OR = 0.6, 95%CI = 0.5-0.7; Pc = 8.2 × 10(-4), OR = 0.8, 95%CI = 0.7-0.9, respectively). In conclusion, the study suggested that a CLEC16A polymorphism may be protective against VKH syndrome in a Chinese Han population. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Comprehensive Proteomics Analysis of the Human Iris Tissue: Ready to Embrace Postgenomics Precision Medicine in Ophthalmology?

PubMed

Murthy, Krishna R; Dammalli, Manjunath; Pinto, Sneha M; Murthy, Kalpana Babu; Nirujogi, Raja Sekhar; Madugundu, Anil K; Dey, Gourav; Subbannayya, Yashwanth; Mishra, Uttam Kumar; Nair, Bipin; Gowda, Harsha; Prasad, T S Keshava

2016-09-01

The annual economic burden of visual disorders in the United States was estimated at $139 billion. Ophthalmology is therefore one of the salient application fields of postgenomics biotechnologies such as proteomics in the pursuit of global precision medicine. Interestingly, the protein composition of the human iris tissue still remains largely unexplored. In this context, the uveal tract constitutes the vascular middle coat of the eye and is formed by the choroid, ciliary body, and iris. The iris forms the anterior most part of the uvea. It is a thin muscular diaphragm with a central perforation called pupil. Inflammation of the uvea is termed uveitis and causes reduced vision or blindness. However, the pathogenesis of the spectrum of diseases causing uveitis is still not very well understood. We investigated the proteome of the iris tissue harvested from healthy donor eyes that were enucleated within 6 h of death using high-resolution Fourier transform mass spectrometry. A total of 4959 nonredundant proteins were identified in the human iris, which included proteins involved in signaling, cell communication, metabolism, immune response, and transport. This study is the first attempt to comprehensively profile the global proteome of the human iris tissue and, thus, offers the potential to facilitate biomedical research into pathological diseases of the uvea such as Behcet's disease, Vogt Koyonagi Harada's disease, and juvenile rheumatoid arthritis. Finally, we make a call to the broader visual health and ophthalmology community that proteomics offers a veritable prospect to obtain a systems scale, functional, and dynamic picture of the eye tissue in health and disease. This knowledge is ultimately pertinent for precision medicine diagnostics and therapeutics innovation to address the pressing needs of the 21st century visual health.

Single center study on ethnic and clinical features of Behcet's disease in Moscow, Russia.

PubMed

Lennikov, Anton; Alekberova, Zemfira; Goloeva, Regina; Kitaichi, Nobuyoshi; Denisov, Lev; Namba, Kenichi; Takeno, Mitsuhiro; Ishigatsubo, Yoshiaki; Mizuki, Nobuhisa; Nasonov, Eugeny; Ishida, Susumu; Ohno, Shigeaki

2015-02-01

For the purpose of investigating Behcet's disease (BD) in Russia, 250 consecutive patients (177 men and 73 women) diagnosed with BD between 1990 and 2010 at the Research Institute of Rheumatology, Russian Academy of Medical Sciences in Moscow were enrolled in this study. The ethnic backgrounds of the patients were reported as follows: 23.2% (58 cases) from Russia, 12.8% (32 cases) from Azerbaijan, 14.4% (36 cases) from Armenia, 8.8% (22 cases) from Chechnya, and 21.6% (55 cases) from Dagestan. The remaining 19.2% (48 cases) were from other regions or of unknown origin. More than half (57.6%) of the Behcet's disease patients originated from Central Asia, specifically Azerbaijan, Armenia, Chechnya, and Dagestan. The mean age at disease onset was 31.5 ± 9.38 (13-60) years old, and the most typical initial manifestations were oral aphthous ulcers. Patients aged 20-39 years old were more commonly affected and displayed a wide clinical spectrum of the disease, with varieties of severe internal organ involvement. The manifestations observed throughout the course of the disease included oral aphthous ulcers (100%), various cutaneous lesions (88.8%), genital ulcers (81.2%), and ocular lesions (54.0%). Besides these, many organs/systems were implicated in patient cases, namely joint (53.2%), vascular (25.2%), neurological (8.0%), gastrointestinal (25.2%), and cardiac (5.6%) systems. Involvements of ocular (p < 0.01) and skin (p < 0.01) lesions were more frequent in men than in women. HLA-B51 and HLA-A26 typing was performed in 127 patients and 508 healthy controls. HLA-B51 was found in 63.0% of BD patients compared to 20.7% of the healthy control subjects (p < 0.001), and HLA-A26 was present in 11.3% of BD patients and 18.9% of the control group. This study shows the presence of BD in Russia, and it is suggested that its prevalence in Central Asian people is much higher than that in White Russian.

Banking brain tissue for research.

PubMed

Klioueva, Natasja; Bovenberg, Jasper; Huitinga, Inge

2017-01-01

Well-characterized human brain tissue is crucial for scientific breakthroughs in research of the human brain and brain diseases. However, the collection, characterization, management, and accessibility of brain human tissue are rather complex. Well-characterized human brain tissue is often provided from private, sometimes small, brain tissue collections by (neuro)pathologic experts. However, to meet the increasing demand for human brain tissue from the scientific community, many professional brain-banking activities aiming at both neurologic and psychiatric diseases as well as healthy controls are currently being initiated worldwide. Professional biobanks are open-access and in many cases run donor programs. They are therefore costly and need effective business plans to guarantee long-term sustainability. Here we discuss the ethical, legal, managerial, and financial aspects of professional brain banks. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of vitro preservation on mechanical properties of brain tissue

NASA Astrophysics Data System (ADS)

Zhang, Wei; Liu, Yi-fan; Liu, Li-fu; Niu, Ying; Ma, Jian-li; Wu, Cheng-wei

2017-05-01

To develop the protective devices for preventing traumatic brain injuries, it requires the accurate characterization of the mechanical properties of brain tissue. For this, it necessary to elucidate the effect of vitro preservation on the mechanical performance of brain tissue as usually the measurements are carried out in vitro. In this paper, the thermal behavior of brain tissue preserved for various period of time was first investigated and the mechanical properties were also measured. Both reveals the deterioration with prolonged preservation duration. The observations of brain tissue slices indicates the brain tissue experiences karyorrhexis and karyorrhexis in sequence, which accounts for the deterioration phenomena.

Decreased expression of the aryl hydrocarbon receptor in ocular Behcet's disease.

PubMed

Wang, Chaokui; Ye, Zi; Kijlstra, Aize; Zhou, Yan; Yang, Peizeng

2014-01-01

Recent studies show that the aryl hydrocarbon receptor (AhR) is involved in immune responses. AhR is activated following interaction with its ligands, such as 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). In this study, we investigated the role of AhR activation by its endogenous ligands in the pathogenesis of ocular Behcet's disease (BD). The expression of AhR was significantly decreased in active BD patients as compared to inactive BD patients and normal controls. Both FICZ and ITE inhibited Th1 and Th17 polarization and induced the expression of IL-22 by PBMCs and by CD4(+)T cells in active BD patients and normal controls. Stimulation of purified CD4(+)T cells with FICZ or ITE caused a decreased expression of RORC, IL-17, IL-23R, and CCR6 and an increased phosphorylation of STAT3 and STAT5. The present study suggests that a decreased AhR expression is associated with disease activity in BD patients. The activation of AhR by either FICZ or ITE was able to inhibit Th1 and Th17 cell polarization. Further studies are needed to investigate whether modulation of AhR might be used in the treatment of BD.

A New Antigen Retrieval Technique for Human Brain Tissue

PubMed Central

Byne, William; Haroutunian, Vahram; García-Villanueva, Mercedes; Rábano, Alberto; García-Amado, María; Prensa, Lucía; Giménez-Amaya, José Manuel

2008-01-01

Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times. PMID:18852880

Mannitol Improves Brain Tissue Oxygenation in a Model of Diffuse Traumatic Brain Injury.

PubMed

Schilte, Clotilde; Bouzat, Pierre; Millet, Anne; Boucheix, Perrine; Pernet-Gallay, Karin; Lemasson, Benjamin; Barbier, Emmanuel L; Payen, Jean-François

2015-10-01

Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury. Experimental study. Neurosciences and physiology laboratories. Adult male Wistar rats. Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult. Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats. The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue without evidence of brain ischemia. Our findings indicate that an antiedematous agent such as mannitol can improve brain tissue oxygenation, possibly by limiting astrocyte swelling and restoring capillary perfusion.

Brain metastasis detection by resonant Raman optical biopsy method

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Cheng, Gangge; Zhou, Lixin; Zhang, Chunyuan; Pu, Yang; Li, Zhongwu; Liu, Yulong; Li, Qingbo; Wang, Wei; Alfano, Robert R.

2014-03-01

Resonant Raman (RR) spectroscopy provides an effective way to enhance Raman signal from particular bonds associated with key molecules due to changes on a molecular level. In this study, RR is used for detection of human brain metastases of five kinds of primary organs of lung, breast, kidney, rectal and orbital in ex-vivo. The RR spectra of brain metastases cancerous tissues were measured and compared with those of normal brain tissues and the corresponding primary cancer tissues. The differences of five types of brain metastases tissues in key bio-components of carotene, tryptophan, lactate, alanine and methyl/methylene group were investigated. The SVM-KNN classifier was used to categorize a set of RR spectra data of brain metastasis of lung cancerous tissues from normal brain tissue, yielding diagnostic sensitivity and specificity at 100% and 75%, respectively. The RR spectroscopy may provide new moleculebased optical probe tools for diagnosis and classification of brain metastatic of cancers.

Spatial cluster analysis of nanoscopically mapped serotonin receptors for classification of fixed brain tissue

NASA Astrophysics Data System (ADS)

Sams, Michael; Silye, Rene; Göhring, Janett; Muresan, Leila; Schilcher, Kurt; Jacak, Jaroslaw

2014-01-01

We present a cluster spatial analysis method using nanoscopic dSTORM images to determine changes in protein cluster distributions within brain tissue. Such methods are suitable to investigate human brain tissue and will help to achieve a deeper understanding of brain disease along with aiding drug development. Human brain tissue samples are usually treated postmortem via standard fixation protocols, which are established in clinical laboratories. Therefore, our localization microscopy-based method was adapted to characterize protein density and protein cluster localization in samples fixed using different protocols followed by common fluorescent immunohistochemistry techniques. The localization microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a two-dimensional image of a brain tissue slice. These nanoscopically mapped proteins can be confined to clusters by applying the proposed statistical spatial analysis. Selected features of such clusters were subsequently used to characterize and classify the tissue. Samples were obtained from different types of patients, fixed with different preparation methods, and finally stored in a human tissue bank. To verify the proposed method, samples of a cryopreserved healthy brain have been compared with epitope-retrieved and paraffin-fixed tissues. Furthermore, samples of healthy brain tissues were compared with data obtained from patients suffering from mental illnesses (e.g., major depressive disorder). Our work demonstrates the applicability of localization microscopy and image analysis methods for comparison and classification of human brain tissues at a nanoscopic level. Furthermore, the presented workflow marks a unique technological advance in the characterization of protein distributions in brain tissue sections.

Psychiatric Brain Banking: Three Perspectives on Current Trends and Future Directions

PubMed Central

Deep-Soboslay, Amy; Benes, Francine M.; Haroutunian, Vahram; Ellis, Justin K.; Kleinman, Joel E.; Hyde, Thomas M.

2011-01-01

Introduction The study of postmortem human brain tissue is central to the advancement of the neurobiological studies of psychiatric illness, particularly for the study of brain-specific isoforms and molecules. Methods The state-of-the-art methods and recommendations for maintaining a successful brain bank for psychiatric disorders are discussed, using the convergence of viewpoints from three brain collections, the National Institute of Mental Health Brain Collection (NIMH), the Harvard Brain Tissue Resource Center (HBTRC), and the Mt. Sinai School of Medicine Brain Bank (MSSM-BB), with diverse research interests and divergent approaches to tissue acquisition. Results While the NIMH obtains donations from medical examiners for its collection, and places particular emphasis on clinical diagnosis, toxicology, and building lifespan control cohorts, the HBTRC is uniquely designed as a repository whose sole purpose is to collect large-volume, high quality brain tissue from community-based donors based on relationships across an expansive nationwide network, and places emphasis on the accessibility of its bank in disseminating tissue and related data to research groups worldwide. The MSSM-BB collection has shown that, with dedication, prospective recruitment is a successful approach to tissue donation, and places particular emphasis on rigorous clinical diagnosis through antemortem contact with donors. The MSSM-BB places great importance on stereological tissue sampling methods for neuroanatomical studies, and frozen tissue sampling approaches that enable multiple assessments (RNA, DNA, protein, enzyme activity, binding, etc.) of the same tissue block. Promising scientific approaches for elucidating the molecular and cellular pathways in brain that may contribute to schizophrenia and/or bipolar disorder, such as cell culture techniques and microarray-based gene expression and genotyping studies are briefly discussed. Conclusions Despite unique perspectives from three established brain collections, there is a consensus that (1) diverse strategies for tissue acquisition, (2) rigor in tissue and diagnostic characterization, (3) the importance of sample accessibility, and (4) continual application of innovative scientific approaches to the study of brain tissue are all integral to the success and future of psychiatric brain banking. The future of neuropsychiatric research depends upon in the availability of high quality brain specimens from large numbers of subjects, including non-psychiatric controls. PMID:20673875

Frequency of brain tissue donation for research after suicide.

PubMed

Longaray, Vanessa K; Padoan, Carolina S; Goi, Pedro D; da Fonseca, Rodrigo C; Vieira, Daniel C; Oliveira, Francine H de; Kapczinski, Flávio; Magalhães, Pedro V

2017-01-01

To describe the frequency of brain tissue donation for research purposes by families of individuals that committed suicide. All requests for brain tissue donation to a brain biorepository made to the families of individuals aged 18-60 years who had committed suicide between March 2014 and February 2016 were included. Cases presenting with brain damage due to acute trauma were excluded. Fifty-six cases of suicide were reported. Of these, 24 fulfilled the exclusion criteria, and 11 others were excluded because no next of kin was found to provide informed consent. Of the 21 remaining cases, brain tissue donation was authorized in nine (tissue fragments in seven and the entire organ in two). Donation of brain tissue from suicide cases for research purposes is feasible. The acceptance rate of 42.8% in our sample is in accordance with international data on such donations, and similar to rates reported for neurodegenerative diseases.

Metastasis Infiltration: An Investigation of the Postoperative Brain-Tumor Interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raore, Bethwel; Schniederjan, Matthew; Prabhu, Roshan

Purpose: This study aims to evaluate brain infiltration of metastatic tumor cells past the main tumor resection margin to assess the biological basis for the use of stereotactic radiosurgery treatment of the tumor resection cavity and visualized resection edge or clinical target volume. Methods and Materials: Resection margin tissue was obtained after gross total resection of a small group of metastatic lesions from a variety of primary sources. The tissue at the border of the tumor and brain tissue was carefully oriented and processed to evaluate the presence of tumor cells within brain tissue and their distance from the resectionmore » margin. Results: Microscopic assessment of the radially oriented tissue samples showed no tumor cells infiltrating the surrounding brain tissue. Among the positive findings were reactive astrocytosis observed on the brain tissue immediately adjacent to the tumor resection bed margin. Conclusions: The lack of evidence of metastatic tumor cell infiltration into surrounding brain suggests the need to target only a narrow depth of the resection cavity margin to minimize normal tissue injury and prevent treatment size-dependent stereotactic radiosurgery complications.« less

NMR imaging of cell phone radiation absorption in brain tissue

PubMed Central

Gultekin, David H.; Moeller, Lothar

2013-01-01

A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry. PMID:23248293

NMR imaging of cell phone radiation absorption in brain tissue.

PubMed

Gultekin, David H; Moeller, Lothar

2013-01-02

A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry.

Macrophages from Behcet's Disease Patients Express Decreased Level of Aryl Hydrocarbon Receptor (AHR) mRNA.

PubMed

Palizgir, Mohammad Taghi; Akhtari, Maryam; Mahmoudi, Mahdi; Mostafaei, Shayan; Rezaeimanesh, Alireza; Akhlaghi, Massoomeh; Shahram, Farhad

2017-10-01

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, connecting environmental stimulators with the immune system. M1 macrophages are a part of immune system that contribute to the inflammatory events in the pathogenesis of Behcet's disease (BD). The effect of AHR on the macrophages in BD patients is still unclear. In this study, we investigated the mRNA expression of AHR in the monocyte-derived and M1 macrophages in active BD patients in comparison to healthy controls. Isolated monocytes from 10 healthy controls and 10 active BD patients were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for 7 days. Cells were then polarized to M1 macrophages by lipopolysaccharide (LPS) and interferon-γ (IFNγ) for 24h. Monocyte purity and macrophage markers expression were analyzed by flow cytometry. Analysis of AHR mRNA expression was performed by SYBR Green real-time PCR. Our results showed that AHR expression is significantly down-regulated in M1 macrophages compare to monocyte-derived macrophages. It was shown that both monocyte-derived macrophages and M1 macrophages from BD patients significantly express lower level of AHR mRNA compared to healthy individuals. Our results demonstrate an anti-inflammatory role for AHR in macrophages, which suggest that decreased AHR expression is associated with pro-inflammatory M1 macrophage and BD susceptibility.

Decreased Expression of the Aryl Hydrocarbon Receptor in Ocular Behcet's Disease

PubMed Central

Wang, Chaokui; Ye, Zi; Kijlstra, Aize; Zhou, Yan; Yang, Peizeng

2014-01-01

Recent studies show that the aryl hydrocarbon receptor (AhR) is involved in immune responses. AhR is activated following interaction with its ligands, such as 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). In this study, we investigated the role of AhR activation by its endogenous ligands in the pathogenesis of ocular Behcet's disease (BD). The expression of AhR was significantly decreased in active BD patients as compared to inactive BD patients and normal controls. Both FICZ and ITE inhibited Th1 and Th17 polarization and induced the expression of IL-22 by PBMCs and by CD4+T cells in active BD patients and normal controls. Stimulation of purified CD4+T cells with FICZ or ITE caused a decreased expression of RORC, IL-17, IL-23R, and CCR6 and an increased phosphorylation of STAT3 and STAT5. The present study suggests that a decreased AhR expression is associated with disease activity in BD patients. The activation of AhR by either FICZ or ITE was able to inhibit Th1 and Th17 cell polarization. Further studies are needed to investigate whether modulation of AhR might be used in the treatment of BD. PMID:25045206

Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

PubMed

Stewart, Daniel C; Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S

2017-01-01

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

PubMed

Guertler, Charlotte A; Okamoto, Ruth J; Schmidt, John L; Badachhape, Andrew A; Johnson, Curtis L; Bayly, Philip V

2018-03-01

The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vitro 3D regeneration-like growth of human patient brain tissue.

PubMed

Tang-Schomer, M D; Wu, W B; Kaplan, D L; Bookland, M J

2018-05-01

In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models. Copyright © 2018 John Wiley & Sons, Ltd.

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats

PubMed Central

Pong, Alice C.; Jugé, Lauriane; Bilston, Lynne E.; Cheng, Shaokoon

2017-01-01

Introduction Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Methods Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Results Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. Conclusions This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus. PMID:28837671

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

PubMed

Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

2017-01-01

Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

Optical pathology of human brain metastasis of lung cancer using combined resonance Raman and spatial frequency spectroscopies

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Pu, Yang; Cheng, Gangge; Zhou, Lixin; Chen, Jun; Zhu, Ke; Alfano, Robert R.

2016-03-01

Raman spectroscopy has become widely used for diagnostic purpose of breast, lung and brain cancers. This report introduced a new approach based on spatial frequency spectra analysis of the underlying tissue structure at different stages of brain tumor. Combined spatial frequency spectroscopy (SFS), Resonance Raman (RR) spectroscopic method is used to discriminate human brain metastasis of lung cancer from normal tissues for the first time. A total number of thirty-one label-free micrographic images of normal and metastatic brain cancer tissues obtained from a confocal micro- Raman spectroscopic system synchronously with examined RR spectra of the corresponding samples were collected from the identical site of tissue. The difference of the randomness of tissue structures between the micrograph images of metastatic brain tumor tissues and normal tissues can be recognized by analyzing spatial frequency. By fitting the distribution of the spatial frequency spectra of human brain tissues as a Gaussian function, the standard deviation, σ, can be obtained, which was used to generate a criterion to differentiate human brain cancerous tissues from the normal ones using Support Vector Machine (SVM) classifier. This SFS-SVM analysis on micrograph images presents good results with sensitivity (85%), specificity (75%) in comparison with gold standard reports of pathology and immunology. The dual-modal advantages of SFS combined with RR spectroscopy method may open a new way in the neuropathology applications.

Impact of Neurodegenerative Diseases on Drug Binding to Brain Tissues: From Animal Models to Human Samples.

PubMed

Ugarte, Ana; Corbacho, David; Aymerich, María S; García-Osta, Ana; Cuadrado-Tejedor, Mar; Oyarzabal, Julen

2018-04-19

Drug efficacy in the central nervous system (CNS) requires an additional step after crossing the blood-brain barrier. Therapeutic agents must reach their targets in the brain to modulate them; thus, the free drug concentration hypothesis is a key parameter for in vivo pharmacology. Here, we report the impact of neurodegeneration (Alzheimer's disease (AD) and Parkinson's disease (PD) compared with healthy controls) on the binding of 10 known drugs to postmortem brain tissues from animal models and humans. Unbound drug fractions, for some drugs, are significantly different between healthy and injured brain tissues (AD or PD). In addition, drugs binding to brain tissues from AD and PD animal models do not always recapitulate their binding to the corresponding human injured brain tissues. These results reveal potentially relevant implications for CNS drug discovery.

Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields.

PubMed

Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

2016-06-21

An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform's size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke's brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields

NASA Astrophysics Data System (ADS)

Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

2016-06-01

An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform’s size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke’s brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

Temperature-dependent elastic properties of brain tissues measured with the shear wave elastography method.

PubMed

Liu, Yan-Lin; Li, Guo-Yang; He, Ping; Mao, Ze-Qi; Cao, Yanping

2017-01-01

Determining the mechanical properties of brain tissues is essential in such cases as the surgery planning and surgical training using virtual reality based simulators, trauma research and the diagnosis of some diseases that alter the elastic properties of brain tissues. Here, we suggest a protocol to measure the temperature-dependent elastic properties of brain tissues in physiological saline using the shear wave elastography method. Experiments have been conducted on six porcine brains. Our results show that the shear moduli of brain tissues decrease approximately linearly with a slope of -0.041±0.006kPa/°C when the temperature T increases from room temperature (~23°C) to body temperature (~37°C). A case study has been further conducted which shows that the shear moduli are insensitive to the temperature variation when T is in the range of 37 to 43°C and will increase when T is higher than 43°C. With the present experimental setup, temperature-dependent elastic properties of brain tissues can be measured in a simulated physiological environment and a non-destructive manner. Thus the method suggested here offers a unique tool for the mechanical characterization of brain tissues with potential applications in brain biomechanics research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms

PubMed Central

Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S.

2017-01-01

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17–16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models. PMID:28582392

Brief Report: The Role of National Brain and Tissue Banks in Research on Autism and Developmental Disorders.

ERIC Educational Resources Information Center

Zielke, H. Ronald; And Others

1996-01-01

This paper describes the establishment and work of two brain and tissue banks, which collect brain and other tissues from newly deceased individuals with autism and make these tissues available to researchers. Issues in tissue collection are identified, including the importance of advance planning, religious concerns of families, and the need for…

Prediction of brain deformations and risk of traumatic brain injury due to closed-head impact: quantitative analysis of the effects of boundary conditions and brain tissue constitutive model.

PubMed

Wang, Fang; Han, Yong; Wang, Bingyu; Peng, Qian; Huang, Xiaoqun; Miller, Karol; Wittek, Adam

2018-05-12

In this study, we investigate the effects of modelling choices for the brain-skull interface (layers of tissues between the brain and skull that determine boundary conditions for the brain) and the constitutive model of brain parenchyma on the brain responses under violent impact as predicted using computational biomechanics model. We used the head/brain model from Total HUman Model for Safety (THUMS)-extensively validated finite element model of the human body that has been applied in numerous injury biomechanics studies. The computations were conducted using a well-established nonlinear explicit dynamics finite element code LS-DYNA. We employed four approaches for modelling the brain-skull interface and four constitutive models for the brain tissue in the numerical simulations of the experiments on post-mortem human subjects exposed to violent impacts reported in the literature. The brain-skull interface models included direct representation of the brain meninges and cerebrospinal fluid, outer brain surface rigidly attached to the skull, frictionless sliding contact between the brain and skull, and a layer of spring-type cohesive elements between the brain and skull. We considered Ogden hyperviscoelastic, Mooney-Rivlin hyperviscoelastic, neo-Hookean hyperviscoelastic and linear viscoelastic constitutive models of the brain tissue. Our study indicates that the predicted deformations within the brain and related brain injury criteria are strongly affected by both the approach of modelling the brain-skull interface and the constitutive model of the brain parenchyma tissues. The results suggest that accurate prediction of deformations within the brain and risk of brain injury due to violent impact using computational biomechanics models may require representation of the meninges and subarachnoidal space with cerebrospinal fluid in the model and application of hyperviscoelastic (preferably Ogden-type) constitutive model for the brain tissue.

Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats.

PubMed

Zhang, Na; Cheng, Gen-Yang; Liu, Xian-Zhi; Zhang, Feng-Jiang

2014-05-01

To investigate the effect of acute renal ischemia reperfusion on brain tissue. Fourty eight rats were randomly divided into four groups (n=12): sham operation group, 30 min ischemia 60 min reperfusion group, 60 min ischemia 60 min reperfusion group, and 120 min ischemia 60 min reperfusion group. The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors. Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time. The detection at the molecular level showed decreased Bcl-2 expression, increased Bax expression, upregulated expression of NF-κB and its downstream factor COX-2/PGE2. Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

PubMed Central

Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

2010-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

Combined Bisulfite Restriction Analysis for brain tissue identification.

PubMed

Samsuwan, Jarunya; Muangsub, Tachapol; Yanatatsaneejit, Pattamawadee; Mutirangura, Apiwat; Kitkumthorn, Nakarin

2018-05-01

According to the tissue-specific methylation database (doi: 10.1016/j.gene.2014.09.060), methylation at CpG locus cg03096975 in EML2 has been preliminarily proven to be specific to brain tissue. In this study, we enlarged sample size and developed a technique for identifying brain tissue in aged samples. Combined Bisulfite Restriction Analysis-for EML2 (COBRA-EML2) technique was established and validated in various organ samples obtained from 108 autopsies. In addition, this technique was also tested for its reliability, minimal DNA concentration detected, and use in aged samples and in samples obtained from specific brain compartments and spinal cord. COBRA-EML2 displayed 100% sensitivity and specificity for distinguishing brain tissue from other tissues, showed high reliability, was capable of detecting minimal DNA concentration (0.015ng/μl), could be used for identifying brain tissue in aged samples. In summary, COBRA-EML2 is a technique to identify brain tissue. This analysis is useful in criminal cases since it can identify the vital organ tissues from small samples acquired from criminal scenes. The results from this analysis can be counted as a medical and forensic marker supporting criminal investigations, and as one of the evidences in court rulings. Copyright © 2018 Elsevier B.V. All rights reserved.

Robotic multimodality stereotactic brain tissue identification: work in progress

NASA Technical Reports Server (NTRS)

Andrews, R.; Mah, R.; Galvagni, A.; Guerrero, M.; Papasin, R.; Wallace, M.; Winters, J.

1997-01-01

Real-time identification of tissue would improve procedures such as stereotactic brain biopsy (SBX), functional and implantation neurosurgery, and brain tumor excision. To standard SBX equipment has been added: (1) computer-controlled stepper motors to drive the biopsy needle/probe precisely; (2) multiple microprobes to track tissue density, detect blood vessels and changes in blood flow, and distinguish the various tissues being penetrated; (3) neural net learning programs to allow real-time comparisons of current data with a normative data bank; (4) three-dimensional graphic displays to follow the probe as it traverses brain tissue. The probe can differentiate substances such as pig brain, differing consistencies of the 'brain-like' foodstuff tofu, and gels made to simulate brain, as well as detect blood vessels imbedded in these substances. Multimodality probes should improve the safety, efficacy, and diagnostic accuracy of SBX and other neurosurgical procedures.

A family of hyperelastic models for human brain tissue

NASA Astrophysics Data System (ADS)

Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

2017-09-01

Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert

2016-01-01

The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.

Effects of Antioxidant N-acetylcysteine Against Paraquat-Induced Oxidative Stress in Vital Tissues of Mice

PubMed Central

Ortiz, Maricelly Santiago; Forti, Kevin Muñoz; Suárez Martinez, Edu B.; Muñoz, Lenin Godoy; Husain, Kazim

2016-01-01

Paraquat (PQ) is a commonly used herbicide that induces oxidative stress via reactive oxygen species (ROS) generation. This study aimed to investigate the effects of the antioxidant N-acetylcysteine (NAC) against PQ-induced oxidative stress in mice. Male Balb/C mice (24) were randomly divided into 4 groups and treated for 3 weeks: 1) control (saline), 2) NAC (0.5% in diet), 3) PQ (20 mg/kg, IP) and 4) combination (PQ + NAC). Afterwards mice were sacrificed and oxidative stress markers were analyzed. Our data showed no significant change in serum antioxidant capacity. PQ enhanced lipid peroxidation (MDA) levels in liver tissue compared to control whereas NAC decreased MDA levels (p<0.05). NAC significantly increased MDA in brain tissue (p<0.05). PQ significantly depleted glutathione (GSH) levels in liver (p=0.001) and brain tissue (p<0.05) but non-significant GSH depletion in lung tissue. NAC counteracted PQ, showing a moderate increase GSH levels in liver and brain tissues. PQ significantly increased 8-oxodeoxyguanosine (8-OH-dG) levels (p<0.05) in liver tissue compared to control without a significant change in brain tissue. NAC treatment ameliorated PQ-induced oxidative DNA damage in the liver tissue. PQ significantly decreased the relative mtDNA amplification and increased the frequency of lesions in liver and brain tissue (p<0.0001), while NAC restored the DNA polymerase activity in liver tissue but not in brain tissue. In conclusion, PQ induced lipid peroxidation, oxidative nuclear DNA and mtDNA damage in liver tissues and depleted liver and brain GSH levels. NAC supplementation ameliorated the PQ-induced oxidative stress response in liver tissue of mice. PMID:27398384

BECon: a tool for interpreting DNA methylation findings from blood in the context of brain.

PubMed

Edgar, R D; Jones, M J; Meaney, M J; Turecki, G; Kobor, M S

2017-08-01

Tissue differences are one of the largest contributors to variability in the human DNA methylome. Despite the tissue-specific nature of DNA methylation, the inaccessibility of human brain samples necessitates the frequent use of surrogate tissues such as blood, in studies of associations between DNA methylation and brain function and health. Results from studies of surrogate tissues in humans are difficult to interpret in this context, as the connection between blood-brain DNA methylation is tenuous and not well-documented. Here, we aimed to provide a resource to the community to aid interpretation of blood-based DNA methylation results in the context of brain tissue. We used paired samples from 16 individuals from three brain regions and whole blood, run on the Illumina 450 K Human Methylation Array to quantify the concordance of DNA methylation between tissues. From these data, we have made available metrics on: the variability of cytosine-phosphate-guanine dinucleotides (CpGs) in our blood and brain samples, the concordance of CpGs between blood and brain, and estimations of how strongly a CpG is affected by cell composition in both blood and brain through the web application BECon (Blood-Brain Epigenetic Concordance; https://redgar598.shinyapps.io/BECon/). We anticipate that BECon will enable biological interpretation of blood-based human DNA methylation results, in the context of brain.

Automatic brain tissue segmentation based on graph filter.

PubMed

Kong, Youyong; Chen, Xiaopeng; Wu, Jiasong; Zhang, Pinzheng; Chen, Yang; Shu, Huazhong

2018-05-09

Accurate segmentation of brain tissues from magnetic resonance imaging (MRI) is of significant importance in clinical applications and neuroscience research. Accurate segmentation is challenging due to the tissue heterogeneity, which is caused by noise, bias filed and partial volume effects. To overcome this limitation, this paper presents a novel algorithm for brain tissue segmentation based on supervoxel and graph filter. Firstly, an effective supervoxel method is employed to generate effective supervoxels for the 3D MRI image. Secondly, the supervoxels are classified into different types of tissues based on filtering of graph signals. The performance is evaluated on the BrainWeb 18 dataset and the Internet Brain Segmentation Repository (IBSR) 18 dataset. The proposed method achieves mean dice similarity coefficient (DSC) of 0.94, 0.92 and 0.90 for the segmentation of white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF) for BrainWeb 18 dataset, and mean DSC of 0.85, 0.87 and 0.57 for the segmentation of WM, GM and CSF for IBSR18 dataset. The proposed approach can well discriminate different types of brain tissues from the brain MRI image, which has high potential to be applied for clinical applications.

Computational analysis of transcranial magnetic stimulation in the presence of deep brain stimulation probes

NASA Astrophysics Data System (ADS)

Syeda, F.; Holloway, K.; El-Gendy, A. A.; Hadimani, R. L.

2017-05-01

Transcranial Magnetic Stimulation is an emerging non-invasive treatment for depression, Parkinson's disease, and a variety of other neurological disorders. Many Parkinson's patients receive the treatment known as Deep Brain Stimulation, but often require additional therapy for speech and swallowing impairment. Transcranial Magnetic Stimulation has been explored as a possible treatment by stimulating the mouth motor area of the brain. We have calculated induced electric field, magnetic field, and temperature distributions in the brain using finite element analysis and anatomically realistic heterogeneous head models fitted with Deep Brain Stimulation leads. A Figure of 8 coil, current of 5000 A, and frequency of 2.5 kHz are used as simulation parameters. Results suggest that Deep Brain Stimulation leads cause surrounding tissues to experience slightly increased E-field (Δ Emax =30 V/m), but not exceeding the nominal values induced in brain tissue by Transcranial Magnetic Stimulation without leads (215 V/m). The maximum temperature in the brain tissues surrounding leads did not change significantly from the normal human body temperature of 37 °C. Therefore, we ascertain that Transcranial Magnetic Stimulation in the mouth motor area may stimulate brain tissue surrounding Deep Brain Stimulation leads, but will not cause tissue damage.

Long-Term Implanted cOFM Probe Causes Minimal Tissue Reaction in the Brain

PubMed Central

Hochmeister, Sonja; Asslaber, Martin; Kroath, Thomas; Pieber, Thomas R.; Sinner, Frank

2014-01-01

This study investigated the histological tissue reaction to long-term implanted cerebral open flow microperfusion (cOFM) probes in the frontal lobe of the rat brain. Most probe-based cerebral fluid sampling techniques are limited in application time due to the formation of a glial scar that hinders substance exchange between brain tissue and the probe. A glial scar not only functions as a diffusion barrier but also alters metabolism and signaling in extracellular brain fluid. cOFM is a recently developed probe-based technique to continuously sample extracellular brain fluid with an intact blood-brain barrier. After probe implantation, a 2 week healing period is needed for blood-brain barrier reestablishment. Therefore, cOFM probes need to stay in place and functional for at least 15 days after implantation to ensure functionality. Probe design and probe materials are optimized to evoke minimal tissue reaction even after a long implantation period. Qualitative and quantitative histological tissue analysis revealed no continuous glial scar formation around the cOFM probe 30 days after implantation and only a minor tissue reaction regardless of perfusion of the probe. PMID:24621608

HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

PubMed

Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

2011-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of Ginkgo biloba extract on apoptosis of brain tissues in rats with acute cerebral infarction and related gene expression.

PubMed

Wu, C; Zhao, X; Zhang, X; Liu, S; Zhao, H; Chen, Y

2015-06-11

We investigated the effect of Ginkgo biloba extract on apoptosis of brain tissues in rats with acute cerebral infarction and apoptosis-related gene expression. Rat models of acute cerebral infarction were constructed using the suture method, and randomly divided into the control group, model, and treatment groups. In the treatment group, 4 mg/kg G. biloba extract was intravenously injected into the rat tail vein. Phosphate-buffered saline solution was injected in the model group. Seventy-two hours after treatment, rats were euthanized, and brain tissues were removed to analyze the changes in caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) mRNA and protein levels, and variation in brain tissue cells' apoptosis indices was measured. Compared with the control group, the model and treatment groups showed significantly upregulated caspase-3, Bcl-2, and Bax mRNA and protein levels in brain tissues, but remarkably downregulated Bcl-2 mRNA and protein levels (P < 0.05). After treatment, in treatment group brain tissues, caspase-3 and Bax mRNA and protein levels were significantly lower than those in the model group, while Bcl-2 mRNA and protein levels were higher than that in the model group (P < 0.05). The model and treatment groups showed increased cell apoptosis indices of brain tissues compared to the control group; after treatment, the apoptosis index in the treatment group was significantly downregulated compared with that in the model group (P < 0.05). In conclusion, G. biloba extract significantly reduced apoptosis in rat brain tissue cells with acute cerebral infarction and thus protected brain tissues.

Identification of the boundary between normal brain tissue and ischemia region using two-photon excitation fluorescence microscopy

NASA Astrophysics Data System (ADS)

Du, Huiping; Wang, Shu; Wang, Xingfu; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

2016-10-01

Ischemic stroke is one of the common neurological diseases, and it is becoming the leading causes of death and permanent disability around the world. Early and accurate identification of the potentially salvageable boundary region of ischemia brain tissues may enable selection of the most appropriate candidates for early stroke therapies. In this work, TPEF microscopy was used to image the microstructures of normal brain tissues, ischemia regions and the boundary region between normal and ischemia brain tissues. The ischemia brain tissues from Sprague-Dawley (SD) rats were subjected to 6 hours of middle cerebral artery occlusion (MCAO). Our study demonstrates that TPEF microscopy has the ability to not only reveal the morphological changes of the neurons but also identify the boundary between normal brain tissue and ischemia region, which correspond well to the hematoxylin and eosin (H and E) stained images. With the development of miniaturized TPEF microscope imaging devices, TPEF microscopy can be developed into an effectively diagnostic and monitoring tool for cerebral ischemia.

Copy number variants and genetic polymorphisms in TBX21, GATA3, Rorc, Foxp3 and susceptibility to Behcet's disease and Vogt-Koyanagi-Harada syndrome.

PubMed

Liao, Dan; Hou, Shengping; Zhang, Jun; Fang, Jing; Liu, Yunjia; Bai, Lin; Cao, Qingfeng; Kijlstra, Aize; Yang, Peizeng

2015-04-15

This study aimed to investigate the role of genetic variants including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of TBX21, GATA3, Rorc and Foxp3 genes in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. Genotyping of 25 SNPs was performed by iPLEX system (Sequenom) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). TaqMan real time PCR was used to assess CNVs. The expression of Rorc and Foxp3 were examined by real-time PCR and cytokine production was measured by ELISA. High Rorc CNV was associated with the susceptibility to BD (P = 8.99 × 10(-8), OR = 3.0), and low Foxp3 CNV predisposed to BD in female patients (P = 1.92 × 10(-5), OR = 3.1). CNVs for the investigated genes were not altered in VKH syndrome. Further functional studies demonstrated that the relative mRNA expression levels of Rorc were increased in individuals with high Rorc copy number, but not for Foxp3. Increased production of IL-1β and IL-6 was found in individuals carrying a high CNV of Rorc. Our study showed that high CNVs of Rorc and low CNVs of Foxp3 confer risk for BD but not for VKH syndrome. The tested 25 SNPs in TBX21, GATA3, Rorc and Foxp3 did not associate with BD and VKH syndrome.

Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet's Disease by Gas Chromatography/Time-of-Flight-Mass Spectrometry.

PubMed

Ahn, Joong Kyong; Kim, Jungyeon; Hwang, Jiwon; Song, Juhwan; Kim, Kyoung Heon; Cha, Hoon-Suk

2017-11-02

Diagnosing Behcet's disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC/TOF-MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF-MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA) model were R ² X of 0.231, R ² Y of 0.804, and Q ² of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974). OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%). We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF-MS.

Postmortem changes in the neuroanatomical characteristics of the primate brain: the hippocampal formation

PubMed Central

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L.; Amaral, David G.

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused, or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger, as compared to perfusion-fixed tissue. Non-phosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well-stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

PubMed

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.

Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child.

PubMed

Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

2015-01-01

Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters.

Multimodality Instrument for Tissue Characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2000-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip is discussed. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network, program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration.

The Importance of Brain Banks for Molecular Neuropathological Research: The New South Wales Tissue Resource Centre Experience

PubMed Central

Dedova, Irina; Harding, Antony; Sheedy, Donna; Garrick, Therese; Sundqvist, Nina; Hunt, Clare; Gillies, Juliette; Harper, Clive G.

2009-01-01

New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC) at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls. This review highlights changes in TRC operational procedures dictated by modern neuroscience, and provides examples of applications of modern molecular techniques to study the neuropathogenesis of many different brain disorders. PMID:19333451

Different modes of herpes simplex virus type 1 spread in brain and skin tissues.

PubMed

Tsalenchuck, Yael; Tzur, Tomer; Steiner, Israel; Panet, Amos

2014-02-01

Herpes simplex virus type 1 (HSV-1) initially infects the skin and subsequently spreads to the nervous system. To investigate and compare HSV-1 mode of propagation in the two clinically relevant tissues, we have established ex vivo infection models, using native tissues of mouse and human skin, as well as mouse brain, maintained in organ cultures. HSV-1, which is naturally restricted to the human, infects and spreads in the mouse and human skin tissues in a similar fashion, thus validating the mouse model. The spread of HSV-1 in the skin was concentric to form typical plaques of limited size, predominantly of cytopathic cells. By contrast, HSV-1 spread in the brain tissue was directed along specific neuronal networks with no apparent cytopathic effect. Two additional differences were noted following infection of the skin and brain tissues. First, only a negligible amount of extracellular progeny virus was produced of the infected brain tissues, while substantial quantity of infectious progeny virus was released to the media of the infected skin. Second, antibodies against HSV-1, added following the infection, effectively restricted viral spread in the skin but have no effect on viral spread in the brain tissue. Taken together, these results reveal that HSV-1 spread within the brain tissue mostly by direct transfer from cell to cell, while in the skin the progeny extracellular virus predominates, thus facilitating the infection to new individuals.

Hyperspectral imaging solutions for brain tissue metabolic and hemodynamic monitoring: past, current and future developments

NASA Astrophysics Data System (ADS)

Giannoni, Luca; Lange, Frédéric; Tachtsidis, Ilias

2018-04-01

Hyperspectral imaging (HSI) technologies have been used extensively in medical research, targeting various biological phenomena and multiple tissue types. Their high spectral resolution over a wide range of wavelengths enables acquisition of spatial information corresponding to different light-interacting biological compounds. This review focuses on the application of HSI to monitor brain tissue metabolism and hemodynamics in life sciences. Different approaches involving HSI have been investigated to assess and quantify cerebral activity, mainly focusing on: (1) mapping tissue oxygen delivery through measurement of changes in oxygenated (HbO2) and deoxygenated (HHb) hemoglobin; and (2) the assessment of the cerebral metabolic rate of oxygen (CMRO2) to estimate oxygen consumption by brain tissue. Finally, we introduce future perspectives of HSI of brain metabolism, including its potential use for imaging optical signals from molecules directly involved in cellular energy production. HSI solutions can provide remarkable insight in understanding cerebral tissue metabolism and oxygenation, aiding investigation on brain tissue physiological processes.

A study on the antioxidant effect of Coriolus versicolor polysaccharide in rat brain tissues.

PubMed

Chen, Jiayu; Jin, Xiaoyan; Zhang, Liting; Yang, Linjun

2013-01-01

The objective of the study was to investigate the antioxidant effect of Chinese medicine Coriolus versicolor polysaccharide on brain tissue and its mechanism in rats. SOD, MDA and GSH-Px levels in rat brain tissues were determined with SD rats as the animal model. The results showed that Coriolus versicolor polysaccharide can reduce the lipid peroxidation level in brain tissues during exhaustive exercise in rats, and can accelerate the removal of free radicals. The study concluded that its antioxidant effect is relatively apparent.

Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

2016-03-01

In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

2010-02-01

Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

The Relationship of Three-Dimensional Human Skull Motion to Brain Tissue Deformation in Magnetic Resonance Elastography Studies

PubMed Central

Badachhape, Andrew A.; Okamoto, Ruth J.; Durham, Ramona S.; Efron, Brent D.; Nadell, Sam J.; Johnson, Curtis L.; Bayly, Philip V.

2017-01-01

In traumatic brain injury (TBI), membranes such as the dura mater, arachnoid mater, and pia mater play a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is an imaging technique developed for noninvasive estimation of soft tissue material parameters. In MRE, dynamic deformation of brain tissue is induced by skull vibrations during magnetic resonance imaging (MRI); however, skull motion and its mode of transmission to the brain remain largely uncharacterized. In this study, displacements of points in the skull, reconstructed using data from an array of MRI-safe accelerometers, were compared to displacements of neighboring material points in brain tissue, estimated from MRE measurements. Comparison of the relative amplitudes, directions, and temporal phases of harmonic motion in the skulls and brains of six human subjects shows that the skull–brain interface significantly attenuates and delays transmission of motion from skull to brain. In contrast, in a cylindrical gelatin “phantom,” displacements of the rigid case (reconstructed from accelerometer data) were transmitted to the gelatin inside (estimated from MRE data) with little attenuation or phase lag. This quantitative characterization of the skull–brain interface will be valuable in the parameterization and validation of computer models of TBI. PMID:28267188

The Relationship of Three-Dimensional Human Skull Motion to Brain Tissue Deformation in Magnetic Resonance Elastography Studies.

PubMed

Badachhape, Andrew A; Okamoto, Ruth J; Durham, Ramona S; Efron, Brent D; Nadell, Sam J; Johnson, Curtis L; Bayly, Philip V

2017-05-01

In traumatic brain injury (TBI), membranes such as the dura mater, arachnoid mater, and pia mater play a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is an imaging technique developed for noninvasive estimation of soft tissue material parameters. In MRE, dynamic deformation of brain tissue is induced by skull vibrations during magnetic resonance imaging (MRI); however, skull motion and its mode of transmission to the brain remain largely uncharacterized. In this study, displacements of points in the skull, reconstructed using data from an array of MRI-safe accelerometers, were compared to displacements of neighboring material points in brain tissue, estimated from MRE measurements. Comparison of the relative amplitudes, directions, and temporal phases of harmonic motion in the skulls and brains of six human subjects shows that the skull-brain interface significantly attenuates and delays transmission of motion from skull to brain. In contrast, in a cylindrical gelatin "phantom," displacements of the rigid case (reconstructed from accelerometer data) were transmitted to the gelatin inside (estimated from MRE data) with little attenuation or phase lag. This quantitative characterization of the skull-brain interface will be valuable in the parameterization and validation of computer models of TBI.

High-sensitivity terahertz imaging of traumatic brain injury in a rat model

NASA Astrophysics Data System (ADS)

Zhao, Hengli; Wang, Yuye; Chen, Linyu; Shi, Jia; Ma, Kang; Tang, Longhuang; Xu, Degang; Yao, Jianquan; Feng, Hua; Chen, Tunan

2018-03-01

We demonstrated that different degrees of experimental traumatic brain injury (TBI) can be differentiated clearly in fresh slices of rat brain tissues using transmission-type terahertz (THz) imaging system. The high absorption region in THz images corresponded well with the injured area in visible images and magnetic resonance imaging results. The THz image and absorption characteristics of dehydrated paraffin-embedded brain slices and the hematoxylin and eosin (H&E)-stained microscopic images were investigated to account for the intrinsic differences in the THz images for the brain tissues suffered from different degrees of TBI and normal tissue aside from water. The THz absorption coefficients of rat brain tissues showed an increase in the aggravation of brain damage, particularly in the high-frequency range, whereas the cell density decreased as the order of mild, moderate, and severe TBI tissues compared with the normal tissue. Our results indicated that the different degrees of TBI were distinguishable owing to the different water contents and probable hematoma components distribution rather than intrinsic cell intensity. These promising results suggest that THz imaging has great potential as an alternative method for the fast diagnosis of TBI.

Effects of high-pressure oxygen therapy on brain tissue water content and AQP4 expression in rabbits with cerebral hemorrhage.

PubMed

Wu, Jing; Chen, Jiong; Guo, Hua; Peng, Fang

2014-12-01

To investigate the effects of different atmosphere absolutes (ATA) of high-pressure oxygen (HPO) on brain tissue water content and Aquaporin-4 (AQP4) expression in rabbits with cerebral hemorrhage. 180 New Zealand white rabbits were selected and randomly divided into normal group (n = 30), control group (n = 30) and cerebral hemorrhage group (n = 120), and cerebral hemorrhage group was divided into group A, B, C and D with 30 rabbits in each group. The groups received 1.0, 1.8, 2.0 and 2.2 ATA of HPO treatments, respectively. Ten rabbits in each group were killed at first, third and fifth day to detect the brain tissue water content and change of AQP4 expression. In cerebral hemorrhage group, brain tissue water content and AQP4 expression after model establishment were first increased, then decreased and reached the maximum on third day (p < 0.05). Brain tissue water content and AQP4 expression in control group and cerebral hemorrhage group were significantly higher than normal group at different time points (p < 0.05). In contrast, brain tissue water content and AQP4 expression in group C were significantly lower than in group A, group B, group D and control group (p < 0.05). In control group, AQP4-positive cells significantly increased after model establishment, which reached maximum on third day, and positive cells in group C were significantly less than in group A, group B and group D. We also found that AQP4 expression were positively correlated with brain tissue water content (r = 0.719, p < 0.05) demonstrated by significantly increased AQP4 expression along with increased brain tissue water content. In conclusion, HPO can decrease AQP4 expression in brain tissue of rabbits with cerebral hemorrhage to suppress the progression of brain edema and promote repairing of injured tissue. 2.0 ATA HPO exerts best effects, which provides an experimental basis for ATA selection of HPO in treating cerebral hemorrhage.

Monitoring brain temperature by time-resolved near-infrared spectroscopy: pilot study

NASA Astrophysics Data System (ADS)

Bakhsheshi, Mohammad Fazel; Diop, Mamadou; St. Lawrence, Keith; Lee, Ting-Yim

2014-05-01

Mild hypothermia (HT) is an effective neuroprotective strategy for a variety of acute brain injuries. However, the wide clinical adaptation of HT has been hampered by the lack of a reliable noninvasive method for measuring brain temperature, since core measurements have been shown to not always reflect brain temperature. The goal of this work was to develop a noninvasive optical technique for measuring brain temperature that exploits both the temperature dependency of water absorption and the high concentration of water in brain (80%-90%). Specifically, we demonstrate the potential of time-resolved near-infrared spectroscopy (TR-NIRS) to measure temperature in tissue-mimicking phantoms (in vitro) and deep brain tissue (in vivo) during heating and cooling, respectively. For deep brain tissue temperature monitoring, experiments were conducted on newborn piglets wherein hypothermia was induced by gradual whole body cooling. Brain temperature was concomitantly measured by TR-NIRS and a thermocouple probe implanted in the brain. Our proposed TR-NIRS method was able to measure the temperature of tissue-mimicking phantoms and brain tissues with a correlation of 0.82 and 0.66 to temperature measured with a thermometer, respectively. The mean difference between the TR-NIRS and thermometer measurements was 0.15°C±1.1°C for the in vitro experiments and 0.5°C±1.6°C for the in vivo measurements.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain.

PubMed

Taoka, Toshiaki; Naganawa, Shinji

2018-04-10

After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the 'glymphatic system', which is a coined word that combines 'gl' for glia cell and 'lymphatic' system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain

PubMed Central

Taoka, Toshiaki; Naganawa, Shinji

2018-01-01

After Kanda’s first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the ‘glymphatic system’, which is a coined word that combines ‘gl’ for glia cell and ‘lymphatic’ system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue. PMID:29367513

Mathematical modelling of blood-brain barrier failure and edema

NASA Astrophysics Data System (ADS)

Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

2015-11-01

Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

Responses of the Human Brain to Mild Dehydration and Rehydration Explored In Vivo by 1H-MR Imaging and Spectroscopy.

PubMed

Biller, A; Reuter, M; Patenaude, B; Homola, G A; Breuer, F; Bendszus, M; Bartsch, A J

2015-12-01

As yet, there are no in vivo data on tissue water changes and associated morphometric changes involved in the osmo-adaptation of normal brains. Our aim was to evaluate osmoadaptive responses of the healthy human brain to osmotic challenges of de- and rehydration by serial measurements of brain volume, tissue fluid, and metabolites. Serial T1-weighted and (1)H-MR spectroscopy data were acquired in 15 healthy individuals at normohydration, on 12 hours of dehydration, and during 1 hour of oral rehydration. Osmotic challenges were monitored by serum measures, including osmolality and hematocrit. MR imaging data were analyzed by using FreeSurfer and LCModel. On dehydration, serum osmolality increased by 0.67% and brain tissue fluid decreased by 1.63%, on average. MR imaging morphometry demonstrated corresponding decreases of cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus. These changes reversed during rehydration. Continuous fluid ingestion of 1 L of water for 1 hour within the scanner lowered serum osmolality by 0.96% and increased brain tissue fluid by 0.43%, on average. Concomitantly, cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus increased. Changes in brain tissue fluid were related to volume changes of the whole brain, the white matter, and hypothalamus/thalamus. Only volume changes of the hypothalamus/thalamus significantly correlated with serum osmolality. This is the first study simultaneously evaluating changes in brain tissue fluid, metabolites, volume, and cortical thickness. Our results reflect cellular volume regulatory mechanisms at a macroscopic level and emphasize that it is essential to control for hydration levels in studies on brain morphometry and metabolism in order to avoid confounding the findings. © 2015 by American Journal of Neuroradiology.

Evaluation of Pharmacologic Agents to Suppress Intraocular Cellular Proliferation Following Trauma

DTIC Science & Technology

1986-07-01

Tracttonal Detachment* aniawl op uVeitis agent-- -- 1 (1-4) or control 1 wk 2 wk 4 wk 6 wk 12 wk Gross Lama* Imadi to Injaetica or drug 61 1 D S L C R F...BIBLIOGRAPHY 1. Mimura Y: The effect of colchicine treatment on ocular lesions in Behcet’s disease. Ophthalmol Jpn 26:902-908, 1985. 2. Brown W O... Treatment of intraocular proliferation with intravitreal injection of triamcinolone acetonide. Am J Ophthalmol 90:810, 1980. 9. Trese MT, Spitznas M

Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir

2014-08-15

The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractionsmore » from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.« less

Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child

PubMed Central

Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

2015-01-01

Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters. PMID:26495031

Brain cancer probed by native fluorescence and stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; He, Yong; Pu, Yang; Li, Qingbo; Wang, Wei; Alfano, Robert R.

2012-12-01

Optical biopsy spectroscopy was applied to diagnosis human brain cancer in vitro. The spectra of native fluorescence, Stokes shift and excitation spectra were obtained from malignant meningioma, benign, normal meningeal tissues and acoustic neuroma benign tissues. The wide excitation wavelength ranges were used to establish the criterion for distinguishing brain diseases. The alteration of fluorescence spectra between normal and abnormal brain tissues were identified by the characteristic fluorophores under the excitation with UV to visible wavelength range. It was found that the ratios of the peak intensities and peak position in both spectra of fluorescence and Stokes shift may be used to diagnose human brain meninges diseases. The preliminary analysis of fluorescence spectral data from cancer and normal meningeal tissues by basic biochemical component analysis model (BBCA) and Bayes classification model based on statistical methods revealed the changes of components, and classified the difference between cancer and normal human brain meningeal tissues in a predictions accuracy rate is 0.93 in comparison with histopathology and immunohistochemistry reports (gold standard).

Backscatter and attenuation properties of mammalian brain tissues

NASA Astrophysics Data System (ADS)

Wijekularatne, Pushpani Vihara

Traumatic Brain Injury (TBI) is a common category of brain injuries, which contributes to a substantial number of deaths and permanent disability all over the world. Ultrasound technology plays a major role in tissue characterization due to its low cost and portability that could be used to bridge a wide gap in the TBI diagnostic process. This research addresses the ultrasonic properties of mammalian brain tissues focusing on backscatter and attenuation. Orientation dependence and spatial averaging of data were analyzed using the same method resulting from insertion of tissue sample between a transducer and a reference reflector. Apparent backscatter transfer function (ABTF) at 1 to 10 MHz, attenuation coefficient and backscatter coefficient (BSC) at 1 to 5 MHz frequency ranges were measured on ovine brain tissue samples. The resulting ABTF was a monotonically decreasing function of frequency and the attenuation coefficient and BSC generally were increasing functions of frequency, results consistent with other soft tissues such as liver, blood and heart.

A Dense Poly(ethylene glycol) Coating Improves Penetration of Large Polymeric Nanoparticles within Brain Tissue

PubMed Central

Nance, Elizabeth A.; Woodworth, Graeme F.; Sailor, Kurt A.; Shih, Ting-Yu; Xu, Qingguo; Swaminathan, Ganesh; Xiang, Dennis; Eberhart, Charles; Hanes, Justin

2013-01-01

Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114-nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm, and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles, spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible. PMID:22932224

Determination of friction coefficient in unconfined compression of brain tissue.

PubMed

Rashid, Badar; Destrade, Michel; Gilchrist, Michael D

2012-10-01

Unconfined compression tests are more convenient to perform on cylindrical samples of brain tissue than tensile tests in order to estimate mechanical properties of the brain tissue because they allow homogeneous deformations. The reliability of these tests depends significantly on the amount of friction generated at the specimen/platen interface. Thus, there is a crucial need to find an approximate value of the friction coefficient in order to predict a possible overestimation of stresses during unconfined compression tests. In this study, a combined experimental-computational approach was adopted to estimate the dynamic friction coefficient μ of porcine brain matter against metal platens in compressive tests. Cylindrical samples of porcine brain tissue were tested up to 30% strain at variable strain rates, both under bonded and lubricated conditions in the same controlled environment. It was established that μ was equal to 0.09±0.03, 0.18±0.04, 0.18±0.04 and 0.20±0.02 at strain rates of 1, 30, 60 and 90/s, respectively. Additional tests were also performed to analyze brain tissue under lubricated and bonded conditions, with and without initial contact of the top platen with the brain tissue, with different specimen aspect ratios and with different lubricants (Phosphate Buffer Saline (PBS), Polytetrafluoroethylene (PTFE) and Silicone). The test conditions (lubricant used, biological tissue, loading velocity) adopted in this study were similar to the studies conducted by other research groups. This study will help to understand the amount of friction generated during unconfined compression of brain tissue for strain rates of up to 90/s. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dielectric properties of dog brain tissue measured in vitro across the 0.3-3 GHz band.

PubMed

Mohammed, Beadaa; Bialkowski, Konstanty; Abbosh, Amin; Mills, Paul C; Bradley, Andrew P

2016-09-22

Dielectric properties of dead Greyhound female dogs' brain tissues at different ages were measured at room temperature across the frequency range of 0.3-3 GHz. Measurements were made on excised tissues, in vitro in the laboratory, to carry out dielectric tests on sample tissues. Each dataset for a brain tissue was parametrized using the Cole-Cole expression, and the relevant Cole-Cole parameters for four tissue types are provided. A comparison was made with the database available in literature for other animals and human brain tissue. Results of two types of tissues (white matter and skull) showed systematic variation in dielectric properties as a function of animal age, whereas no significant change related to age was noticed for other tissues. Results provide critical information regarding dielectric properties of animal tissues for a realistic animal head model that can be used to verify the validity and reliability of a microwave head scanner for animals prior to testing on live animals. Bioelectromagnetics. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Brain tissue segmentation based on DTI data

PubMed Central

Liu, Tianming; Li, Hai; Wong, Kelvin; Tarokh, Ashley; Guo, Lei; Wong, Stephen T.C.

2008-01-01

We present a method for automated brain tissue segmentation based on the multi-channel fusion of diffusion tensor imaging (DTI) data. The method is motivated by the evidence that independent tissue segmentation based on DTI parametric images provides complementary information of tissue contrast to the tissue segmentation based on structural MRI data. This has important applications in defining accurate tissue maps when fusing structural data with diffusion data. In the absence of structural data, tissue segmentation based on DTI data provides an alternative means to obtain brain tissue segmentation. Our approach to the tissue segmentation based on DTI data is to classify the brain into two compartments by utilizing the tissue contrast existing in a single channel. Specifically, because the apparent diffusion coefficient (ADC) values in the cerebrospinal fluid (CSF) are more than twice that of gray matter (GM) and white matter (WM), we use ADC images to distinguish CSF and non-CSF tissues. Additionally, fractional anisotropy (FA) images are used to separate WM from non-WM tissues, as highly directional white matter structures have much larger fractional anisotropy values. Moreover, other channels to separate tissue are explored, such as eigenvalues of the tensor, relative anisotropy (RA), and volume ratio (VR). We developed an approach based on the Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm that combines these two-class maps to obtain a complete tissue segmentation map of CSF, GM, and WM. Evaluations are provided to demonstrate the performance of our approach. Experimental results of applying this approach to brain tissue segmentation and deformable registration of DTI data and spoiled gradient-echo (SPGR) data are also provided. PMID:17804258

Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue.

PubMed

Zhang, Jing; Fan, Yimeng; He, Min; Ma, Xuelei; Song, Yanlin; Liu, Ming; Xu, Jianguo

2017-05-30

Raman spectroscopy could be applied to distinguish tumor from normal tissues. This meta-analysis was conducted to assess the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. PubMed and Embase were searched to identify suitable studies prior to Jan 1st, 2016. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), diagnostic odds ratio (DOR), and constructed summary receiver operating characteristics (SROC) curves to identity the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. A total of six studies with 1951 spectra were included. For glioma, the pooled sensitivity and specificity of Raman spectroscopy were 0.96 (95% CI 0.94-0.97) and 0.99 (95% CI 0.98-0.99), respectively. The area under the curve (AUC) was 0.9831. For meningioma, the pooled sensitivity and specificity were 0.98 (95% CI 0.94-1.00) and 1.00 (95% CI 0.98-1.00), respectively. The AUC was 0.9955. This meta-analysis suggested that Raman spectroscopy could be an effective and accurate tool for differentiating glioma and meningioma from normal brain tissue, which would help us both avoid removal of normal tissue and minimize the volume of residual tumor.

The Identification of Aluminum in Human Brain Tissue Using Lumogallion and Fluorescence Microscopy

PubMed Central

Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

2016-01-01

Aluminum in human brain tissue is implicated in the etiologies of neurodegenerative diseases including Alzheimer’s disease. While methods for the accurate and precise measurement of aluminum in human brain tissue are widely acknowledged, the same cannot be said for the visualization of aluminum. Herein we have used transversely-heated graphite furnace atomic absorption spectrometry to measure aluminum in the brain of a donor with Alzheimer’s disease, and we have developed and validated fluorescence microscopy and the fluor lumogallion to show the presence of aluminum in the same tissue. Aluminum is observed as characteristic orange fluorescence that is neither reproduced by other metals nor explained by autofluorescence. This new and relatively simple method to visualize aluminum in human brain tissue should enable more rigorous testing of the aluminum hypothesis of Alzheimer’s disease (and other neurological conditions) in the future. PMID:27472886

Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; An Nguyen, Thien; Alfano, Robert R.

2014-06-01

Two-photon (2P) excitation of the second singlet (S) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S2 state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf.

PubMed

Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; Nguyen, Thien An; Alfano, Robert R

2014-06-01

Two-photon (2P) excitation of the second singlet (S₂) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S₂ state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S₂ state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

Conformable actively multiplexed high-density surface electrode array for brain interfacing

DOEpatents

Rogers, John; Kim, Dae-Hyeong; Litt, Brian; Viventi, Jonathan

2015-01-13

Provided are methods and devices for interfacing with brain tissue, specifically for monitoring and/or actuation of spatio-temporal electrical waveforms. The device is conformable having a high electrode density and high spatial and temporal resolution. A conformable substrate supports a conformable electronic circuit and a barrier layer. Electrodes are positioned to provide electrical contact with a brain tissue. A controller monitors or actuates the electrodes, thereby interfacing with the brain tissue. In an aspect, methods are provided to monitor or actuate spatio-temporal electrical waveform over large brain surface areas by any of the devices disclosed herein.

Unifying framework for multimodal brain MRI segmentation based on Hidden Markov Chains.

PubMed

Bricq, S; Collet, Ch; Armspach, J P

2008-12-01

In the frame of 3D medical imaging, accurate segmentation of multimodal brain MR images is of interest for many brain disorders. However, due to several factors such as noise, imaging artifacts, intrinsic tissue variation and partial volume effects, tissue classification remains a challenging task. In this paper, we present a unifying framework for unsupervised segmentation of multimodal brain MR images including partial volume effect, bias field correction, and information given by a probabilistic atlas. Here-proposed method takes into account neighborhood information using a Hidden Markov Chain (HMC) model. Due to the limited resolution of imaging devices, voxels may be composed of a mixture of different tissue types, this partial volume effect is included to achieve an accurate segmentation of brain tissues. Instead of assigning each voxel to a single tissue class (i.e., hard classification), we compute the relative amount of each pure tissue class in each voxel (mixture estimation). Further, a bias field estimation step is added to the proposed algorithm to correct intensity inhomogeneities. Furthermore, atlas priors were incorporated using probabilistic brain atlas containing prior expectations about the spatial localization of different tissue classes. This atlas is considered as a complementary sensor and the proposed method is extended to multimodal brain MRI without any user-tunable parameter (unsupervised algorithm). To validate this new unifying framework, we present experimental results on both synthetic and real brain images, for which the ground truth is available. Comparison with other often used techniques demonstrates the accuracy and the robustness of this new Markovian segmentation scheme.

Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

PubMed

Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

2009-01-01

This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

In vivo evaluation of needle force and friction stress during insertion at varying insertion speed into the brain.

PubMed

Casanova, Fernando; Carney, Paul R; Sarntinoranont, Malisa

2014-11-30

Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in tissue damage which can promote flowback along the needle track and improper targeting. The goal of this study was to evaluate friction stress (calculated from needle insertion force) as a measure of tissue contact and damage during needle insertion for varying insertion speeds. Forces and surface dimpling during needle insertion were measured in rat brain in vivo. Needle retraction forces were used to calculate friction stresses. These measures were compared to track damage from a previous study. Differences between brain tissues and soft hydrogels were evaluated for varying insertion speeds: 0.2, 2, and 10mm/s. In brain tissue, average insertion force and surface dimpling increased with increasing insertion speed. Average friction stress along the needle-tissue interface decreased with insertion speed (from 0.58 ± 0.27 to 0.16 ± 0.08 kPa). Friction stress varied between brain regions: cortex (0.227 ± 0.27 kPa), external capsule (0.222 ± 0.19 kPa), and CPu (0.383 ± 0.30 kPa). Hydrogels exhibited opposite trends for dimpling and friction stress with insertion speed. Previously, increasing needle damage with insertion speed has been measured with histological methods. Friction stress appears to decrease with increasing tissue damage and decreasing tissue contact, providing the potential for in vivo and real time evaluation along the needle track. Force derived friction stress decreased with increasing insertion speed and was smaller within white matter regions. Hydrogels exhibited opposite trends to brain tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

Non-invasive intraoperative optical coherence tomography of the resection cavity during surgery of intrinsic brain tumors

NASA Astrophysics Data System (ADS)

Giese, A.; Böhringer, H. J.; Leppert, J.; Kantelhardt, S. R.; Lankenau, E.; Koch, P.; Birngruber, R.; Hüttmann, G.

2006-02-01

Optical coherence tomography (OCT) is a non-invasive imaging technique with a micrometer resolution. It allows non-contact / non-invasive analysis of central nervous system tissues with a penetration depth of 1-3,5 mm reaching a spatial resolution of approximately 4-15 μm. We have adapted spectral-domain OCT (SD-OCT) and time-domain OCT (TD-OCT) for intraoperative detection of residual tumor during brain tumor surgery. Human brain tumor tissue and areas of the resection cavity were analyzed during the resection of gliomas using this new technology. The site of analysis was registered using a neuronavigation system and biopsies were taken and submitted to routine histology. We have used post image acquisition processing to compensate for movements of the brain and to realign A-scan images for calculation of a light attenuation factor. OCT imaging of normal cortex and white matter showed a typical light attenuation profile. Tumor tissue depending on the cellularity of the specimen showed a loss of the normal light attenuation profile resulting in altered light attenuation coefficients compared to normal brain. Based on this parameter and the microstructure of the tumor tissue, which was entirely absent in normal tissue, OCT analysis allowed the discrimination of normal brain tissue, invaded brain, solid tumor tissue, and necrosis. Following macroscopically complete resections OCT analysis of the resection cavity displayed the typical microstructure and light attenuation profile of tumor tissue in some specimens, which in routine histology contained microscopic residual tumor tissue. We have demonstrated that this technology may be applied to the intraoperative detection of residual tumor during resection of human gliomas.

Enhancement of Sexual Behavior in Female Rats by Neonatal Transplantation of Brain Tissue from Males

NASA Astrophysics Data System (ADS)

Arendash, Gary W.; Gorski, Roger A.

1982-09-01

Transplantation of preoptic tissue from male rat neonates into the preoptic area of female littermates increased masculine and feminine sexual behavior in the recipients during adulthood. This suggests that functional connections develop between the transplanted neural tissue and the host brain. A new intraparenchymal brain transplantation technique was used to achieve these results.

Multimodal optical coherence tomography for in vivo imaging of brain tissue structure and microvascular network at glioblastoma

NASA Astrophysics Data System (ADS)

Yashin, Konstantin S.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Karabut, Maria M.; Elagin, Vadim V.; Sirotkina, Marina A.; Medyanik, Igor A.; Kravets, L. Y.; Gladkova, Natalia D.

2017-02-01

In the case of infiltrative brain tumors the surgeon faces difficulties in determining their boundaries to achieve total resection. The aim of the investigation was to evaluate the performance of multimodal OCT (MM OCT) for differential diagnostics of normal brain tissue and glioma using an experimental model of glioblastoma. The spectral domain OCT device that was used for the study provides simultaneously two modes: cross-polarization and microangiographic OCT. The comparative analysis of the both OCT modalities images from tumorous and normal brain tissue areas concurrently with histologic correlation shows certain difference between when accordingly to morphological and microvascular tissue features.

Influence of strain rate on indentation response of porcine brain.

PubMed

Qian, Long; Zhao, Hongwei; Guo, Yue; Li, Yuanshang; Zhou, Mingxing; Yang, Liguo; Wang, Zhiwei; Sun, Yifan

2018-06-01

Knowledge of brain tissue mechanical properties may be critical for formulating hypotheses about some specific diseases mechanisms and its accurate simulations such as traumatic brain injury (TBI) and tumor growth. Compared to traditional tests (e.g. tensile and compression), indentation shows superiority by virtue of its pinpoint and nondestructive/quasi-nondestructive. As a viscoelastic material, the properties of brain tissue depend on the strain rate by definition. However most efforts focus on the aspect of velocity in the field of brain indentation, rather than strain rate. The influence of strain rate on indentation response of brain tissue is taken little attention. Further, by comparing different results from literatures, it is also obvious that strain rate rather than velocity is more appropriate to characterize mechanical properties of brain. In this paper, to systematically characterize the influence of strain rate, a series of indentation-relaxation tests n = 210) are performed on the cortex of porcine brain using a custom-designed indentation device. The mechanical response that correlates with indenter diameters, depths of indentation and velocities, is revealed for the indentation portion, and elastic behavior of brain tissue is analyzed as the function of strain rate. Similarly, a linear viscoelastic model with a Prony series is employed for the indentation-relaxation portion, wherein the brain tissue shows more viscous and responds more quickly with increasing strain rate. Understanding the effect of strain rate on mechanical properties of brain indentation may be far-reaching for brain injury biomechanics and accurate simulations, but be important for bridging between indentation results of different literatures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Near infrared Raman spectra of human brain lipids

NASA Astrophysics Data System (ADS)

Krafft, Christoph; Neudert, Lars; Simat, Thomas; Salzer, Reiner

2005-05-01

Human brain tissue, in particular white matter, contains high lipid content. These brain lipids can be divided into three principal classes: neutral lipids including the steroid cholesterol, phospholipids and sphingolipids. Major lipids in normal human brain tissue are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, sphingomyelin, galactocerebrosides, gangliosides, sulfatides and cholesterol. Minor lipids are cholesterolester and triacylglycerides. During transformation from normal brain tissue to tumors, composition and concentration of lipids change in a specific way. Therefore, analysis of lipids might be used as a diagnostic parameter to distinguish normal tissue from tumors and to determine the tumor type and tumor grade. Raman spectroscopy has been suggested as an analytical tool to detect these changes even under intra-operative conditions. We recorded Raman spectra of the 12 major and minor brain lipids with 785 nm excitation in order to identify their spectral fingerprints for qualitative and quantitative analyses.

VA's National PTSD Brain Bank: a National Resource for Research.

PubMed

Friedman, Matthew J; Huber, Bertrand R; Brady, Christopher B; Ursano, Robert J; Benedek, David M; Kowall, Neil W; McKee, Ann C

2017-08-25

The National PTSD Brain Bank (NPBB) is a brain tissue biorepository established to support research on the causes, progression, and treatment of PTSD. It is a six-part consortium led by VA's National Center for PTSD with participating sites at VA medical centers in Boston, MA; Durham, NC; Miami, FL; West Haven, CT; and White River Junction, VT along with the Uniformed Services University of Health Sciences. It is also well integrated with VA's Boston-based brain banks that focus on Alzheimer's disease, ALS, chronic traumatic encephalopathy, and other neurological disorders. This article describes the organization and operations of NPBB with specific attention to: tissue acquisition, tissue processing, diagnostic assessment, maintenance of a confidential data biorepository, adherence to ethical standards, governance, accomplishments to date, and future challenges. Established in 2014, NPBB has already acquired and distributed brain tissue to support research on how PTSD affects brain structure and function.

Fingolimod inhibits brain atrophy and promotes brain-derived neurotrophic factor in an animal model of multiple sclerosis.

PubMed

Smith, Paul A; Schmid, Cindy; Zurbruegg, Stefan; Jivkov, Magali; Doelemeyer, Arno; Theil, Diethilde; Dubost, Valérie; Beckmann, Nicolau

2018-05-15

Longitudinal brain atrophy quantification is a critical efficacy measurement in multiple sclerosis (MS) clinical trials and the determination of No Evidence of Disease Activity (NEDA). Utilising fingolimod as a clinically validated therapy we evaluated the use of repeated brain tissue volume measures during chronic experimental autoimmune encephalomyelitis (EAE) as a new preclinical efficacy measure. Brain volume changes were quantified using magnetic resonance imaging (MRI) at 7 Tesla and correlated to treatment-induced brain derived neurotrophic factor (BDNF) measured in blood, cerebrospinal fluid, spinal cord and brain. Serial brain MRI measurements revealed slow progressive brain volume loss in vehicle treated EAE mice despite a stable clinical score. Fingolimod (1 mg/kg) significantly ameliorated brain tissue atrophy in the cerebellum and striatum when administered from established EAE disease onwards. Fingolimod-dependent tissue preservation was associated with induction of BDNF specifically within the brain and co-localized with neuronal soma. In contrast, therapeutic teriflunomide (3 mg/kg) treatment failed to inhibit CNS autoimmune mediated brain degeneration. Finally, weekly anti-IL-17A antibody (15 mg/kg) treatment was highly efficacious and preserved whole brain, cerebellum and striatum volume. Fingolimod-mediated BDNF increases within the CNS may contribute to limiting progressive tissue loss during chronic neuroinflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

[The usefulness of in vitro interferon-gamma assay for differential diagnosis between intestinal tuberculosis and Crohns disease].

PubMed

Lee, Jung Nam; Ryu, Dong Yup; Park, Sung Han; You, Hyun Seok; Lee, Bong Eun; Kim, Dong Uk; Kim, Tae Oh; Heo, Jeong; Kim, Gwang Ha; Song, Geun Am; Kim, Suk; Park, Do Youn

2010-06-01

It is difficult to clinically and endoscopically differentiate intestinal tuberculosis (ITB) and Crohns disease (CD). The aim of this study was to evaluate the usefulness of in vitro interferon-gamma (INF-gamma) assay for differential diagnosis between ITB and CD. Sixty patients for whom differential diagnosis between ITB and CD was difficult were enrolled between January 2007 and January 2009. The INF-gamma-producing T-cell response to early secreted antigenic target 6 and culture filtrate protein 10 were measured by T-SPOT.TB blood test in vitro. We evaluated the usefulness of T-SPOT.TB blood test by comparing its results with the final diagnosis. Twenty and forty patients were revealed to be positive and negative in T-SPOT.TB blood test, respectively. Of the 20 patients found to be positive, 12 patients (60%) were finally diagnosed as ITB, 6 patients as CD, and 2 patients as Behcets enterocolitis. Of the 40 patients with negative results, 38 patients (95%) were diagnosed as CD; one as Behcets enterocolitis; one as nonspecific colitis; none as ITB. The sensitivity and specificity of T-SPOT.TB blood test for ITB were 100% and 83.3%, respectively. Positive and negative predictive values of T-SPOT.TB blood test for ITB were 60.0% and 100%, respectively. When differential diagnosis between ITB and CD is difficult, T-SPOT.TB blood test may be a helpful and rapid diagnostic tool to exclude ITB. Prospective large-scaled studies are required for further evaluation of the usefulness of T-SPOT.TB blood test for differential diagnosis between ITB and CD.

Behcet's disease in Budd-Chiari syndrome.

PubMed

Desbois, Anne Claire; Rautou, Pierre Emmanuel; Biard, Lucie; Belmatoug, Nadia; Wechsler, Bertrand; Resche-Rigon, Mathieu; Zarrouk, Virginie; Fantin, Bruno; de Chambrun, M Pineton; Cacoub, Patrice; Valla, Dominique; Saadoun, David; Plessier, Aurélie

2014-01-01

Behcet's disease (BD) is a well-known cause of Budd-Chiari syndrome (BCS). Data are lacking on the presentation and outcome of BCS related to BD. We investigated the relationship between BD and BCS in 14 patients with both diseases and compared the results to 92 BCS patients without BD. Male gender (p = 0.003), North African origin (P = 0.007) and inferior vena cava obstruction (P < 0.0001) were more frequent in patients with BD and BCS than in those with BCS alone and the plasma C-reactive protein level was higher (p = 0.003). Two of the patients with the combined diseases underwent recanalization of the vena cava and the hepatic veins, none received transjugular intrahepatic portosystemic shunts (TIPS), one received a surgical shunt and one underwent liver transplantation. TIPS were less frequent in patients with BD and BCS than in those with BCS alone (P = 0.019). Eighty six per cent of patients with BCS and BD received corticosteroids and immunosuppressive therapy. The 5-year transplantation-free survival rate was 63% in patients with BCS alone and 91% in those without BD (P = 0.11). In our series and in the literature, a high number of patients [12 (61.5%) and 11 (64.7%) respectively] treated with anticoagulation and corticosteroids and/or immunosuppressants did not require invasive treatment. This study shows a higher frequency of IVC obstruction in patients with BCS and BD. Medical treatment with anticoagulation and immunosuppressive agents may improve the symptoms of BCS. Therefore early management with immunosuppressive and anticoagulation therapy appears to be the treatment of choice in patients with BCS and BD.

Epileptic seizures in Neuro-Behcet disease: why some patients develop seizure and others not?

PubMed

Kutlu, Gulnihal; Semercioglu, Sencer; Ucler, Serap; Erdal, Abidin; Inan, Levent E

2015-03-01

Behcet disease (BD) is a chronic relapsing inflammatory disorder. Neuro BD (NBD) is seen in approximately 5% of all patients. The aim of this study is to investigate the frequency, type and prognosis of epileptic seizures in different forms of NBD. All files of 42 patients with NBD were evaluated between 2006 and 2012, retrospectively. The demographic data, the presentation of NBD, clinical findings including seizures, EEG and neuroimaging findings were reviewed. The mean age of patients was 35.02±8.43 years. Thirty (71.4%) patients were male; the remaining 12 of them were female. Twenty-four patients had brainstem lesions; 16 patients had cerebral venous thrombosis. Spinal cord involvement was seen in two patients. Seven patients had epileptic seizures (six partial onset seizures with or without secondary generalization). Six of them had cerebral sinus thrombosis (CVT). Four patients had a seizure as the first symptom of the thrombosis. One patient had late onset seizure due to chronic venous infarct. The other patient with seizure had brainstem involvement. The remaining was diagnosed as epilepsy before the determination of NBD. CVT seen in BD seems to be the main risk factor for epileptic seizures in patients with NBD. The prognosis is usually good especially in patients with CVT. Epileptic seizures in patients with brainstem involvement may be an indicator for poor prognosis. Superior sagittal thrombosis or cortical infarct would be predictor of seizures occurrence because of the high ratio in patients with seizures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Quantifying structural alterations in Alzheimer's disease brains using quantitative phase imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, Moosung; Lee, Eeksung; Jung, JaeHwang; Yu, Hyeonseung; Kim, Kyoohyun; Yoon, Jonghee; Lee, Shinhwa; Jeong, Yong; Park, YongKeun

2017-02-01

Imaging brain tissues is an essential part of neuroscience because understanding brain structure provides relevant information about brain functions and alterations associated with diseases. Magnetic resonance imaging and positron emission tomography exemplify conventional brain imaging tools, but these techniques suffer from low spatial resolution around 100 μm. As a complementary method, histopathology has been utilized with the development of optical microscopy. The traditional method provides the structural information about biological tissues to cellular scales, but relies on labor-intensive staining procedures. With the advances of illumination sources, label-free imaging techniques based on nonlinear interactions, such as multiphoton excitations and Raman scattering, have been applied to molecule-specific histopathology. Nevertheless, these techniques provide limited qualitative information and require a pulsed laser, which is difficult to use for pathologists with no laser training. Here, we present a label-free optical imaging of mouse brain tissues for addressing structural alteration in Alzheimer's disease. To achieve the mesoscopic, unlabeled tissue images with high contrast and sub-micrometer lateral resolution, we employed holographic microscopy and an automated scanning platform. From the acquired hologram of the brain tissues, we could retrieve scattering coefficients and anisotropies according to the modified scattering-phase theorem. This label-free imaging technique enabled direct access to structural information throughout the tissues with a sub-micrometer lateral resolution and presented a unique means to investigate the structural changes in the optical properties of biological tissues.

In vivo mapping of current density distribution in brain tissues during deep brain stimulation (DBS)

NASA Astrophysics Data System (ADS)

Sajib, Saurav Z. K.; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

2017-01-01

New methods for in vivo mapping of brain responses during deep brain stimulation (DBS) are indispensable to secure clinical applications. Assessment of current density distribution, induced by internally injected currents, may provide an alternative method for understanding the therapeutic effects of electrical stimulation. The current flow and pathway are affected by internal conductivity, and can be imaged using magnetic resonance-based conductivity imaging methods. Magnetic resonance electrical impedance tomography (MREIT) is an imaging method that can enable highly resolved mapping of electromagnetic tissue properties such as current density and conductivity of living tissues. In the current study, we experimentally imaged current density distribution of in vivo canine brains by applying MREIT to electrical stimulation. The current density maps of three canine brains were calculated from the measured magnetic flux density data. The absolute current density values of brain tissues, including gray matter, white matter, and cerebrospinal fluid were compared to assess the active regions during DBS. The resulting current density in different tissue types may provide useful information about current pathways and volume activation for adjusting surgical planning and understanding the therapeutic effects of DBS.

Effects of positive end-expiratory pressure on brain tissue oxygen pressure of severe traumatic brain injury patients with acute respiratory distress syndrome: A pilot study.

PubMed

Nemer, Sérgio Nogueira; Caldeira, Jefferson B; Santos, Ricardo G; Guimarães, Bruno L; Garcia, João Márcio; Prado, Darwin; Silva, Ricardo T; Azeredo, Leandro M; Faria, Eduardo R; Souza, Paulo Cesar P

2015-12-01

To verify whether high positive end-expiratory pressure levels can increase brain tissue oxygen pressure, and also their effects on pulse oxygen saturation, intracranial pressure, and cerebral perfusion pressure. Twenty traumatic brain injury patients with acute respiratory distress syndrome were submitted to positive end-expiratory pressure levels of 5, 10, and 15 cm H2O progressively. The 3 positive end-expiratory pressure levels were used during 20 minutes for each one, whereas brain tissue oxygen pressure, oxygen saturation, intracranial pressure, and cerebral perfusion pressure were recorded. Brain tissue oxygen pressure and oxygen saturation increased significantly with increasing positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.0001 and P=.0001 respectively). Intracranial pressure and cerebral perfusion pressure did not differ significantly with increasing positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.16 and P=.79 respectively). High positive end-expiratory pressure levels increased brain tissue oxygen pressure and oxygen saturation, without increase in intracranial pressure or decrease in cerebral perfusion pressure. High positive end-expiratory pressure levels can be used in severe traumatic brain injury patients with acute respiratory distress syndrome as a safe alternative to improve brain oxygenation. Copyright © 2015 Elsevier Inc. All rights reserved.

Pharmacokinetics and brain penetration of carbapenems in mice.

PubMed

Matsumoto, Kazuaki; Kurihara, Yuji; Kuroda, Yuko; Hori, Seiji; Kizu, Junko

2016-05-01

An adverse effect associated with the administration of carbapenems is central nervous system (CNS) toxicity, with higher brain concentrations of carbapenems being linked to an increased risk of seizures. However, the pharmacokinetics and brain penetration of carbapenems have not yet been examined. Thus, the aim of this in vivo investigation was to determine the pharmacokinetics and brain penetration of carbapenems in mice. Blood samples and brain tissue samples were obtained 10, 20, 30, 60, and 120 min after the subcutaneous administration of carbapenems (91 mg/kg). We obtained the following values for the pharmacokinetic parameters of carbapenems in mice: 1.20-1.71 L/h/kg for CLtotal/F, 1.41-2.03 h(-1) for Ke, 0.34-0.51 h for T1/2, 0.66-0.95 L/kg for Vss/F, 0.49-0.73 h for MRT, 83.46-110.58 μg/mL for Cmax, plasma, and 0.28-0.83 μg/g for Cmax, brain tissue. The AUC0-∞ of the carbapenems tested in plasma were in the following order: doripenem > meropenem > biapenem > imipenem, and in brain tissue were: imipenem > doripenem > meropenem > biapenem. The degrees of brain tissue penetration, defined as the AUC0-∞, brain tissue/fAUC0-∞, plasma ratio, were 0.016 for imipenem, 0.004 for meropenem, 0.002 for biapenem, and 0.008 for doripenem. The results of the present study demonstrated that, of the carbapenems examined, imipenem penetrated brain tissue to the greatest extent. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research.

PubMed

Walton, Esther; Hass, Johanna; Liu, Jingyu; Roffman, Joshua L; Bernardoni, Fabio; Roessner, Veit; Kirsch, Matthias; Schackert, Gabriele; Calhoun, Vince; Ehrlich, Stefan

2016-03-01

Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns the extent to which epigenetic signatures measured in more accessible tissues such as blood can serve as a surrogate marker for the brain. Here, we aimed (1) to investigate the blood-brain correspondence of DNA methylation using a within-subject design and (2) to identify changes in DNA methylation of brain-related biological pathways in schizophrenia.We obtained paired blood and temporal lobe biopsy samples simultaneously from 12 epilepsy patients during neurosurgical treatment. Using the Infinium 450K methylation array we calculated similarity of blood and brain DNA methylation for each individual separately. We applied our findings by performing gene set enrichment analyses (GSEA) of peripheral blood DNA methylation data (Infinium 27K) of 111 schizophrenia patients and 122 healthy controls and included only Cytosine-phosphate-Guanine (CpG) sites that were significantly correlated across tissues.Only 7.9% of CpG sites showed a statistically significant, large correlation between blood and brain tissue, a proportion that although small was significantly greater than predicted by chance. GSEA analysis of schizophrenia data revealed altered methylation profiles in pathways related to precursor metabolites and signaling peptides.Our findings indicate that most DNA methylation markers in peripheral blood do not reliably predict brain DNA methylation status. However, a subset of peripheral data may proxy methylation status of brain tissue. Restricting the analysis to these markers can identify meaningful epigenetic differences in schizophrenia and potentially other brain disorders. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Predicting Intracranial Pressure and Brain Tissue Oxygen Crises in Patients With Severe Traumatic Brain Injury.

PubMed

Myers, Risa B; Lazaridis, Christos; Jermaine, Christopher M; Robertson, Claudia S; Rusin, Craig G

2016-09-01

To develop computer algorithms that can recognize physiologic patterns in traumatic brain injury patients that occur in advance of intracranial pressure and partial brain tissue oxygenation crises. The automated early detection of crisis precursors can provide clinicians with time to intervene in order to prevent or mitigate secondary brain injury. A retrospective study was conducted from prospectively collected physiologic data. intracranial pressure, and partial brain tissue oxygenation crisis events were defined as intracranial pressure of greater than or equal to 20 mm Hg lasting at least 15 minutes and partial brain tissue oxygenation value of less than 10 mm Hg for at least 10 minutes, respectively. The physiologic data preceding each crisis event were used to identify precursors associated with crisis onset. Multivariate classification models were applied to recorded data in 30-minute epochs of time to predict crises between 15 and 360 minutes in the future. The neurosurgical unit of Ben Taub Hospital (Houston, TX). Our cohort consisted of 817 subjects with severe traumatic brain injury. Our algorithm can predict the onset of intracranial pressure crises with 30-minute advance warning with an area under the receiver operating characteristic curve of 0.86 using only intracranial pressure measurements and time since last crisis. An analogous algorithm can predict the start of partial brain tissue oxygenation crises with 30-minute advanced warning with an area under the receiver operating characteristic curve of 0.91. Our algorithms provide accurate and timely predictions of intracranial hypertension and tissue hypoxia crises in patients with severe traumatic brain injury. Almost all of the information needed to predict the onset of these events is contained within the signal of interest and the time since last crisis.

Detection of Human Brain Cancer Infiltration ex vivo and in vivo Using Quantitative Optical Coherence Tomography*

PubMed Central

Kut, Carmen; Chaichana, Kaisorn L.; Xi, Jiefeng; Raza, Shaan M.; Ye, Xiaobu; McVeigh, Elliot R.; Rodriguez, Fausto J.; Quinones-Hinojosa, Alfredo; Li, Xingde

2015-01-01

More complete brain cancer resection can prolong survival and delay recurrence. However, it is challenging to distinguish cancer from non-cancer tissues intraoperatively, especially at the transitional, infiltrative zones. This is especially critical in eloquent regions (e.g. speech and motor areas). This study tested the feasibility of label-free, quantitative optical coherence tomography (OCT) for differentiating cancer from non-cancer in human brain tissues. Fresh ex vivo human brain tissues were obtained from 32 patients with grades II-IV brain cancer and 5 patients with non-cancer brain pathologies. Based on volumetric OCT imaging data, pathologically confirmed brain cancer tissues (both high-grade and low-grade) had significantly lower optical attenuation values at both cancer core and infiltrated zones when compared with non-cancer white matter, and OCT achieved high sensitivity and specificity at an attenuation threshold of 5.5 mm-1 for brain cancer patients. We also used this attenuation threshold to confirm the intraoperative feasibility of performing in vivo OCT-guided surgery using a murine model harboring human brain cancer. Our OCT system was capable of processing and displaying a color-coded optical property map in real time at a rate of 110-215 frames per second, or 1.2-2.4 seconds for an 8-16 mm3 tissue volume, thus providing direct visual cues for cancer versus non-cancer areas. Our study demonstrates the translational and practical potential of OCT in differentiating cancer from non-cancer tissue. Its intraoperative use may facilitate safe and extensive resection of infiltrative brain cancers and consequently lead to improved outcomes when compared with current clinical standards. PMID:26084803

Extracellular Nucleotides in Exercise: Possible Effect on Brain Metabolism.

ERIC Educational Resources Information Center

Forrester, Tom

1979-01-01

A review of experiments which demonstrate the release of ATP from skeletal muscle, cardiac muscle, and active brain tissue. Effects of exogenously applied ATP to brain tissue are discussed in relation to whole body exercise. (Author/SA)

A spatiotemporal atlas of MR intensity, tissue probability and shape of the fetal brain with application to segmentation

PubMed Central

Habas, Piotr A.; Kim, Kio; Corbett-Detig, James M.; Rousseau, Francois; Glenn, Orit A.; Barkovich, A. James; Studholme, Colin

2010-01-01

Modeling and analysis of MR images of the developing human brain is a challenge due to rapid changes in brain morphology and morphometry. We present an approach to the construction of a spatiotemporal atlas of the fetal brain with temporal models of MR intensity, tissue probability and shape changes. This spatiotemporal model is created from a set of reconstructed MR images of fetal subjects with different gestational ages. Groupwise registration of manual segmentations and voxelwise nonlinear modeling allow us to capture the appearance, disappearance and spatial variation of brain structures over time. Applying this model to atlas-based segmentation, we generate age-specific MR templates and tissue probability maps and use them to initialize automatic tissue delineation in new MR images. The choice of model parameters and the final performance are evaluated using clinical MR scans of young fetuses with gestational ages ranging from 20.57 to 24.71 weeks. Experimental results indicate that quadratic temporal models can correctly capture growth-related changes in the fetal brain anatomy and provide improvement in accuracy of atlas-based tissue segmentation. PMID:20600970

Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

PubMed

Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

2017-06-22

Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro terahertz spectroscopy of gelatin-embedded human brain tumors: a pilot study

NASA Astrophysics Data System (ADS)

Chernomyrdin, N. V.; Gavdush, A. A.; Beshplav, S.-I. T.; Malakhov, K. M.; Kucheryavenko, A. S.; Katyba, G. M.; Dolganova, I. N.; Goryaynov, S. A.; Karasik, V. E.; Spektor, I. E.; Kurlov, V. N.; Yurchenko, S. O.; Komandin, G. A.; Potapov, A. A.; Tuchin, V. V.; Zaytsev, K. I.

2018-04-01

We have performed the in vitro terahertz (THz) spectroscopy of human brain tumors. In order to fix tissues for the THz measurements, we have applied the gelatin embedding. It allows for preserving tissues from hydration/dehydration and sustaining their THz response similar to that of the freshly-excised tissues for a long time after resection. We have assembled an experimental setup for the reflection-mode measurements of human brain tissues based on the THz pulsed spectrometer. We have used this setup to study in vitro the refractive index and the amplitude absorption coefficient of 2 samples of malignant glioma (grade IV), 1 sample of meningioma (grade I), and samples of intact tissues. We have observed significant differences between the THz responses of normal and pathological tissues of the brain. The results of this paper highlight the potential of the THz technology in the intraoperative neurodiagnosis of tumors relying on the endogenous labels of tumorous tissues.

Gene expression profiles help identify the tissue of origin for metastatic brain cancers.

PubMed

Wu, Alan H B; Drees, Julia C; Wang, Hangpin; VandenBerg, Scott R; Lal, Anita; Henner, William D; Pillai, Raji

2010-04-26

Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases. This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

PubMed Central

2010-01-01

Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers. PMID:20420692

Effect of baculovirus P35 protein on apoptosis in brain tissue of rats with acute cerebral infarction.

PubMed

Ji, J F; Ma, X H

2015-08-10

We explored the effect of baculovirus P35 protein on apoptosis in the brain tissue of rats with acute cerebral infarction (ACI). A rat model of middle cerebral artery infarction was created. The rats were randomly divided into sham, model, and treatment groups. Baculovirus P35 protein was injected into the intracranial arteries of the treatment group rats. The rats in the model group were given an equal volume of phosphate-buffered saline. The rats were sacrificed after 72 h and the brain tissue was separated. The levels of caspase-3, Bcl-2, and Bax mRNA, the brain cell apoptosis index, and the infarct size were determined. After 72 h, the levels of caspase-3 and Bax mRNA in the model and treatment groups were significantly greater than in the sham group, and the levels of Bcl-2 mRNA were significantly smaller (P < 0.05). The levels of caspase-3 and Bax mRNA were significantly lower in the treatment group than in the model group, and the level of Bcl-2 mRNA was significantly greater (P < 0.05). Compared with the sham group, the brain tissue apoptosis index and the cerebral infarction area increased significantly in the model and treatment groups (P < 0.05). The brain tissue apoptosis index and cerebral infarction area in the treatment group were significantly lower than in the model group (P < 0.05). Baculovirus P35 protein can effectively inhibit brain cell apoptosis in rats with ACI. It delayed apoptosis and necrosis in subjects with ACI tissue and had a protective effect on brain tissue.

Quantitative assessment of brain tissue oxygenation in porcine models of cardiac arrest and cardiopulmonary resuscitation using hyperspectral near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Lotfabadi, Shahin S.; Toronov, Vladislav; Ramadeen, Andrew; Hu, Xudong; Kim, Siwook; Dorian, Paul; Hare, Gregory M. T.

2014-03-01

Near-infrared spectroscopy (NIRS) is a non-invasive tool to measure real-time tissue oxygenation in the brain. In an invasive animal experiment we were able to directly compare non-invasive NIRS measurements on the skull with invasive measurements directly on the brain dura matter. We used a broad-band, continuous-wave hyper-spectral approach to measure tissue oxygenation in the brain of pigs under the conditions of cardiac arrest, cardiopulmonary resuscitation (CPR), and defibrillation. An additional purpose of this research was to find a correlation between mortality due to cardiac arrest and inadequacy of the tissue perfusion during attempts at resuscitation. Using this technique we measured the changes in concentrations of oxy-hemoglobin [HbO2] and deoxy-hemoglobin [HHb] to quantify the tissue oxygenation in the brain. We also extracted cytochrome c oxidase changes Δ[Cyt-Ox] under the same conditions to determine increase or decrease in cerebral oxygen delivery. In this paper we proved that applying CPR, [HbO2] concentration and tissue oxygenation in the brain increase while [HHb] concentration decreases which was not possible using other measurement techniques. We also discovered a similar trend in changes of both [Cyt-Ox] concentration and tissue oxygen saturation (StO2). Both invasive and non-invasive measurements showed similar results.

Multimodality instrument for tissue characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2004-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration. The use of this system will make surgical procedures safer, more accurate, and more efficient. Other applications of this system include the detection, prognosis and treatment of breast cancer, prostate cancer, spinal diseases, and use in general exploratory surgery.

Therapeutic Ultrasound Enhancement of Drug Delivery to Soft Tissues

NASA Astrophysics Data System (ADS)

Lewis, George; Wang, Peng; Lewis, George; Olbricht, William

2009-04-01

Effects of exposure to 1.58 MHz focused ultrasound on transport of Evans Blue Dye (EBD) in soft tissues are investigated when an external pressure gradient is applied to induce convective flow through the tissue. The magnitude of the external pressure gradient is chosen to simulate conditions in brain parenchyma during convection-enhanced drug delivery (CED) to the brain. EBD uptake and transport are measured in equine brain, avian muscle and agarose brain-mimicking phantoms. Results show that ultrasound enhances EBD uptake and transport, and the greatest enhancement occurs when the external pressure gradient is applied. The results suggest that exposure of the brain parenchyma to ultrasound could enhance penetration of material infused into the brain during CED therapy.

Development of an experimental model of brain tissue heterotopia in the lung

PubMed Central

Quemelo, Paulo Roberto Veiga; Sbragia, Lourenço; Peres, Luiz Cesar

2007-01-01

Summary The presence of heterotopic brain tissue in the lung is a rare abnormality. The cases reported thus far are usually associated with neural tube defects (NTD). As there are no reports of experimental models of NTD that present this abnormality, the objective of the present study was to develop a surgical method of brain tissue heterotopia in the lung. We used 24 pregnant Swiss mice divided into two groups of 12 animals each, denoted 17GD and 18GD according to the gestational day (GD) when caesarean section was performed to collect the fetuses. Surgery was performed on the 15th GD, one fetus was removed by hysterectomy and its brain tissue was cut into small fragments and implanted in the lung of its litter mates. Thirty-four live fetuses were obtained from the 17GD group. Of these, eight (23.5%) were used as control (C), eight (23.5%) were sham operated (S) and 18 (52.9%) were used for pulmonary brain tissue implantation (PBI). Thirty live fetuses were obtained from the females of the 18GD group. Of these, eight (26.6%) were C, eight (26.6%) S and 14 (46.6%) were used for PBI. Histological examination of the fetal trunks showed implantation of GFAP-positive brain tissue in 85% of the fetuses of the 17GD group and in 100% of those of the 18GD group, with no significant difference between groups for any of the parameters analysed. The experimental model proved to be efficient and of relatively simple execution, showing complete integration of the brain tissue with pulmonary and pleural tissue and thus representing a model that will permit the study of different aspects of cell implantation and interaction. PMID:17877535

Biochemical Fractionation and Stable Isotope Dilution Liquid Chromatography-mass Spectrometry for Targeted and Microdomain-specific Protein Quantification in Human Postmortem Brain Tissue*

PubMed Central

MacDonald, Matthew L.; Ciccimaro, Eugene; Prakash, Amol; Banerjee, Anamika; Seeholzer, Steven H.; Blair, Ian A.; Hahn, Chang-Gyu

2012-01-01

Synaptic architecture and its adaptive changes require numerous molecular events that are both highly ordered and complex. A majority of neuropsychiatric illnesses are complex trait disorders, in which multiple etiologic factors converge at the synapse via many signaling pathways. Investigating the protein composition of synaptic microdomains from human patient brain tissues will yield valuable insights into the interactions of risk genes in many disorders. These types of studies in postmortem tissues have been limited by the lack of proper study paradigms. Thus, it is necessary not only to develop strategies to quantify protein and post-translational modifications at the synapse, but also to rigorously validate them for use in postmortem human brain tissues. In this study we describe the development of a liquid chromatography-selected reaction monitoring method, using a stable isotope-labeled neuronal proteome standard prepared from the brain tissue of a stable isotope-labeled mouse, for the multiplexed quantification of target synaptic proteins in mammalian samples. Additionally, we report the use of this method to validate a biochemical approach for the preparation of synaptic microdomain enrichments from human postmortem prefrontal cortex. Our data demonstrate that a targeted mass spectrometry approach with a true neuronal proteome standard facilitates accurate and precise quantification of over 100 synaptic proteins in mammalian samples, with the potential to quantify over 1000 proteins. Using this method, we found that protein enrichments in subcellular fractions prepared from human postmortem brain tissue were strikingly similar to those prepared from fresh mouse brain tissue. These findings demonstrate that biochemical fractionation methods paired with targeted proteomic strategies can be used in human brain tissues, with important implications for the study of neuropsychiatric disease. PMID:22942359

Cranial irradiation increases tumor growth in experimental breast cancer brain metastasis.

PubMed

Hamilton, Amanda M; Wong, Suzanne M; Wong, Eugene; Foster, Paula J

2018-05-01

Whole-brain radiotherapy is the standard of care for patients with breast cancer with multiple brain metastases and, although this treatment has been essential in the management of existing brain tumors, there are many known negative consequences associated with the irradiation of normal brain tissue. In our study, we used in vivo magnetic resonance imaging analysis to investigate the influence of radiotherapy-induced damage of healthy brain on the arrest and growth of metastatic breast cancer cells in a mouse model of breast cancer brain metastasis. We observed that irradiated, but otherwise healthy, neural tissue had an increased propensity to support metastatic growth compared with never-irradiated controls. The elucidation of the impact of irradiation on normal neural tissue could have implications in clinical patient management, particularly in patients with residual systemic disease or with residual radio-resistant brain cancer. Copyright © 2018 John Wiley & Sons, Ltd.

Effects of acupuncture on tissue oxygenation of the rat brain.

PubMed

Chen, G S; Erdmann, W

1978-04-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by smypathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture points (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible and was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase in inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes increased brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients.

Metals in tissues of migrant semipalmated sandpipers (Calidris pusilla) from Delaware Bay, New Jersey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burger, Joanna, E-mail: burger@biology.rutgers.edu; Environmental and Occupational Health Sciences Institute; Gochfeld, Michael

2014-08-15

There is an abundance of field data on levels of metals for feathers in a variety of birds, but relatively few data for tissues, especially for migrant species from one location. In this paper we examine the levels of arsenic, cadmium, chromium, lead, manganese, mercury and selenium in muscle, liver, brain, fat and breast feathers from migrant semipalmated sandpipers (Calidris pusilla) collected from Delaware Bay, New Jersey. Our primary objectives were to (1) examine variation as a function of tissue, (2) determine the relationship of metal levels among tissues, and (3) determine the selenium:mercury molar ratio in different tissues sincemore » selenium is thought to protect against mercury toxicity. We were also interested in whether the large physiological changes that occur while shorebirds are on Delaware Bay (e.g. large weight gains in 2–3 weeks) affected metal levels, especially in the brain. There were significant differences among tissues for all metals. The brain had the lowest levels of arsenic and cadmium, and was tied for the lowest levels of all other metals except lead and selenium. Correlations among metals in tissues were varied, with mercury levels being positively correlated for muscle and brain, and for liver and breast feathers. Weights vary among individuals at the Delaware Bay stopover, as they arrive light, and gain weight prior to migration north. Bird weight and levels of arsenic, cadmium, and selenium in the brain were negatively correlated, while they were positively correlated for lead. There was no positive correlation for mercury in the brain as a function of body weight. The selenium:mercury molar ratio varied significantly among tissues, with brain (ratio of 141) and fat having the highest ratios, and liver and breast feathers having the lowest. In all cases, the ratio was above 21, suggesting the potential for amelioration of mercury toxicity. - Highlights: • Metal levels were examined for migrant semipalmated sandpipers. • There were differences in metal levels among internal tissues. • Brain had the lowest levels of arsenic and cadmium. • Bird weight and arsenic, cadmium, and selenium levels in brain were negatively correlated. • Selenium:mercury molar ratio varied among tissues (21–141, suggesting protection)« less

Compression stiffening of brain and its effect on mechanosensing by glioma cells

NASA Astrophysics Data System (ADS)

Pogoda, Katarzyna; Chin, LiKang; Georges, Penelope C.; Byfield, FitzRoy J.; Bucki, Robert; Kim, Richard; Weaver, Michael; Wells, Rebecca G.; Marcinkiewicz, Cezary; Janmey, Paul A.

2014-07-01

Many cell types, including neurons, astrocytes and other cells of the central nervous system, respond to changes in the extracellular matrix or substrate viscoelasticity, and increased tissue stiffness is a hallmark of several disease states, including fibrosis and some types of cancers. Whether the malignant tissue in brain, an organ that lacks the protein-based filamentous extracellular matrix of other organs, exhibits the same macroscopic stiffening characteristic of breast, colon, pancreatic and other tumors is not known. In this study we show that glioma cells, like normal astrocytes, respond strongly in vitro to substrate stiffness in the range of 100 to 2000 Pa, but that macroscopic (mm to cm) tissue samples isolated from human glioma tumors have elastic moduli in the order of 200 Pa that are indistinguishable from those of normal brain. However, both normal brain and glioma tissues increase their shear elastic moduli under modest uniaxial compression, and glioma tissue stiffens more strongly under compression than normal brain. These findings suggest that local tissue stiffness has the potential to alter glial cell function, and that stiffness changes in brain tumors might arise not from increased deposition or crosslinking of the collagen-rich extracellular matrix, but from pressure gradients that form within the tumors in vivo.

Mary Jane Hogue (1883-1962): A pioneer in human brain tissue culture.

PubMed

Zottoli, Steven J; Seyfarth, Ernst-August

2018-05-16

The ability to maintain human brain explants in tissue culture was a critical step in the use of these cells for the study of central nervous system disorders. Ross G. Harrison (1870-1959) was the first to successfully maintain frog medullary tissue in culture in 1907, but it took another 38 years before successful culture of human brain tissue was accomplished. One of the pioneers in this achievement was Mary Jane Hogue (1883-1962). Hogue was born into a Quaker family in 1883 in West Chester, Pennsylvania, and received her undergraduate degree from Goucher College in Baltimore, Maryland. Research with the developmental biologist Theodor Boveri (1862-1915) in Würzburg, Germany, resulted in her Ph.D. (1909). Hogue transitioned from studying protozoa to the culture of human brain tissue in the 1940s and 1950s, when she was one of the first to culture cells from human fetal, infant, and adult brain explants. We review Hogue's pioneering contributions to the study of human brain cells in culture, her putative identification of progenitor neuroblast and/or glioblast cells, and her use of the cultures to study the cytopathogenic effects of poliovirus. We also put Hogue's work in perspective by discussing how other women pioneers in tissue culture influenced Hogue and her research.

Mimicking brain tissue binding in an in vitro model of the blood-brain barrier illustrates differences between in vitro and in vivo methods for assessing the rate of brain penetration.

PubMed

Heymans, Marjolein; Sevin, Emmanuel; Gosselet, Fabien; Lundquist, Stefan; Culot, Maxime

2018-06-01

Assessing the rate of drug delivery to the central nervous system (CNS) in vitro has been used for decades to predict whether CNS drug candidates are likely to attain their pharmacological targets, located within the brain parenchyma, at an effective dose. The predictive value of in vitro blood-brain barrier (BBB) models is therefore frequently assessed by comparing in vitro BBB permeability, usually quoted as the endothelial permeability coefficient (P e ) or apparent permeability (P app ), to their rate of BBB permeation measured in vivo, the latter being commonly assessed in rodents. In collaboration with AstraZeneca (DMPK department, Södertälje, Sweden), the in vitro BBB permeability (P app and P e ) of 27 marketed CNS drugs has been determined using a bovine in vitro BBB model and compared to their in vivo permeability (P vivo ), obtained by rat in-situ brain perfusion. The latter was taken from published data from Summerfield et al. (2007). This comparison confirmed previous reports, showing a strong in vitro/in vivo correlation for hydrophilic compounds, characterized by low brain tissue binding and a weak correlation for lipophilic compounds, characterized by high brain tissue binding. This observation can be explained by the influence of brain tissue binding on the uptake of drugs into the CNS in vivo and the absence of possible brain tissue binding in vitro. The use of glial cells (GC) in the in vitro BBB model to mimic brain tissue binding and the introduction of a new calculation method for in vitro BBB permeability (P vitro ) resulted in a strong correlation between the in vitro and in vivo rate of BBB permeation for the whole set of compounds. These findings might facilitate further in vitro to in vivo extrapolation for CNS drug candidates. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Development and Validation of a Method for Alcohol Analysis in Brain Tissue by Headspace Gas Chromatography with Flame Ionization Detector

PubMed Central

Chun, Hao-Jung; Poklis, Justin L.; Poklis, Alphonse; Wolf, Carl E.

2016-01-01

Ethanol is the most widely used and abused drug. While blood is the preferred specimen for analysis, tissue specimens such as brain serve as alternative specimens for alcohol analysis in post-mortem cases where blood is unavailable or contaminated. A method was developed using headspace gas chromatography with flame ionization detection (HS-GC-FID) for the detection and quantification of ethanol, acetone, isopropanol, methanol and n-propanol in brain tissue specimens. Unfixed volatile-free brain tissue specimens were obtained from the Department of Pathology at Virginia Commonwealth University. Calibrators and controls were prepared from 4-fold diluted homogenates of these brain tissue specimens, and were analyzed using t-butanol as the internal standard. The chromatographic separation was performed with a Restek BAC2 column. A linear calibration was generated for all analytes (mean r2 > 0.9992) with the limits of detection and quantification of 100–110 mg/kg. Matrix effect from the brain tissue was determined by comparing the slopes of matrix prepared calibration curves with those of aqueous calibration curves; no significant differences were observed for ethanol, acetone, isopropanol, methanol and n-propanol. The bias and the CVs for all volatile controls were ≤10%. The method was also evaluated for carryover, selectivity, interferences, bench-top stability and freeze-thaw stability. The HS-GC-FID method was determined to be reliable and robust for the analysis of ethanol, acetone, isopropanol, methanol and n-propanol concentrations in brain tissue, effectively expanding the specimen options for post-mortem alcohol analysis. PMID:27488829

Hyper- and viscoelastic modeling of needle and brain tissue interaction.

PubMed

Lehocky, Craig A; Yixing Shi; Riviere, Cameron N

2014-01-01

Deep needle insertion into brain is important for both diagnostic and therapeutic clinical interventions. We have developed an automated system for robotically steering flexible needles within the brain to improve targeting accuracy. In this work, we have developed a finite element needle-tissue interaction model that allows for the investigation of safe parameters for needle steering. The tissue model implemented contains both hyperelastic and viscoelastic properties to simulate the instantaneous and time-dependent responses of brain tissue. Several needle models were developed with varying parameters to study the effects of the parameters on tissue stress, strain and strain rate during needle insertion and rotation. The parameters varied include needle radius, bevel angle, bevel tip fillet radius, insertion speed, and rotation speed. The results will guide the design of safe needle tips and control systems for intracerebral needle steering.

Numerical analysis of the diffusive mass transport in brain tissues with applications to optical sensors

NASA Astrophysics Data System (ADS)

Neculae, Adrian P.; Otte, Andreas; Curticapean, Dan

2013-03-01

In the brain-cell microenvironment, diffusion plays an important role: apart from delivering glucose and oxygen from the vascular system to brain cells, it also moves informational substances between cells. The brain is an extremely complex structure of interwoven, intercommunicating cells, but recent theoretical and experimental works showed that the classical laws of diffusion, cast in the framework of porous media theory, can deliver an accurate quantitative description of the way molecules are transported through this tissue. The mathematical modeling and the numerical simulations are successfully applied in the investigation of diffusion processes in tissues, replacing the costly laboratory investigations. Nevertheless, modeling must rely on highly accurate information regarding the main parameters (tortuosity, volume fraction) which characterize the tissue, obtained by structural and functional imaging. The usual techniques to measure the diffusion mechanism in brain tissue are the radiotracer method, the real time iontophoretic method and integrative optical imaging using fluorescence microscopy. A promising technique for obtaining the values for characteristic parameters of the transport equation is the direct optical investigation using optical fibers. The analysis of these parameters also reveals how the local geometry of the brain changes with time or under pathological conditions. This paper presents a set of computations concerning the mass transport inside the brain tissue, for different types of cells. By measuring the time evolution of the concentration profile of an injected substance and using suitable fitting procedures, the main parameters characterizing the tissue can be determined. This type of analysis could be an important tool in understanding the functional mechanisms of effective drug delivery in complex structures such as the brain tissue. It also offers possibilities to realize optical imaging methods for in vitro and in vivo measurements using optical fibers. The model also may help in radiotracer biomarker models for the understanding of the mechanism of action of new chemical entities.

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage.

PubMed

Stiefel, Michael F; Heuer, Gregory G; Abrahams, John M; Bloom, Stephanie; Smith, Michelle J; Maloney-Wilensky, Eileen; Grady, M Sean; LeRoux, Peter D

2004-10-01

Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.

Advantages of analyzing postmortem brain samples in routine forensic drug screening-Case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD).

PubMed

Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar; Linnet, Kristian

2017-09-01

Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34-10.8μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration levels. The cause of death in case 1 was collision-induced brain injury, while it was drowning in case 2 and 3 and thus not drug intoxication. However, the toxicological findings could help explain the decedent's inability to cope with brain injury or drowning incidents. The presented findings could help establish reference concentrations in brain samples and assist in interpretation of results from forensic drug screening in brain tissue. This is to the author's knowledge the first report of LSD, iso-LSD, and oxo-HO-LSD measured in brain tissue samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting therapeutics across the blood brain barrier (BBB), prerequisite towards thrombolytic therapy for cerebrovascular disorders-an overview and advancements.

PubMed

Pulicherla, K K; Verma, Mahendra Kumar

2015-04-01

Cerebral tissues possess highly selective and dynamic protection known as blood brain barrier (BBB) that regulates brain homeostasis and provides protection against invading pathogens and various chemicals including drug molecules. Such natural protection strictly monitors entry of drug molecules often required for the management of several diseases and disorders including cerebral vascular and neurological disorders. However, in recent times, the ischemic cerebrovascular disease and clinical manifestation of acute arterial thrombosis are the most common causes of mortality and morbidity worldwide. The management of cerebral Ischemia requires immediate infusion of external thrombolytic into systemic circulation and must cross the blood brain barrier. The major challenge with available thrombolytic is their poor affinity towards the blood brain barrier and cerebral tissue subsequently. In the clinical practice, a high dose of thrombolytic often prescribed to deliver drugs across the blood brain barrier which results in drug dependent toxicity leading to damage of neuronal tissues. In recent times, more emphasis was given to utilize blood brain barrier transport mechanism to deliver drugs in neuronal tissue. The blood brain barrier expresses a series of receptor on membrane became an ideal target for selective drug delivery. In this review, the author has given more emphasis molecular biology of receptor on blood brain barrier and their potential as a carrier for drug molecules to cerebral tissues. Further, the use of nanoscale design and real-time monitoring for developed therapeutic to encounter drug dependent toxicity has been reviewed in this study.

Better diet quality relates to larger brain tissue volumes: The Rotterdam Study.

PubMed

Croll, Pauline H; Voortman, Trudy; Ikram, M Arfan; Franco, Oscar H; Schoufour, Josje D; Bos, Daniel; Vernooij, Meike W

2018-05-16

To investigate the relation of diet quality with structural brain tissue volumes and focal vascular lesions in a dementia-free population. From the population-based Rotterdam Study, 4,447 participants underwent dietary assessment and brain MRI scanning between 2005 and 2015. We excluded participants with an implausible energy intake, prevalent dementia, or cortical infarcts, leaving 4,213 participants for the current analysis. A diet quality score (0-14) was calculated reflecting adherence to Dutch dietary guidelines. Brain MRI was performed to obtain information on brain tissue volumes, white matter lesion volume, lacunes, and cerebral microbleeds. The associations of diet quality score and separate food groups with brain structures were assessed using multivariable linear and logistic regression. We found that better diet quality related to larger brain volume, gray matter volume, white matter volume, and hippocampal volume. Diet quality was not associated with white matter lesion volume, lacunes, or microbleeds. High intake of vegetables, fruit, whole grains, nuts, dairy, and fish and low intake of sugar-containing beverages were associated with larger brain volumes. A better diet quality is associated with larger brain tissue volumes. These results suggest that the effect of nutrition on neurodegeneration may act via brain structure. More research, in particular longitudinal research, is needed to unravel direct vs indirect effects between diet quality and brain health. © 2018 American Academy of Neurology.

Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain.

PubMed

Herbst, Eric A F; Holloway, Graham P

2015-02-15

Mitochondrial function in the brain is traditionally assessed through analysing respiration in isolated mitochondria, a technique that possesses significant tissue and time requirements while also disrupting the cooperative mitochondrial reticulum. We permeabilized brain tissue in situ to permit analysis of mitochondrial respiration with the native mitochondrial morphology intact, removing the need for isolation time and minimizing tissue requirements to ∼2 mg wet weight. The permeabilized brain technique was validated against the traditional method of isolated mitochondria and was then further applied to assess regional variation in the mouse brain with ischaemia-reperfusion injuries. A transgenic mouse model overexpressing catalase within mitochondria was applied to show the contribution of mitochondrial reactive oxygen species to ischaemia-reperfusion injuries in different brain regions. This technique enhances the accessibility of addressing physiological questions in small brain regions and in applying transgenic mouse models to assess mechanisms regulating mitochondrial function in health and disease. Mitochondria function as the core energy providers in the brain and symptoms of neurodegenerative diseases are often attributed to their dysregulation. Assessing mitochondrial function is classically performed in isolated mitochondria; however, this process requires significant isolation time, demand for abundant tissue and disruption of the cooperative mitochondrial reticulum, all of which reduce reliability when attempting to assess in vivo mitochondrial bioenergetics. Here we introduce a method that advances the assessment of mitochondrial respiration in the brain by permeabilizing existing brain tissue to grant direct access to the mitochondrial reticulum in situ. The permeabilized brain preparation allows for instant analysis of mitochondrial function with unaltered mitochondrial morphology using significantly small sample sizes (∼2 mg), which permits the analysis of mitochondrial function in multiple subregions within a single mouse brain. Here this technique was applied to assess regional variation in brain mitochondrial function with acute ischaemia-reperfusion injuries and to determine the role of reactive oxygen species in exacerbating dysfunction through the application of a transgenic mouse model overexpressing catalase within mitochondria. Through creating accessibility to small regions for the investigation of mitochondrial function, the permeabilized brain preparation enhances the capacity for examining regional differences in mitochondrial regulation within the brain, as the majority of genetic models used for unique approaches exist in the mouse model. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated networkmore » (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.« less

Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis.

PubMed

Yan, Kun; Fu, Zongming; Yang, Chen; Zhang, Kai; Jiang, Shanshan; Lee, Dong-Hoon; Heo, Hye-Young; Zhang, Yi; Cole, Robert N; Van Eyk, Jennifer E; Zhou, Jinyuan

2015-08-01

To investigate the biochemical origin of the amide photon transfer (APT)-weighted hyperintensity in brain tumors. Seven 9 L gliosarcoma-bearing rats were imaged at 4.7 T. Tumor and normal brain tissue samples of equal volumes were prepared with a coronal rat brain matrix and a tissue biopsy punch. The total tissue protein and the cytosolic subproteome were extracted from both samples. Protein samples were analyzed using two-dimensional gel electrophoresis, and the proteins with significant abundance changes were identified by mass spectrometry. There was a significant increase in the cytosolic protein concentration in the tumor, compared to normal brain regions, but the total protein concentrations were comparable. The protein profiles of the tumor and normal brain tissue differed significantly. Six cytosolic proteins, four endoplasmic reticulum proteins, and five secreted proteins were considerably upregulated in the tumor. Our experiments confirmed an increase in the cytosolic protein concentration in tumors and identified several key proteins that may cause APT-weighted hyperintensity.

Dexamethasone increases production of C-type natriuretic peptide in the sheep brain.

PubMed

Wilson, Michele O; McNeill, Bryony A; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

2017-10-01

Although C-type natriuretic peptide (CNP) has high abundance in brain tissues and cerebrospinal fluid (CSF), the source and possible factors regulating its secretion within the central nervous system (CNS) are unknown. Here we report the dynamic effects of a single IV bolus of dexamethasone or saline solution on plasma, CSF, CNS and pituitary tissue content of CNP products in adult sheep, along with changes in CNP gene expression in selected tissues. Both CNP and NTproCNP (the amino-terminal product of proCNP) in plasma and CSF showed dose-responsive increases lasting 12-16 h after dexamethasone, whereas other natriuretic peptides were unaffected. CNS tissue concentrations of CNP and NTproCNP were increased by dexamethasone in all of the 12 regions examined. Abundance was highest in limbic tissues, pons and medulla oblongata. Relative to controls, CNP gene expression ( NPPC ) was upregulated by dexamethasone in 5 of 7 brain tissues examined. Patterns of responses differed in pituitary tissue. Whereas the abundance of CNP in both lobes of the pituitary gland greatly exceeded that of brain tissues, neither CNP nor NTproCNP concentration was affected by dexamethasone, despite an increase in NPPC expression. This is the first report of enhanced production and secretion of CNP in brain tissues in response to a corticosteroid. Activation of CNP secretion within CNS tissues by dexamethasone, not exhibited by other natriuretic peptides, suggests an important role for CNP in settings of acute stress. Differential findings in pituitary tissues likely relate to altered processing of proCNP storage and secretion. © 2017 Society for Endocrinology.

Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

PubMed Central

Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

2014-01-01

Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue. PMID:25368644

MEASUREMENT OF SMALL MECHANICAL VIBRATIONS OF BRAIN TISSUE EXPOSED TO EXTREMELY-LOW-FREQUENCY ELECTRIC FIELDS

EPA Science Inventory

Electromagnetic fields can interact with biological tissue both electrically and mechanically. This study investigated the mechanical interaction between brain tissue and an extremely-low-frequency (ELF) electric field by measuring the resultant vibrational amplitude. The exposur...

The adult brain tissue response to hollow fiber membranes of varying surface architecture with or without cotransplanted cells

NASA Astrophysics Data System (ADS)

Zhang, Ning

A variety of biomaterials have been chronically implanted into the central nervous system (CNS) for repair or therapeutic purposes. Regardless of the application, chronic implantation of materials into the CNS induces injury and elicits a wound healing response, eventually leading to the formation of a dense extracellular matrix (ECM)-rich scar tissue that is associated with the segregation of implanted materials from the surrounding normal tissue. Often this reaction results in impaired performance of indwelling CNS devices. In order to enhance the performance of biomaterial-based implantable devices in the CNS, this thesis investigated whether adult brain tissue response to implanted biomaterials could be manipulated by changing biomaterial surface properties or further by utilizing the biology of co-transplanted cells. Specifically, the adult rat brain tissue response to chronically implanted poly(acrylonitrile-vinylchloride) (PAN-PVC) hollow fiber membranes (HFMs) of varying surface architecture were examined temporally at 2, 4, and 12 weeks postimplantation. Significant differences were discovered in the brain tissue response to the PAN-PVC HFMs of varying surface architecture at 4 and 12 weeks. To extend this work, whether the soluble factors derived from a co-transplanted cellular component further affect the brain tissue response to an implanted HFM in a significant way was critically exploited. The cells used were astrocytes, whose ability to influence scar formation process following CNS injury by physical contact with the host tissue had been documented in the literature. Data indicated for the first time that astrocyte-derived soluble factors ameliorate the adult brain tissue reactivity toward HFM implants in an age-dependent manner. While immature astrocytes secreted soluble factors that suppressed the brain tissue reactivity around the implants, mature astrocytes secreted factors that enhanced the gliotic response. These findings prove the feasibility of ameliorating the CNS tissue reactivity toward biomaterials implants by varying biomaterial surface properties or incorporating scar-reductive factors derived from functional cells into implant constructs, therefore, provide guidance in the design of more integrative biomaterial-based implantable devices for CNS repair.

Detection of radiation-induced brain necrosis in live rats using label-free time-resolved fluorescence spectroscopy (TRFS) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hartl, Brad A.; Ma, Htet S. W.; Sridharan, Shamira; Hansen, Katherine; Klich, Melanie; Perks, Julian; Kent, Michael; Kim, Kyoungmi; Fragoso, Ruben; Marcu, Laura

2017-02-01

Differentiating radiation-induced necrosis from recurrent tumor in the brain remains a significant challenge to the neurosurgeon. Clinical imaging modalities are not able to reliably discriminate the two tissue types, making biopsy location selection and surgical management difficult. Label-free fluorescence lifetime techniques have previously been shown to be able to delineate human brain tumor from healthy tissues. Thus, fluorescence lifetime techniques represent a potential means to discriminate the two tissues in real-time during surgery. This study aims to characterize the endogenous fluorescence lifetime signatures from radiation induced brain necrosis in a tumor-free rat model. Fischer rats received a single fraction of 60 Gy of radiation to the right hemisphere using a linear accelerator. Animals underwent a terminal live surgery after gross necrosis had developed, as verified with MRI. During surgery, healthy and necrotic brain tissue was measured with a fiber optic needle connected to a multispectral fluorescence lifetime system. Measurements of the necrotic tissue showed a 48% decrease in intensity and 20% increase in lifetimes relative to healthy tissue. Using a support vector machine classifier and leave-one-out validation technique, the necrotic tissue was correctly classified with 94% sensitivity and 97% specificity. Spectral contribution analysis also confirmed that the primary source of fluorescence contrast lies within the redox and bound-unbound population shifts of nicotinamide adenine dinucleotide. A clinical trial is presently underway to measure these tissue types in humans. These results show for the first time that radiation-induced necrotic tissue in the brain contains significantly different metabolic signatures that are detectable with label-free fluorescence lifetime techniques.

Light interference as a possible stressor altering HSP70 and its gene expression levels in brain and hepatic tissues of golden spiny mice.

PubMed

Ashkenazi, Lilach; Haim, Abraham

2012-11-15

Light at night and light interference (LI) disrupt the natural light:dark cycle, causing alterations at physiological and molecular levels, partly by suppressing melatonin (MLT) secretion at night. Heat shock proteins (HSPs) can be activated in response to environmental changes. We assessed changes in gene expression and protein level of HSP70 in brain and hepatic tissues of golden spiny mice (Acomys russatus) acclimated to LI for two (SLI), seven (MLI) and 21 nights (LLI). The effect of MLT treatment on LI-mice was also assessed. HSP70 levels increased in brain and hepatic tissues after SLI, whereas after MLI and LLI, HSP70 decreased to control levels. Changes in HSP70 levels as a response to MLT occurred after SLI only in hepatic tissue. However, hsp70 expression following SLI increased in brain tissue, but not in hepatic tissue. MLT treatment and SLI caused a decrease in hsp70 levels in brain tissue and an increase in hsp70 in hepatic tissue. SLI acclimation elicited a stress response in A. russatus, as expressed by increased HSP70 levels and gene expression. Longer acclimation decreases protein and gene expression to their control levels. We conclude that for brain and hepatic tissues of A. russatus, LI is a short-term stressor. Our results also revealed that A. russatus can acclimate to LI, possibly because of its circadian system plasticity, which allows it to behave both as a nocturnal and as a diurnal rodent. To the best of our knowledge, this is the first study showing the effect of LI as a stressor at the cellular level, by activating HSP70.

Distribution of lead in the brain tissues from DNTC patients using synchrotron radiation microbeams

NASA Astrophysics Data System (ADS)

Ide-Ektessabi, Ari; Ota, Yukihide; Ishihara, Ryoko; Mizuno, Yutaka; Takeuchi, Tohru

2005-12-01

Diffuse neurofibrillary tangles with calcification (DNTC) is a form of dementia with certain characteristics. Its pathology is characterized by cerebrum atrophy, calcification on globus pallidus and dentate nucleus and diffuse neurofibrillary tangles without senile plaques. In the present study brain tissues were prepared from patients with patients DNTC, calcified and non-calcified Alzheimer's disease (AD) patients. The brain tissues were examined non-destructively by X-ray fluorescence (XRF) spectroscopy using synchrotron radiation (SR) microbeams for trace metallic elements Ca, Fe, Cu, Zn and Pb. The XRF analysis showed that there were Pb concentrations in the calcified areas in the brain tissues with both DNTC and AD but there was none in those with non-calcified AD.

Brain Sex Matters: estrogen in cognition and Alzheimer’s disease

PubMed Central

Li, Rena; Cui, Jie; Shen, Yong

2014-01-01

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissues such as liver, heart, muscle, bone and the brain. During the past decade, increasing evidence suggests that brain estrogen can not only be synthesized by neurons, but also by astrocytes. Brain estrogen also works locally at the site of synthesis in paracrine and/or intracrine fashion to maintain important tissue-specific functions. Here, we will focus on the biology of brain estrogen and its impact on cognitive function and Alzheimer’s disease. This comprehensive review provides new insights into brain estrogens by presenting a better understanding of the tissue-specific estrogen effects and their roles in healthy ageing and cognitive function. PMID:24418360

Expression of hypoxia-inducible carbonic anhydrases in brain tumors

PubMed Central

Proescholdt, Martin A.; Mayer, Christina; Kubitza, Marion; Schubert, Thomas; Liao, Shu-Yuan; Stanbridge, Eric J.; Ivanov, Sergey; Oldfield, Edward H.; Brawanski, Alexander; Merrill, Marsha J.

2005-01-01

Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel–Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1α staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target. PMID:16212811

Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative diagnosis of brain tumors.

PubMed

Snuderl, Matija; Wirth, Dennis; Sheth, Sameer A; Bourne, Sarah K; Kwon, Churl-Su; Ancukiewicz, Marek; Curry, William T; Frosch, Matthew P; Yaroslavsky, Anna N

2013-01-01

Intraoperative diagnosis plays an important role in accurate sampling of brain tumors, limiting the number of biopsies required and improving the distinction between brain and tumor. The goal of this study was to evaluate dye-enhanced multimodal confocal imaging for discriminating gliomas from nonglial brain tumors and from normal brain tissue for diagnostic use. We investigated a total of 37 samples including glioma (13), meningioma (7), metastatic tumors (9) and normal brain removed for nontumoral indications (8). Tissue was stained in 0.05 mg/mL aqueous solution of methylene blue (MB) for 2-5 minutes and multimodal confocal images were acquired using a custom-built microscope. After imaging, tissue was formalin fixed and paraffin embedded for standard neuropathologic evaluation. Thirteen pathologists provided diagnoses based on the multimodal confocal images. The investigated tumor types exhibited distinctive and complimentary characteristics in both the reflectance and fluorescence responses. Images showed distinct morphological features similar to standard histology. Pathologists were able to distinguish gliomas from normal brain tissue and nonglial brain tumors, and to render diagnoses from the images in a manner comparable to haematoxylin and eosin (H&E) slides. These results confirm the feasibility of multimodal confocal imaging for intravital intraoperative diagnosis. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

NASA Robotic Neurosurgery Testbed

NASA Technical Reports Server (NTRS)

Mah, Robert

1997-01-01

The detection of tissue interface (e.g., normal tissue, cancer, tumor) has been limited clinically to tactile feedback, temperature monitoring, and the use of a miniature ultrasound probe for tissue differentiation during surgical operations, In neurosurgery, the needle used in the standard stereotactic CT or MRI guided brain biopsy provides no information about the tissue being sampled. The tissue sampled depends entirely upon the accuracy with which the localization provided by the preoperative CT or MRI scan is translated to the intracranial biopsy site. In addition, no information about the tissue being traversed by the needle (e.g., a blood vessel) is provided. Hemorrhage due to the biopsy needle tearing a blood vessel within the brain is the most devastating complication of stereotactic CT/MRI guided brain biopsy. A robotic neurosurgery testbed has been developed at NASA Ames Research Center as a spin-off of technologies from space, aeronautics and medical programs. The invention entitled "Robotic Neurosurgery Leading to Multimodality Devices for Tissue Identification" is nearing a state ready for commercialization. The devices will: 1) improve diagnostic accuracy and precision of general surgery, with near term emphasis on stereotactic brain biopsy, 2) automate tissue identification, with near term emphasis on stereotactic brain biopsy, to permit remote control of the procedure, and 3) reduce morbidity for stereotactic brain biopsy. The commercial impact from this work is the potential development of a whole new generation of smart surgical tools to increase the safety, accuracy and efficiency of surgical procedures. Other potential markets include smart surgical tools for tumor ablation in neurosurgery, general exploratory surgery, prostate cancer surgery, and breast cancer surgery.

NASA Robotic Neurosurgery Testbed

NASA Technical Reports Server (NTRS)

Mah, Robert

1997-01-01

The detection of tissue interface (e.g., normal tissue, cancer, tumor) has been limited clinically to tactile feedback, temperature monitoring, and the use of a miniature ultrasound probe for tissue differentiation during surgical operations. In neurosurgery, the needle used in the standard stereotactic CT (Computational Tomography) or MRI (Magnetic Resonance Imaging) guided brain biopsy provides no information about the tissue being sampled. The tissue sampled depends entirely upon the accuracy with which the localization provided by the preoperative CT or MRI scan is translated to the intracranial biopsy site. In addition, no information about the tissue being traversed by the needle (e.g., a blood vessel) is provided. Hemorrhage due to the biopsy needle tearing a blood vessel within the brain is the most devastating complication of stereotactic CT/MRI guided brain biopsy. A robotic neurosurgery testbed has been developed at NASA Ames Research Center as a spin-off of technologies from space, aeronautics and medical programs. The invention entitled 'Robotic Neurosurgery Leading to Multimodality Devices for Tissue Identification' is nearing a state ready for commercialization. The devices will: 1) improve diagnostic accuracy and precision of general surgery, with near term emphasis on stereotactic brain biopsy, 2) automate tissue identification, with near term emphasis on stereotactic brain biopsy, to permit remote control of the procedure, and 3) reduce morbidity for stereotactic brain biopsy. The commercial impact from this work is the potential development of a whole new generation of smart surgical tools to increase the safety, accuracy and efficiency of surgical procedures. Other potential markets include smart surgical tools for tumor ablation in neurosurgery, general exploratory surgery, prostate cancer surgery, and breast cancer surgery.

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

PubMed Central

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain. PMID:27057543

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder.

PubMed

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

[Effects of Geometrical Dimensions and Material Properties on the Rotation Characteristics of Head].

PubMed

Chen, Yue; Cui, Shihai; Li, Haiyan; Ruan, Shijie

2016-08-01

The validated finite element head model(FEHM)of a 3-year-old child,a 6-year-old child and a 50 th percentile adult were used to investigate the effects of head dimension and material parameters of brain tissues on the head rotational responses based on experimental design.Results showed that the effects of head dimension and directions of rotation on the head rotational responses were not significant under the same rotational loading condition,and the same results appeared in the viscoelastic material parameters of brain tissues.However,the head rotational responses were most sensitive to the shear modulus(G)of brain tissues relative to decay constant(β)and bulk modulus(K).Therefore,the selection of material parameters of brain tissues is most important to the accuracy of simulation results,especially in the study of brain injury criterion under the rotational loading conditions.

The biochemical, nanomechanical and chemometric signatures of brain cancer

NASA Astrophysics Data System (ADS)

Abramczyk, Halina; Imiela, Anna

2018-01-01

Raman spectroscopy and imaging combined with AFM topography and mechanical indentation by AFM have been shown to be an effective tool for analysis and discrimination of human brain tumors from normal structures. Raman methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n = 5) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma (IV grade), and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational spectra and Raman images we provide a real-time feedback that is label-free method to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, and proteins. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm- 1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the lipid and protein contents of tumorous brain tissue compared to the non-tumor tissue. Almost all brain tumors have the Raman intensity ratios significantly higher (1.99 ± 0.026) than that found in non-tumor brain tissue, which is 1.456 ± 0.02, and indicates that the relative amount of lipids compared to proteins is significantly higher in the normal brain tissue. Mechanical indentation using AFM on sliced human brain tissues (medulloblastoma, grade IV) revealed that the mechanical properties of this tissue are strongly heterogeneous, between 1.8 and 75.7 kPa, and the mean of 27.16 kPa. The sensitivity and specificity obtained directly from PLSDA and cross validation gives a sensitivity and specificity of 98.5% and 96% and 96.3% and 92% for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development.

Age dependence of dielectric properties of bovine brain and ocular tissues in the frequency range of 400 MHz to 18 GHz

NASA Astrophysics Data System (ADS)

Schmid, Gernot; Überbacher, Richard

2005-10-01

In order to identify possible age-dependent dielectric properties of brain and eye tissues in the frequency range of 400 MHz to 18 GHz, measurements on bovine grey and white matter as well as on cornea, lens (cortical) and the vitreous body were performed using a commercially available open-ended coaxial probe and a computer-controlled vector network analyser. Freshly excised tissues of 52 animals of two age groups (42 adult animals, i.e. 16-24 month old and 10 young animals, i.e. 4-6 month old calves) were examined within 8 min (brain tissue) and 15 min (eye tissue), respectively, of the animals' death. Tissue temperatures for the measurements were 32 ± 1 °C and 25 ± 1 °C for brain and eye tissues, respectively. Statistical analysis of the measured data revealed significant differences in the dielectric properties of white matter and cortical lens tissue between the adult and the young group. In the case of white matter the mean values of conductivity and permittivity of young tissue were 15%-22% and 12%-15%, respectively, higher compared to the adult tissue in the considered frequency range. Similarly, young cortical lens tissue was 25%-76% higher in conductivity and 27%-39% higher in permittivity than adult cortical lens tissue.

Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

PubMed Central

Rabeneck, Demi B.; Martines, Roosecelis B.; Reagan-Steiner, Sarah; Ermias, Yokabed; Estetter, Lindsey B.C.; Suzuki, Tadaki; Ritter, Jana; Keating, M. Kelly; Hale, Gillian; Gary, Joy; Muehlenbachs, Atis; Lambert, Amy; Lanciotti, Robert; Oduyebo, Titilope; Meaney-Delman, Dana; Bolaños, Fernando; Saad, Edgar Alberto Parra; Shieh, Wun-Ju; Zaki, Sherif R.

2017-01-01

Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections. PMID:27959260

Gene expression changes with age in skin, adipose tissue, blood and brain.

PubMed

Glass, Daniel; Viñuela, Ana; Davies, Matthew N; Ramasamy, Adaikalavan; Parts, Leopold; Knowles, David; Brown, Andrew A; Hedman, Asa K; Small, Kerrin S; Buil, Alfonso; Grundberg, Elin; Nica, Alexandra C; Di Meglio, Paola; Nestle, Frank O; Ryten, Mina; Durbin, Richard; McCarthy, Mark I; Deloukas, Panagiotis; Dermitzakis, Emmanouil T; Weale, Michael E; Bataille, Veronique; Spector, Tim D

2013-07-26

Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age. Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues. Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.

Tissue-like Neural Probes for Understanding and Modulating the Brain.

PubMed

Hong, Guosong; Viveros, Robert D; Zwang, Theodore J; Yang, Xiao; Lieber, Charles M

2018-03-19

Electrophysiology tools have contributed substantially to understanding brain function, yet the capabilities of conventional electrophysiology probes have remained limited in key ways because of large structural and mechanical mismatches with respect to neural tissue. In this Perspective, we discuss how the general goal of probe design in biochemistry, that the probe or label have a minimal impact on the properties and function of the system being studied, can be realized by minimizing structural, mechanical, and topological differences between neural probes and brain tissue, thus leading to a new paradigm of tissue-like mesh electronics. The unique properties and capabilities of the tissue-like mesh electronics as well as future opportunities are summarized. First, we discuss the design of an ultraflexible and open mesh structure of electronics that is tissue-like and can be delivered in the brain via minimally invasive syringe injection like molecular and macromolecular pharmaceuticals. Second, we describe the unprecedented tissue healing without chronic immune response that leads to seamless three-dimensional integration with a natural distribution of neurons and other key cells through these tissue-like probes. These unique characteristics lead to unmatched stable long-term, multiplexed mapping and modulation of neural circuits at the single-neuron level on a year time scale. Last, we offer insights on several exciting future directions for the tissue-like electronics paradigm that capitalize on their unique properties to explore biochemical interactions and signaling in a "natural" brain environment.

In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

PubMed

Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

2016-05-01

High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

Evidence for brain glucose dysregulation in Alzheimer's disease.

PubMed

An, Yang; Varma, Vijay R; Varma, Sudhir; Casanova, Ramon; Dammer, Eric; Pletnikova, Olga; Chia, Chee W; Egan, Josephine M; Ferrucci, Luigi; Troncoso, Juan; Levey, Allan I; Lah, James; Seyfried, Nicholas T; Legido-Quigley, Cristina; O'Brien, Richard; Thambisetty, Madhav

2018-03-01

It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Copyright © 2017 the Alzheimer's Association. All rights reserved.

Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from Rat Brain Tissue Implanted with Silver Nanoparticles

NASA Astrophysics Data System (ADS)

Muller, Ludovic; Baldwin, Kathrine; Barbacci, Damon C.; Jackson, Shelley N.; Roux, Aurélie; Balaban, Carey D.; Brinson, Bruce E.; McCully, Michael I.; Lewis, Ernest K.; Schultz, J. Albert; Woods, Amina S.

2017-08-01

Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in serial sections of brain tissue is achieved within <10% tolerance by selecting argentated instead of alkali cationized ions. The imaging of brain tissues spotted with pure standards was used to demonstrate that Ag cationized ceramide and diacylglycerol ions are from intact, endogenous species. In contrast, almost all Ag cationized fatty acid ions are a result of fragmentations of numerous lipid types having the fatty acid as a subunit. Almost no argentated intact fatty acid ions come from the pure fatty acid standard on tissue.

In vivo three-photon microscopy of subcortical structures within an intact mouse brain

NASA Astrophysics Data System (ADS)

Horton, Nicholas G.; Wang, Ke; Kobat, Demirhan; Clark, Catharine G.; Wise, Frank W.; Schaffer, Chris B.; Xu, Chris

2013-03-01

Two-photon fluorescence microscopy enables scientists in various fields including neuroscience, embryology and oncology to visualize in vivo and ex vivo tissue morphology and physiology at a cellular level deep within scattering tissue. However, tissue scattering limits the maximum imaging depth of two-photon fluorescence microscopy to the cortical layer within mouse brain, and imaging subcortical structures currently requires the removal of overlying brain tissue or the insertion of optical probes. Here, we demonstrate non-invasive, high-resolution, in vivo imaging of subcortical structures within an intact mouse brain using three-photon fluorescence microscopy at a spectral excitation window of 1,700 nm. Vascular structures as well as red fluorescent protein-labelled neurons within the mouse hippocampus are imaged. The combination of the long excitation wavelength and the higher-order nonlinear excitation overcomes the limitations of two-photon fluorescence microscopy, enabling biological investigations to take place at a greater depth within tissue.

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

PubMed

Vedam-Mai, V; Krock, N; Ullman, M; Foote, K D; Shain, W; Smith, K; Yachnis, A T; Steindler, D; Reynolds, B; Merritt, S; Pagan, F; Marjama-Lyons, J; Hogarth, P; Resnick, A S; Zeilman, P; Okun, M S

2011-08-01

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

Organization of brain tissue - Is the brain a noisy processor.

NASA Technical Reports Server (NTRS)

Adey, W. R.

1972-01-01

This paper presents some thoughts on functional organization in cerebral tissue. 'Spontaneous' wave and unit firing are considered as essential phenomena in the handling of information. Various models are discussed which have been suggested to describe the pseudorandom behavior of brain cells, leading to a view of the brain as an information processor and its role in learning, memory, remembering and forgetting.

Brain extraction from normal and pathological images: A joint PCA/Image-Reconstruction approach.

PubMed

Han, Xu; Kwitt, Roland; Aylward, Stephen; Bakas, Spyridon; Menze, Bjoern; Asturias, Alexander; Vespa, Paul; Van Horn, John; Niethammer, Marc

2018-08-01

Brain extraction from 3D medical images is a common pre-processing step. A variety of approaches exist, but they are frequently only designed to perform brain extraction from images without strong pathologies. Extracting the brain from images exhibiting strong pathologies, for example, the presence of a brain tumor or of a traumatic brain injury (TBI), is challenging. In such cases, tissue appearance may substantially deviate from normal tissue appearance and hence violates algorithmic assumptions for standard approaches to brain extraction; consequently, the brain may not be correctly extracted. This paper proposes a brain extraction approach which can explicitly account for pathologies by jointly modeling normal tissue appearance and pathologies. Specifically, our model uses a three-part image decomposition: (1) normal tissue appearance is captured by principal component analysis (PCA), (2) pathologies are captured via a total variation term, and (3) the skull and surrounding tissue is captured by a sparsity term. Due to its convexity, the resulting decomposition model allows for efficient optimization. Decomposition and image registration steps are alternated to allow statistical modeling of normal tissue appearance in a fixed atlas coordinate system. As a beneficial side effect, the decomposition model allows for the identification of potentially pathological areas and the reconstruction of a quasi-normal image in atlas space. We demonstrate the effectiveness of our approach on four datasets: the publicly available IBSR and LPBA40 datasets which show normal image appearance, the BRATS dataset containing images with brain tumors, and a dataset containing clinical TBI images. We compare the performance with other popular brain extraction models: ROBEX, BEaST, MASS, BET, BSE and a recently proposed deep learning approach. Our model performs better than these competing approaches on all four datasets. Specifically, our model achieves the best median (97.11) and mean (96.88) Dice scores over all datasets. The two best performing competitors, ROBEX and MASS, achieve scores of 96.23/95.62 and 96.67/94.25 respectively. Hence, our approach is an effective method for high quality brain extraction for a wide variety of images. Copyright © 2018 Elsevier Inc. All rights reserved.

Relationship between concentrations of lutein and StARD3 among pediatric and geriatric human brain tissue

USDA-ARS?s Scientific Manuscript database

Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and c...

Time-resolved fluorescence spectroscopy of human brain tumors

NASA Astrophysics Data System (ADS)

Marcu, Laura; Thompson, Reid C.; Garde, Smita; Sedrak, Mark; Black, Keith L.; Yong, William H.

2002-05-01

Fluorescence spectroscopy of the endogenous emission of brain tumors has been researched as a potentially important method for the intraoperative localization of brain tumor margins. In this study, we investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) for demarcation of primary brain tumors by studying the time-resolved spectra of gliomas of different histologic grades. Time-resolved fluorescence (3 ns, 337 nm excitation) from excised human brain tumor show differences between the time-resolved emission of malignant glioma and normal brain tissue (gray and white matter). Our findings suggest that brain tumors can be differentiated from normal brain tissue based upon unique time-resolved fluorescence signature.

Medical diagnosis imaging systems: image and signal processing applications aided by fuzzy logic

NASA Astrophysics Data System (ADS)

Hata, Yutaka

2010-04-01

First, we describe an automated procedure for segmenting an MR image of a human brain based on fuzzy logic for diagnosing Alzheimer's disease. The intensity thresholds for segmenting the whole brain of a subject are automatically determined by finding the peaks of the intensity histogram. After these thresholds are evaluated in a region growing, the whole brain can be identified. Next, we describe a procedure for decomposing the obtained whole brain into the left and right cerebral hemispheres, the cerebellum and the brain stem. Our method then identified the whole brain, the left cerebral hemisphere, the right cerebral hemisphere, the cerebellum and the brain stem. Secondly, we describe a transskull sonography system that can visualize the shape of the skull and brain surface from any point to examine skull fracture and some brain diseases. We employ fuzzy signal processing to determine the skull and brain surface. The phantom model, the animal model with soft tissue, the animal model with brain tissue, and a human subjects' forehead is applied in our system. The all shapes of the skin surface, skull surface, skull bottom, and brain tissue surface are successfully determined.

Non-destructive optical clearing technique enhances optical coherence tomography (OCT) for real-time, 3D histomorphometry of brain tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Paul, Akshay; Chang, Theodore H.; Chou, Li-Dek; Ramalingam, Tirunelveli S.

2016-03-01

Evaluation of neurodegenerative disease often requires examination of brain morphology. Volumetric analysis of brain regions and structures can be used to track developmental changes, progression of disease, and the presence of transgenic phenotypes. Current standards for microscopic investigation of brain morphology are limited to detection of superficial structures at a maximum depth of 300μm. While histological techniques can provide detailed cross-sections of brain structures, they require complicated tissue preparation and the ultimate destruction of the sample. A non-invasive, label-free imaging modality known as Optical Coherence Tomography (OCT) can produce 3-dimensional reconstructions through high-speed, cross-sectional scans of biological tissue. Although OCT allows for the preservation of intact samples, the highly scattering and absorbing properties of biological tissue limit imaging depth to 1-2mm. Optical clearing agents have been utilized to increase imaging depth by index matching and lipid digestion, however, these contemporary techniques are expensive and harsh on tissues, often irreversibly denaturing proteins. Here we present an ideal optical clearing agent that offers ease-of-use and reversibility. Similar to how SeeDB has been effective for microscopy, our fructose-based, reversible optical clearing technique provides improved OCT imaging and functional immunohistochemical mapping of disease. Fructose is a natural, non-toxic sugar with excellent water solubility, capable of increasing tissue transparency and reducing light scattering. We will demonstrate the improved depth-resolving performance of OCT for enhanced whole-brain imaging of normal and diseased murine brains following a fructose clearing treatment. This technique potentially enables rapid, 3-dimensional evaluation of biological tissues at axial and lateral resolutions comparable to histopathology.

Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats.

PubMed

Kopjar, Nevenka; Žunec, Suzana; Mendaš, Gordana; Micek, Vedran; Kašuba, Vilena; Mikolić, Anja; Lovaković, Blanka Tariba; Milić, Mirta; Pavičić, Ivan; Čermak, Ana Marija Marjanović; Pizent, Alica; Lucić Vrdoljak, Ana; Želježić, Davor

2018-01-05

In this 28 day-study, we evaluated the effects of the insecticide chlorpyrifos orally administered to Wistar rats at doses 0.160, 0.015, and 0.010 mg/kg b. w./day. Following treatment, total cholinesterase activity and activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were measured. Oxidative stress responses were evaluated using a battery of endpoints to establish lipid peroxidation, changes in total antioxidant capacity, level of reactive oxygen species (ROS), glutathione (GSH) level and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase. Using HPLC-UV DAD analysis, levels of the parent compound and its main metabolite 3,5,6-trichloro-2-pyridinol in plasma and brain tissue were measured. The genotoxic effect was estimated using alkaline comet assay in leukocytes and brain tissue. The exposure did not result in significant effects on total cholinesterase, AChE and BChE activity in plasma and brain tissue. Lipid peroxidation slightly increased both in plasma and brain tissue. Total antioxidant capacity, ROS and GSH levels were marginally influenced by the exposure. Treatment led to significant increases of GSH-Px activity in blood, SOD activity in erythrocytes and a slight increase of catalase activity in plasma. HPLC-UV DAD analysis revealed the presence of both the parent compound and its main metabolite in the plasma of all of the experimental animals and brain tissue of the animals treated at the two higher doses. All of the tested doses of chlorpyrifos were slightly genotoxic, both to leukocytes and brain tissue. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of solid-phase microextraction coupled with liquid chromatography for analysis of tramadol in brain tissue using its molecularly imprinted polymer.

PubMed

Habibi-Khorasani, Monireh; Mohammadpour, Amir Hooshang; Mohajeri, Seyed Ahmad

2017-02-01

In this work, performance of a molecularly imprinted polymer (MIP) as a selective solid-phase microextraction sorbent for the extraction and enrichment of tramadol in aqueous solution and rabbit brain tissue, is described. Binding properties of MIPs were studied in comparison with their nonimprinted polymer (NIP). Ten milligrams of the optimized MIP was then evaluated as a sorbent, for preconcentration, in molecularly imprinted solid-phase microextraction (MISPME) of tramadol from aqueous solution and rabbit brain tissue. The analytical method was calibrated in the range of 0.004 ppm (4 ng mL -1 ) and 10 ppm (10 μg mL -1 ) in aqueous media and in the ranges of 0.01 and 10 ppm in rabbit brain tissue, respectively. The results indicated significantly higher binding affinity of MIPs to tramadol, in comparison with NIP. The MISPME procedure was developed and optimized with a recovery of 81.12-107.54% in aqueous solution and 76.16-91.20% in rabbit brain tissue. The inter- and intra-day variation values were <8.24 and 5.06%, respectively. Finally the calibrated method was applied for determination of tramadol in real rabbit brain tissue samples after administration of a lethal dose. Our data demonstrated the potential of MISPME for rapid, sensitive and cost-effective sample analysis. Copyright © 2016 John Wiley & Sons, Ltd.

Tissue Probability Map Constrained 4-D Clustering Algorithm for Increased Accuracy and Robustness in Serial MR Brain Image Segmentation

PubMed Central

Xue, Zhong; Shen, Dinggang; Li, Hai; Wong, Stephen

2010-01-01

The traditional fuzzy clustering algorithm and its extensions have been successfully applied in medical image segmentation. However, because of the variability of tissues and anatomical structures, the clustering results might be biased by the tissue population and intensity differences. For example, clustering-based algorithms tend to over-segment white matter tissues of MR brain images. To solve this problem, we introduce a tissue probability map constrained clustering algorithm and apply it to serial MR brain image segmentation, i.e., a series of 3-D MR brain images of the same subject at different time points. Using the new serial image segmentation algorithm in the framework of the CLASSIC framework, which iteratively segments the images and estimates the longitudinal deformations, we improved both accuracy and robustness for serial image computing, and at the mean time produced longitudinally consistent segmentation and stable measures. In the algorithm, the tissue probability maps consist of both the population-based and subject-specific segmentation priors. Experimental study using both simulated longitudinal MR brain data and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data confirmed that using both priors more accurate and robust segmentation results can be obtained. The proposed algorithm can be applied in longitudinal follow up studies of MR brain imaging with subtle morphological changes for neurological disorders. PMID:26566399

Soft Tissue Phantoms for Realistic Needle Insertion: A Comparative Study.

PubMed

Leibinger, Alexander; Forte, Antonio E; Tan, Zhengchu; Oldfield, Matthew J; Beyrau, Frank; Dini, Daniele; Rodriguez Y Baena, Ferdinando

2016-08-01

Phantoms are common substitutes for soft tissues in biomechanical research and are usually tuned to match tissue properties using standard testing protocols at small strains. However, the response due to complex tool-tissue interactions can differ depending on the phantom and no comprehensive comparative study has been published to date, which could aid researchers to select suitable materials. In this work, gelatin, a common phantom in literature, and a composite hydrogel developed at Imperial College, were matched for mechanical stiffness to porcine brain, and the interactions during needle insertions within them were analyzed. Specifically, we examined insertion forces for brain and the phantoms; we also measured displacements and strains within the phantoms via a laser-based image correlation technique in combination with fluorescent beads. It is shown that the insertion forces for gelatin and brain agree closely, but that the composite hydrogel better mimics the viscous nature of soft tissue. Both materials match different characteristics of brain, but neither of them is a perfect substitute. Thus, when selecting a phantom material, both the soft tissue properties and the complex tool-tissue interactions arising during tissue manipulation should be taken into consideration. These conclusions are presented in tabular form to aid future selection.

High-contrast differentiation resolution 3D imaging of rodent brain by X-ray computed microtomography

NASA Astrophysics Data System (ADS)

Zikmund, T.; Novotná, M.; Kavková, M.; Tesařová, M.; Kaucká, M.; Szarowská, B.; Adameyko, I.; Hrubá, E.; Buchtová, M.; Dražanová, E.; Starčuk, Z.; Kaiser, J.

2018-02-01

The biomedically focused brain research is largely performed on laboratory mice considering a high homology between the human and mouse genomes. A brain has an intricate and highly complex geometrical structure that is hard to display and analyse using only 2D methods. Applying some fast and efficient methods of brain visualization in 3D will be crucial for the neurobiology in the future. A post-mortem analysis of experimental animals' brains usually involves techniques such as magnetic resonance and computed tomography. These techniques are employed to visualize abnormalities in the brains' morphology or reparation processes. The X-ray computed microtomography (micro CT) plays an important role in the 3D imaging of internal structures of a large variety of soft and hard tissues. This non-destructive technique is applied in biological studies because the lab-based CT devices enable to obtain a several-micrometer resolution. However, this technique is always used along with some visualization methods, which are based on the tissue staining and thus differentiate soft tissues in biological samples. Here, a modified chemical contrasting protocol of tissues for a micro CT usage is introduced as the best tool for ex vivo 3D imaging of a post-mortem mouse brain. This way, the micro CT provides a high spatial resolution of the brain microscopic anatomy together with a high tissue differentiation contrast enabling to identify more anatomical details in the brain. As the micro CT allows a consequent reconstruction of the brain structures into a coherent 3D model, some small morphological changes can be given into context of their mutual spatial relationships.

Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

PubMed

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

2009-01-01

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

Time-dependent diffuse reflectance spectroscopy for in vivo characterization of pediatric epileptogenic brain lesions

NASA Astrophysics Data System (ADS)

Oh, Sanghoon; Ragheb, John; Bhatia, Sanjiv; Sandberg, David; Johnson, Mahlon; Fernald, Bradley; Lin, Wei-Chiang

2008-02-01

Optical spectroscopy for in vivo tissue diagnosis is performed traditionally in a static manner; a snap shot of the tissue biochemical and morphological characteristics is captured through the interaction between light and the tissue. This approach does not capture the dynamic nature of a living organ, which is critical to the studies of brain disorders such as epilepsy. Therefore, a time-dependent diffuse reflectance spectroscopy system with a fiber-optic probe was designed and developed. The system was designed to acquire broadband diffuse reflectance spectra (240 ~ 932 nm) at an acquisition rate of 33 Hz. The broadband spectral acquisition feature allows simultaneous monitoring of various physiological characteristics of tissues. The utility of such a system in guiding pediatric epilepsy surgery was tested in a pilot clinical study including 13 epilepsy patients and seven brain tumor patients. The control patients were children undergoing suregery for brain tumors in which measurements were taken from normal brain exposed during the surgery. Diffuse reflectance spectra were acquired for 12 seconds from various parts of the brain of the patients during surgery. Recorded spectra were processed and analyzed in both spectral and time domains to gain insights into the dynamic changes in, for example, hemodynamics of the investigated brain tissue. One finding from this pilot study is that unsynchronized alterations in local blood oxygenation and local blood volume were observed in epileptogenic cortex. These study results suggest the advantage of using a time-dependent diffuse reflectance spectroscopy system to study epileptogenic brain in vivo.

The meningeal lymphatic system: a route for HIV brain migration?

PubMed

Lamers, Susanna L; Rose, Rebecca; Ndhlovu, Lishomwa C; Nolan, David J; Salemi, Marco; Maidji, Ekaterina; Stoddart, Cheryl A; McGrath, Michael S

2016-06-01

Two innovative studies recently identified functional lymphatic structures in the meninges that may influence the development of HIV-associated neurological disorders (HAND). Until now, blood vessels were assumed to be the sole transport system by which HIV-infected monocytes entered the brain by bypassing a potentially hostile blood-brain barrier through inflammatory-mediated semi-permeability. A cascade of specific chemokine signals promote monocyte migration from blood vessels to surrounding brain tissues via a well-supported endothelium, where the cells differentiate into tissue macrophages capable of productive HIV infection. Lymphatic vessels on the other hand are more loosely organized than blood vessels. They absorb interstitial fluid from bodily tissues where HIV may persist and exchange a variety of immune cells (CD4(+) T cells, monocytes, macrophages, and dendritic cells) with surrounding tissues through discontinuous endothelial junctions. We propose that the newly discovered meningeal lymphatics are key to HIV migration among viral reservoirs and brain tissue during periods of undetectable plasma viral loads due to suppressive combinational antiretroviral therapy, thus redefining the migration process in terms of a blood-lymphatic transport system.

[Effects of mercazolyl and L-thyroxine on the antiedematous activity of immunotropic preparations during development of toxic brain edema and swelling].

PubMed

Platonov, I A; Anashchenkova, T A; Andreeva, T A

2008-01-01

Dysfunction of thyroid gland plays an important role in the pathogenesis of brain edema and swelling. Toxic brain edema and swelling was modeled under condition of hypo- and hyperfunction of thyroid gland. Mercazolyl and L-thyroxine ambiguously influence the development of toxic brain edema and swelling in rats. L-thyroxin (35.7 microg/kg) favors increase in the water content in brain tissue, which can be considered as synergism with the edematous factor and the formation of brain tissue susceptibility to the development of brain edema and swelling. The administration of mercazolyl (5 mg/kg) and L-thyroxin (35.7 microg/kg) with thymogen (10 microg/kg), thymalin (1.2 mg/kg), cycloferon (0.5 mg/kg) results in decreasing brain tissue density as compared to intact animals. Dysfunction of the thyroid gland leads to changes in pharmacodynamics of immune preparations, which results in a decrease of their antiedematous activity.

miR-23a, miR-146a and miR-301a confer predisposition to Vogt-Koyanagi-Harada syndrome but not to Behcet's disease.

PubMed

Hou, Shengping; Ye, Zi; Liao, Dan; Bai, Lin; Liu, Yunjia; Zhang, Jun; Kijlstra, Aize; Yang, Peizeng

2016-01-28

Ninety-eight miRNAs are involved in the immune response. However, the genetic roles of these miRNAs remain unclear in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome. This study aimed to explore the association and functional roles of copy number variants (CNV) in several miRNAs with BD and VKH syndrome. Genotyping of CNVs was examined by TaqMan PCR. The expression of miR-23a, transfection efficiency and cytokine production were measured by real-time PCR, flow cytometry or ELISA. First, replication and combined studies for miR-23a, miR-146a and miR-301a demonstrated a similar association with VKH syndrome (Combined: P = 5.53 × 10(-8); P = 8.43 × 10(-31); P = 9.23 × 10(-8), respectively). No association of CNVs of the above mentioned miRNAs was observed in BD patients. mRNA expression of miR-23a showed a positive association with its copy numbers. Additionally, individuals with high copy number of miR-23a show an increased production of interleukin-6 (IL-6), but not IL-8 and monocyte chemoattractant protein-1 (MCP-1) by stimulated PBMCs. miR-23a transfected ARPE-19 cells modulated the production of IL-6 and IL-8, but not MCP-1. Our results suggest that CNVs of miR-146a, miR-23a and miR-301a confer susceptibility to VKH syndrome, but not to BD. The contribution of miR-23a to VKH syndrome may be mediated by increasing the production of IL-6.

Behcet disease combined with Sjogren syndrome: A unique case report and literature review.

PubMed

Ju, Fang-He; Xu, Ting-Zhen; Hong, Hui-Hua; Mao, He; Wang, Meng; Wang, Zhen

2018-03-01

Behcet disease(BD) and Sjogren syndrome(SS) are separate conditions that rarely concomitantly affect an individual. In theory,mild symptoms of patients with BD or SS are easy to igore and,thus,remain undiagnosed. There,it is reasonable to believe there may be some clinical cases of combined diseases that go undiscovered and which needs to be taken seriously. In addition,it has been suggested that herpes simplex virus(HSV) types 1 and 2 are associated with BD,but have not been shown to be correlated to the direct pathogenesis of BD. The role of HSV in BD needs more research and attention. Here,we report a young woman who had both BD and SS. The first symptom of the disease was fever. However,the HSV type 1 IgG and HSV type 2 IgM antibody results were positive in our case and,which rendered this case unique. BD and SS concomitantly affect the individual,and BD was the acute type. IV methylprednisolone was used for 9 days and then oral glucocorticoids was used to instead,and the treatment works very well. BD and SS can concomitantly affect an individual,and we believe that HSV-2 may be directly related to the pathogenesis of BD. The nature of BD as an auto-inflammatory disorder, autoimmune disorder, or both, is controversial. If we can find more patients who combined affected these two disease, it might helpful for us to understand the nature of BD. For patients with clinical diagnosis of BD or SS,we need to be alert that it may combinded the other disease. Long term follow up and detailed inspection are important means to avoid undiscovered.

Risk factor assessment and prognosis of eye involvement in Behcet's disease in Turkey.

PubMed

Demiroğlu, H; Barişta, I; Dündar, S

1997-04-01

Behcet's disease (BD) shows great regional differences in clinical manifestations and prognosis, including eye involvement. Thus, it is hard to predict in which patient the eyes will be involved and what the outcome will be. In this study we assessed various risk factors for eye involvement and attempted to predict the visual outcome in our patient population in Turkey. Data from a total of 224 patients with BD, diagnosed between 1982 and 1996, were analyzed retrospectively. A detailed physical examination and ophthalmologic work up were performed on each patient. Factors that might contribute to eye involvement were investigated, after which prognostic factors for vision were evaluated. Eighty-eight patients had eye involvement during a median follow-up of 32 months. The risk of involvement was highest within the first year of diagnosis. Young age was the most significant factor for eye involvement (P < 0.0001), but vascular thrombosis, central nervous system (CNS) involvement, and male gender were other risk factors (P < 0.001; P < 0.01; and P < 0.05, respectively). The most important determinant for the prognosis of vision was CNS involvement (P < 0.0001). Vascular thrombosis and an age of < or = 32 were other risk factors for visual impairment (P < 0.001 and P < 0.05, respectively). The risk of eye involvement and prognosis for vision were similar with different treatment regimens (P > 0.05). It is suggested that the first 2 years after diagnosis is the most critical period for eye involvement, and conventional forms of therapy generally are unsuccessful in preventing such involvement. It seems reasonable to treat patients who are at increased risk for eye involvement more aggressively, especially within the first 2 years of disease onset.

Potential metabolomic biomarkers for reliable diagnosis of Behcet's disease using gas chromatography/ time-of-flight-mass spectrometry.

PubMed

Ahn, Joong Kyong; Kim, Jungyeon; Hwang, Jiwon; Song, Juhwan; Kim, Kyoung Heon; Cha, Hoon-Suk

2018-05-01

Although many diagnostic criteria of Behcet's disease (BD) have been developed and revised by experts, diagnosing BD is still complicated and challenging. No metabolomic studies on serum have been attempted to improve the diagnosis and to identify potential biomarkers of BD. The purposes of this study were to investigate distinctive metabolic changes in serum samples of BD patients and to identify metabolic candidate biomarkers for reliable diagnosis of BD using the metabolomics platform. Metabolomic profiling of 90 serum samples from 45 BD patients and 45 healthy controls (HCs) were performed via gas chromatography with time-of-flight mass spectrometry (GC/TOF-MS) with multivariate statistical analyses. A total of 104 metabolites were identified from samples. The serum metabolite profiles obtained from GC/TOF-MS analysis can distinguish BD patients from HC group in discovery set. The variation values of the partial least squared-discrimination analysis (PLS-DA) model are R 2 X of 0.246, R 2 Y of 0.913 and Q 2 of 0.852, respectively, indicating strong explanation and prediction capabilities of the model. A panel of five metabolic biomarkers, namely, decanoic acid, fructose, tagatose, linoleic acid and oleic acid were selected and adequately validated as putative biomarkers of BD (sensitivity 100%, specificity 97.1%, area under the curve 0.998) in the discovery set and independent set. The PLS_DA model showed clear discrimination of BD and HC groups by the five metabolic biomarkers in independent set. This is the first report on characteristic metabolic profiles and potential metabolite biomarkers in serum for reliable diagnosis of BD using GC/TOF-MS. Copyright © 2017. Published by Elsevier SAS.

Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

PubMed

Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

2014-01-01

The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539). Copyright © 2013 by the Research Society on Alcoholism.

Using autopsy brain tissue to study alcohol-related brain damage in the genomic age

PubMed Central

Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

2013-01-01

The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain disease (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951–61) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539–52). PMID:24033426

Simultaneous measurement of brain tissue oxygen partial pressure, temperature, and global oxygen consumption during hibernation, arousal, and euthermy in non-sedated and non-anesthetized Arctic ground squirrels.

PubMed

Ma, Yilong; Wu, Shufen

2008-09-30

This study reports an online temperature correction method for determining tissue oxygen partial pressure P(tO2) in the striatum and a novel simultaneous measurement of brain P(tO2) and temperature (T(brain)) in conjunction with global oxygen consumption V(O2) in non-sedated and non-anesthetized freely moving Arctic ground squirrels (AGS, Spermophilus parryii). This method fills an important research gap-the lack of a suitable method for physiologic studies of tissue P(O2) in hibernating or other cool-blooded species. P(tO2) in AGS brain during euthermy (21.22+/-2.06 mmHg) is significantly higher (P=0.016) than during hibernation (13.21+/-0.46 mmHg) suggests brain oxygenation in the striatum is normoxic during euthermy and hypoxic during hibernation. These results in P(tO2) are different from blood oxygen partial pressure P(aO2) in AGS, which are significantly lower during euthermy than during hibernation and are actually hypoxic during euthermy and normoxic during hibernation in our previous study. This intriguing difference between the P(O2) of brain tissue and blood during these two physiological states suggests that regional mechanisms in the brain play a role in maintaining tissue oxygenation and protect against hypoxia during hibernation.

Frozen tissue preparation for high-resolution multiplex histological analyses of human brain specimens.

PubMed

Shao, Fangjie; Jiang, Wenhong; Gao, Qingqing; Li, Baizhou; Sun, Chongran; Wang, Qiyuan; Chen, Qin; Sun, Bing; Shen, Hong; Zhu, Keqing; Zhang, Jianmin; Liu, Chong

2017-10-01

The availability of a comprehensive tissue library is essential for elucidating the function and pathology of human brains. Considering the irreplaceable status of the formalin-fixation-paraffin-embedding (FFPE) preparation in routine pathology and the advantage of ultra-low temperature to preserve nucleic acids and proteins for multi-omics studies, these methods have become major modalities for the construction of brain tissue libraries. Nevertheless, the use of FFPE and snap-frozen samples is limited in high-resolution histological analyses because the preparation destroys tissue integrity and/or many important cellular markers. To overcome these limitations, we detailed a protocol to prepare and analyze frozen human brain samples that is particularly suitable for high-resolution multiplex immunohistological studies. As an alternative, we offered an optimized procedure to rescue snap-frozen tissues for the same purpose. Importantly, we provided a guideline to construct libraries of frozen tissue with minimal effort, cost and space. Taking advantage of this new tissue preparation modality to nicely preserve the cellular information that was otherwise damaged using conventional methods and to effectively remove tissue autofluorescence, we described the high-resolution landscape of the cellular composition in both lower-grade gliomas and glioblastoma multiforme samples. Our work showcases the great value of fixed frozen tissue in understanding the cellular mechanisms of CNS functions and abnormalities.

Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31P-MRS chemical shift imaging at 4 Tesla.

PubMed

Jensen, J Eric; Miller, Jodi; Williamson, Peter C; Neufeld, Richard W J; Menon, Ravi S; Malla, Ashok; Manchanda, Rahul; Schaefer, Betsy; Densmore, Maria; Drost, Dick J

2006-03-31

Altered high energy and membrane metabolism, measured with phosphorus magnetic resonance spectroscopy (31P-MRS), has been inconsistently reported in schizophrenic patients in several anatomical brain regions implicated in the pathophysiology of this illness, with little attention to the effects of brain tissue type on the results. Tissue regression analysis correlates brain tissue type to measured metabolite levels, allowing for the extraction of "pure" estimated grey and white matter compartment metabolite levels. We use this tissue analysis technique on a clinical dataset of first episode schizophrenic patients and matched controls to investigate the effect of brain tissue specificity on altered energy and membrane metabolism. In vivo brain spectra from two regions, (a) the fronto-temporal-striatal region and (b) the frontal-lobes, were analyzed from 12 first episode schizophrenic patients and 11 matched controls from a (31)P chemical shift imaging (CSI) study at 4 Tesla (T) field strength. Tissue regression analyses using voxels from each region were performed relating metabolite levels to tissue content, examining phosphorus metabolite levels in grey and white matter compartments. Compared with controls, the first episode schizophrenic patient group showed significantly increased adenosine triphosphate levels (B-ATP) in white matter and decreased B-ATP levels in grey matter in the fronto-temporal-striatal region. No significant metabolite level differences were found in grey or white matter compartments in the frontal cortex. Tissue regression analysis reveals grey and white matter specific aberrations in high-energy phosphates in first episode schizophrenia. Although past studies report inconsistent regional differences in high-energy phosphate levels in schizophrenia, the present analysis suggests more widespread differences that seem to be strongly related to tissue type. Our data suggest that differences in grey and white matter tissue content between past studies may account for some of the variance in the literature.

[Alterations of glial fibrillary acidic protein in rat brain after gamma knife irradiation].

PubMed

Ma, Z M; Jiang, B; Ma, J R

2001-08-28

To study glial fibrillary acidic protein (GFAP) immunoreactivity in different time and water content of the rat brain treated with gamma knife radiotherapy and to understand the alteration course of the brain lesion after a single high dose radiosurgical treatment. In the brains of the normal rats were irradiated by gamma knife with 160 Gy-high dose. The irradiated rats were then killed on the 1st day, 7th day, 14th day, and 28th day after radiotherapy, respectively. The positive cells of GFAP in brain tissue were detected by immunostaining; the water content of the brain tissue was measured by microgravimetry. The histological study of the irradiated brain tissue was performed with H.E. and examined under light microscope. The numbers of GFAP-positive astrocytes began to increase on the 1st day after gamma knife irradiation. It was enlarged markedly in the number and size of GFAP-stained astrocytes over the irradiated areas. Up to the 28th day, circumscribed necrosis foci (4 mm in diameter) was seen in the central area of the target. In the brain tissue around the necrosis, GFAP-positive astrocytes significantly increased (P < 0.01, compared with the control group). The swelling of cells in irradiated region was observed on the 1st day; after irradiation endothelial cells degenerated and red blood cells escaped from blood vessel on the 7th day; leakage of Evans blue dye was observed in the target region on the 14th day. There was a significant decrease of specific gravity in the irradiated brain tissue the 14th and 28th day after irradiation. The results suggest that GFAP can be used as a marker for the radiation-induced brain injury. The brain edema and disruption of brain-blood barrier can be occurred during the acute stage after irradiation.

Effects of tissue optical properties on time-resolved fluorescence measurements from brain tumors: an experimental and computational study

NASA Astrophysics Data System (ADS)

Butte, Pramod V.; Vishwanath, Karthik; Pikul, Brian K.; Mycek, Mary-Ann; Marcu, Laura

2003-07-01

Time-Resolved Laser-Induced Fluorescence Spectroscopy (tr-LIFS) offers the potential for intra-operative diagnosis of primary brain tumors. However, both the intrinsic properties of endogenous fluorophores and the optical properties of brain tissue could affect the fluorescence measurements from brain. Scattering has been demonstrated to increase, for instance, detected lifetimes by 10-20% in media less scattering than the brain. The overall goal of this study is to investigate experimentally and computationally how optical properties of distinct types of brain tissue (normal porcine white and gray matter) affect the propagation of the excitation pulse and fluorescent transients and the detected fluorescence lifetime. A time-domain tr-LIFS apparatus (fast digitizer and gated detection) was employed to measure the propagation of ultra-short pulsed light through brain specimens (1-2.5-mm source-detector separation; 0.100-mm increment). A Monte Carlo model for semi-infinite turbid media was used to simulate time-resolved light propagation for arbitrary source-detector fiber geometries and optical fiber specifications; and to record spatially- and temporally resolved information. We determined a good correlation between experimental and computational results. Our findings provide means for quantification of time-resolved fluorescence spectra from healthy and diseased brain tissue.

Bioavailability and tissue distribution of Dechloranes in wild frogs (Rana limnocharis) from an e-waste recycling area in Southeast China.

PubMed

Li, Long; Wang, Wenyue; Lv, Quanxia; Ben, Yujie; Li, Xinghong

2014-03-01

Dechlorane Plus (DP), a flame retardant used as an alternative to decabromodiphenylether, has been frequently detected in organisms, indicating its bioaccumulation and biomagnification potential in aquatic and terrestrial species. However, little data is available on the bioaccumulation of DP in amphibians. Dechlorane Plus and its analogs (DPs) were detected in the liver, muscle and brain tissues of wild frogs (Rana limnocharis), which were collected from an e-waste recycling site, Southeast China. DP, Mirex, Dec 602 and a dechlorinated compound of DP (anti-Cl11-DP) varied in the range of 2.01-291, 0.650-179, 0.260-12.4, and not detected (nd)-8.67 ng/g lipid weight, respectively. No difference of tissue distribution was found for syn-DP, Mirex and Dec 602 between the liver and muscle tissue (liver/muscle concentration ratio close to 1, p > 0.05). However, higher retention was observed for anti-DP and anti-Cl11-DP in the frog muscle relative to the liver tissue (liver/muscle concentration ratio < 1, p < 0.05). Additionally, the blood-brain barrier was found to work efficiently to suppress these compounds entering brain tissues in this species (liver/brain concentration ratio > 1, p < 0.05), and the molecular weight was a key factor impacting the extent of the blood-brain barrier. Compared to levels in the muscle and brain tissue, a preferential enrichment of syn-DP was observed in the liver tissue, suggesting the occurrence of stereo-selective bioaccumulation in the wild frog. Copyright © 2014 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators.

PubMed

Lamba, Vishal; Yasuda, Kazuto; Lamba, Jatinder K; Assem, Mahfoud; Davila, Julio; Strom, Stephen; Schuetz, Erin G

2004-09-15

To gain insight on the expression of pregnane X receptor (PXR), we analyzed PXR.1 and PXR alternatively spliced transcripts in a panel of 36 human tissues. PXR.1 was expressed in many more tissues than previously determined, including human bone marrow and select regions of the human brain. In each of these tissues, we observed alternative splicing of various exons of PXR that generated multiple distinct PXR isoforms. The most abundant PXR alternative mRNA transcripts lacked 111 nucleotides, deleting 37 amino acids from the PXR LBD (PXR.2), or lacked 123 nt, deleting 41 amino acids from the PXR LBD (PXR.3). CYP3A4, a gene transcriptionally regulated by PXR, showed incomplete overlap with PXR in its tissue distribution. Quantitation of PXR mRNAs in human liver demonstrated that PXR.2 and PXR.3 represented 6.7% and 0.32% of total PXR mRNA transcripts. Brain expression of PXR prompted analysis of whether some brain acting chemicals were PXR ligands. The neurosteroids allopregnanolone and pregnanolone activated PXR and induced transcription of a CYP3A4-luciferase reporter. Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues.

A combination of experimental measurement, constitutive damage model, and diffusion tensor imaging to characterize the mechanical properties of the human brain.

PubMed

Karimi, Alireza; Rahmati, Seyed Mohammadali; Razaghi, Reza

2017-09-01

Understanding the mechanical properties of the human brain is deemed important as it may subject to various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the frontal lobe of the human brain. The constrained nonlinear minimization method was employed to identify the brain coefficients according to the axial and transversal compressive data. The pseudo-elastic damage model data was also well compared with that of the experimental data and it not only up to the primary loading but also the discontinuous softening could well address the mechanical behavior of the brain tissue.

Syringomyelia

MedlinePlus

... which brain tissue protrudes into your spinal canal (Chiari malformation). Other causes of syringomyelia include spinal cord tumors, ... protrusion of brain tissue into your spinal canal (Chiari malformation), symptoms generally may begin between ages 25 and ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emin, David, E-mail: emin@unm.edu; Akhtari, Massoud; Ellingson, B. M.

We analyze the transient-dc and frequency-dependent electrical conductivities between blocking electrodes. We extend this analysis to measurements of ions’ transport in freshly excised bulk samples of human brain tissue whose complex cellular structure produces blockages. The associated ionic charge-carrier density and diffusivity are consistent with local values for sodium cations determined non-invasively in brain tissue by MRI (NMR) and diffusion-MRI (spin-echo NMR). The characteristic separation between blockages, about 450 microns, is very much shorter than that found for sodium-doped gel proxies for brain tissue, >1 cm.

POWER DENSITY, FIELD INTENSITY, AND CARRIER FREQUENCY DETERMINANTS OF RF-ENERGY-INDUCED CALCIUM-ION EFFLUX FROM BRAIN TISSUE

EPA Science Inventory

To explain a carrier frequency dependence reported for radiofrequency (RF)-induced calcium-ion efflux from brain tissue, a chick-brain hemisphere bathed in buffer solution is modeled as a sphere within the uniform field of the incident electromagnetic wave. Calculations on a sphe...

Optical imaging characterizing brain response to thermal insult in injured rodent

NASA Astrophysics Data System (ADS)

Abookasis, David; Shaul, Oren; Meitav, Omri; Pinhasi, Gadi A.

2018-02-01

We used spatially modulated optical imaging system to assess the effect of temperature elevation on intact brain tissue in a mouse heatstress model. Heatstress or heatstroke is a medical emergency defined by abnormally elevated body temperature that causes biochemical, physiological and hematological changes. During experiments, brain temperature was measured concurrently with a thermal camera while core body temperature was monitored with rectal thermocouple probe. Changes in a battery of macroscopic brain physiological parameters, such as hemoglobin oxygen saturation level, cerebral water content, as well as intrinsic tissue optical properties were monitored during temperature elevation. These concurrent changes reflect the pathophysiology of the brain during heatstress and demonstrate successful monitoring of thermoregulation mechanisms. In addition, the variation of tissue refractive index was calculated showing a monotonous decrease with increasing wavelength. We found increased temperature to greatly affect both the scattering properties and refractive index which represent cellular and subcellular swelling indicative of neuronal damage. The overall trends detected in brain tissue parameters were consistent with previous observations using conventional medical devices and optical modalities.

Fluorescence laminar optical tomography for brain imaging: system implementation and performance evaluation.

PubMed

Azimipour, Mehdi; Sheikhzadeh, Mahya; Baumgartner, Ryan; Cullen, Patrick K; Helmstetter, Fred J; Chang, Woo-Jin; Pashaie, Ramin

2017-01-01

We present our effort in implementing a fluorescence laminar optical tomography scanner which is specifically designed for noninvasive three-dimensional imaging of fluorescence proteins in the brains of small rodents. A laser beam, after passing through a cylindrical lens, scans the brain tissue from the surface while the emission signal is captured by the epi-fluorescence optics and is recorded using an electron multiplication CCD sensor. Image reconstruction algorithms are developed based on Monte Carlo simulation to model light–tissue interaction and generate the sensitivity matrices. To solve the inverse problem, we used the iterative simultaneous algebraic reconstruction technique. The performance of the developed system was evaluated by imaging microfabricated silicon microchannels embedded inside a substrate with optical properties close to the brain as a tissue phantom and ultimately by scanning brain tissue in vivo. Details of the hardware design and reconstruction algorithms are discussed and several experimental results are presented. The developed system can specifically facilitate neuroscience experiments where fluorescence imaging and molecular genetic methods are used to study the dynamics of the brain circuitries.

Polyploidization of glia in neural development links tissue growth to blood-brain barrier integrity.

PubMed

Unhavaithaya, Yingdee; Orr-Weaver, Terry L

2012-01-01

Proper development requires coordination in growth of the cell types composing an organ. Many plant and animal cells are polyploid, but how these polyploid tissues contribute to organ growth is not well understood. We found the Drosophila melanogaster subperineurial glia (SPG) to be polyploid, and ploidy is coordinated with brain mass. Inhibition of SPG polyploidy caused rupture of the septate junctions necessary for the blood-brain barrier. Thus, the increased SPG cell size resulting from polyploidization is required to maintain the SPG envelope surrounding the growing brain. Polyploidization likely is a conserved strategy to coordinate tissue growth during organogenesis, with potential vertebrate examples.

Proton MRS of the peritumoral brain.

PubMed

Chernov, Mikhail F; Kubo, Osami; Hayashi, Motohiro; Izawa, Masahiro; Maruyama, Takashi; Usukura, Masao; Ono, Yuko; Hori, Tomokatsu; Takakura, Kintomo

2005-02-15

Long-echo (TR: 2000 ms, TE: 136 ms) proton MRS of the cerebral tissue in the vicinity to intracranial lesion was done in 15 patients, mainly with parenchymal brain tumors. Significant decrease of N-acetylaspartate (NAA) (P<0.001) and more frequent presence of lactate (P<0.01) comparing with distant normal white matter were found in the perilesional brain tissue. The level of NAA in the perilesional brain tissue had negative associations with presence of lactate in the lesion (P<0.05), excess of lactate in the lesion compared to perilesional brain (P<0.01), grade of the perilesional edema (P<0.01) and patient's age (P<0.05). Multivariate analysis disclosed that identification of lactate in the lesion is associated with lower relative NAA content in the perilesional brain tissue, independently on the presence or absence of any other factor, including brain edema (P<0.001). In patients with lobar lesions who had at least one epileptic seizure during course of their disease the relative NAA content in the perilesional brain was significantly lower, comparing with those who were seizure-free (P<0.05). Therefore, lactate diffused from the tumor, or other metabolites secreted by lactate-producing neoplasm, should be considered as important contributors to the neuronal dysfunction in the surrounding brain. Decrease of NAA in the vicinity to intracranial lesions may reflect neuronal alteration responsible for associated epilepsy.

Ganoderma Lucidum Protects Rat Brain Tissue Against Trauma-Induced Oxidative Stress.

PubMed

Özevren, Hüseyin; İrtegün, Sevgi; Deveci, Engin; Aşır, Fırat; Pektanç, Gülsüm; Deveci, Şenay

2017-10-01

Traumatic brain injury causes tissue damage, breakdown of cerebral blood flow and metabolic regulation. This study aims to investigate the protective influence of antioxidant Ganoderma lucidum ( G. lucidum ) polysaccharides (GLPs) on brain injury in brain-traumatized rats. Sprague-Dawley conducted a head-traumatized method on rats by dropping off 300 g weight from 1 m height. Groups were categorized as control, G. lucidum , trauma, trauma+ G. lucidum (20 mL/kg per day via gastric gavage). Brain tissues were dissected from anesthetized rats 7 days after injury. For biochemical analysis, malondialdehyde, glutathione and myeloperoxidase values were measured. In histopathological examination, neuronal damage in brain cortex and changes in blood brain barrier were observed. In the analysis of immunohistochemical and western blot, p38 mitogen-activated protein kinase, vascular endothelial growth factor and cluster of differentiation 68 expression levels were shown. These analyzes demonstrated the beneficial effects of GLPs on brain injury. We propose that GLPs treatment after brain injury could be an alternative treatment to decraseing inflammation and edema, preventing neuronal and glial cells degeneration if given in appropriate dosage and in particular time intervals.

Evaluating Temperature Changes of Brain Tissue Due to Induced Heating of Cell Phone Waves.

PubMed

Forouharmajd, Farhad; Pourabdian, Siamak; Ebrahimi, Hossein

2018-01-01

Worries have recently been increased in the absorption of radiofrequency waves and their destructing effects on human health by increasing use of cell phones (mobile phones). This study performed to determine the thermal changes due to mobile phone radio frequency waves in gray and white brain tissue. This study is an empirical study, where the thermal changes of electromagnetic waves resulted from cell phones (900 MHZ, specific absorption rate for head 1.18 w/kg) on the 15 brain tissue of a cow were analyzed in a compartment with three different thickness of 2 mm, 12 mm, and 22 mm, for 15 min. The Lutron thermometer (model: MT-917) with 0.01°C precision was used for measuring the tissue temperature. For each thickness was measured three times. Data analysis is done by Lutron and MATLAB software packages. In confronting of the tissue with the cell phone, the temperature was increased by 0.53°C in the 2 mm thickness that is the gray matter of the brain, increased by 0.99°C in the 12 mm thickness, and also increased by 0.92°C in the 22 mm thickness. Brain temperature showed higher rates than the base temperature after 15 min of confrontation with cell phone waves in all the three thicknesses. Cell phone radiated radio frequency waves were effective on increasing brain tissue temperature, and this temperature increase has cumulative effect on the tissue, being higher, for some time after the confrontation than the time with no confrontation.

Evaluating Temperature Changes of Brain Tissue Due to Induced Heating of Cell Phone Waves

PubMed Central

Forouharmajd, Farhad; Pourabdian, Siamak; Ebrahimi, Hossein

2018-01-01

Background: Worries have recently been increased in the absorption of radiofrequency waves and their destructing effects on human health by increasing use of cell phones (mobile phones). This study performed to determine the thermal changes due to mobile phone radio frequency waves in gray and white brain tissue. Methods: This study is an empirical study, where the thermal changes of electromagnetic waves resulted from cell phones (900 MHZ, specific absorption rate for head 1.18 w/kg) on the 15 brain tissue of a cow were analyzed in a compartment with three different thickness of 2 mm, 12 mm, and 22 mm, for 15 min. The Lutron thermometer (model: MT-917) with 0.01°C precision was used for measuring the tissue temperature. For each thickness was measured three times. Data analysis is done by Lutron and MATLAB software packages. Results: In confronting of the tissue with the cell phone, the temperature was increased by 0.53°C in the 2 mm thickness that is the gray matter of the brain, increased by 0.99°C in the 12 mm thickness, and also increased by 0.92°C in the 22 mm thickness. Brain temperature showed higher rates than the base temperature after 15 min of confrontation with cell phone waves in all the three thicknesses. Conclusions: Cell phone radiated radio frequency waves were effective on increasing brain tissue temperature, and this temperature increase has cumulative effect on the tissue, being higher, for some time after the confrontation than the time with no confrontation. PMID:29861880

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy.

PubMed Central

Lilge, L.; Olivo, M. C.; Schatz, S. W.; MaGuire, J. A.; Patterson, M. S.; Wilson, B. C.

1996-01-01

The applicability and limitations of a photodynamic threshold model, used to describe quantitatively the in vivo response of tissues to photodynamic therapy, are currently being investigated in a variety of normal and malignant tumour tissues. The model states that tissue necrosis occurs when the number of photons absorbed by the photosensitiser per unit tissue volume exceeds a threshold. New Zealand White rabbits were sensitised with porphyrin-based photosensitisers. Normal brain or intracranially implanted VX2 tumours were illuminated via an optical fibre placed into the tissue at craniotomy. The light fluence distribution in the tissue was measured by multiple interstitial optical fibre detectors. The tissue concentration of the photosensitiser was determined post mortem by absorption spectroscopy. The derived photodynamic threshold values for normal brain are significantly lower than for VX2 tumour for all photosensitisers examined. Neuronal damage is evident beyond the zone of frank necrosis. For Photofrin the threshold decreases with time delay between photosensitiser administration and light treatment. No significant difference in threshold is found between Photofrin and haematoporphyrin derivative. The threshold in normal brain (grey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid. The results confirm the very high sensitivity of normal brain to porphyrin photodynamic therapy and show the importance of in situ light fluence monitoring during photodynamic irradiation. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8562339

Characterization of a Raman spectroscopy probe system for intraoperative brain tissue classification

PubMed Central

Desroches, Joannie; Jermyn, Michael; Mok, Kelvin; Lemieux-Leduc, Cédric; Mercier, Jeanne; St-Arnaud, Karl; Urmey, Kirk; Guiot, Marie-Christine; Marple, Eric; Petrecca, Kevin; Leblond, Frédéric

2015-01-01

A detailed characterization study is presented of a Raman spectroscopy system designed to maximize the volume of resected cancer tissue in glioma surgery based on in vivo molecular tissue characterization. It consists of a hand-held probe system measuring spectrally resolved inelastically scattered light interacting with tissue, designed and optimized for in vivo measurements. Factors such as linearity of the signal with integration time and laser power, and their impact on signal to noise ratio, are studied leading to optimal data acquisition parameters. The impact of ambient light sources in the operating room is assessed and recommendations made for optimal operating conditions. In vivo Raman spectra of normal brain, cancer and necrotic tissue were measured in 10 patients, demonstrating that real-time inelastic scattering measurements can distinguish necrosis from vital tissue (including tumor and normal brain tissue) with an accuracy of 87%, a sensitivity of 84% and a specificity of 89%. PMID:26203368

Aluminium in brain tissue in familial Alzheimer's disease.

PubMed

Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

2017-03-01

The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Effects of acupuncture on tissue-oxygenation of the rat brain.

PubMed

Chen, G S; Erdmann, W

1977-01-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by sympathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex of the animals through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture loci (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible. The effect was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase of inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes an increase of brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients. Dilatation of cerebral vascular vessels and improvement of autoregulation in the brain by acupuncture stimulation may also explain the effectiveness of acupuncture in the treatment of migraine headache.

SU-E-T-587: Optimal Volumetric Modulated Arc Radiotherapy Treatment Planning Technique for Multiple Brain Metastases with Increasing Number of Arcs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keeling, V; Hossain, S; Hildebrand, K

Purpose: To show improvements in dose conformity and normal brain tissue sparing using an optimal planning technique (OPT) against clinically acceptable planning technique (CAP) in the treatment of multiple brain metastases. Methods: A standardized international benchmark case with12 intracranial tumors was planned using two different VMAT optimization methods. Plans were split into four groups with 3, 6, 9, and 12 targets each planned with 3, 5, and 7 arcs using Eclipse TPS. The beam geometries were 1 full coplanar and half non-coplanar arcs. A prescription dose of 20Gy was used for all targets. The following optimization criteria was used (OPTmore » vs. CAP): (No upper limit vs.108% upper limit for target volume), (priority 140–150 vs. 75–85 for normal-brain-tissue), and (selection of automatic sparing Normal-Tissue-Objective (NTO) vs. Manual NTO). Both had priority 50 to critical structures such as brainstem and optic-chiasm, and both had an NTO priority 150. Normal-brain-tissue doses along with Paddick Conformity Index (PCI) were evaluated. Results: In all cases PCI was higher for OPT plans. The average PCI (OPT,CAP) for all targets was (0.81,0.64), (0.81,0.63), (0.79,0.57), and (0.72,0.55) for 3, 6, 9, and 12 target plans respectively. The percent decrease in normal brain tissue volume (OPT/CAP*100) achieved by OPT plans was (reported as follows: V4, V8, V12, V16, V20) (184, 343, 350, 294, 371%), (192, 417, 380, 299, 360%), and (235, 390, 299, 281, 502%) for the 3, 5, 7 arc 12 target plans, respectively. The maximum brainstem dose decreased for the OPT plan by 4.93, 4.89, and 5.30 Gy for 3, 5, 7 arc 12 target plans, respectively. Conclusion: Substantial increases in PCI, critical structure sparing, and decreases in normal brain tissue dose were achieved by eliminating upper limits from optimization, using automatic sparing of normal tissue function with high priority, and a high priority to normal brain tissue.« less

Protection of cortex by overlying meninges tissue during dynamic indentation of the adolescent brain.

PubMed

MacManus, David B; Pierrat, Baptiste; Murphy, Jeremiah G; Gilchrist, Michael D

2017-07-15

Traumatic brain injury (TBI) has become a recent focus of biomedical research with a growing international effort targeting material characterization of brain tissue and simulations of trauma using computer models of the head and brain to try to elucidate the mechanisms and pathogenesis of TBI. The meninges, a collagenous protective tri-layer, which encloses the entire brain and spinal cord has been largely overlooked in these material characterization studies. This has resulted in a lack of accurate constitutive data for the cranial meninges, particularly under dynamic conditions such as those experienced during head impacts. The work presented here addresses this lack of data by providing for the first time, in situ large deformation material properties of the porcine dura-arachnoid mater composite under dynamic indentation. It is demonstrated that this tissue is substantially stiffer (shear modulus, μ=19.10±8.55kPa) and relaxes at a slower rate (τ 1 =0.034±0.008s, τ 2 =0.336±0.077s) than the underlying brain tissue (μ=6.97±2.26kPa, τ 1 =0.021±0.007s, τ 2 =0.199±0.036s), reducing the magnitudes of stress by 250% and 65% for strains that arise during indentation-type deformations in adolescent brains. We present the first mechanical analysis of the protective capacity of the cranial meninges using in situ micro-indentation techniques. Force-relaxation tests are performed on in situ meninges and cortex tissue, under large strain dynamic micro-indentation. A quasi-linear viscoelastic model is used subsequently, providing time-dependent mechanical properties of these neural tissues under loading conditions comparable to what is experienced in TBI. The reported data highlights the large differences in mechanical properties between these two tissues. Finite element simulations of the indentation experiments are also performed to investigate the protective capacity of the meninges. These simulations show that the meninges protect the underlying brain tissue by reducing the overall magnitude of stress by 250% and up to 65% for strains. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Brain herniation

MedlinePlus

... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, P; Park, P; Li, H

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated withmore » PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.« less

Effect of dietary docosahexaenoic acid (DHA) in phospholipids or triglycerides on brain DHA uptake and accretion.

PubMed

Kitson, Alex P; Metherel, Adam H; Chen, Chuck T; Domenichiello, Anthony F; Trépanier, Marc-Olivier; Berger, Alvin; Bazinet, Richard P

2016-07-01

Tracer studies suggest that phospholipid DHA (PL-DHA) more effectively targets the brain than triglyceride DHA (TAG-DHA), although the mechanism and whether this translates into higher brain DHA concentrations are not clear. Rats were gavaged with [U-(3)H]PL-DHA and [U-(3)H]TAG-DHA and blood sampled over 6h prior to collection of brain regions and other tissues. In another experiment, rats were supplemented for 4weeks with TAG-DHA (fish oil), PL-DHA (roe PL) or a mixture of both for comparison to a low-omega-3 diet. Brain regions and other tissues were collected, and blood was sampled weekly. DHA accretion rates were estimated using the balance method. [U-(3)H]PL-DHA rats had higher radioactivity in cerebellum, hippocampus and remainder of brain, with no differences in other tissues despite higher serum lipid radioactivity in [U-(3)H]TAG-DHA rats. TAG-DHA, PL-DHA or a mixture were equally effective at increasing brain DHA. There were no differences between DHA-supplemented groups in brain region, whole-body, or tissue DHA accretion rates except heart and serum TAG where the PL-DHA/TAG-DHA blend was higher than TAG-DHA. Apparent DHA β-oxidation was not different between DHA-supplemented groups. This indicates that more labeled DHA enters the brain when consumed as PL; however, this may not translate into higher brain DHA concentrations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Effects of Changing Water Content, Relaxation Times, and Tissue Contrast on Tissue Segmentation and Measures of Cortical Anatomy in MR Images

PubMed Central

Bansal, Ravi; Hao, Xuejun; Liu, Feng; Xu, Dongrong; Liu, Jun; Peterson, Bradley S.

2013-01-01

Water content is the dominant chemical compound in the brain and it is the primary determinant of tissue contrast in magnetic resonance (MR) images. Water content varies greatly between individuals, and it changes dramatically over time from birth through senescence of the human life span. We hypothesize that the effects that individual- and age-related variations in water content have on contrast of the brain in MR images also has important, systematic effects on in vivo, MRI-based measures of regional brain volumes. We also hypothesize that changes in water content and tissue contrast across time may account for age-related changes in regional volumes, and that differences in water content or tissue contrast across differing neuropsychiatric diagnoses may account for differences in regional volumes across diagnostic groups. We demonstrate in several complementary ways that subtle variations in water content across age and tissue compartments alter tissue contrast, and that changing tissue contrast in turn alters measures of the thickness and volume of the cortical mantle: (1) We derive analytic relations describing how age-related changes in tissue relaxation times produce age-related changes in tissue gray-scale intensity values and tissue contrast; (2) We vary tissue contrast in computer-generated images to assess its effects on tissue segmentation and volumes of gray matter and white matter; and (3) We use real-world imaging data from adults with either Schizophrenia or Bipolar Disorder and age- and sex-matched healthy adults to assess the ways in which variations in tissue contrast across diagnoses affects group differences in tissue segmentation and associated volumes. We conclude that in vivo MRI-based morphological measures of the brain, including regional volumes and measures of cortical thickness, are a product of, or at least are confounded by, differences in tissue contrast across individuals, ages, and diagnostic groups, and that differences in tissue contrast in turn likely derive from corresponding differences in water content of the brain across individuals, ages, and diagnostic groups. PMID:24055410

A non-aggressive, highly efficient, enzymatic method for dissociation of human brain-tumors and brain-tissues to viable single-cells.

PubMed

Volovitz, Ilan; Shapira, Netanel; Ezer, Haim; Gafni, Aviv; Lustgarten, Merav; Alter, Tal; Ben-Horin, Idan; Barzilai, Ori; Shahar, Tal; Kanner, Andrew; Fried, Itzhak; Veshchev, Igor; Grossman, Rachel; Ram, Zvi

2016-06-01

Conducting research on the molecular biology, immunology, and physiology of brain tumors (BTs) and primary brain tissues requires the use of viably dissociated single cells. Inadequate methods for tissue dissociation generate considerable loss in the quantity of single cells produced and in the produced cells' viability. Improper dissociation may also demote the quality of data attained in functional and molecular assays due to the presence of large quantities cellular debris containing immune-activatory danger associated molecular patterns, and due to the increased quantities of degraded proteins and RNA. Over 40 resected BTs and non-tumorous brain tissue samples were dissociated into single cells by mechanical dissociation or by mechanical and enzymatic dissociation. The quality of dissociation was compared for all frequently used dissociation enzymes (collagenase, DNase, hyaluronidase, papain, dispase) and for neutral protease (NP) from Clostridium histolyticum. Single-cell-dissociated cell mixtures were evaluated for cellular viability and for the cell-mixture dissociation quality. Dissociation quality was graded by the quantity of subcellular debris, non-dissociated cell clumps, and DNA released from dead cells. Of all enzymes or enzyme combinations examined, NP (an enzyme previously not evaluated on brain tissues) produced dissociated cell mixtures with the highest mean cellular viability: 93 % in gliomas, 85 % in brain metastases, and 89 % in non-tumorous brain tissue. NP also produced cell mixtures with significantly less cellular debris than other enzymes tested. Dissociation using NP was non-aggressive over time-no changes in cell viability or dissociation quality were found when comparing 2-h dissociation at 37 °C to overnight dissociation at ambient temperature. The use of NP allows for the most effective dissociation of viable single cells from human BTs or brain tissue. Its non-aggressive dissociative capacity may enable ambient-temperature shipping of tumor pieces in multi-center clinical trials, meanwhile being dissociated. As clinical grade NP is commercially available it can be easily integrated into cell-therapy clinical trials in neuro-oncology. The high quality viable cells produced may enable investigators to conduct more consistent research by avoiding the experimental artifacts associated with the presence dead cells or cellular debris.

Clinical efficacy of positron emission tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heiss, W.D.; Pawlick, G.; Herholz, K.

1987-01-01

The contents of this book are: Brain: Cerebral Vascular Disease; Brain: Movement Disorders; Brain: Epilepsy and Pediatric Neurology; Brain: Dementias; Brain: Schizophrenia; Heart: Angina Pectoris; Heart: Infarction; Lungs; Soft Tissue Tumors; and Brain Tumors.

Over-hydration detection in brain by magnetic induction spectroscopy

NASA Astrophysics Data System (ADS)

González, César A.; Pérez, María; Hevia, Nidiyare; Arámbula, Fernándo; Flores, Omar; Aguilar, Eliot; Hinojosa, Ivonne; Joskowicz, Leo; Rubinsky, Boris

2010-04-01

Detection and continuous monitoring of edema in the brain in early stages is useful for assessment of medical condition and treatment. We have proposed a solution in which the bulk measurements of the tissue electrical properties to detect edema or in general accumulation of fluids are made through measurement of the magnetic induction phase shift between applied and measured currents at different frequencies (Magnetic Induction Spectroscopy; MIS). Magnetic Resonant Imaging (MRI) has been characterized because its capability to detect different levels of brain tissue hydration by differences in diffusion-weighted (DW) sequences and it's involve apparent diffusion coefficient (ADC). The objective of this study was to explore the viability to use measurements of the bulk tissue electrical properties to detect edema or in general accumulation of fluids by MIS. We have induced a transitory and generalized tissue over-hydration condition in ten volunteers ingesting 1.5 to 2 liters of water in ten minutes. Basal and over-hydration conditions were monitored by MIS and MRI. Changes in the inductive phase shift at certain frequencies were consistent with changes in the brain tissue hydration level observed by DW-ADC. The results suggest that MIS has the potential to detect pathologies associated to changes in the content of fluids in brain tissue such as edema and hematomas.

Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.

PubMed

Bonar, Nicolle A; Petersen, Christian P

2017-03-01

Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarian Schmidtea mediterranea as a model, we identify β1-integrin as a crucial regulator of blastema architecture. β1-integrin(RNAi) animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesized in vitro We identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized in β1-integrin(RNAi) animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema. © 2017. Published by The Company of Biologists Ltd.

Extracting morphologies from third harmonic generation images of structurally normal human brain tissue.

PubMed

Zhang, Zhiqing; Kuzmin, Nikolay V; Groot, Marie Louise; de Munck, Jan C

2017-06-01

The morphologies contained in 3D third harmonic generation (THG) images of human brain tissue can report on the pathological state of the tissue. However, the complexity of THG brain images makes the usage of modern image processing tools, especially those of image filtering, segmentation and validation, to extract this information challenging. We developed a salient edge-enhancing model of anisotropic diffusion for image filtering, based on higher order statistics. We split the intrinsic 3-phase segmentation problem into two 2-phase segmentation problems, each of which we solved with a dedicated model, active contour weighted by prior extreme. We applied the novel proposed algorithms to THG images of structurally normal ex-vivo human brain tissue, revealing key tissue components-brain cells, microvessels and neuropil, enabling statistical characterization of these components. Comprehensive comparison to manually delineated ground truth validated the proposed algorithms. Quantitative comparison to second harmonic generation/auto-fluorescence images, acquired simultaneously from the same tissue area, confirmed the correctness of the main THG features detected. The software and test datasets are available from the authors. z.zhang@vu.nl. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Multimodality stereotactic brain tissue identification: the NASA smart probe project

NASA Technical Reports Server (NTRS)

Andrews, R.; Mah, R.; Aghevli, A.; Freitas, K.; Galvagni, A.; Guerrero, M.; Papsin, R.; Reed, C.; Stassinopoulos, D.

1999-01-01

Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures. Copyright 2000 S. Karger AG, Basel.

Adoptive transfer of T regulatory cells inhibits lipopolysaccharide-induced inflammation in fetal brain tissue in a late-pregnancy preterm birth mouse model.

PubMed

Wang, Fan; Xiao, Mi; Chen, Ru-Juan; Lin, Xiao-Jie; Siddiq, Muhammad; Liu, Li

2017-02-01

To evaluate the effect of regulatory T cells (Tregs) on the inflammation resulting from lipopolysaccharide (LPS) challenge in prenatal brain tissue, Tregs isolated from pregnant mice were transferred into model mice, and the expression levels of fork head family transcription factor (Foxp3), interleukin-6 (IL-6), CD68 (a marker of microglia), and toll-like receptor 4 (TLR-4) were assessed in the fetal brain tissue. Foxp3, IL-6, and TLR-4 expression were detected by polymerase chain reaction and Western blot; CD68 expression level was detected using immunochemical analysis. Foxp3, IL-6, TLR-4, and CD68 expressions in fetal brain were significantly induced by maternal LPS administration, and the increased expression levels were markedly reduced by adoptive transfer of Tregs. Maternal LPS exposure significantly induced inflammation in perinatal brain tissue, and Tregs negatively regulated this LPS-induced inflammation. © 2016 International Federation for Cell Biology.

Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

DTIC Science & Technology

2015-10-01

tomography images. The CT image densities in Hounsfield units (HU) of the brain were translated into corresponding optical properties (absorption...derived the Hounsfield units and optical properties of brain tissues such as white/gray matter. 13-15 The segmentation software generated an optical map...treatment protocol. Head CT image densities (in Hounsfield Units /HU) are segmented and translated into optical properties of the brain tissue

Enzymatic Digestion of Eye and Brain Tissues of Sockeye and Coho Salmon, and Dusky Rockfish Commercially Harvested in Alaska

USDA-ARS?s Scientific Manuscript database

Potential feed ingredients with high lipid content were made by enzymatic digestion followed by centrifugation of eye tissue from dusky rockfish (Sebastes ciliatos), coho salmon (Oncorhynchus kisutch), and sockeye salmon (Oncorhynchus nerka) and brain tissue from sockeye salmon. Materials with high ...

Use of a rapid brain-sampling technique in a physiologic preparation: effects of morphine, ketamine, and halothane on tissue energy intermediates.

PubMed

Dedrick, D F; Sherer, Y D; Biebuyck, J F

1975-06-01

A new method of rapid sampling of brain tissue, "freeze-blowing," has been used to compare the neurochemistry of the brain during anesthesia with that in the awake state. The method avoids anoxia associated with the sampling process. Physiologic variables, including body temperature, blood-gas tensions and blood pressure, were carefully monitored and controlled in the experimental animals. None of the agents tested (halothane, morphine, and ketamine) reduced the brain tissue high-energy phosphate reserved. All three drugs doubled glucose levels. Morphine lowered both lactate and the lactate/pyruvate ratio. Uniformly, the three anesthetic agents led to twofold increases of brain cyclic 3'-5' adenosine monophosphate concentrations. These changes suggest a possible role for cyclic nucleotides in central neurotransmission.

Autism BrainNet: A network of postmortem brain banks established to facilitate autism research.

PubMed

Amaral, David G; Anderson, Matthew P; Ansorge, Olaf; Chance, Steven; Hare, Carolyn; Hof, Patrick R; Miller, Melissa; Nagakura, Ikue; Pickett, Jane; Schumann, Cynthia; Tamminga, Carol

2018-01-01

Autism spectrum disorder (ASD or autism) is a neurodevelopmental condition that affects over 1% of the population worldwide. Developing effective preventions and treatments for autism will depend on understanding the genetic perturbations and underlying neuropathology of the disorder. While evidence from magnetic resonance imaging and other noninvasive techniques points to altered development and organization of the autistic brain, these tools lack the resolution for identifying the cellular and molecular underpinnings of the disorder. Postmortem studies of high-quality human brain tissue currently represent the only viable option to pursuing these types of studies. However, the availability of high-quality ASD brain tissue has been extremely limited. Here we describe the establishment of a privately funded tissue bank, Autism BrainNet, a network of brain collection sites that work in a coordinated fashion to develop an adequate library of human postmortem brain tissues. Autism BrainNet was initiated as a collaboration between the Simons Foundation and Autism Speaks, and is currently funded by the Simons Foundation Autism Research Initiative. Autism BrainNet has collection sites (nodes) in California, Texas, New York, and Massachusetts; an affiliated, international node is located in Oxford, England. All donations to this network become part of a consolidated pool of tissue that is distributed to qualified investigators worldwide to carry out autism research. An essential component of this program is a widespread outreach program that highlights the need for postmortem brain donations to families affected by autism, led by the Autism Science Foundation. Challenges include an outreach campaign that deals with a disorder beginning in early childhood, collecting an adequate number of donations to deal with the high level of biologic heterogeneity of autism, and preparing this limited resource for optimal distribution to the greatest number of investigators. Copyright © 2018 Elsevier B.V. All rights reserved.

Regular aerobic exercise correlates with reduced anxiety and incresed levels of irisin in brain and white adipose tissue.

PubMed

Uysal, Nazan; Yuksel, Oguz; Kizildag, Servet; Yuce, Zeynep; Gumus, Hikmet; Karakilic, Aslı; Guvendi, Guven; Koc, Basar; Kandis, Sevim; Ates, Mehmet

2018-05-29

We have recently shown that regular voluntary aerobic exercised rats have low levels of anxiety. Irisin is an exercise-induced myokine that is produced by many tissues; and the role it plays in anxiolytic behavior is unknown. In this study we aimed to investigate the correlation between anxiety like behavior and irisin levels following regular voluntary aerobic exercise in male mice. We've have shown that anxiety levels decreased in exercised mice, while irisin levels increased in the brain, brown adipose tissue, white adipose tissue, kidney, and pancreas tissues. No significant difference of irisin levels in the liver, muscle and serum were detected in the exercise group, when compared to controls. In addition, there was a strong positive correlation between brain irisin levels and activity in middle area of open field test and in the open arms of elevated plus maze test; both which are indicators of low anxiety levels. Our results suggest that decrease in anxiolytic behavior due to regular voluntary exercise may be associated with locally produced brain irisin. White adipose tissue irisin levels also correlated very strongly with low anxiety. However, no serum irisin increase was detected, ruling out the possibility of increased peripheral irisin levels affecting the brain via the bloodstream. Further research is necessary to explain the mechanisms of which peripheral and central irisin effects anxiety and the brain region affected. Copyright © 2018 Elsevier B.V. All rights reserved.

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

PubMed Central

Zhou, Tao; Hong, Guosong; Fu, Tian-Ming; Yang, Xiao; Schuhmann, Thomas G.; Viveros, Robert D.; Lieber, Charles M.

2017-01-01

Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2–12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future. PMID:28533392

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain.

PubMed

Zhou, Tao; Hong, Guosong; Fu, Tian-Ming; Yang, Xiao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

2017-06-06

Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2-12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future.

Banking for the future: an Australian experience in brain banking.

PubMed

Sarris, M; Garrick, T M; Sheedy, D; Harper, C G

2002-06-01

The New South Wales (NSW) Tissue Resource Centre (TRC) has been set up to provide Australian and international researchers with fixed and frozen brain tissue from cases that are well characterised, both clinically and pathologically, for projects related to neuropsychiatric and alcohol-related disorders. A daily review of the Department of Forensic Medicine provides initial information regarding a potential collection. If the case adheres to the strict inclusion criteria, the pathologist performing the postmortem examination is approached regarding retention of the brain tissue. The next of kin of the deceased is then contacted requesting permission to retain the brain for medical research. Cases are also obtained through donor programmes, where donors are assessed and consent to donate their brain during life. Once the brain is removed at autopsy, the brain is photographed, weighed and the volume determined, the brainstem and cerebellum are removed. The two hemispheres are divided, one hemisphere is fresh frozen and one fixed (randomised). Prior to freezing, the hemisphere is sliced into 1-cm coronal slices and a set of critical area blocks is taken. All frozen tissues are kept bagged at -80 degrees C. The other hemisphere is fixed in 15% buffered formalin for 2 weeks, embedded in agar and sliced at 3-mm intervals in the coronal plane. Tissue blocks from these slices are used for neuropathological analysis to exclude any other pathology. The TRC currently has 230 cases of both fixed and frozen material that has proven useful in a range of techniques in many research projects. These techniques include quantitative analyses of brain regions using neuropathological, neurochemical, neuropharmacological and gene expression assays.

The biochemical, nanomechanical and chemometric signatures of brain cancer.

PubMed

Abramczyk, Halina; Imiela, Anna

2018-01-05

Raman spectroscopy and imaging combined with AFM topography and mechanical indentation by AFM have been shown to be an effective tool for analysis and discrimination of human brain tumors from normal structures. Raman methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n=5) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma (IV grade), and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational spectra and Raman images we provide a real-time feedback that is label-free method to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, and proteins. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845cm -1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the lipid and protein contents of tumorous brain tissue compared to the non-tumor tissue. Almost all brain tumors have the Raman intensity ratios significantly higher (1.99±0.026) than that found in non-tumor brain tissue, which is 1.456±0.02, and indicates that the relative amount of lipids compared to proteins is significantly higher in the normal brain tissue. Mechanical indentation using AFM on sliced human brain tissues (medulloblastoma, grade IV) revealed that the mechanical properties of this tissue are strongly heterogeneous, between 1.8 and 75.7kPa, and the mean of 27.16kPa. The sensitivity and specificity obtained directly from PLSDA and cross validation gives a sensitivity and specificity of 98.5% and 96% and 96.3% and 92% for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

NASA Astrophysics Data System (ADS)

Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

2016-07-01

Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

Digital tissue and what it may reveal about the brain.

PubMed

Morgan, Josh L; Lichtman, Jeff W

2017-10-30

Imaging as a means of scientific data storage has evolved rapidly over the past century from hand drawings, to photography, to digital images. Only recently can sufficiently large datasets be acquired, stored, and processed such that tissue digitization can actually reveal more than direct observation of tissue. One field where this transformation is occurring is connectomics: the mapping of neural connections in large volumes of digitized brain tissue.

Brain Tumors

MedlinePlus

A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

High-resolution x-ray absorption spectroscopy studies of metal compounds in neurodegenerative brain tissue

NASA Astrophysics Data System (ADS)

Collingwood, J. F.; Mikhaylova, A.; Davidson, M. R.; Batich, C.; Streit, W. J.; Eskin, T.; Terry, J.; Barrea, R.; Underhill, R. S.; Dobson, J.

2005-01-01

Fluorescence mapping and microfocus X-ray absorption spectroscopy are used to detect, locate and identify iron biominerals and other inorganic metal accumulations in neurodegenerative brain tissue at sub-cellular resolution (<5 microns). Recent progress in developing the technique is reviewed. Synchrotron X-rays are used to map tissue sections for metals of interest, and XANES and XAFS are used to characterise anomalous concentrations of the metals in-situ so that they can be correlated with tissue structures and disease pathology. Iron anomalies associated with biogenic magnetite, ferritin and haemoglobin are located and identified in an avian tissue model with a pixel resolution ~5 microns. Subsequent studies include brain tissue sections from transgenic Huntington's mice, and the first high-resolution mapping and identification of iron biominerals in human Alzheimer's and control autopsy brain tissue. Technical developments include use of microfocus diffraction to obtain structural information about biominerals in-situ, and depositing sample location grids by lithography for the location of anomalies by conventional microscopy. The combined techniques provide a breakthrough in the study of both intra- and extra-cellular iron compounds and related metals in tissue. The information to be gained from this approach has implications for future diagnosis and treatment of neurodegeneration, and for our understanding of the mechanisms involved.

Biological fiducial point based registration for multiple brain tissues reconstructed from different imaging modalities

NASA Astrophysics Data System (ADS)

Wu, Huiqun; Zhou, Gangping; Geng, Xingyun; Zhang, Xiaofeng; Jiang, Kui; Tang, Lemin; Zhou, Guomin; Dong, Jiancheng

2013-10-01

With the development of computer aided navigation system, more and more tissues shall be reconstructed to provide more useful information for surgical pathway planning. In this study, we aimed to propose a registration framework for different reconstructed tissues from multi-modalities based on some fiducial points on lateral ventricles. A male patient with brain lesion was admitted and his brain scans were performed by different modalities. Then, the different brain tissues were segmented in different modality with relevant suitable algorithms. Marching cubes were calculated for three dimensional reconstructions, and then the rendered tissues were imported to a common coordinate system for registration. Four pairs of fiducial markers were selected to calculate the rotation and translation matrix using least-square measure method. The registration results were satisfied in a glioblastoma surgery planning as it provides the spatial relationship between tumors and surrounding fibers as well as vessels. Hence, our framework is of potential value for clinicians to plan surgery.

Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes.

PubMed

Aydin, Suleyman; Kuloglu, Tuncay; Aydin, Suna; Eren, Mehmet Nesimi; Yilmaz, Musa; Kalayci, Mehmet; Sahin, Ibrahim; Kocaman, Nevin; Citil, Cihan; Kendir, Yalcin

2013-08-01

We have investigated how diabetes affects the expression of adropin (ADR) in rat brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The rats in the diabetic group were administered an intraperitoneal (i.p.) injection of a single dose of 60 mg/kg streptozotocin (STZ) dissolved in a 0.1 M phosphate-citrate buffer (pH 4.5). The rats were maintained in standard laboratory conditions in a temperature between 21 and 23 °C and a relative humidity of 70 %, under a 12-h light/dark cycle. The animals were fed a standard commercial pellet diet. After 10 weeks, the animals were sacrified. ADR concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to follow the expression of the hormones in the brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The quantities were then compared. Increased ADR immunoreaction was seen in the brain, cerebellum, kidneys, heart, liver, and pancreas in the diabetes-induced rats compared to control subjects. ADR was detected in the brain (vascular area, pia mater, neuroglial cell, and neurons), cerebellum (neuroglial cells, Purkinje cells, vascular areas, and granular layer), kidneys (glomerulus, peritubular interstitial cells, and peritubular capillary endothelial cells), heart (endocardium, myocardium, and epicardium), liver (sinusoidal cells), and pancreas (serous acini). Its concentrations (based on mg/wet weight tissues) in these tissues were measured by using ELISA showed that the levels of ADR were higher in the diabetic rats compared to the control rats. Tissue ADR levels based on mg/wet weight tissues were as follows: Pancreas > liver > kidney > heart > brain > cerebellar tissues. Evidence is presented that shows ADR is expressed in various tissues in the rats and its levels increased in STZ-induced diabetes; however, this effect on the pathophysiology of the disorder remains to be understood.

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues.

PubMed

Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R; Romer, Micah; Tufik, Sergio; Pack, Allan I

2013-05-30

Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed "sleep specific" changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a ubiquitous role in reducing cellular metabolic stress in both brain and peripheral tissues. Finally, our data suggest a novel role for sleep in synchronizing transcription in peripheral tissues.

Brain Cancer—Patient Version

Cancer.gov

Brain cancer refers to growths of malignant cells in tissues of the brain. Tumors that start in the brain are called primary brain tumors. Tumors that spread to the brain are called metastatic brain tumors. Start here to find information on brain cancer treatment, research, and statistics.

Coexistence of multiple sclerosis and ankylosing spondylitis: Report of four cases from Russia and review of the literature.

PubMed

Fominykh, Vera; Shevtsova, Tatyana; Arzumanian, Narine; Brylev, Lev

2017-10-01

Multiple sclerosis is a chronic demyelinating disorder of the central nervous system. There are many cases of multiple sclerosis - like syndrome and demyelinating disorders in systemic lupus erythematosus, Sjogren disease, Behcet disease and other autoimmune conditions. Coexistence of ankylosing spondylitis and multiple sclerosis usually is rare but in this article we report 4 Russian patients with concomitant multiple sclerosis and ankylosing spondylitis diseases. None of these patients received anti-tumor necrosis factor alpha therapy prior to diagnosis of multiple sclerosis. Pathogenesis, diagnostic and treatment challenges are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrogen-Rich Saline Attenuates Brain Injury Induced by Cardiopulmonary Bypass and Inhibits Microvascular Endothelial Cell Apoptosis Via the PI3K/Akt/GSK3β Signaling Pathway in Rats.

PubMed

Chen, Keyan; Wang, Nan; Diao, Yugang; Dong, Wanwei; Sun, YingJie; Liu, Lidan; Wu, Xiuying

2017-01-01

Cardiopulmonary bypass (CPB) is prone to inducing brain injury during open heart surgery. A hydrogen-rich solution (HRS) can prevent oxidation and apoptosis, and inhibit inflammation. This study investigated effects of HRS on brain injury induced by CPB and regulatory mechanisms of the PI3K/Akt/GSK3β signaling pathway. A rat CPB model and an in vitro cell hypoxia model were established. After HRS treatment, Rat behavior was measured using neurological deficit score; Evans blue (EB) was used to assess permeability of the blood-brain barrier (BBB); HE staining was used to observe pathological changes; Inflammatory factors and brain injury markers were detected by ELISA; the PI3K/Akt/GSK3β pathway-related proteins and apoptosis were assessed by western blot, immunohistochemistry and qRT -PCR analyses of brain tissue and neurons. After CPB, brain tissue anatomy was disordered, and cell structure was abnormal. Brain tissue EB content increased. There was an increase in the number of apoptotic cells, an increase in expression of Bax and caspase-3, a decrease in expression of Bcl2, and increases in levels of Akt, GSK3β, P-Akt, and P-GSK3β in brain tissue. HRS treatment attenuated the inflammatory reaction ,brain tissue EB content was significantly reduced and significantly decreased expression levels of Bax, caspase-3, Akt, GSK3β, P-Akt, and P-GSK3β in the brain. After adding the PI3K signaling pathway inhibitor, LY294002, to rat cerebral microvascular endothelial cells (CMECs), HRS could reduce activated Akt expression and downstream regulatory gene phosphorylation of GSK3β expression, and inhibit CMEC apoptosis. The PI3K/Akt/GSK3β signaling pathway plays an important role in the mechanism of CPB-induced brain injury. HRS can reduce CPB-induced brain injury and inhibit CMEC apoptosis through the PI3K/Akt/GSK3β signaling pathway. © 2017 The Author(s). Published by S. Karger AG, Basel.

In vivo dose response relationship between physostigmine and cholinesterase activity in RBC and tissues of rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somani, S.M.; Dube, S.N.

1989-01-01

Dose response of physostigmine (Phy) was studied in rat using various doses. Rats were sacrificed 15 min after Phy administration. Blood and tissues were analyzed for ChE activity by radiometric method and Phy concentration by HPLC method. A comparison of ChE values in different tissues of rats indicated that ChE activity was highest in brain and least in diaphragm. The enzyme activity was eleven times more in brain as compared to diaphragm. Phy produced a dose-dependent inhibition of ChE in RBC, brain and diaphragm from 50 to 200 {mu}g/kg, then ChE inhibition was plateaued from 200 to 500 {mu}g/kg inmore » these tissues. A dose related ChE inhibition was seen in heart and thigh muscle from 50 to 500 {mu}g/kg. Phy concentration increased linearly from 50 to 400 {mu}g/kg in plasma, brain, heart and thigh muscle. These results indicate that ChE inhibition is linear up to 200 {mu}g/kg in RBC, 150 {mu}g/kg in brain and 300 {mu}g/kg in heart. This linearity is not consistent in other tissues.« less

Cortical Enhanced Tissue Segmentation of Neonatal Brain MR Images Acquired by a Dedicated Phased Array Coil

PubMed Central

Shi, Feng; Yap, Pew-Thian; Fan, Yong; Cheng, Jie-Zhi; Wald, Lawrence L.; Gerig, Guido; Lin, Weili; Shen, Dinggang

2010-01-01

The acquisition of high quality MR images of neonatal brains is largely hampered by their characteristically small head size and low tissue contrast. As a result, subsequent image processing and analysis, especially for brain tissue segmentation, are often hindered. To overcome this problem, a dedicated phased array neonatal head coil is utilized to improve MR image quality by effectively combing images obtained from 8 coil elements without lengthening data acquisition time. In addition, a subject-specific atlas based tissue segmentation algorithm is specifically developed for the delineation of fine structures in the acquired neonatal brain MR images. The proposed tissue segmentation method first enhances the sheet-like cortical gray matter (GM) structures in neonatal images with a Hessian filter for generation of cortical GM prior. Then, the prior is combined with our neonatal population atlas to form a cortical enhanced hybrid atlas, which we refer to as the subject-specific atlas. Various experiments are conducted to compare the proposed method with manual segmentation results, as well as with additional two population atlas based segmentation methods. Results show that the proposed method is capable of segmenting the neonatal brain with the highest accuracy, compared to other two methods. PMID:20862268

Mesh electronics: a new paradigm for tissue-like brain probes.

PubMed

Hong, Guosong; Yang, Xiao; Zhou, Tao; Lieber, Charles M

2018-06-01

Existing implantable neurotechnologies for understanding the brain and treating neurological diseases have intrinsic properties that have limited their capability to achieve chronically-stable brain interfaces with single-neuron spatiotemporal resolution. These limitations reflect what has been dichotomy between the structure and mechanical properties of living brain tissue and non-living neural probes. To bridge the gap between neural and electronic networks, we have introduced the new concept of mesh electronics probes designed with structural and mechanical properties such that the implant begins to 'look and behave' like neural tissue. Syringe-implanted mesh electronics have led to the realization of probes that are neuro-attractive and free of the chronic immune response, as well as capable of stable long-term mapping and modulation of brain activity at the single-neuron level. This review provides a historical overview of a 10-year development of mesh electronics by highlighting the tissue-like design, syringe-assisted delivery, seamless neural tissue integration, and single-neuron level chronic recording stability of mesh electronics. We also offer insights on unique near-term opportunities and future directions for neuroscience and neurology that now are available or expected for mesh electronics neurotechnologies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A cross-circulated bicephalic model of head transplantation.

PubMed

Li, Peng-Wei; Zhao, Xin; Zhao, Yun-Long; Wang, Bing-Jian; Song, Yang; Shen, Zi-Long; Jiang, Hong-Jun; Jin, Hai; Canavero, Sergio; Ren, Xiao-Ping

2017-06-01

A successful cephalosomatic anastomosis ("head transplant") requires, among others, the ability to control long-term immune rejection and avoidance of ischemic events during the head transference phase. We developed a bicephalic model of head transplantation to study these aspects. The thoracic aorta and superior vena cava of a donor rat were anastomosed with the carotid artery and extracorporeal veins of a recipient rat by vascular grafts. Before thoracotomy in the donor rat, the axillary artery and vein of the donor were connected to the carotid and the extracranial vein of the third rat through a silicone tube. The silicone tube was passed through a peristaltic pump to ensure donor brain tissue blood supply. There is no ischemia reperfusion injury in donor brain tissue analyzed by electroencephalogram. Postoperative donor has pain reflex and corneal reflex. Peristaltic pump application can guarantee the blood supply of donor brain tissue per unit time, while the application of temperature change device to the silicone tube can protect the brain tissue hypothermia, postoperative experimental data show that there is no brain tissue ischemia during the whole operation. The application of vascular grafting can also provide the possibility of long-term survival of the model. © 2017 John Wiley & Sons Ltd.

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain.

PubMed

Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

2013-02-22

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement.

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain

PubMed Central

Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

2013-01-01

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement. PMID:23256194

Preparation of silica nanoparticles loaded with nootropics and their in vivo permeation through blood-brain barrier.

PubMed

Jampilek, Josef; Zaruba, Kamil; Oravec, Michal; Kunes, Martin; Babula, Petr; Ulbrich, Pavel; Brezaniova, Ingrid; Opatrilova, Radka; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain.

Preparation of Silica Nanoparticles Loaded with Nootropics and Their In Vivo Permeation through Blood-Brain Barrier

PubMed Central

Zaruba, Kamil; Kunes, Martin; Ulbrich, Pavel; Brezaniova, Ingrid; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain. PMID:26075264

DRAG REDUCING POLYMER ENCHANCES MICROVASCULAR PERFUSION IN THE TRAUMATIZED BRAIN WITH INTRACRANIAL HYPERTENSION

PubMed Central

Bragin, Denis E.; Thomson, Susan; Bragina, Olga; Statom, Gloria; Kameneva, Marina V.; Nemoto, Edwin M.

2016-01-01

SUMMARY Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood soluble non-toxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and limb, but have not yet been studied in the brain. Recently, we demonstrated that that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using the in-vivo 2-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow and, as a result, reduced tissue hypoxia in both un-traumatized and traumatized rat brains at high ICP. Our study suggests that DRP could be an effective treatment for improving microvascular flow in brain ischemia caused by high ICP after TBI. PMID:27165871

The detection of brain oedema with frequency-dependent phase shift electromagnetic induction.

PubMed

González, César A; Rubinsky, Boris

2006-06-01

The spectroscopic distribution of inductive phase shift in the brain as a function of the relative volume of oedema was evaluated with theoretical and experimental methods in the frequency range 1 to 8 MHz. The theoretical study employed a simple mathematical model of electromagnetic induction in tissue and brain tissue data available from the literature to calculate the phase shift as a function of oedema in the bulk of the brain. Experimental data were generated from bulk measurements of ex vivo homogenized pig brain tissue mixed with various volumes of physiological saline in a volume sample typical of the human brain. There is good agreement between the analytical and the experimental results. Detectable changes in phase shift begin from a frequency of about 3 MHz to 4 MHz in the tested compositions and volume. The phase shift increases with frequency and fluid content. The results suggest that measuring phase shift in the bulk of the brain has the potential for becoming a robust means for non-contact detection of oedema in the brain.

Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, SH.; Ballmann, C.; Quarles, C. A.

2009-03-10

The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixedmore » in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.« less

Dipole estimation errors due to not incorporating anisotropic conductivities in realistic head models for EEG source analysis

NASA Astrophysics Data System (ADS)

Hallez, Hans; Staelens, Steven; Lemahieu, Ignace

2009-10-01

EEG source analysis is a valuable tool for brain functionality research and for diagnosing neurological disorders, such as epilepsy. It requires a geometrical representation of the human head or a head model, which is often modeled as an isotropic conductor. However, it is known that some brain tissues, such as the skull or white matter, have an anisotropic conductivity. Many studies reported that the anisotropic conductivities have an influence on the calculated electrode potentials. However, few studies have assessed the influence of anisotropic conductivities on the dipole estimations. In this study, we want to determine the dipole estimation errors due to not taking into account the anisotropic conductivities of the skull and/or brain tissues. Therefore, head models are constructed with the same geometry, but with an anisotropically conducting skull and/or brain tissue compartment. These head models are used in simulation studies where the dipole location and orientation error is calculated due to neglecting anisotropic conductivities of the skull and brain tissue. Results show that not taking into account the anisotropic conductivities of the skull yields a dipole location error between 2 and 25 mm, with an average of 10 mm. When the anisotropic conductivities of the brain tissues are neglected, the dipole location error ranges between 0 and 5 mm. In this case, the average dipole location error was 2.3 mm. In all simulations, the dipole orientation error was smaller than 10°. We can conclude that the anisotropic conductivities of the skull have to be incorporated to improve the accuracy of EEG source analysis. The results of the simulation, as presented here, also suggest that incorporation of the anisotropic conductivities of brain tissues is not necessary. However, more studies are needed to confirm these suggestions.

Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.

PubMed

Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping

2015-04-01

Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

PubMed Central

Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

2016-01-01

Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied, the changes in mechanical properties were modest. Moreover, the effect of ventricular enlargement is not limited to the CC+PVWM and ventral internal capsule, the extent of microstructural changes vary between brain regions, and there is regional and temporal variation in brain tissue stiffness during hydrocephalus development. PMID:26848844

Diattenuation of brain tissue and its impact on 3D polarized light imaging

PubMed Central

Menzel, Miriam; Reckfort, Julia; Weigand, Daniel; Köse, Hasan; Amunts, Katrin; Axer, Markus

2017-01-01

3D-polarized light imaging (3D-PLI) reconstructs nerve fibers in histological brain sections by measuring their birefringence. This study investigates another effect caused by the optical anisotropy of brain tissue – diattenuation. Based on numerical and experimental studies and a complete analytical description of the optical system, the diattenuation was determined to be below 4 % in rat brain tissue. It was demonstrated that the diattenuation effect has negligible impact on the fiber orientations derived by 3D-PLI. The diattenuation signal, however, was found to highlight different anatomical structures that cannot be distinguished with current imaging techniques, which makes Diattenuation Imaging a promising extension to 3D-PLI. PMID:28717561

In situ characterization of the brain-microdevice interface using Device Capture Histology

PubMed Central

Woolley, Andrew J.; Desai, Himanshi A.; Steckbeck, Mitchell A.; Patel, Neil K.; Otto, Kevin J.

2011-01-01

Accurate assessment of brain-implantable microdevice bio-integration remains a formidable challenge. Prevailing histological methods require device extraction prior to tissue processing, often disrupting and removing the tissue of interest which had been surrounding the device. The Device-Capture Histology method, presented here, overcomes many limitations of the conventional Device-Explant Histology method, by collecting the device and surrounding tissue intact for subsequent labeling. With the implant remaining in situ, accurate and precise imaging of the morphologically preserved tissue at the brain/microdevice interface can then be collected and quantified. First, this article presents the Device-Capture Histology method for obtaining and processing the intact, undisturbed microdevice-tissue interface, and images using fluorescent labeling and confocal microscopy. Second, this article gives examples of how to quantify features found in the captured peridevice tissue. We also share histological data capturing 1) the impact of microdevice implantation on tissue, 2) the effects of an experimental anti-inflammatory coating, 3) a dense grouping of cell nuclei encapsulating a long-term implant, and 4) atypical oligodendrocyte organization neighboring a longterm implant. Data sets collected using the Device-Capture Histology method are presented to demonstrate the significant advantages of processing the intact microdevice-tissue interface, and to underscore the utility of the method in understanding the effects of the brain-implantable microdevices on nearby tissue. PMID:21802446

The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication

PubMed Central

Ouzzine, Mohamed; Gulberti, Sandrine; Ramalanjaona, Nick; Magdalou, Jacques; Fournel-Gigleux, Sylvie

2014-01-01

UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-D-glucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds) by the linkage of glucuronic acid from the high energy donor, UDP-α-D-glucuronic acid. In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier (BBB). They are also associated to brain interfaces devoid of BBB, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues. Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine (DA) that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed. PMID:25389387

Cost-effective elimination of lipofuscin fluorescence from formalin-fixed brain tissue by white phosphor light emitting diode array.

PubMed

Sun, Yulong; Chakrabartty, Avi

2016-12-01

Autofluorescence of aldehyde-fixed tissues greatly hinders fluorescence microscopy. In particular, lipofuscin, an autofluorescent component of aged brain tissue, complicates fluorescence imaging of tissue in neurodegenerative diseases. Background and lipofuscin fluorescence can be reduced by greater than 90% through photobleaching using white phosphor light emitting diode arrays prior to treatment with fluorescent probes. We compared the effect of photobleaching versus established chemical quenchers on the quality of fluorescent staining in formalin-fixed brain tissue of frontotemporal dementia with tau-positive inclusions. Unlike chemical quenchers, which reduced fluorescent probe signals as well as background, photobleaching treatment had no effect on probe fluorescence intensity while it effectively reduced background and lipofuscin fluorescence. The advantages and versatility of photobleaching over established methods are discussed.

Histological quantification of brain tissue inflammatory cell infiltration after focal cerebral infarction: a systematic review.

PubMed

Russek, Natanya S; Jensen, Matthew B

2014-03-01

Ischemic stroke is a leading cause of death and disability, and current treatments to limit tissue injury and improve recovery are limited. Cerebral infarction is accompanied by intense brain tissue inflammation involving many inflammatory cell types that may cause both negative and positive effects on outcomes. Many potential neuroprotective and neurorestorative treatments may affect, and be affected by, this inflammatory cell infiltration, so that accurate quantification of this tissue response is needed. We performed a systematic review of histological methods to quantify brain tissue inflammatory cell infiltration after cerebral infarction. We found reports of multiple techniques to quantify different inflammatory cell types. We found no direct comparison studies and conclude that more research is needed to optimize the assessment of this important stroke outcome.

Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity

PubMed Central

Puig, Kendra L.; Floden, Angela M.; Adhikari, Ramchandra; Golovko, Mikhail Y.; Combs, Colin K.

2012-01-01

Background Middle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. Methodology/Principal Findings To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. Conclusions/Significance Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-α and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokine secretion with no obvious effects on adipocyte culture phenotype. These data support the hypothesis that high fat diet-dependent obesity results in concomitant pro-inflammatory changes in brain and adipose tissue that is characterized, in part, by increased levels of APP that may be contributing specifically to inflammatory changes that occur. PMID:22276186

Neurosurgical patties: adhesion and damage mitigation.

PubMed

Stratton-Powell, Ashley A; Anderson, Ian A; Timothy, Jake; Kapur, Nikil; Culmer, Peter

2015-07-01

Neurosurgical patties are textile pads used during most neurosurgical operations to protect tissues, manage the fluid environment, control hemostasis, and aid tissue manipulation. Recent research has suggested that, contrary to their aim, patties adhere to brain tissue and cause damage during removal. This study aimed to characterize and quantify the degree of and consequences resulting from adhesion between neurosurgical patties and brain tissue. Using a customized peel apparatus, the authors performed 90° peel tests on 5 patty products: Policot, Telfa, Americot, Delicot, and Ray-Cot (n = 247) from American Surgical Company. They tested 4 conditions: wet patty on glass (control), wet patty on wet brain peeled at 5 mm/sec (wet), dry patty on wet brain peeled at 5 mm/sec (dry), and wet patty on wet brain peeled at 20 mm/sec (speed). The interaction between patty and tissue was analyzed using peel-force traces and pre-peel histological analysis. Adhesion strength differed between patty products (p < 0.001) and conditions (p < 0.001). Adhesion strength was greatest for Delicot patties under wet (2.22 mN/mm) and dry (9.88 mN/mm) conditions. For all patties, damage at the patty-tissue interface was proportional to the degree of fiber contact. When patties were irrigated, mechanical adhesion was reduced by up to 550% compared with dry usage. For all patty products, mechanical (destructive) and liquid-mediated (nondestructive) adhesion caused damage to neural tissue. The greatest adhesion occurred with Delicot patties. To mitigate patty adhesion and neural tissue damage, surgeons should consider regular irrigation to be essential during neurosurgical procedures.

Microsurgery Simulator of Cerebral Aneurysm Clipping with Interactive Cerebral Deformation Featuring a Virtual Arachnoid.

PubMed

Shono, Naoyuki; Kin, Taichi; Nomura, Seiji; Miyawaki, Satoru; Saito, Toki; Imai, Hideaki; Nakatomi, Hirofumi; Oyama, Hiroshi; Saito, Nobuhito

2018-05-01

A virtual reality simulator for aneurysmal clipping surgery is an attractive research target for neurosurgeons. Brain deformation is one of the most important functionalities necessary for an accurate clipping simulator and is vastly affected by the status of the supporting tissue, such as the arachnoid membrane. However, no virtual reality simulator implementing the supporting tissue of the brain has yet been developed. To develop a virtual reality clipping simulator possessing interactive brain deforming capability closely dependent on arachnoid dissection and apply it to clinical cases. Three-dimensional computer graphics models of cerebral tissue and surrounding structures were extracted from medical images. We developed a new method for modifiable cerebral tissue complex deformation by incorporating a nonmedical image-derived virtual arachnoid/trabecula in a process called multitissue integrated interactive deformation (MTIID). MTIID made it possible for cerebral tissue complexes to selectively deform at the site of dissection. Simulations for 8 cases of actual clipping surgery were performed before surgery and evaluated for their usefulness in surgical approach planning. Preoperatively, each operative field was precisely reproduced and visualized with the virtual brain retraction defined by users. The clear visualization of the optimal approach to treating the aneurysm via an appropriate arachnoid incision was possible with MTIID. A virtual clipping simulator mainly focusing on supporting tissues and less on physical properties seemed to be useful in the surgical simulation of cerebral aneurysm clipping. To our knowledge, this article is the first to report brain deformation based on supporting tissues.

Proliferation zones in the axolotl brain and regeneration of the telencephalon

PubMed Central

2013-01-01

Background Although the brains of lower vertebrates are known to exhibit somewhat limited regeneration after incisional or stab wounds, the Urodele brain exhibits extensive regeneration after massive tissue removal. Discovering whether and how neural progenitor cells that reside in the ventricular zones of Urodeles proliferate to mediate tissue repair in response to injury may produce novel leads for regenerative strategies. Here we show that endogenous neural progenitor cells resident to the ventricular zone of Urodeles spontaneously proliferate, producing progeny that migrate throughout the telencephalon before terminally differentiating into neurons. These progenitor cells appear to be responsible for telencephalon regeneration after tissue removal and their activity may be up-regulated by injury through an olfactory cue. Results There is extensive proliferation of endogenous neural progenitor cells throughout the ventricular zone of the adult axolotl brain. The highest levels are observed in the telencephalon, especially the dorsolateral aspect, and cerebellum. Lower levels are observed in the mesencephalon and rhombencephalon. New cells produced in the ventricular zone migrate laterally, dorsally and ventrally into the surrounding neuronal layer. After migrating from the ventricular zone, the new cells primarily express markers of neuronal differentiative fates. Large-scale telencephalic tissue removal stimulates progenitor cell proliferation in the ventricular zone of the damaged region, followed by proliferation in the tissue that surrounds the healing edges of the wound until the telencephalon has completed regeneration. The proliferative stimulus appears to reside in the olfactory system, because telencephalic regeneration does not occur in the brains of olfactory bulbectomized animals in which the damaged neural tissue simply heals over. Conclusion There is a continual generation of neuronal cells from neural progenitor cells located within the ventricular zone of the axolotl brain. Variable rates of proliferation were detected across brain regions. These neural progenitor cells appear to mediate telencephalic tissue regeneration through an injury-induced olfactory cue. Identification of this cue is our future goal. PMID:23327114

Proliferation zones in the axolotl brain and regeneration of the telencephalon.

PubMed

Maden, Malcolm; Manwell, Laurie A; Ormerod, Brandi K

2013-01-17

Although the brains of lower vertebrates are known to exhibit somewhat limited regeneration after incisional or stab wounds, the Urodele brain exhibits extensive regeneration after massive tissue removal. Discovering whether and how neural progenitor cells that reside in the ventricular zones of Urodeles proliferate to mediate tissue repair in response to injury may produce novel leads for regenerative strategies. Here we show that endogenous neural progenitor cells resident to the ventricular zone of Urodeles spontaneously proliferate, producing progeny that migrate throughout the telencephalon before terminally differentiating into neurons. These progenitor cells appear to be responsible for telencephalon regeneration after tissue removal and their activity may be up-regulated by injury through an olfactory cue. There is extensive proliferation of endogenous neural progenitor cells throughout the ventricular zone of the adult axolotl brain. The highest levels are observed in the telencephalon, especially the dorsolateral aspect, and cerebellum. Lower levels are observed in the mesencephalon and rhombencephalon. New cells produced in the ventricular zone migrate laterally, dorsally and ventrally into the surrounding neuronal layer. After migrating from the ventricular zone, the new cells primarily express markers of neuronal differentiative fates. Large-scale telencephalic tissue removal stimulates progenitor cell proliferation in the ventricular zone of the damaged region, followed by proliferation in the tissue that surrounds the healing edges of the wound until the telencephalon has completed regeneration. The proliferative stimulus appears to reside in the olfactory system, because telencephalic regeneration does not occur in the brains of olfactory bulbectomized animals in which the damaged neural tissue simply heals over. There is a continual generation of neuronal cells from neural progenitor cells located within the ventricular zone of the axolotl brain. Variable rates of proliferation were detected across brain regions. These neural progenitor cells appear to mediate telencephalic tissue regeneration through an injury-induced olfactory cue. Identification of this cue is our future goal.

Oxidative stress induced by 1.8 GHz radio frequency electromagnetic radiation and effects of garlic extract in rats.

PubMed

Avci, Bahattin; Akar, Ayşegül; Bilgici, Birşen; Tunçel, Özgür Korhan

2012-11-01

We aimed to study the oxidative damage induced by radiofrequency electromagnetic radiation (RF-EMR) emitted by mobile telephones and the protective effect of garlic extract used as an anti-oxidant against this damage. A total of 66 albino Wistar rats were divided into three groups. The first group of rats was given 1.8 GHz, 0.4 W/kg specific absorption rate (SAR) for 1 h a day for three weeks. The second group was given 500 mg/kg garlic extract in addition to RF-EMR. The third group of rats was used as the control group. At the end of the study, blood and brain tissue samples were collected from the rats. After the RF-EMR exposed, the advanced oxidation protein product (AOPP) levels of brain tissue increased compared with the control group (p < 0.001). Garlic administration accompanying the RF-EMR, on the other hand, significantly reduced AOPP levels in brain tissue (p < 0.001). The serum nitric oxide (NO) levels significantly increased both in the first and second group (p < 0.001). However, in the group for which garlic administration accompanied that of RF-EMR, there was no difference in serum NO levels compared with the RF-EMR exposed group (p > 0.05). There was no significant difference among the groups with respect to malondialdehyde (MDA) levels in brain tissue and blood samples (p > 0.05). Similarly, no difference was detected among the groups regarding serum paroxonase (PON) levels (p > 0.05). We did not detect any PON levels in the brain tissue. The exposure of RF-EMR similar to 1.8 GHz Global system for mobile communication (GSM) leads to protein oxidation in brain tissue and an increase in serum NO. We observed that garlic administration reduced protein oxidation in brain tissue and that it did not have any effects on serum NO levels.

Injectable Reactive Biocomposites For Bone Healing In Critical-Size Rabbit Calvarial Defects

DTIC Science & Technology

2012-03-29

defects (i.e. be conformable), provide temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of...temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of biologics. In this study, we evaluated the...complex defects (i.e. be conformable), harden to provide temporary protection until tissue remodels (i.e. be settable), and enhance tissue regeneration

Fluorescence Imaging/Agents in Tumor Resection.

PubMed

Stummer, Walter; Suero Molina, Eric

2017-10-01

Intraoperative fluorescence imaging allows real-time identification of diseased tissue during surgery without being influenced by brain shift and surgery interruption. 5-Aminolevulinic acid, useful for malignant gliomas and other tumors, is the most broadly explored compound approved for fluorescence-guided resection. Intravenous fluorescein sodium has recently received attention, highlighting tumor tissue based on extravasation at the blood-brain barrier (defective in many brain tumors). Fluorescein in perfused brain, unselective extravasation in brain perturbed by surgery, and propagation with edema are concerns. Fluorescein is not approved but targeted fluorochromes with affinity to brain tumor cells, in development, may offer future advantages. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of valerian consumption during pregnancy on cortical volume and the levels of zinc and copper in the brain tissue of mouse fetus.

PubMed

Mahmoudian, Alireza; Rajaei, Ziba; Haghir, Hossein; Banihashemian, Shahaboldin; Hami, Javad

2012-04-01

The aim of the present study was to determine the effects of valerian (Valeriana officinalis) consumption in pregnancy on cortical volume and the levels of zinc and copper, two essential elements that affect brain development and function, in the brain tissues of mouse fetuses. Pregnant female mice were treated with either saline or 1.2 g/kg body weight valerian extract intraperitoneally daily on gestation days (GD) 7 to 17. On GD 20, mice were sacrificed and their fetuses were collected. Fetal brains were dissected, weighed and processed for histological analysis. The volume of cerebral cortex was estimated by the Cavalieri principle. The levels of zinc and copper in the brain tissues were measured by atomic absorption spectroscopy. The results indicated that valerian consumption in pregnancy had no significant effect on brain weight, cerebral cortex volume and copper level in fetal brain. However,it significantly decreased the level of zinc in the brain (P<0.05). Using valerian during midgestation do not have an adverse effect on cerebral cortex; however,it caused a significant decrease in zinc level in the fetal brain. This suggests that valerian use should be limited during pregnancy.

ANTIRABIES ANTIBODY RESPONSE IN MAN TO VACCINE MADE FROM INFECTED SUCKLING-MOUSE BRAINS.

PubMed

FUENZALIDA, E; PALACIOS, R; BORGONO, J M

1964-01-01

Antirabies vaccines produced from infected brains of adult mammals have always had the potentiality of causing post-vaccinal paralysis or allergic encephalitis in man. Attempts in recent years either to remove the paralytic factor from brain-tissue vaccines or to use as the virus source infected tissue other than nervous tissue (e.g., chick embryos) have usually resulted in a substantial reduction of the specific antirabies potency.The authors' laboratory had previously developed a vaccine made from infected suckling-mouse brains in which the virus was inactivated by ultraviolet irradiation. This vaccine was found highly potent in animal tests and low in organ-specific antigens. Others have found the brains of newborn mammals to be free of the allergic encephalitic factor. The studies reported in this paper show that the antirabies antibody responses to a 14-dose course of this suckling-mouse-brain vaccine in children are at a high level even when the vaccine is used at a 1% tissue concentration. There was no evidence of deleterious reactions to this treatment in 31 children.It is concluded that these results justify a long-term trial of this vaccine for antirabies prophylaxis in man.

Antirabies antibody response in man to vaccine made from infected suckling-mouse brains

PubMed Central

Fuenzalida, E.; Palacios, R.; Borgoño, J. M.

1964-01-01

Antirabies vaccines produced from infected brains of adult mammals have always had the potentiality of causing post-vaccinal paralysis or allergic encephalitis in man. Attempts in recent years either to remove the paralytic factor from brain-tissue vaccines or to use as the virus source infected tissue other than nervous tissue (e.g., chick embryos) have usually resulted in a substantial reduction of the specific antirabies potency. The authors' laboratory had previously developed a vaccine made from infected suckling-mouse brains in which the virus was inactivated by ultraviolet irradiation. This vaccine was found highly potent in animal tests and low in organ-specific antigens. Others have found the brains of newborn mammals to be free of the allergic encephalitic factor. The studies reported in this paper show that the antirabies antibody responses to a 14-dose course of this suckling-mouse-brain vaccine in children are at a high level even when the vaccine is used at a 1% tissue concentration. There was no evidence of deleterious reactions to this treatment in 31 children. It is concluded that these results justify a long-term trial of this vaccine for antirabies prophylaxis in man. PMID:14163964

Effect of dexamethasone on gliosis, ischemia, and dopamine extraction during microdialysis sampling in brain tissue.

PubMed

Jaquins-Gerstl, Andrea; Shu, Zhan; Zhang, Jing; Liu, Yansheng; Weber, Stephen G; Michael, Adrian C

2011-10-15

Microdialysis sampling of the brain is an analytical technique with numerous applications in neuroscience and the neurointensive care of brain-injured human patients. Even so, implanting microdialysis probes into brain tissue causes a penetration injury that triggers gliosis (the activation and proliferation of glial cells) and ischemia (the interruption of blood flow). Thus, the probe samples injured tissue. Mitigating the effects of the penetration injury might refine the technique. The synthetic glucocorticoid dexamethasone is a potent anti-inflammatory and immunosuppressant substance. We performed microdialysis in the rat brain for 5 days, with and without dexamethasone in the perfusion fluid (10 μM for the first 24 h and 2 μM thereafter). On the first and fourth day of the perfusion, we performed dopamine no-net-flux measurements. On the fifth day, we sectioned and stained the brain tissue and examined it by fluorescence microscopy. Although dexamethasone profoundly inhibited gliosis and ischemia around the probe tracks it had only modest effects on dopamine no-net-flux results. These findings show that dexamethasone is highly effective at suppressing gliosis and ischemia but is limited in its neuroprotective activity. © 2011 American Chemical Society

Composite technique for regional neurochemical studies: measurement of energy and neurotransmitter metabolites in single tissue sample.

PubMed

Djuricic, B M; Ueki, Y; Spatz, M

1985-06-01

A combined method is described for the determination of various metabolites from a single tissue sample of the brain. It comprises a quick inactivation of cerebral enzymes by microwave irradiation, easy separation of the desired brain regions, and perchloric acid extraction of tissue substances, which are assayed either by specific enzymatic techniques or by HPLC with electrochemical detection. The obtained values of most energy and neurotransmitter metabolites in the brain are in agreement with those reported using other methods. However, this technique, in contrast to the brain freezing in vitro or freeze-blowing, provides a more efficient procedure for rapid arrest of cerebral metabolism even in the deep brain structures and is therefore suitable for detection of early changes particularly those occurring in experimental pathological conditions such as ischemia.

MRI-induced heating of deep brain stimulation leads

NASA Astrophysics Data System (ADS)

Mohsin, Syed A.; Sheikh, Noor M.; Saeed, Usman

2008-10-01

The radiofrequency (RF) field used in magnetic resonance imaging is scattered by medical implants. The scattered field of a deep brain stimulation lead can be very intense near the electrodes stimulating the brain. The effect is more pronounced if the lead behaves as a resonant antenna. In this paper, we examine the resonant length effect. We also use the finite element method to compute the near field for (i) the lead immersed in inhomogeneous tissue (fat, muscle, and brain tissues) and (ii) the lead connected to an implantable pulse generator. Electric field, specific absorption rate and induced temperature rise distributions have been obtained in the brain tissue surrounding the electrodes. The worst-case scenario has been evaluated by neglecting the effect of blood perfusion. The computed values are in good agreement with in vitro measurements made in the laboratory.

Determination of pharmacological levels of harmane, harmine and harmaline in mammalian brain tissue, cerebrospinal fluid and plasma by high-performance liquid chromatography with fluorimetric detection.

PubMed

Moncrieff, J

1989-11-24

Increased blood aldehyde levels, as occur in alcohol intoxication, could lead to the formation of beta-carbolines such as harmane by condensation with indoleamines. Endogenous beta-carbolines, therefore, should occur in specific brain areas where indoleamine concentrations are high, whilst exogenous beta-carbolines should exhibit an even distribution. The author presents direct and sensitive methods for assaying the beta-carbolines harmane, harmine and harmaline in brain tissue, cerebrospinal fluid and plasma at picogram sample concentrations using reversed-phase high-performance liquid chromatography with fluorimetric detection and minimal sample preparation. Using these assay methods, it was found that the distribution of beta-carbolines from a source exogenous to the brain results in a relatively even distribution within the brain tissue.

Significance of Brain Tissue Oxygenation and the Arachidonic Acid Cascade in Stroke

PubMed Central

Rink, Cameron

2011-01-01

Abstract The significance of the hypoxia component of stroke injury is highlighted by hypermetabolic brain tissue enriched with arachidonic acid (AA), a 22:6n-3 polyunsaturated fatty acid. In an ischemic stroke environment in which cerebral blood flow is arrested, oxygen-starved brain tissue initiates the rapid cleavage of AA from the membrane phospholipid bilayer. Once free, AA undergoes both enzyme-independent and enzyme-mediated oxidative metabolism, resulting in the formation of number of biologically active metabolites which themselves contribute to pathological stroke outcomes. This review is intended to examine two divergent roles of molecular dioxygen in brain tissue as (1) a substrate for life-sustaining homeostatic metabolism of glucose and (2) a substrate for pathogenic metabolism of AA under conditions of stroke. Recent developments in research concerning supplemental oxygen therapy as an intervention to correct the hypoxic component of stroke injury are discussed. Antioxid. Redox Signal. 14, 1889–1903. PMID:20673202

Toxicology of 2,4-dichlorophenoxyacetic acid (2,4-D) and its determination in serum and brain tissue using gas chromatography-electron-capture detection.

PubMed

Oliveira, G H; Palermo-Neto, J

1995-01-01

A gas-liquid chromatographic method with an electron-capture detector was applied for 2,4-dichlorophenoxyacetic acid (2,4-D) determination in the serum and brain tissue of rats acutely intoxicated with the dimethylamine salt of 2,4-D. After extraction with ethyl ether, 2,4-D derivatization was performed using 2-chloroethanol and BCI3. The average recovery values found for serum and brain tissue were 98.5 +/- 4.8 and 93.3 +/- 7.5, respectively. The sensitivity limit of the method was 250 ng/mL for serum and 300 ng/g for brain tissue. The toxic effects of 2,4-D in rats were observed within one-half hour after its oral administration. Results suggest that the toxic mechanism of 2,4-D is related to an action on the central nervous system.

3D variational brain tumor segmentation using Dirichlet priors on a clustered feature set.

PubMed

Popuri, Karteek; Cobzas, Dana; Murtha, Albert; Jägersand, Martin

2012-07-01

Brain tumor segmentation is a required step before any radiation treatment or surgery. When performed manually, segmentation is time consuming and prone to human errors. Therefore, there have been significant efforts to automate the process. But, automatic tumor segmentation from MRI data is a particularly challenging task. Tumors have a large diversity in shape and appearance with intensities overlapping the normal brain tissues. In addition, an expanding tumor can also deflect and deform nearby tissue. In our work, we propose an automatic brain tumor segmentation method that addresses these last two difficult problems. We use the available MRI modalities (T1, T1c, T2) and their texture characteristics to construct a multidimensional feature set. Then, we extract clusters which provide a compact representation of the essential information in these features. The main idea in this work is to incorporate these clustered features into the 3D variational segmentation framework. In contrast to previous variational approaches, we propose a segmentation method that evolves the contour in a supervised fashion. The segmentation boundary is driven by the learned region statistics in the cluster space. We incorporate prior knowledge about the normal brain tissue appearance during the estimation of these region statistics. In particular, we use a Dirichlet prior that discourages the clusters from the normal brain region to be in the tumor region. This leads to a better disambiguation of the tumor from brain tissue. We evaluated the performance of our automatic segmentation method on 15 real MRI scans of brain tumor patients, with tumors that are inhomogeneous in appearance, small in size and in proximity to the major structures in the brain. Validation with the expert segmentation labels yielded encouraging results: Jaccard (58%), Precision (81%), Recall (67%), Hausdorff distance (24 mm). Using priors on the brain/tumor appearance, our proposed automatic 3D variational segmentation method was able to better disambiguate the tumor from the surrounding tissue.

Brain tissue oxygen tension is more indicative of oxygen diffusion than oxygen delivery and metabolism in patients with traumatic brain injury.

PubMed

Rosenthal, Guy; Hemphill, J Claude; Sorani, Marco; Martin, Christine; Morabito, Diane; Obrist, Walter D; Manley, Geoffrey T

2008-06-01

Despite the growing clinical use of brain tissue oxygen monitoring, the specific determinants of low brain tissue oxygen tension (P(bt)O2) following severe traumatic brain injury (TBI) remain poorly defined. The objective of this study was to evaluate whether P(bt)O2 more closely reflects variables related to cerebral oxygen diffusion or reflects cerebral oxygen delivery and metabolism. Prospective observational study. Level I trauma center. Fourteen TBI patients with advanced neuromonitoring underwent an oxygen challenge (increase in FiO2 to 1.0) to assess tissue oxygen reactivity, pressure challenge (increase in mean arterial pressure) to assess autoregulation, and CO2 challenge (hyperventilation) to assess cerebral vasoreactivity. None. P(bt)O2 was measured directly with a parenchymal probe in the least-injured hemisphere. Local cerebral blood flow (CBF) was measured with a parenchymal thermal diffusion probe. Cerebral venous blood gases were drawn from a jugular bulb venous catheter. We performed 119 measurements of PaO2, arterial oxygen content (CaO2), jugular bulb venous oxygen tension (PVO2), venous oxygen content (CVO2), arteriovenous oxygen content difference (AVDO2), and local cerebral metabolic rate of oxygen (locCMRO2). In multivariable analysis adjusting for various variables of cerebral oxygen delivery and metabolism, the only statistically significant relationship was that between P(bt)O2 and the product of CBF and cerebral arteriovenous oxygen tension difference (AVTO2), suggesting a strong association between brain tissue oxygen tension and diffusion of dissolved plasma oxygen across the blood-brain barrier. Measurements of P(bt)O2 represent the product of CBF and the cerebral AVTO2 rather than a direct measurement of total oxygen delivery or cerebral oxygen metabolism. This improved understanding of the cerebral physiology of P(bt)O2 should enhance the clinical utility of brain tissue oxygen monitoring in patients with TBI.

Effect of neuromonitor-guided titrated care on brain tissue hypoxia after opioid overdose cardiac arrest.

PubMed

Elmer, Jonathan; Flickinger, Katharyn L; Anderson, Maighdlin W; Koller, Allison C; Sundermann, Matthew L; Dezfulian, Cameron; Okonkwo, David O; Shutter, Lori A; Salcido, David D; Callaway, Clifton W; Menegazzi, James J

2018-04-18

Brain tissue hypoxia may contribute to preventable secondary brain injury after cardiac arrest. We developed a porcine model of opioid overdose cardiac arrest and post-arrest care including invasive, multimodal neurological monitoring of regional brain physiology. We hypothesized brain tissue hypoxia is common with usual post-arrest care and can be prevented by modifying mean arterial pressure (MAP) and arterial oxygen concentration (PaO 2 ). We induced opioid overdose and cardiac arrest in sixteen swine, attempted resuscitation after 9 min of apnea, and randomized resuscitated animals to three alternating 6-h blocks of standard or titrated care. We invasively monitored physiological parameters including brain tissue oxygen (PbtO 2 ). During standard care blocks, we maintained MAP > 65 mmHg and oxygen saturation 94-98%. During titrated care, we targeted PbtO2 > 20 mmHg. Overall, 10 animals (63%) achieved ROSC after a median of 12.4 min (range 10.8-21.5 min). PbtO 2 was higher during titrated care than standard care blocks (unadjusted β = 0.60, 95% confidence interval (CI) 0.42-0.78, P < 0.001). In an adjusted model controlling for MAP, vasopressors, sedation, and block sequence, PbtO 2 remained higher during titrated care (adjusted β = 0.75, 95%CI 0.43-1.06, P < 0.001). At three predetermined thresholds, brain tissue hypoxia was significantly less common during titrated care blocks (44 vs 2% of the block duration spent below 20 mmHg, P < 0.001; 21 vs 0% below 15 mmHg, P < 0.001; and, 7 vs 0% below 10 mmHg, P = .01). In this model of opioid overdose cardiac arrest, brain tissue hypoxia is common and treatable. Further work will elucidate best strategies and impact of titrated care on functional outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

In Vivo Investigation of the Effectiveness of a Hyper-viscoelastic Model in Simulating Brain Retraction

NASA Astrophysics Data System (ADS)

Li, Ping; Wang, Weiwei; Zhang, Chenxi; An, Yong; Song, Zhijian

2016-07-01

Intraoperative brain retraction leads to a misalignment between the intraoperative positions of the brain structures and their previous positions, as determined from preoperative images. In vitro swine brain sample uniaxial tests showed that the mechanical response of brain tissue to compression and extension could be described by the hyper-viscoelasticity theory. The brain retraction caused by the mechanical process is a combination of brain tissue compression and extension. In this paper, we first constructed a hyper-viscoelastic framework based on the extended finite element method (XFEM) to simulate intraoperative brain retraction. To explore its effectiveness, we then applied this framework to an in vivo brain retraction simulation. The simulation strictly followed the clinical scenario, in which seven swine were subjected to brain retraction. Our experimental results showed that the hyper-viscoelastic XFEM framework is capable of simulating intraoperative brain retraction and improving the navigation accuracy of an image-guided neurosurgery system (IGNS).

Effect of intravenous gadolinium-DTPA on diffusion-weighted imaging of brain tumors: a short temporal interval assessment.

PubMed

Li, Xiang; Qu, Jin-Rong; Luo, Jun-Peng; Li, Jing; Zhang, Hong-Kai; Shao, Nan-Nan; Kwok, Keith; Zhang, Shou-Ning; Li, Yan-le; Liu, Cui-Cui; Zee, Chi-Shing; Li, Hai-Liang

2014-09-01

To determine the effect of intravenous administration of gadolinium (Gd) contrast medium (Gd-DTPA) on diffusion-weighted imaging (DWI) for the evaluation of normal brain parenchyma vs. brain tumor following a short temporal interval. Forty-four DWI studies using b values of 0 and 1000 s/mm(2) were performed before, immediately after, 1 min after, 3 min after, and 5 min after the administration of Gd-DTPA on 62 separate lesions including 15 meningioma, 17 glioma and 30 metastatic lesions. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) values of the brain tumor lesions and normal brain tissues were measured on pre- and postcontrast images. Statistical analysis using paired t-test between precontrast and postcontrast data were obtained on three brain tumors and normal brain tissue. The SNR and CNR of brain tumors and the SNR of normal brain tissue showed no statistical differences between pre- and postcontrast (P > 0.05). The ADC values on the three cases of brain tumors demonstrated significant initial increase on the immediate time point (P < 0.01) and decrease on following the 1 min time point (P < 0.01) after contrast. Significant decrease of ADC value was still found at 3min and 5min time point in the meningioma group (P < 0.01) with gradual normalization over time. The ADC values of normal brain tissues demonstrated significant initial elevation on the immediately postcontrast DWI sequence (P < 0.01). Contrast medium can cause a slight but statistically significant change on the ADC value within a short temporal interval after the contrast administration. The effect is both time and lesion-type dependent. © 2013 Wiley Periodicals, Inc.

Accumulation of polybrominated diphenyl ethers in the brain compared with the levels in other tissues among different vertebrates from an e-waste recycling site.

PubMed

Zhao, Yaxian; Li, Yuanyuan; Qin, Xiaofei; Lou, Qinqin; Qin, Zhanfen

2016-11-01

This study aimed to investigate the accumulation of polybrominated diphenyl ethers (PBDEs) in the brain compared with that in other tissues among different vertebrates. We collected mice, chickens, ducks, frogs, and fish from an e-waste recycling region in Taizhou, China, and measured PBDE concentrations in brain, liver and muscle tissues. The levels of PBDE in the tissues of mice, chickens, ducks, frogs and fish ranged 0.45-206, 0.06-18.8, 1.83-112, 2.75-108, and 0.02-32.0 ng/g wet weight, respectively. Preferential distribution in the liver and muscle relative to the brain was observed for PBDEs in mice, chickens, ducks and frogs. However, a high retention in the brain compared to the liver and muscle was observed in fish. Comparison of the brain/liver concentration (B/L) ratios revealed differences in PBDEs accumulation in the brain among these vertebrates. PBDEs accumulation in the brain was greatest in fish, followed by frogs, while the lowest accumulation occurred in the brains of mammals and birds. The findings apparently coincided with the evolution of the blood-brain barrier (BBB) across vertebrates, i.e. the BBB of fish might be less efficient than those of mammals, birds and amphibian. Low brominated congeners (such as BDE-28, BDE-47 and BDE-99) were predominant in the brains of investigated vertebrates, whereas BDE-209 was most abundant in liver and muscle tissues of mice, chickens and ducks. Significant differences in B/L ratios among PBDE congeners were found in both mice and chickens (p < 0.05). Particularly in mice, the B/L ratios of PBDE congeners presented a declining trend with increased bromine number. Our findings suggested that low brominated congeners might have a higher capacity to penetrate the BBB and accumulate in the brain, whereas high brominated congeners such as BDE-209 might have less potency to pass through the barrier. Further experimental studies are needed to confirm our findings. Copyright © 2016 Elsevier Ltd. All rights reserved.

A new use for long-term frozen brain tissue: Golgi impregnation

PubMed Central

Melendez-Ferro, Miguel; Perez-Costas, Emma; Roberts, Rosalinda C.

2009-01-01

The study of dendritic spine shape and number has become a standard in the analysis of synaptic transmission anomalies since a considerable number of neuropsychiatric and neurological diseases have their foundation in alterations in these structures. One of the best ways to study possible alterations of dendritic spines is the use of Golgi impregnation. Although usually the Golgi method implies the use of fresh or fixed tissue, here we report the use of Golgi-Cox for the staining of human and animal brain tissue kept frozen for long periods of time. We successfully applied the Golgi-Cox method to human brain tissue stored for up to 15 years in a freezer. The technique produced reliable and reproducible impregnation of dendrites and dendritic spines in different cortical areas. We also applied the same technique to rat brain frozen for up to one year, obtaining the same satisfactory results. The fact that Golgi-Cox can be successfully applied to this type of tissue adds a new value for hundreds of frozen human or animal brains kept in the freezers of the laboratories, that otherwise would not be useful for anything else. Researchers other than neuroanatomists, i.e. in fields such as biochemistry and molecular biology can also benefit from a simple and reliable technique that can be applied to tissue left from their primary experiments. PMID:18789970

Genetic differences between blood- and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences.

PubMed Central

Korber, B T; Kunstman, K J; Patterson, B K; Furtado, M; McEvilly, M M; Levy, R; Wolinsky, S M

1994-01-01

Human immunodeficiency virus type 1 (HIV-1) sequences were generated from blood and from brain tissue obtained by stereotactic biopsy from six patients undergoing a diagnostic neurosurgical procedure. Proviral DNA was directly amplified by nested PCR, and 8 to 36 clones from each sample were sequenced. Phylogenetic analysis of intrapatient envelope V3-V5 region HIV-1 DNA sequence sets revealed that brain viral sequences were clustered relative to the blood viral sequences, suggestive of tissue-specific compartmentalization of the virus in four of the six cases. In the other two cases, the blood and brain virus sequences were intermingled in the phylogenetic analyses, suggesting trafficking of virus between the two tissues. Slide-based PCR-driven in situ hybridization of two of the patients' brain biopsy samples confirmed our interpretation of the intrapatient phylogenetic analyses. Interpatient V3 region brain-derived sequence distances were significantly less than blood-derived sequence distances. Relative to the tip of the loop, the set of brain-derived viral sequences had a tendency towards negative or neutral charge compared with the set of blood-derived viral sequences. Entropy calculations were used as a measure of the variability at each position in alignments of blood and brain viral sequences. A relatively conserved set of positions were found, with a significantly lower entropy in the brain-than in the blood-derived viral sequences. These sites constitute a brain "signature pattern," or a noncontiguous set of amino acids in the V3 region conserved in viral sequences derived from brain tissue. This brain-derived signature pattern was also well preserved among isolates previously characterized in vitro as macrophage tropic. Macrophage-monocyte tropism may be the biological constraint that results in the conservation of the viral brain signature pattern. Images PMID:7933130

Nonthermal ablation in the rat brain using focused ultrasound and an ultrasound contrast agent: long-term effects

PubMed Central

McDannold, Nathan; Zhang, Yongzhi; Vykhodtseva, Natalia

2016-01-01

OBJECTIVE Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently under investigation as a less invasive alternative to radiosurgery and resection. A major limitation of the method is that its use is currently restricted to centrally located brain targets. The combination of FUS and a microbubble-based ultrasound contrast agent greatly reduces the ultrasound exposure level needed to ablate brain tissue and could be an effective means to increase the “treatment envelope” for FUS in the brain. This method, however, ablates tissue through a different mechanism: destruction of the microvasculature. It is not known whether nonthermal FUS ablation in substantial volumes of tissue can safely be performed without unexpected effects. The authors investigated this question by ablating volumes in the brains of normal rats. METHODS Overlapping sonications were performed in rats (n = 15) to ablate a volume in 1 hemisphere per animal. The sonications (10-msec bursts at 1 Hz for 60 seconds; peak negative pressure 0.8 MPa) were combined with the ultrasound contrast agent Optison (100 μl/kg). The rats were followed with MRI for 4–9 weeks after FUS, and the brains were examined with histological methods. RESULTS Two weeks after sonication and later, the lesions appeared as cyst-like areas in T2-weighted MR images that were stable over time. Histological examination demonstrated well-defined lesions consisting of a cyst-like cavity that remained lined by astrocytic tissue. Some white matter structures within the sonicated area were partially intact. CONCLUSIONS The results of this study indicate that nonthermal FUS ablation can be used to safely ablate tissue volumes in the brain without unexpected delayed effects. The findings are encouraging for the use of this ablation method in the brain. PMID:26848919

Human primitive brain displays negative mitochondrial-nuclear expression correlation of respiratory genes.

PubMed

Barshad, Gilad; Blumberg, Amit; Cohen, Tal; Mishmar, Dan

2018-06-14

Oxidative phosphorylation (OXPHOS), a fundamental energy source in all human tissues, requires interactions between mitochondrial (mtDNA)- and nuclear (nDNA)-encoded protein subunits. Although such interactions are fundamental to OXPHOS, bi-genomic coregulation is poorly understood. To address this question, we analyzed ∼8500 RNA-seq experiments from 48 human body sites. Despite well-known variation in mitochondrial activity, quantity, and morphology, we found overall positive mtDNA-nDNA OXPHOS genes' co-expression across human tissues. Nevertheless, negative mtDNA-nDNA gene expression correlation was identified in the hypothalamus, basal ganglia, and amygdala (subcortical brain regions, collectively termed the "primitive" brain). Single-cell RNA-seq analysis of mouse and human brains revealed that this phenomenon is evolutionarily conserved, and both are influenced by brain cell types (involving excitatory/inhibitory neurons and nonneuronal cells) and by their spatial brain location. As the "primitive" brain is highly oxidative, we hypothesized that such negative mtDNA-nDNA co-expression likely controls for the high mtDNA transcript levels, which enforce tight OXPHOS regulation, rather than rewiring toward glycolysis. Accordingly, we found "primitive" brain-specific up-regulation of lactate dehydrogenase B ( LDHB ), which associates with high OXPHOS activity, at the expense of LDHA , which promotes glycolysis. Analyses of co-expression, DNase-seq, and ChIP-seq experiments revealed candidate RNA-binding proteins and CEBPB as the best regulatory candidates to explain these phenomena. Finally, cross-tissue expression analysis unearthed tissue-dependent splice variants and OXPHOS subunit paralogs and allowed revising the list of canonical OXPHOS transcripts. Taken together, our analysis provides a comprehensive view of mito-nuclear gene co-expression across human tissues and provides overall insights into the bi-genomic regulation of mitochondrial activities. © 2018 Barshad et al.; Published by Cold Spring Harbor Laboratory Press.

Differential Responses of Brain, Gonad and Muscle Steroid Levels to Changes in Social Status and Sex in a Sequential and Bidirectional Hermaphroditic Fish

PubMed Central

Lorenzi, Varenka; Earley, Ryan L.; Grober, Matthew S.

2012-01-01

Sex steroids can both modulate and be modulated by behavior, and their actions are mediated by complex interactions among multiple hormone sources and targets. While gonadal steroids delivered via circulation can affect behavior, changes in local brain steroid synthesis also can modulate behavior. The relative steroid load across different tissues and the association of these levels with rates of behavior have not been well studied. The bluebanded goby (Lythrypnus dalli) is a sex changing fish in which social status determines sexual phenotype. We examined changes in steroid levels in brain, gonad and body muscle at either 24 hours or 6 days after social induction of protogynous sex change, and from individuals in stable social groups not undergoing sex change. For each tissue, we measured levels of estradiol (E2), testosterone (T) and 11-ketotestosterone (KT). Females had more T than males in the gonads, and more E2 in all tissues but there was no sex difference in KT. For both sexes, E2 was higher in the gonad than in other tissues while androgens were higher in the brain. During sex change, brain T levels dropped while brain KT increased, and brain E2 levels did not change. We found a positive relationship between androgens and aggression in the most dominant females but only when the male was removed from the social group. The results demonstrate that steroid levels are responsive to changes in the social environment, and that their concentrations vary in different tissues. Also, we suggest that rapid changes in brain androgen levels might be important in inducing behavioral and/or morphological changes associated with protogynous sex change. PMID:23251444

Alterations in DNA Methylation of Fkbp5 as a Determinant of Blood-brain Correlation of Glucocorticoid Exposure

PubMed Central

Ewald, Erin R.; Wand, Gary S.; Seifuddin, Fayaz; Yang, Xiaoju; Tamashiro, Kellie L.; Potash, James B.; Zandi, Peter; Lee, Richard S.

2014-01-01

Summary Background Epigenetic studies that utilize peripheral tissues to identify molecular substrates of neuropsychiatric disorders rely on the assumption that disease-relevant, cellular alterations that occur in the brain are mirrored and detectable in peripheral tissues such as blood. We sought to test this assumption by using a mouse model of Cushing’s disease and asking whether epigenetic changes induced by glucocorticoids can be correlated between these tissue types. Methods Mice were treated with different doses of glucocorticoids in their drinking water for four weeks to assess gene expression and DNA methylation (DNAm) changes in the stress response gene Fkbp5. Results Significant linear relationships were observed between DNAm and four-week mean plasma corticosterone levels for both blood (R2 = 0.68, P = 7.1×10−10) and brain (R2 = 0.33, P = 0.001). Further, degree of methylation change in blood correlated significantly with both methylation (R2 = 0.49, P = 2.7×10−5) and expression (R2 = 0.43, P = 3.5×10−5) changes in hippocampus, with the notable observation that methylation changes occurred at different intronic regions between blood and brain tissues. Conclusion Although our findings are limited to several intronic CpGs in a single gene, our results demonstrate that DNA from blood can be used to assess dynamic, glucocorticoid-induced changes occurring in the brain. However, for such correlation analyses to be effective, tissue-specific locations of these epigenetic changes may need to be considered when investigating brain-relevant changes in peripheral tissues. PMID:24767625

Alterations in DNA methylation of Fkbp5 as a determinant of blood-brain correlation of glucocorticoid exposure.

PubMed

Ewald, Erin R; Wand, Gary S; Seifuddin, Fayaz; Yang, Xiaoju; Tamashiro, Kellie L; Potash, James B; Zandi, Peter; Lee, Richard S

2014-06-01

Epigenetic studies that utilize peripheral tissues to identify molecular substrates of neuropsychiatric disorders rely on the assumption that disease-relevant, cellular alterations that occur in the brain are mirrored and detectable in peripheral tissues such as blood. We sought to test this assumption by using a mouse model of Cushing's disease and asking whether epigenetic changes induced by glucocorticoids can be correlated between these tissue types. Mice were treated with different doses of glucocorticoids in their drinking water for four weeks to assess gene expression and DNA methylation (DNAm) changes in the stress response gene Fkbp5. Significant linear relationships were observed between DNAm and four-week mean plasma corticosterone levels for both blood (R(2)=0.68, P=7.1×10(-10)) and brain (R(2)=0.33, P=0.001). Further, degree of methylation change in blood correlated significantly with both methylation (R(2)=0.49, P=2.7×10(-5)) and expression (R(2)=0.43, P=3.5×10(-5)) changes in hippocampus, with the notable observation that methylation changes occurred at different intronic regions between blood and brain tissues. Although our findings are limited to several intronic CpGs in a single gene, our results demonstrate that DNA from blood can be used to assess dynamic, glucocorticoid-induced changes occurring in the brain. However, for such correlation analyses to be effective, tissue-specific locations of these epigenetic changes may need to be considered when investigating brain-relevant changes in peripheral tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fitted hyperelastic parameters for Human brain tissue from reported tension, compression, and shear tests.

PubMed

Moran, Richard; Smith, Joshua H; García, José J

2014-11-28

The mechanical properties of human brain tissue are the subject of interest because of their use in understanding brain trauma and in developing therapeutic treatments and procedures. To represent the behavior of the tissue, we have developed hyperelastic mechanical models whose parameters are fitted in accordance with experimental test results. However, most studies available in the literature have fitted parameters with data of a single type of loading, such as tension, compression, or shear. Recently, Jin et al. (Journal of Biomechanics 46:2795-2801, 2013) reported data from ex vivo tests of human brain tissue under tension, compression, and shear loading using four strain rates and four different brain regions. However, they do not report parameters of energy functions that can be readily used in finite element simulations. To represent the tissue behavior for the quasi-static loading conditions, we aimed to determine the best fit of the hyperelastic parameters of the hyperfoam, Ogden, and polynomial strain energy functions available in ABAQUS for the low strain rate data, while simultaneously considering all three loading modes. We used an optimization process conducted in MATLAB, calling iteratively three finite element models developed in ABAQUS that represent the three loadings. Results showed a relatively good fit to experimental data in all loading modes using two terms in the energy functions. Values for the shear modulus obtained in this analysis (897-1653Pa) are in the range of those presented in other studies. These energy-function parameters can be used in brain tissue simulations using finite element models. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain invasion assessability in meningiomas is related to meningioma size and grade, and can be improved by extensive sampling of the surgically removed meningioma specimen.

PubMed

Pizem, Joze; Velnar, Tomaz; Prestor, Borut; Mlakar, Jernej; Popovic, Mara

2014-01-01

Despite the important prognostic value of brain invasion in meningiomas, little attention has been paid to its massessment, and the parameters associated with brain invasion assessability (identification of brain tissue in the surgical specimen) are not well characterized. The aim of our study was to determine the parameters that are associated with brain invasion assessability and brain invasion in meningiomas. By binary logistic regression analysis, we studied the association of various clinical and pathologic parameters with brain invasion assessabilitym and brain invasion in 294 meningiomas: 149 unselected consecutive meningiomas with extensive sampling, diagnosed in 2009 and 2010, collected prospectively, and 145 meningiomas diagnosed in 1999 and 2000 when little attention was paid to brain invasion assessment. Meningioma grade, size and number of tissue blocks were independent predictors of brain invasion assessability. Brain tissue was identified in 78 of 233 (33%) benign, 33 of 51 (65%) atypical, and 10 of 10 (100%) malignant meningiomas. In univariate analysis, group (prospective vs.retrospective), type (recurrent vs. primary), cleavability, meningioma grade and mitotic count were predictors of brain invasion, while only meningioma grade, and group retained predictive value in multivariate analysis. Brain invasion, when assessable, was identified in 22 of 78 (28%) benign, 21 of 33 (64%) atypical, and 10 of 10 (100%) malignant meningiomas. Brain invasion assessability is related to meningioma grade and size and can be improved by extensive sampling of meningioma surgical.

Characterization and localization of /sup 3/H-arginine8-vasopressin binding to rat kidney and brain tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorsa, D.M.; Majumdar, L.A.; Petracca, F.M.

Anatomic, behavioral and pharmacologic evidence suggests that arginine8-vasopressin (AVP) serves as a CNS neurotransmitter or neuromodulator. AVP binding to membrane and tissue slice preparations from brain and kidney was characterized, and the anatomical distribution of these binding sites was examined. Conditions for the binding assay were optimized using kidney medullary tissue. Binding of /sup 3/H-AVP (S.A. . 30-51 Ci/mmol, NEN) to brain and kidney membranes and tissue slices was saturable, temperature dependent, linearly related to protein concentration (or number of tissue slices), reversible, and specific since the ability of cold AVP to displace /sup 3/H-AVP from binding was greater thanmore » oxytocin and other related peptide fragments. Autoradiographic localization of /sup 3/H-AVP binding was restricted to kidney medullary tissue. In brain tissue, /sup 3/H-AVP binding was found to occur in concentrated foci. Brainstem areas such as the nucleus tractus solitarius (NTS) showed a high density of AVP binding sites. Since local injections of AVP into the NTS have been shown to influence blood pressure, the present study presents the first anatomical evidence for the presence of AVP specific binding sites which might mediate this effect.« less

Histopathological effects, responses of oxidative stress, inflammation, apoptosis biomarkers and alteration of gene expressions related to apoptosis, oxidative stress, and reproductive system in chlorpyrifos-exposed common carp (Cyprinus carpio L.).

PubMed

Altun, Serdar; Özdemir, Selçuk; Arslan, Harun

2017-11-01

In this study, we aimed to identify the toxic effects of chlorpyrifos exposure on the tissues of common carp. For this purpose, we evaluated histopathological changes in the brain, gills, liver, kidney, testis, and ovaries after 21 days of chlorpyrifos exposure. Activation of 8-OHdG, cleaved caspase-3, and iNOS were assesed by immunofluorescence assay in chlorpyrifos-exposed brain and liver tissue. Additionally, we measured the expression levels of caspase-3, caspase-8, iNOS, MT1, CYP1A, and CYP3A genes in chlorpyrifos-exposed brain tissue, as well as the expression levels of FSH and LH genes in chlorpyrifos-exposed ovaries, using qRT-PCR. We observed severe histopathological lesions, including inflammation, degeneration, necrosis, and hemorrhage, in the evaluated tissues of common carp after both high and low levels of exposure to chlorpyrifos. We detected strong and diffuse signs of immunofluorescence reaction for 8-OHdG, iNOS, and cleaved caspase-3 in the chlorpyrifos-exposed brain and liver tissues. Furthermore, we found that chlorpyrifos exposure significantly upregulated the expressions of caspase-3, caspase-8, iNOS, and MT1, and also moderately upregulated CYP1A and CYP3A in the brain tissue of exposed carp. We also noted downregulation of FSH and LH gene expressions in chlorpyrifos-exposed ovary tissues. Based on our results, chlorpyrifos toxication caused crucial histopathological lesions in vital organs, induced oxidative stress, inflammation, and apoptosis in liver and brain tissues, and triggered reproductive sterility in common carp. Therefore, we can propose that chlorpyrifos toxication is highly dangerous to the health of common carp. Moreover, chlorpyrifos pollution in the water could threaten the common carp population. Use of chlorpyrifos should be restricted, and aquatic systems should be monitored for chlorpyrifos pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reflection imaging of China ink-perfused brain vasculature using confocal laser-scanning microscopy after clarification of brain tissue by the Spalteholz method.

PubMed

Gutierre, R C; Vannucci Campos, D; Mortara, R A; Coppi, A A; Arida, R M

2017-04-01

Confocal laser-scanning microscopy is a useful tool for visualizing neurons and glia in transparent preparations of brain tissue from laboratory animals. Currently, imaging capillaries and venules in transparent brain tissues requires the use of fluorescent proteins. Here, we show that vessels can be imaged by confocal laser-scanning microscopy in transparent cortical, hippocampal and cerebellar preparations after clarification of China ink-injected specimens by the Spalteholz method. This method may be suitable for global, three-dimensional, quantitative analyses of vessels, including stereological estimations of total volume and length and of surface area of vessels, which constitute indirect approaches to investigate angiogenesis. © 2017 Anatomical Society.

An Australian Brain Bank: a critical investment with a high return!

PubMed

Sheedy, D; Garrick, T; Dedova, I; Hunt, C; Miller, R; Sundqvist, N; Harper, C

2008-09-01

Research into neuropsychiatric disorders, including alcohol-related problems, is limited in part by the lack of appropriate animal models. However, the development of new technologies in pathology and molecular biology means that many more questions can be addressed using appropriately stored human brain tissues. The New South Wales Tissue Resource Centre (TRC) in the University of Sydney (Australia) is a human brain bank that can provide tissues to the neuroscience research community studying alcohol-related brain disorders, schizophrenia, depression and bipolar disorders. Carefully standardised operational protocols and integrated information systems means that the TRC can provide high quality, accurately characterised, tissues for research. A recent initiative, the pre-mortem donor program called "Using our Brains", encourages individuals without neuropsychiatric illness to register as control donors, a critical group for all research. Community support for this program is strong with over 2,000 people registering their interest. Discussed herein are the protocols pertaining to this multifaceted facility and the benefits of investment, both scientific and financial, to neuroscience researchers and the community at large.

Quantitative measurement of intact alpha-synuclein proteoforms from post-mortem control and Parkinson's disease brain tissue by intact protein mass spectrometry.

PubMed

Kellie, John F; Higgs, Richard E; Ryder, John W; Major, Anthony; Beach, Thomas G; Adler, Charles H; Merchant, Kalpana; Knierman, Michael D

2014-07-23

A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue from Parkinson's cases and controls. The method was used to test the hypothesis that pathology associated brain tissue will have a different profile of post-translationally modified alpha-synuclein than the control samples. Validation of the sample processing steps, mass spectrometry based measurements, and data processing steps were performed. The intact protein quantitation method features extraction and integration of m/z data from each charge state of a detected alpha-synuclein species and fitting of the data to a simple linear model which accounts for concentration and charge state variability. The quantitation method was validated with serial dilutions of intact protein standards. Using the method on the human brain samples, several previously unreported modifications in alpha-synuclein were identified. Low levels of phosphorylated alpha synuclein were detected in brain tissue fractions enriched for Lewy body pathology and were marginally significant between PD cases and controls (p = 0.03).

Prediction of brain tissue temperature using near-infrared spectroscopy.

PubMed

Holper, Lisa; Mitra, Subhabrata; Bale, Gemma; Robertson, Nicola; Tachtsidis, Ilias

2017-04-01

Broadband near-infrared spectroscopy (NIRS) can provide an endogenous indicator of tissue temperature based on the temperature dependence of the water absorption spectrum. We describe a first evaluation of the calibration and prediction of brain tissue temperature obtained during hypothermia in newborn piglets (animal dataset) and rewarming in newborn infants (human dataset) based on measured body (rectal) temperature. The calibration using partial least squares regression proved to be a reliable method to predict brain tissue temperature with respect to core body temperature in the wavelength interval of 720 to 880 nm with a strong mean predictive power of [Formula: see text] (animal dataset) and [Formula: see text] (human dataset). In addition, we applied regression receiver operating characteristic curves for the first time to evaluate the temperature prediction, which provided an overall mean error bias between NIRS predicted brain temperature and body temperature of [Formula: see text] (animal dataset) and [Formula: see text] (human dataset). We discuss main methodological aspects, particularly the well-known aspect of over- versus underestimation between brain and body temperature, which is relevant for potential clinical applications.

Transmission in near-infrared optical windows for deep brain imaging.

PubMed

Shi, Lingyan; Sordillo, Laura A; Rodríguez-Contreras, Adrián; Alfano, Robert

2016-01-01

Near-infrared (NIR) radiation has been employed using one- and two-photon excitation of fluorescence imaging at wavelengths 650-950 nm (optical window I) for deep brain imaging; however, longer wavelengths in NIR have been overlooked due to a lack of suitable NIR-low band gap semiconductor imaging detectors and/or femtosecond laser sources. This research introduces three new optical windows in NIR and demonstrates their potential for deep brain tissue imaging. The transmittances are measured in rat brain tissue in the second (II, 1,100-1,350 nm), third (III, 1,600-1,870 nm), and fourth (IV, centered at 2,200 nm) NIR optical tissue windows. The relationship between transmission and tissue thickness is measured and compared with the theory. Due to a reduction in scattering and minimal absorption, window III is shown to be the best for deep brain imaging, and windows II and IV show similar but better potential for deep imaging than window I. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Brain Tissue Compartment Density Estimated Using Diffusion-Weighted MRI Yields Tissue Parameters Consistent With Histology

PubMed Central

Sepehrband, Farshid; Clark, Kristi A.; Ullmann, Jeremy F.P.; Kurniawan, Nyoman D.; Leanage, Gayeshika; Reutens, David C.; Yang, Zhengyi

2015-01-01

We examined whether quantitative density measures of cerebral tissue consistent with histology can be obtained from diffusion magnetic resonance imaging (MRI). By incorporating prior knowledge of myelin and cell membrane densities, absolute tissue density values were estimated from relative intra-cellular and intra-neurite density values obtained from diffusion MRI. The NODDI (neurite orientation distribution and density imaging) technique, which can be applied clinically, was used. Myelin density estimates were compared with the results of electron and light microscopy in ex vivo mouse brain and with published density estimates in a healthy human brain. In ex vivo mouse brain, estimated myelin densities in different sub-regions of the mouse corpus callosum were almost identical to values obtained from electron microscopy (Diffusion MRI: 42±6%, 36±4% and 43±5%; electron microscopy: 41±10%, 36±8% and 44±12% in genu, body and splenium, respectively). In the human brain, good agreement was observed between estimated fiber density measurements and previously reported values based on electron microscopy. Estimated density values were unaffected by crossing fibers. PMID:26096639

Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering.

PubMed

Cheng, Tzu-Yun; Chen, Ming-Hong; Chang, Wen-Han; Huang, Ming-Yuan; Wang, Tzu-Wei

2013-03-01

Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer β-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA(16)-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwartz, C.; Gavin, P.

This report describes research performed at the WSU College of Veterinary Medicine in which a large animal model was developed and used to study the effects of boron neutron capture therapy (BNCT) on normal and neoplastic canine brain tissue. The studies were performed using borocaptate sodium (BSH) and epithermal neutrons and had two major foci: biodistribution of BSH in animals with spontaneously occurring brain tumors; and effects of BNCT in normal and neoplastic brain tissue.

Interactive Medical Volume Visualization for Surgical Operations

DTIC Science & Technology

2001-10-25

the preprocessing and processing stages, related medical brain tissues, which are skull, white matter, gray matter and pathology ( tumor ), are segmented ...from 12 or 16 bit data depths. NMR segmentation plays an important role in our work, because, classifying brain tissues from NMR slices requires an...performing segmentation of brain structures. Our segmentation process uses Self Organizing Feature Maps (SOFM) [12]. In SOM, on the contrary to Feedback

Determination of the neuropharmacological drug nodakenin in rat plasma and brain tissues by liquid chromatography tandem mass spectrometry: Application to pharmacokinetic studies.

PubMed

Song, Yingshi; Yan, Huiyu; Xu, Jingbo; Ma, Hongxi

2017-09-01

A rapid and sensitive liquid chromatography tandem mass spectrometry detection using selected reaction monitoring in positive ionization mode was developed and validated for the quantification of nodakenin in rat plasma and brain. Pareruptorin A was used as internal standard. A single step liquid-liquid extraction was used for plasma and brain sample preparation. The method was validated with respect to selectivity, precision, accuracy, linearity, limit of quantification, recovery, matrix effect and stability. Lower limit of quantification of nodakenin was 2.0 ng/mL in plasma and brain tissue homogenates. Linear calibration curves were obtained over concentration ranges of 2.0-1000 ng/mL in plasma and brain tissue homogenates for nodakenin. Intra-day and inter-day precisions (relative standard deviation, RSD) were <15% in both biological media. This assay was successfully applied to plasma and brain pharmacokinetic studies of nodakenin in rats after intravenous administration. Copyright © 2017 John Wiley & Sons, Ltd.

Application of Quantitative MRI for Brain Tissue Segmentation at 1.5 T and 3.0 T Field Strengths

PubMed Central

West, Janne; Blystad, Ida; Engström, Maria; Warntjes, Jan B. M.; Lundberg, Peter

2013-01-01

Background Brain tissue segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) are important in neuroradiological applications. Quantitative Mri (qMRI) allows segmentation based on physical tissue properties, and the dependencies on MR scanner settings are removed. Brain tissue groups into clusters in the three dimensional space formed by the qMRI parameters R1, R2 and PD, and partial volume voxels are intermediate in this space. The qMRI parameters, however, depend on the main magnetic field strength. Therefore, longitudinal studies can be seriously limited by system upgrades. The aim of this work was to apply one recently described brain tissue segmentation method, based on qMRI, at both 1.5 T and 3.0 T field strengths, and to investigate similarities and differences. Methods In vivo qMRI measurements were performed on 10 healthy subjects using both 1.5 T and 3.0 T MR scanners. The brain tissue segmentation method was applied for both 1.5 T and 3.0 T and volumes of WM, GM, CSF and brain parenchymal fraction (BPF) were calculated on both field strengths. Repeatability was calculated for each scanner and a General Linear Model was used to examine the effect of field strength. Voxel-wise t-tests were also performed to evaluate regional differences. Results Statistically significant differences were found between 1.5 T and 3.0 T for WM, GM, CSF and BPF (p<0.001). Analyses of main effects showed that WM was underestimated, while GM and CSF were overestimated on 1.5 T compared to 3.0 T. The mean differences between 1.5 T and 3.0 T were -66 mL WM, 40 mL GM, 29 mL CSF and -1.99% BPF. Voxel-wise t-tests revealed regional differences of WM and GM in deep brain structures, cerebellum and brain stem. Conclusions Most of the brain was identically classified at the two field strengths, although some regional differences were observed. PMID:24066153

SU-E-T-331: Dosimetric Impact of Multileaf Collimator Leaf Width On Stereotactic Radiosurgery (SRS) RapidArc Treatment Plans for Single and Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Keeling, V; Ahmad, S

Purpose: To determine the effects of multileaf collimator (MLC) leaf width on normal-brain-tissue doses and dose conformity of SRS RapidArc treatment plans for brain tumors. Methods: Ten patients with 24 intracranial tumors (seven with 1–2 and three with 4–6 lesions) were planned using RapidArc for both Varian Millennium 120 MLC (5 mm leaf width) and high definition (HD) MLC (2.5 mm leaf width). Between 2 and 8 arcs were used with two full coplanar arcs and the rest non-coplanar half arcs. 6 MV beams were used and plans were optimized with a high priority to the Normal Tissue Objective (tomore » achieve dose conformity and sharp dose fall-off) and normal brain tissue. Calculation was done using AAA on a 1 mm grid size. The prescription dose ranged from 14–22 Gy. Plans were normalized such that 99% of the target received the prescription dose. Identical beam geometries, optimizations, calculations, and normalizations were used for both plans. Paddick Conformity Index (PCI), V4, V8 and V12 Gy for normal brain tissue and Integral Dose were used for analysis. Results: In all cases, HD MLC plans performed better in sparing normal brain tissue, achieving a higher PCI with a lower Integral Dose. The average PCI for all 24 targets was 0.75±0.23 and 0.70±0.23 (p ≤0.0015) for HD MLC and Millennium MLC plans, respectively. The average ratio of normal brain doses for Millennium MLC to HD MLC plans was 1.30±0.16, 1.27±0.15, and 1.31±0.18 for the V4, V8, and V12, respectively. The differences in normal brain dose for all criteria were statistically significant with p-value < 0.02. On average Millennium MLC plans had a 16% higher integral dose than HD MLC plans. Conclusion: Significantly better dose conformity with reduced volume of normal brain tissue and integral dose was achieved with HD MLC plans compared to Millennium MLC plans.« less

All brains are made of this: a fundamental building block of brain matter with matching neuronal and glial masses.

PubMed

Mota, Bruno; Herculano-Houzel, Suzana

2014-01-01

How does the size of the glial and neuronal cells that compose brain tissue vary across brain structures and species? Our previous studies indicate that average neuronal size is highly variable, while average glial cell size is more constant. Measuring whole cell sizes in vivo, however, is a daunting task. Here we use chi-square minimization of the relationship between measured neuronal and glial cell densities in the cerebral cortex, cerebellum, and rest of brain in 27 mammalian species to model neuronal and glial cell mass, as well as the neuronal mass fraction of the tissue (the fraction of tissue mass composed by neurons). Our model shows that while average neuronal cell mass varies by over 500-fold across brain structures and species, average glial cell mass varies only 1.4-fold. Neuronal mass fraction varies typically between 0.6 and 0.8 in all structures. Remarkably, we show that two fundamental, universal relationships apply across all brain structures and species: (1) the glia/neuron ratio varies with the total neuronal mass in the tissue (which in turn depends on variations in average neuronal cell mass), and (2) the neuronal mass per glial cell, and with it the neuronal mass fraction and neuron/glia mass ratio, varies with average glial cell mass in the tissue. We propose that there is a fundamental building block of brain tissue: the glial mass that accompanies a unit of neuronal mass. We argue that the scaling of this glial mass is a consequence of a universal mechanism whereby numbers of glial cells are added to the neuronal parenchyma during development, irrespective of whether the neurons composing it are large or small, but depending on the average mass of the glial cells being added. We also show how evolutionary variations in neuronal cell mass, glial cell mass and number of neurons suffice to determine the most basic characteristics of brain structures, such as mass, glia/neuron ratio, neuron/glia mass ratio, and cell densities.

Neocortical Transplants in the Mammalian Brain Lack a Blood-Brain Barrier to Macromolecules

NASA Astrophysics Data System (ADS)

Rosenstein, Jeffrey M.

1987-02-01

In order to determine whether the blood-brain barrier was present in transplants of central nervous tissue, fetal neocortex, which already possesses blood-brain and blood-cerebrospinal fluid barriers to protein, was grafted into the undamaged fourth ventricle or directly into the neocortex of recipient rats. Horseradish peroxidase or a conjugated human immunoglobulin G-peroxidase molecule was systemically administered into the host. These proteins were detected within the cortical transplants within 2 minutes regardless of the age of the donor or postoperative time. At later times these compounds, which normally do not cross the blood-brain barrier, inundated the grafts and adjacent host brain and also entered the cerebrospinal fluid. Endogenous serum albumin detected immunocytochemically in untreated hosts had a comparable although less extensive distribution. Thus, transplants of fetal central nervous tissue have permanent barrier dysfunction, probably due to microvascular changes, and are not integrated physiologically within the host. Blood-borne compounds, either systemically administered or naturally occurring, which should never contact normal brain tissue, have direct access to these transplants and might affect neuronal function.

Photoacoustic imaging for transvascular drug delivery to the rat brain

NASA Astrophysics Data System (ADS)

Watanabe, Ryota; Sato, Shunichi; Tsunoi, Yasuyuki; Kawauchi, Satoko; Takemura, Toshiya; Terakawa, Mitsuhiro

2015-03-01

Transvascular drug delivery to the brain is difficult due to the blood-brain barrier (BBB). Thus, various methods for safely opening the BBB have been investigated, for which real-time imaging methods are desired both for the blood vessels and distribution of a drug. Photoacoustic (PA) imaging, which enables depth-resolved visualization of chromophores in tissue, would be useful for this purpose. In this study, we performed in vivo PA imaging of the blood vessels and distribution of a drug in the rat brain by using an originally developed compact PA imaging system with fiber-based illumination. As a test drug, Evans blue (EB) was injected to the tail vein, and a photomechanical wave was applied to the targeted brain tissue to increase the permeability of the blood vessel walls. For PA imaging of blood vessels and EB distribution, nanosecond pulses at 532 nm and 670 nm were used, respectively. We clearly visualized blood vessels with diameters larger than 50 μm and the distribution of EB in the brain, showing spatiotemporal characteristics of EB that was transvascularly delivered to the target tissue in the brain.

Embedding and Chemical Reactivation of Green Fluorescent Protein in the Whole Mouse Brain for Optical Micro-Imaging

PubMed Central

Gang, Yadong; Zhou, Hongfu; Jia, Yao; Liu, Ling; Liu, Xiuli; Rao, Gong; Li, Longhui; Wang, Xiaojun; Lv, Xiaohua; Xiong, Hanqing; Yang, Zhongqin; Luo, Qingming; Gong, Hui; Zeng, Shaoqun

2017-01-01

Resin embedding has been widely applied to fixing biological tissues for sectioning and imaging, but has long been regarded as incompatible with green fluorescent protein (GFP) labeled sample because it reduces fluorescence. Recently, it has been reported that resin-embedded GFP-labeled brain tissue can be imaged with high resolution. In this protocol, we describe an optimized protocol for resin embedding and chemical reactivation of fluorescent protein labeled mouse brain, we have used mice as experiment model, but the protocol should be applied to other species. This method involves whole brain embedding and chemical reactivation of the fluorescent signal in resin-embedded tissue. The whole brain embedding process takes a total of 7 days. The duration of chemical reactivation is ~2 min for penetrating 4 μm below the surface in the resin-embedded brain. This protocol provides an efficient way to prepare fluorescent protein labeled sample for high-resolution optical imaging. This kind of sample was demonstrated to be imaged by various optical micro-imaging methods. Fine structures labeled with GFP across a whole brain can be detected. PMID:28352214

Tissue mechanics regulate brain development, homeostasis and disease

PubMed Central

Barnes, J. Matthew

2017-01-01

ABSTRACT All cells sense and integrate mechanical and biochemical cues from their environment to orchestrate organismal development and maintain tissue homeostasis. Mechanotransduction is the evolutionarily conserved process whereby mechanical force is translated into biochemical signals that can influence cell differentiation, survival, proliferation and migration to change tissue behavior. Not surprisingly, disease develops if these mechanical cues are abnormal or are misinterpreted by the cells – for example, when interstitial pressure or compression force aberrantly increases, or the extracellular matrix (ECM) abnormally stiffens. Disease might also develop if the ability of cells to regulate their contractility becomes corrupted. Consistently, disease states, such as cardiovascular disease, fibrosis and cancer, are characterized by dramatic changes in cell and tissue mechanics, and dysregulation of forces at the cell and tissue level can activate mechanosignaling to compromise tissue integrity and function, and promote disease progression. In this Commentary, we discuss the impact of cell and tissue mechanics on tissue homeostasis and disease, focusing on their role in brain development, homeostasis and neural degeneration, as well as in brain cancer. PMID:28043968

Calculation of Absorbed Dose in Target Tissue and Equivalent Dose in Sensitive Tissues of Patients Treated by BNCT Using MCNP4C

NASA Astrophysics Data System (ADS)

Zamani, M.; Kasesaz, Y.; Khalafi, H.; Pooya, S. M. Hosseini

Boron Neutron Capture Therapy (BNCT) is used for treatment of many diseases, including brain tumors, in many medical centers. In this method, a target area (e.g., head of patient) is irradiated by some optimized and suitable neutron fields such as research nuclear reactors. Aiming at protection of healthy tissues which are located in the vicinity of irradiated tissue, and based on the ALARA principle, it is required to prevent unnecessary exposure of these vital organs. In this study, by using numerical simulation method (MCNP4C Code), the absorbed dose in target tissue and the equiavalent dose in different sensitive tissues of a patiant treated by BNCT, are calculated. For this purpose, we have used the parameters of MIRD Standard Phantom. Equiavelent dose in 11 sensitive organs, located in the vicinity of target, and total equivalent dose in whole body, have been calculated. The results show that the absorbed dose in tumor and normal tissue of brain equal to 30.35 Gy and 0.19 Gy, respectively. Also, total equivalent dose in 11 sensitive organs, other than tumor and normal tissue of brain, is equal to 14 mGy. The maximum equivalent doses in organs, other than brain and tumor, appear to the tissues of lungs and thyroid and are equal to 7.35 mSv and 3.00 mSv, respectively.

Neurosurgical sapphire handheld probe for intraoperative optical diagnostics, laser coagulation and aspiration of malignant brain tissue

NASA Astrophysics Data System (ADS)

Shikunova, Irina A.; Zaytsev, Kirill I.; Stryukov, Dmitrii O.; Dubyanskaya, Evgenia N.; Kurlov, Vladimir N.

2017-07-01

In this paper, a handheld contact probe based on sapphire shaped crystal was developed for the intraoperative optical diagnosis and aspiration of malignant brain tissue combined with the laser hemostasis. Such a favorable combination of several functions in a single instrument significantly increases its clinical relevance. It makes possible highly-accurate real-time detection and removal of either large-scale malignancies or even separate invasive cancer cells. The proposed neuroprobe was integrated into the clinical neurosurgical workflow for the intraoperative fluorescence identification and removal of malignant tissues of the brain.

VARIATION IN CHOLINESTERASE ACTIVITY IN TISSUES OF RATS AT DIFFERENT TIMES AFTER IRRADIATION (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zubkova, S.R.; Chernavskaya, N.M.

1959-06-11

It was found that a single lethal dose (1000 r) changes the cholinesterase activity in the brain, liver, and blood serum. After 5 hr and 45 min the cholinesterase activity in tissues drops from the normal level (15.9% in blood serum, 20.6% in the brain, and 18.4% in the liver). After three days the activity changes in various tissues: in the liver it continues to drop, in the brain it rises but does not reach the standard level, and it increases sharply in the blood serum. (R.V.J.)

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice.

PubMed

Cahill, Lindsay S; Gazdzinski, Lisa M; Tsui, Albert Ky; Zhou, Yu-Qing; Portnoy, Sharon; Liu, Elaine; Mazer, C David; Hare, Gregory Mt; Kassner, Andrea; Sled, John G

2017-03-01

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO 2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia.

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice

PubMed Central

Gazdzinski, Lisa M; Tsui, Albert KY; Zhou, Yu-Qing; Portnoy, Sharon; Liu, Elaine; Mazer, C David; Hare, Gregory MT; Kassner, Andrea; Sled, John G

2016-01-01

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia. PMID:27165012

Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

PubMed

Kizil, Caghan; Iltzsche, Anne; Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

2015-01-01

Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

Tissue distribution and depuration kinetics of waterborne 14C-labeled light PAHs in mummichog (Fundulus heteroclitus).

PubMed

Valdez Domingos, F X; Oliveira Ribeiro, C A; Pelletier, É; Rouleau, C

2011-04-01

Light polycyclic aromatic hydrocarbons (PAHs) of petrogenic origin are commonly found in estuaries and coastal areas. Though they are known to be toxic to fish, little is known about their uptake and tissue distribution. This paper reports on the results of a study on uptake, elimination, and tissue distribution of three waterborne 14C-labeled PAHs in the mummichog, Fundulus heteroclitus, using whole-body autoradiography. After a 24 h exposure to 1 μCi·L(-1) of 14C-naphthalene, 14C-1-naphthol, and 14C-phenanthrene, fish were transferred to clean water and tissue distribution examined after 0, 1, 3, 7, 14, and 21 days of depuration. All compounds were readily accumulated by fish and were also rapidly eliminated (t0.5 range=1.1 to 3.0 days). Most of the radioactivity in naphthalene- and phenanthrene-treated fish was found in gall bladder≫liver>intestinal lumen. In naphthol-exposed fish, an important labeling of some brain areas was observed. Brain of naphthalene-exposed fish was also labeled after 24 h depuration, indicating that exposure to naphthalene may result in metabolite accumulation in the brain. This is the first study showing that naphthalene, naphthol, and/or unidentified metabolite(s) can accumulate in brain tissues, which may impair normal brain function.

Piezosurgery prevents brain tissue damage: an experimental study on a new rat model.

PubMed

Pavlíková, G; Foltán, R; Burian, M; Horká, E; Adámek, S; Hejčl, A; Hanzelka, T; Sedý, J

2011-08-01

Piezosurgery is a promising meticulous system for bone cutting, based on ultrasound microvibrations. It is thought that the impact of piezosurgery on the integrity of soft tissue is generally low, but it has not been examined critically. The authors undertook an experimental study to evaluate the brain tissue response to skull bone removal using piezosurgery compared with a conventional drilling method. In Wistar male rats, a circular bone window was drilled to the parietal bone using piezosurgery on one side and a conventional bone drill on the other side. The behavioural performance of animals was evaluated using the motor BBB test and sensory plantar test. The brains of animals were evaluated by magnetic resonance imaging (MRI) and histology. The results of MRI showed significantly increased depth and width of the brain lesion in the region of conventional drilling compared with the region where piezosurgery was used. Cresylviolet and NF 160 staining confirmed these findings. There was no significant difference in any of the behavioural tests between the two groups. In conclusion, piezosurgery is a safe method for the performance of osteotomy in close relation to soft tissue, including an extremely injury-sensitive tissue such as brain. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Brain tissue deforms similarly to filled elastomers and follows consolidation theory

NASA Astrophysics Data System (ADS)

Franceschini, G.; Bigoni, D.; Regitnig, P.; Holzapfel, G. A.

2006-12-01

Slow, large deformations of human brain tissue—accompanying cranial vault deformation induced by positional plagiocephaly, occurring during hydrocephalus, and in the convolutional development—has surprisingly received scarce mechanical investigation. Since the effects of these deformations may be important, we performed a systematic series of in vitro experiments on human brain tissue, revealing the following features. (i) Under uniaxial (quasi-static), cyclic loading, brain tissue exhibits a peculiar nonlinear mechanical behaviour, exhibiting hysteresis, Mullins effect and residual strain, qualitatively similar to that observed in filled elastomers. As a consequence, the loading and unloading uniaxial curves have been found to follow the Ogden nonlinear elastic theory of rubber (and its variants to include Mullins effect and permanent strain). (ii) Loaded up to failure, the "shape" of the stress/strain curve qualitatively changes, evidencing softening related to local failure. (iii) Uniaxial (quasi-static) strain experiments under controlled drainage conditions provide the first direct evidence that the tissue obeys consolidation theory involving fluid migration, with properties similar to fine soils, but having much smaller volumetric compressibility. (iv) Our experimental findings also support the existence of a viscous component of the solid phase deformation. Brain tissue should, therefore, be modelled as a porous, fluid-saturated, nonlinear solid with very small volumetric (drained) compressibility.

Correlative analysis of head kinematics and brain's tissue response: a computational approach toward understanding the mechanisms of blast TBI

NASA Astrophysics Data System (ADS)

Sarvghad-Moghaddam, H.; Rezaei, A.; Ziejewski, M.; Karami, G.

2017-11-01

Upon impingement of blast waves on the head, stress waves generated at the interface of the skull are transferred into the cranium and the brain tissue and may cause mild to severe blast traumatic brain injury. The intensity of the shock front, defined by the blast overpressure (BoP), that is, the blast-induced peak static overpressure, significantly affects head kinematics as well as the tissue responses of the brain. While evaluation of global linear and rotational accelerations may be feasible, an experimental determination of dynamic responses of the brain in terms of intracranial pressure (ICP), maximum shear stress (MSS), and maximum principal strain (MPS) is almost impossible. The main objective of this study is to investigate possible correlations between head accelerations and the brain's ICP, MSS, and MPS. To this end, three different blasts were simulated by modeling the detonation of 70, 200, and 500 g of TNT at a fixed distance from the head, corresponding to peak BoPs of 0.52, 1.2, and 2 MPa, respectively. A nonlinear multi-material finite element algorithm was implemented in the LS-DYNA explicit solver. Fluid-solid interaction between the blast waves and head was modeled using a penalty-based method. Strong correlations were found between the brain's dynamic responses and both global linear and rotational accelerations at different blast intensities (R^{2 }≥98%), implying that global kinematic parameters of the head might be strong predictors of brain tissue biomechanical parameters.

Uptake of selenium and mercury by captive mink: Results of a controlled feeding experiment.

PubMed

Evans, R D; Grochowina, N M; Basu, N; O'Connor, E M; Hickie, B E; Rouvinen-Watt, K; Evans, H E; Chan, H M

2016-02-01

Captive, juvenile, ranch-bred, male mink (Neovison vison) were fed diets containing various concentrations of methyl-mercury (MeHg) and selenium (Se) for a period of 13 weeks and then sacrificed to determine total Hg levels in fur, blood, brain, liver and kidneys and total Se concentrations in brain tissue. As MeHg concentrations in the diet increased, concentrations of total Hg in the tissues also increased with the highest level occurring in the fur > liver = kidney > brain > blood. Concentrations of Hg in the fur were correlated (r(2) > 0.97) with liver, kidney, blood and brain concentrations. The addition of Se to the mink diet did not appear to affect most tissue concentrations of total Hg nor did it affect the partitioning of Hg between the liver:blood, kidney:blood and brain:blood; however, partitioning of Hg between fur and blood was apparently affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantification of brain lipids by FTIR spectroscopy and partial least squares regression

NASA Astrophysics Data System (ADS)

Dreissig, Isabell; Machill, Susanne; Salzer, Reiner; Krafft, Christoph

2009-01-01

Brain tissue is characterized by high lipid content. Its content decreases and the lipid composition changes during transformation from normal brain tissue to tumors. Therefore, the analysis of brain lipids might complement the existing diagnostic tools to determine the tumor type and tumor grade. Objective of this work is to extract lipids from gray matter and white matter of porcine brain tissue, record infrared (IR) spectra of these extracts and develop a quantification model for the main lipids based on partial least squares (PLS) regression. IR spectra of the pure lipids cholesterol, cholesterol ester, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, galactocerebroside and sulfatide were used as references. Two lipid mixtures were prepared for training and validation of the quantification model. The composition of lipid extracts that were predicted by the PLS regression of IR spectra was compared with lipid quantification by thin layer chromatography.

Amelioration of ischemic brain damage by peritoneal dialysis

PubMed Central

Godino, María del Carmen; Romera, Victor G.; Sánchez-Tomero, José Antonio; Pacheco, Jesus; Canals, Santiago; Lerma, Juan; Vivancos, José; Moro, María Angeles; Torres, Magdalena; Lizasoain, Ignacio; Sánchez-Prieto, José

2013-01-01

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patients. PMID:23999426

The NSW Brain Tissue Resource Centre: Banking for Alcohol and Major Neuropsychiatric Disorders Research

PubMed Central

Sutherland, G.T.; Sheedy, D.; Stevens, J.; McCrossin, T.; Smith, C.C.; van Roijen, M.; Kril, J.J.

2016-01-01

The New South Wales Brain Tissue Resource Centre (NSWBTRC) at the University of Sydney (Australia) is an established human brain bank providing tissue to the neuroscience research community for investigations on alcohol-related brain damage and major psychiatric illnesses such as schizophrenia. The NSWBTRC relies on wide community engagement to encourage those with and without neuropsychiatric illness to consent to donation through its allied research programs. The subsequent provision of high-quality samples relies on standardized operational protocols, associated clinical data, quality control measures, integrated information systems, robust infrastructure, and governance. These processes are continually augmented to complement the changes in internal and external governance as well as the complexity and diversity of advanced investigation techniques. This report provides an overview of the dynamic process of brain banking and discusses the challenges of meeting the future needs of researchers, including synchronicity with other disease-focus collections. PMID:27139235

RAPD Profiling, DNA Fragmentation, and Histomorphometric Examination in Brains of Wistar Rats Exposed to Indoor 2.5 Ghz Wi-Fi Devices Radiation.

PubMed

Ibitayo, A O; Afolabi, O B; Akinyemi, A J; Ojiezeh, T I; Adekoya, K O; Ojewunmi, O O

2017-01-01

The advent of Wi-Fi connected high technology devices in executing day-to-day activities is fast evolving especially in developing countries of the world and hence the need to assess its safety among others. The present study was conducted to investigate the injurious effect of radiofrequency emissions from installed Wi-Fi devices in brains of young male rats. Animals were divided into four equal groups; group 1 served as control while groups 2, 3, and 4 were exposed to 2.5 Ghz at intervals of 30, 45, and 60 consecutive days with free access to food and water ad libitum. Alterations in harvested brain tissues were confirmed by histopathological analyses which showed vascular congestion and DNA damage in the brain was assayed using agarose gel electrophoresis. Histomorphometry analyses of their brain tissues showed perivascular congestion and tissue damage as well.

A Hybrid Hierarchical Approach for Brain Tissue Segmentation by Combining Brain Atlas and Least Square Support Vector Machine

PubMed Central

Kasiri, Keyvan; Kazemi, Kamran; Dehghani, Mohammad Javad; Helfroush, Mohammad Sadegh

2013-01-01

In this paper, we present a new semi-automatic brain tissue segmentation method based on a hybrid hierarchical approach that combines a brain atlas as a priori information and a least-square support vector machine (LS-SVM). The method consists of three steps. In the first two steps, the skull is removed and the cerebrospinal fluid (CSF) is extracted. These two steps are performed using the toolbox FMRIB's automated segmentation tool integrated in the FSL software (FSL-FAST) developed in Oxford Centre for functional MRI of the brain (FMRIB). Then, in the third step, the LS-SVM is used to segment grey matter (GM) and white matter (WM). The training samples for LS-SVM are selected from the registered brain atlas. The voxel intensities and spatial positions are selected as the two feature groups for training and test. SVM as a powerful discriminator is able to handle nonlinear classification problems; however, it cannot provide posterior probability. Thus, we use a sigmoid function to map the SVM output into probabilities. The proposed method is used to segment CSF, GM and WM from the simulated magnetic resonance imaging (MRI) using Brainweb MRI simulator and real data provided by Internet Brain Segmentation Repository. The semi-automatically segmented brain tissues were evaluated by comparing to the corresponding ground truth. The Dice and Jaccard similarity coefficients, sensitivity and specificity were calculated for the quantitative validation of the results. The quantitative results show that the proposed method segments brain tissues accurately with respect to corresponding ground truth. PMID:24696800

Focused Ultrasound Immunotherapy for Central Nervous System Pathologies: Challenges and Opportunities

PubMed Central

Curley, Colleen T.; Sheybani, Natasha D.; Bullock, Timothy N.; Price, Richard J.

2017-01-01

Immunotherapy is rapidly emerging as the cornerstone for the treatment of several forms of metastatic cancer, as well as for a host of other pathologies. Meanwhile, several new high-profile studies have uncovered remarkable linkages between the central nervous and immune systems. With these recent developments, harnessing the immune system for the treatment of brain pathologies is a promising strategy. Here, we contend that MR image-guided focused ultrasound (FUS) represents a noninvasive approach that will allow for favorable therapeutic immunomodulation in the setting of the central nervous system. One obstacle to effective immunotherapeutic drug delivery to the brain is the blood brain barrier (BBB), which refers to the specialized structure of brain capillaries that prevents transport of most therapeutics from the blood into brain tissue. When applied in the presence of circulating microbubbles, FUS can safely and transiently open the BBB to facilitate the delivery of immunotherapeutic agents into the brain parenchyma. Furthermore, it has been demonstrated that physical perturbations of the tissue microenvironment via FUS can modulate immune response in both normal and diseased tissue. In this review article, we provide an overview of FUS energy regimens and corresponding tissue bioeffects, followed by a review of the literature pertaining to FUS for therapeutic antibody delivery in normal brain and preclinical models of brain disease. We provide an overview of studies that demonstrate FUS-mediated immune modulation in both the brain and peripheral settings. Finally, we provide remarks on challenges facing FUS immunotherapy and opportunities for future expansion in this area. PMID:29109764

Image guided constitutive modeling of the silicone brain phantom

NASA Astrophysics Data System (ADS)

Puzrin, Alexander; Skrinjar, Oskar; Ozan, Cem; Kim, Sihyun; Mukundan, Srinivasan

2005-04-01

The goal of this work is to develop reliable constitutive models of the mechanical behavior of the in-vivo human brain tissue for applications in neurosurgery. We propose to define the mechanical properties of the brain tissue in-vivo, by taking the global MR or CT images of a brain response to ventriculostomy - the relief of the elevated intracranial pressure. 3D image analysis translates these images into displacement fields, which by using inverse analysis allow for the constitutive models of the brain tissue to be developed. We term this approach Image Guided Constitutive Modeling (IGCM). The presented paper demonstrates performance of the IGCM in the controlled environment: on the silicone brain phantoms closely simulating the in-vivo brain geometry, mechanical properties and boundary conditions. The phantom of the left hemisphere of human brain was cast using silicon gel. An inflatable rubber membrane was placed inside the phantom to model the lateral ventricle. The experiments were carried out in a specially designed setup in a CT scanner with submillimeter isotropic voxels. The non-communicative hydrocephalus and ventriculostomy were simulated by consequently inflating and deflating the internal rubber membrane. The obtained images were analyzed to derive displacement fields, meshed, and incorporated into ABAQUS. The subsequent Inverse Finite Element Analysis (based on Levenberg-Marquardt algorithm) allowed for optimization of the parameters of the Mooney-Rivlin non-linear elastic model for the phantom material. The calculated mechanical properties were consistent with those obtained from the element tests, providing justification for the future application of the IGCM to in-vivo brain tissue.

ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS

PubMed Central

Bredel, Markus; Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; Elverfeldt, Dominik v.; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.

2014-01-01

BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR. CONCLUSIONS: Our data illustrate how anomalous splicing of a tissue-regulated exon in a constituent of an oncogenic signaling pathway eliminates its tumor suppressor function and promotes tumorigenesis. This paradigm of malignant glial transformation as a consequence of tissue-specific alternative exon splicing in a tumor suppressor, may have widespread applicability in explaining how changes in critical tissue-specific regulatory mechanisms reprogram normal development to oncogenesis. SECONDARY CATEGORY: n/a.

Tissue and organ donation for research in forensic pathology: the MRC Sudden Death Brain and Tissue Bank.

PubMed

Millar, T; Walker, R; Arango, J-C; Ironside, J W; Harrison, D J; MacIntyre, D J; Blackwood, D; Smith, C; Bell, J E

2007-12-01

Novel methodological approaches to the investigation of brain and non-central nervous system disorders have led to increased demand for well-characterized, high quality human tissue samples, particularly from control cases. In the setting of the new Human Tissue legislation, we sought to determine whether relatives who have been suddenly bereaved are willing to grant authorization for research use of post mortem tissue samples and organs in sufficient numbers to support the establishment of a brain and tissue bank based in the forensic service. Research authorization was sought from families on the day prior to forensic post mortem examination followed up by written confirmation. We have to date selected individuals who have died suddenly (age range 1-89 years) and who were likely to have normal brains or who had displayed symptoms of a CNS disorder of interest to researchers, including psychiatric disorders. One hundred and eleven families have been approached during the first 2 years of this project. Research use of tissue samples was authorized by 96% of families and 17% agreed to whole brain donation. Audit of families' experience does not suggest that they are further distressed by being approached. Respondents expressed a clear view that the opportunity for research donation should be open to all bereaved families. Despite the sometimes long post mortem intervals, the quality of tissue samples is good, as assessed by a range of markers including Agilent BioAnalyzer quantification of RNA integrity (mean value 6.4). We conclude that the vast majority of families are willing to support research use of post mortem tissues even in the context of sudden bereavement and despite previous adverse publicity. The potential for acquisition of normal CNS and non-CNS tissues and of various hard-to-get CNS disorders suggests that efforts to access the forensic post mortem service for research material are eminently worthwhile. (c) 2007 Pathological Society of Great Britain and Ireland

NMR-based metabolomics approach to study the toxicity of lambda-cyhalothrin to goldfish (Carassius auratus).

PubMed

Li, Minghui; Wang, Junsong; Lu, Zhaoguang; Wei, Dandan; Yang, Minghua; Kong, Lingyi

2014-01-01

In this study, a (1)H nuclear magnetic resonance (NMR) based metabolomics approach was applied to investigate the toxicity of lambda-cyhalothrin (LCT) in goldfish (Carassius auratus). LCT showed tissue-specific damage to gill, heart, liver and kidney tissues of goldfish. NMR profiling combined with statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) was developed to discern metabolite changes occurring after one week LCT exposure in brain, heart and kidney tissues of goldfish. LCT exposure influenced levels of many metabolites (e.g., leucine, isoleucine and valine in brain and kidney; lactate in brain, heart and kidney; alanine in brain and kidney; choline in brain, heart and kidney; taurine in brain, heart and kidney; N-acetylaspartate in brain; myo-inositol in brain; phosphocreatine in brain and heart; 2-oxoglutarate in brain; cis-aconitate in brain, and etc.), and broke the balance of neurotransmitters and osmoregulators, evoked oxidative stress, disturbed metabolisms of energy and amino acids. The implication of glutamate-glutamine-gamma-aminobutyric axis in LCT induced toxicity was demonstrated for the first time. Our findings demonstrated the applicability and potential of metabolomics approach for the elucidation of toxicological effects of pesticides and the underlying mechanisms, and the discovery of biomarkers for pesticide pollution in aquatic environment. Copyright © 2013 Elsevier B.V. All rights reserved.

Sapphire implant based neuro-complex for deep-lying brain tumors phototheranostics

NASA Astrophysics Data System (ADS)

Sharova, A. S.; Maklygina, YU S.; Yusubalieva, G. M.; Shikunova, I. A.; Kurlov, V. N.; Loschenov, V. B.

2018-01-01

The neuro-complex as a combination of sapphire implant optical port and osteoplastic biomaterial "Collapan" as an Aluminum phthalocyanine nanoform photosensitizer (PS) depot was developed within the framework of this study. The main goals of such neuro-complex are to provide direct access of laser radiation to the brain tissue depth and to transfer PS directly to the pathological tissue location that will allow multiple optical phototheranostics of the deep-lying tumor region without repeated surgical intervention. The developed complex spectral-optical properties research was carried out by photodiagnostics method using the model sample: a brain tissue phantom. The optical transparency of sapphire implant allows obtaining a fluorescent signal with high accuracy, comparable to direct measurement "in contact" with the tissue.

Wavelet-domain de-noising of OCT images of human brain malignant glioma

NASA Astrophysics Data System (ADS)

Dolganova, I. N.; Aleksandrova, P. V.; Beshplav, S.-I. T.; Chernomyrdin, N. V.; Dubyanskaya, E. N.; Goryaynov, S. A.; Kurlov, V. N.; Reshetov, I. V.; Potapov, A. A.; Tuchin, V. V.; Zaytsev, K. I.

2018-04-01

We have proposed a wavelet-domain de-noising technique for imaging of human brain malignant glioma by optical coherence tomography (OCT). It implies OCT image decomposition using the direct fast wavelet transform, thresholding of the obtained wavelet spectrum and further inverse fast wavelet transform for image reconstruction. By selecting both wavelet basis and thresholding procedure, we have found an optimal wavelet filter, which application improves differentiation of the considered brain tissue classes - i.e. malignant glioma and normal/intact tissue. Namely, it allows reducing the scattering noise in the OCT images and retaining signal decrement for each tissue class. Therefore, the observed results reveals the wavelet-domain de-noising as a prospective tool for improved characterization of biological tissue using the OCT.

Quantitative analysis of transcranial and intraparenchymal light penetration in human cadaver brain tissue.

PubMed

Tedford, Clark E; DeLapp, Scott; Jacques, Steven; Anders, Juanita

2015-04-01

Photobiomodulation (PBM) also known as low-level light therapy has been used successfully for the treatment of injury and disease of the nervous system. The use of PBM to treat injury and diseases of the brain requires an in-depth understanding of light propagation through tissues including scalp, skull, meninges, and brain. This study investigated the light penetration gradients in the human cadaver brain using a Transcranial Laser System with a 30 mm diameter beam of 808 nm wavelength light. In addition, the wavelength-dependence of light scatter and absorbance in intraparenchymal brain tissue using 660, 808, and 940 nm wavelengths was investigated. Intact human cadaver heads (n = 8) were obtained for measurement of light propagation through the scalp/skull/meninges and into brain tissue. The cadaver heads were sectioned in either the transverse or mid-sagittal. The sectioned head was mounted into a cranial fixture with an 808 nm wavelength laser system illuminating the head from beneath with either pulsed-wave (PW) or continuous-wave (CW) laser light. A linear array of nine isotropic optical fibers on a 5 mm pitch was inserted into the brain tissue along the optical axis of the beam. Light collected from each fiber was delivered to a multichannel power meter. As the array was lowered into the tissue, the power from each probe was recorded at 5 mm increments until the inner aspect of the dura mater was reached. Intraparenchymal light penetration measurements were made by delivering a series of wavelengths (660, 808, and 940 nm) through a separate optical fiber within the array, which was offset from the array line by 5 mm. Local light penetration was determined and compared across the selected wavelengths. Unfixed cadaver brains provide good anatomical localization and reliable measurements of light scatter and penetration in the CNS tissues. Transcranial application of 808 nm wavelength light penetrated the scalp, skull, meninges, and brain to a depth of approximately 40 mm with an effective attenuation coefficient for the system of 2.22 cm(-1) . No differences were observed in the results between the PW and CW laser light. The intraparenchymal studies demonstrated less absorption and scattering for the 808 nm wavelength light compared to the 660 or 940 nm wavelengths. Transcranial light measurements of unfixed human cadaver brains allowed for determinations of light penetration variables. While unfixed human cadaver studies do not reflect all the conditions seen in the living condition, comparisons of light scatter and penetration and estimates of fluence levels can be used to establish further clinical dosing. The 808 nm wavelength light demonstrated superior CNS tissue penetration. © 2015 Wiley Periodicals, Inc.

Dynamics of Viral and Proviral Loads of Feline Immunodeficiency Virus within the Feline Central Nervous System during the Acute Phase following Intravenous Infection

PubMed Central

Ryan, G.; Klein, D.; Knapp, E.; Hosie, M. J.; Grimes, T.; Mabruk, M. J. E. M. F.; Jarrett, O.; Callanan, J. J.

2003-01-01

Animal models of human immunodeficiency virus 1, such as feline immunodeficiency virus (FIV), provide the opportunities to dissect the mechanisms of early interactions of the virus with the central nervous system (CNS). The aims of the present study were to evaluate viral loads within CNS, cerebrospinal fluid (CSF), ocular fluid, and the plasma of cats in the first 23 weeks after intravenous inoculation with FIVGL8. Proviral loads were also determined within peripheral blood mononuclear cells (PBMCs) and brain tissue. In this acute phase of infection, virus entered the brain in the majority of animals. Virus distribution was initially in a random fashion, with more diffuse brain involvement as infection progressed. Virus in the CSF was predictive of brain parenchymal infection. While the peak of virus production in blood coincided with proliferation within brain, more sustained production appeared to continue in brain tissue. In contrast, proviral loads in the brain decreased to undetectable levels in the presence of a strengthening PBMC load. A final observation in this study was that there was no direct correlation between viral loads in regions of brain or ocular tissue and the presence of histopathology. PMID:12805447

Understanding the pathophysiology of schizophrenia: Contributions from the Melbourne Psychiatric Brain Bank.

PubMed

Dean, Brian; Copolov, David; Scarr, Elizabeth

2016-11-01

The Melbourne Psychiatric Brain Bank came into existence 25years ago. This review focusses on lines of research that have used tissue from the Brain Bank over periods of time. Hence there is a discussion on the significance of changes in levels of serotonin 2A receptors in the cortex of patients with schizophrenia and the relevance of such changes with regards to the pathophysiology of the disorder. The extensive contribution made by studies using tissue from the Melbourne Psychiatric Brain Bank to understanding the role of muscarinic receptors in the pathophysiology and treatment of schizophrenia is summarised. Finally, findings using brain bank tissue and "omics" technologies are reviewed. In each case, findings using tissue from the Melbourne Psychiatric Brain Bank is placed in context with research carried out on human postmortem CNS in schizophrenia and with findings in other lines of research that can help explain the causes or consequences of changes in CNS molecular cytoarchitecture. This timely review of data from the Melbourne Psychiatric Brain Bank reinforces the challenges faced in trying to increase our understanding of the molecular pathophysiology of schizophrenia. Continuing to increase our understanding of the disorder is important as a precursor to identifying new drug targets that can be exploited to improve the treatment of a disorder where treatment resistance remains a significant problem (Millan et al., 2016). Copyright © 2016 Elsevier B.V. All rights reserved.

Cerebral oxygenation in traumatic brain injury; Can a non-invasive frequency domain near-infrared spectroscopy device detect changes in brain tissue oxygen tension as well as the established invasive monitor?

PubMed

Davies, David James; Clancy, Michael; Dehghani, Hamid; Lucas, Samuel John Edwin; Forcione, Mario; Yakoub, Kamal Makram; Belli, Antonio

2018-06-07

The cost and highly invasive nature of brain monitoring modality in traumatic brain injury patients currently restrict its utility to specialist neurological intensive care settings. We aim to test the abilities of a frequency domain near-infrared spectroscopy (FD-NIRS) device in predicting changes in invasively measured brain tissue oxygen tension. Individuals admitted to a United Kingdom specialist major trauma centre were contemporaneously monitored with an FD-NIRS device and invasively measured brain tissue oxygen tension probe. Area under the curve receiver operating characteristic (AUROC) statistical analysis was utilised to assess the predictive power of FD-NIRS in detecting both moderate and severe hypoxia (20 and 10 mmHg, respectively), as measured invasively. 16 individuals were prospectively recruited to the investigation. Severe hypoxic episodes were detected in 9 of these individuals, with the NIRS demonstrating a broad range of predictive abilities (AUROC 0.68-0.88) from relatively poor to good. Moderate hypoxic episodes were detected in seven individuals with similar predictive performance (AUROC 0.576 - 0.905). A variable performance in the predictive powers of this FD-NIRS device to detect changes in brain tissue oxygen was demonstrated. Consequently, this enhanced NIRS technology has not demonstrated sufficient ability to replace the established invasive measurement.

Hyperpolarized xenon magnetic resonance of the lung and the brain

NASA Astrophysics Data System (ADS)

Venkatesh, Arvind Krishnamachari

2001-04-01

Hyperpolarized noble gas Magnetic Resonance Imaging (MRI) is a new diagnostic modality that has been used successfully for lung imaging. Xenon is soluble in blood and inhaled xenon is transported to the brain via circulating blood. Xenon also accumulates in the lipid rich white matter of the brain. Hyperpolarized xenon can hence be used as a tissue- sensitive probe of brain function. The goals of this study were to identify the NMR resonances of xenon in the rat brain and evaluate the role of hyperpolarized xenon for brain MRI. We have developed systems to produce sufficient volumes of hyperpolarized xenon for in vivo brain experiments. The specialized instrumentation developed include an apparatus for optical pump-cell manufacture and high purity gas manifolds for filling cells. A hyperpolarized gas delivery system was designed to ventilate small animals with hyperpolarized xenon for transport to the brain. The T1 of xenon dissolved in blood indicates that the lifetime of xenon in the blood is sufficient for significant magnetization to be transferred to distal tissues. A variety of carrier agents for intravenous delivery of hyperpolarized xenon were tested for transport to distal tissues. Using our new gas delivery system, high SNR 129Xe images of rat lungs were obtained. Spectroscopy with hyperpolarized xenon indicated that xenon was transported from the lungs to the blood and tissues with intact magnetization. After preliminary studies that indicated the feasibility for in vivo rat brain studies, experiments were performed with adult rats and young rats with different stages of white matter development. Both in vivo and in vitro experiments showed the prominence of one peak from xenon in the rat brain, which was assigned to brain lipids. Cerebral brain perfusion was calculated from the wash-out of the hyperpolarized xenon signal in the brain. An increase in brain perfusion during maturation was observed. These experiments showed that hyperpolarized xenon MRI can be used to develop unique approaches to studying white matter and gray matter in the brain. Some of the possible applications of hyperpolarized xenon MRI in the brain are clinical diagnosis of white matter diseases, functional MRI (fMRI) and measurement of cerebral blood perfusion.

Computational deconvolution of genome wide expression data from Parkinson's and Huntington's disease brain tissues using population-specific expression analysis

PubMed Central

Capurro, Alberto; Bodea, Liviu-Gabriel; Schaefer, Patrick; Luthi-Carter, Ruth; Perreau, Victoria M.

2015-01-01

The characterization of molecular changes in diseased tissues gives insight into pathophysiological mechanisms and is important for therapeutic development. Genome-wide gene expression analysis has proven valuable for identifying biological processes in neurodegenerative diseases using post mortem human brain tissue and numerous datasets are publically available. However, many studies utilize heterogeneous tissue samples consisting of multiple cell types, all of which contribute to global gene expression values, confounding biological interpretation of the data. In particular, changes in numbers of neuronal and glial cells occurring in neurodegeneration confound transcriptomic analyses, particularly in human brain tissues where sample availability and controls are limited. To identify cell specific gene expression changes in neurodegenerative disease, we have applied our recently published computational deconvolution method, population specific expression analysis (PSEA). PSEA estimates cell-type-specific expression values using reference expression measures, which in the case of brain tissue comprises mRNAs with cell-type-specific expression in neurons, astrocytes, oligodendrocytes and microglia. As an exercise in PSEA implementation and hypothesis development regarding neurodegenerative diseases, we applied PSEA to Parkinson's and Huntington's disease (PD, HD) datasets. Genes identified as differentially expressed in substantia nigra pars compacta neurons by PSEA were validated using external laser capture microdissection data. Network analysis and Annotation Clustering (DAVID) identified molecular processes implicated by differential gene expression in specific cell types. The results of these analyses provided new insights into the implementation of PSEA in brain tissues and additional refinement of molecular signatures in human HD and PD. PMID:25620908

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays.

PubMed

Panuccio, Gabriella; Colombi, Ilaria; Chiappalone, Michela

2018-05-15

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuronal network interactions and their modulation by electrical stimulation. As compared to conventional extracellular recording techniques, they provide the added advantages of a greater number of observation points and a known inter-electrode distance, which allow studying the propagation path and speed of electrophysiological signals. However, tissue oxygenation may be greatly impaired during MEA recording, requiring a high perfusion rate, which comes at the cost of decreased signal-to-noise ratio and higher oscillations in the experimental temperature. Electrical stimulation further stresses the brain tissue, making it difficult to pursue prolonged recording/stimulation epochs. Moreover, electrical modulation of brain slice activity needs to target specific structures/pathways within the brain slice, requiring that electrode mapping be easily and quickly performed live during the experiment. Here, we illustrate how to perform the recording and electrical modulation of 4-aminopyridine (4AP)-induced epileptiform activity in rodent brain slices using planar MEAs. We show that the brain tissue obtained from mice outperforms rat brain tissue and is thus better suited for MEA experiments. This protocol guarantees the generation and maintenance of a stable epileptiform pattern that faithfully reproduces the electrophysiological features observed with conventional field potential recording, persists for several hours, and outlasts sustained electrical stimulation for prolonged epochs. Tissue viability throughout the experiment is achieved thanks to the use of a small-volume custom recording chamber allowing for laminar flow and quick solution exchange even at low (1 mL/min) perfusion rates. Quick MEA mapping for real-time monitoring and selection of stimulating electrodes is performed by a custom graphic user interface (GUI).

Tissue redox activity as a hallmark of carcinogenesis: from early to terminal stages of cancer.

PubMed

Bakalova, Rumiana; Zhelev, Zhivko; Aoki, Ichio; Saga, Tsuneo

2013-05-01

The study aimed to clarify the dynamics of tissue redox activity (TRA) in cancer progression and assess the importance of this parameter for therapeutic strategies. The experiments were carried out on brain tissues of neuroblastoma-bearing, glioma-bearing, and healthy mice. TRA was visualized in vivo by nitroxide-enhanced MRI on anesthetized animals or in vitro by electron paramagnetic resonance spectroscopy on isolated tissue specimens. Two biochemical parameters were analyzed in parallel: tissue total antioxidant capacity (TTAC) and plasma levels of matrix metalloproteinases (MMP). In the early stage of cancer, the brain tissues were characterized by a shorter-lived MRI signal than that from healthy brains (indicating a higher reducing activity for the nitroxide radical), which was accompanied by an enhancement of TTAC and MMP9 plasma levels. In the terminal stage of cancer, tissues in both hemispheres were characterized by a longer-lived MRI signal than in healthy brains (indicating a high-oxidative activity) that was accompanied by a decrease in TTAC and an increase in the MMP2/MMP9 plasma levels. Cancer progression also affected the redox potential of tissues distant from the primary tumor locus (liver and lung). Their oxidative status increased in both stages of cancer. The study shows that tissue redox balance is very sensitive to the progression of cancer and can be used as a diagnostic marker of carcinogenesis. The study also suggests that the noncancerous tissues of a cancer-bearing organism are susceptible to oxidative damage and should be considered a therapeutic target. ©2013 AACR.

Quantification of petroleum-type hydrocarbons in avian tissue

USGS Publications Warehouse

Gay, M.L.; Belisle, A.A.; Patton, J.F.

1980-01-01

Methods were developed for the analysis of 16 hydrocarbons in avian tissue. Mechanical extraction with pentane was followed by clean-up on Florisil and Silicar. Residues were determined by gas—liquid chromatography and gas—liquid, chromatography—mass spectrometry. The method was applied to the analysis of liver, kidney, fat, and brain tissue of mallard ducks (Anas platyrhynchos) fed a mixture of hydrocarbons. Measurable concentrations of all compounds analyzed were present in all tissues except brain. Highest concentrations were in fat.

Rescuing Perishable Neuroanatomical Information from a Threatened Biodiversity Hotspot: Remote Field Methods for Brain Tissue Preservation Validated by Cytoarchitectonic Analysis, Immunohistochemistry, and X-Ray Microcomputed Tomography.

PubMed

Hughes, Daniel F; Walker, Ellen M; Gignac, Paul M; Martinez, Anais; Negishi, Kenichiro; Lieb, Carl S; Greenbaum, Eli; Khan, Arshad M

2016-01-01

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, are increasingly threatened. There is a need to accelerate collection efforts in these regions before threatened or endangered species become extinct. The diverse geographical, ecological, genetic, morphological, and behavioral data generated from the on-site collection of an individual specimen are useful for many scientific purposes. However, traditional methods for specimen preparation in the field do not permit researchers to retrieve neuroanatomical data, disregarding potentially useful data for increasing our understanding of brain diversity. These data have helped clarify brain evolution, deciphered relationships between structure and function, and revealed constraints and selective pressures that provide context about the evolution of complex behavior. Here, we report our field-testing of two commonly used laboratory-based techniques for brain preservation while on a collecting expedition in the Congo Basin and Albertine Rift, two poorly known regions associated with the Eastern Afromontane biodiversity hotspot. First, we found that transcardial perfusion fixation and long-term brain storage, conducted in remote field conditions with no access to cold storage laboratory equipment, had no observable impact on cytoarchitectural features of lizard brain tissue when compared to lizard brain tissue processed under laboratory conditions. Second, field-perfused brain tissue subjected to prolonged post-fixation remained readily compatible with subsequent immunohistochemical detection of neural antigens, with immunostaining that was comparable to that of laboratory-perfused brain tissue. Third, immersion-fixation of lizard brains, prepared under identical environmental conditions, was readily compatible with subsequent iodine-enhanced X-ray microcomputed tomography, which facilitated the non-destructive imaging of the intact brain within its skull. In summary, we have validated multiple approaches to preserving intact lizard brains in remote field conditions with limited access to supplies and a high degree of environmental exposure. This protocol should serve as a malleable framework for researchers attempting to rescue perishable and irreplaceable morphological and molecular data from regions of disappearing biodiversity. Our approach can be harnessed to extend the numbers of species being actively studied by the neuroscience community, by reducing some of the difficulty associated with acquiring brains of animal species that are not readily available in captivity.

Rescuing Perishable Neuroanatomical Information from a Threatened Biodiversity Hotspot: Remote Field Methods for Brain Tissue Preservation Validated by Cytoarchitectonic Analysis, Immunohistochemistry, and X-Ray Microcomputed Tomography

PubMed Central

Hughes, Daniel F.; Walker, Ellen M.; Gignac, Paul M.; Martinez, Anais; Negishi, Kenichiro; Lieb, Carl S.; Greenbaum, Eli

2016-01-01

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, are increasingly threatened. There is a need to accelerate collection efforts in these regions before threatened or endangered species become extinct. The diverse geographical, ecological, genetic, morphological, and behavioral data generated from the on-site collection of an individual specimen are useful for many scientific purposes. However, traditional methods for specimen preparation in the field do not permit researchers to retrieve neuroanatomical data, disregarding potentially useful data for increasing our understanding of brain diversity. These data have helped clarify brain evolution, deciphered relationships between structure and function, and revealed constraints and selective pressures that provide context about the evolution of complex behavior. Here, we report our field-testing of two commonly used laboratory-based techniques for brain preservation while on a collecting expedition in the Congo Basin and Albertine Rift, two poorly known regions associated with the Eastern Afromontane biodiversity hotspot. First, we found that transcardial perfusion fixation and long-term brain storage, conducted in remote field conditions with no access to cold storage laboratory equipment, had no observable impact on cytoarchitectural features of lizard brain tissue when compared to lizard brain tissue processed under laboratory conditions. Second, field-perfused brain tissue subjected to prolonged post-fixation remained readily compatible with subsequent immunohistochemical detection of neural antigens, with immunostaining that was comparable to that of laboratory-perfused brain tissue. Third, immersion-fixation of lizard brains, prepared under identical environmental conditions, was readily compatible with subsequent iodine-enhanced X-ray microcomputed tomography, which facilitated the non-destructive imaging of the intact brain within its skull. In summary, we have validated multiple approaches to preserving intact lizard brains in remote field conditions with limited access to supplies and a high degree of environmental exposure. This protocol should serve as a malleable framework for researchers attempting to rescue perishable and irreplaceable morphological and molecular data from regions of disappearing biodiversity. Our approach can be harnessed to extend the numbers of species being actively studied by the neuroscience community, by reducing some of the difficulty associated with acquiring brains of animal species that are not readily available in captivity. PMID:27196138

Novel strategies of Raman imaging for brain tumor research.

PubMed

Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

2017-10-17

Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real-time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I 2930 /I 2845 at 2930 and 2845 cm -1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that levels of the saturated fatty acids were significantly reduced in the high grade medulloblastoma samples compared with non-tumor brain samples and low grade astrocytoma. Differences were also noted in the n-6/n-3 polyunsaturated fatty acids (PUFA) content between medulloblastoma and non-tumor brain samples. The content of the oleic acid (OA) was significantly smaller in almost all brain high grade brain tumors than that observed in the control samples. It indicates that the fatty acid composition of human brain tumors differs from that found in non-tumor brain tissue. The iodine number N I for the normal brain tissue is 60. For comparison OA has 87, docosahexaenoic acid (DHA) 464, α-linolenic acid (ALA) 274. The high grade tumors have the iodine numbers between that for palmitic acid, stearic acid, arachidic acid (N I =0) and oleic acid (N I =87). Most low grade tumors have N I similar to that of OA. The iodine number for arachidonic acid (AA) (N I =334) is much higher than those observed for all studied samples.

Novel strategies of Raman imaging for brain tumor research

PubMed Central

Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

2017-01-01

Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real–time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm-1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that levels of the saturated fatty acids were significantly reduced in the high grade medulloblastoma samples compared with non-tumor brain samples and low grade astrocytoma. Differences were also noted in the n-6/n-3 polyunsaturated fatty acids (PUFA) content between medulloblastoma and non-tumor brain samples. The content of the oleic acid (OA) was significantly smaller in almost all brain high grade brain tumors than that observed in the control samples. It indicates that the fatty acid composition of human brain tumors differs from that found in non-tumor brain tissue. The iodine number NI for the normal brain tissue is 60. For comparison OA has 87, docosahexaenoic acid (DHA) 464, α-linolenic acid (ALA) 274. The high grade tumors have the iodine numbers between that for palmitic acid, stearic acid, arachidic acid (NI=0) and oleic acid (NI=87). Most low grade tumors have NI similar to that of OA. The iodine number for arachidonic acid (AA) (NI=334) is much higher than those observed for all studied samples. PMID:29156720

The effects of vitamin E on brain derived neurotrophic factor, tissues oxidative damage and learning and memory of juvenile hypothyroid rats.

PubMed

Baghcheghi, Yousef; Beheshti, Farimah; Shafei, Mohammad Naser; Salmani, Hossein; Sadeghnia, Hamid Reza; Soukhtanloo, Mohammad; Anaeigoudari, Akbar; Hosseini, Mahmoud

2018-06-01

The effects of vitamin E (Vit E) on brain derived neurotrophic factor (BDNF) and brain tissues oxidative damage as well as on learning and memory impairments in juvenile hypothyroid rats were examined. The rats were grouped as: (1) Control; (2) Propylthiouracil (PTU); (3) PTU-Vit E and (4) Vit E. PTU was added to their drinking water (0.05%) during 6 weeks. Vit E (20 mg/kg) was daily injected (IP). Morris water maze (MWM) and passive avoidance (PA) were carried out. The animals were deeply anesthetized and the brain tissues were removed for biochemical measurements. PTU increased the escape latency and traveled path in MWM (P < 0.001). It also shortened the latency to enter the dark compartment of PA as well as the time spent in the target quadrant in probe trial of MWM (P < 0.01-P < 0.001). All the effects of PTU were reversed by Vit E (P < 0.01-P < 0.001). PTU administration attenuated thiol and BDNF content as well as the activities of superoxide dismutase (SOD) and catalase (CAT) in the brain tissues while increased molondialdehyde (MDA). Moreover, Vit E improved BDNF, thiol, SOD and CAT while diminished MDA. The results of the present study showed that Vit E improved BDNF and prevented from brain tissues oxidative damage as well as learning and memory impairments in juvenile hypothyroid rats.

Confocal laser endomicroscopy for brain tumor surgery: a milestone journey from microscopy to cellular surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Charalampaki, Cleopatra

2017-02-01

The aim in brain tumor surgery is maximal tumor resection with minimal damage of normal neuronal tissue. Today diagnosis of tumor and definition of tumor borders intraoperatively is based on various visualization methods as well as on the histopathologic examination of a limited number of biopsy specimens via frozen sections. Unfortunately, intraoperative histopathology bears several shortcomings, and many biopsies are inconclusive. Therefore, the desirable treatment could be to have the ability to identify intraoperative cellular structures, and differentiate tumor from normal functional brain tissue on a cellular level. To achieve this goal new technological equipment integrated with new surgical concepts is needed.Confocal Laser Endomicroscopy (CLE) is an imaging technique which provides microscopic information of tissue in real-time. We are able to use these technique to perform intraoperative "optical biopsies" in bringing the microscope inside to the patients brain through miniaturized fiber-optic probes, and allow real-time histopathology. In our knowledge we are worldwide the only one neurosurgical group using CLE intraoperative for brain tumor surgery. We can detect and characterize intraoperative tumor cells, providing immediate online diagnosis without the need for frozen sections. It also provides delineation of borders between tumor and normal tissue on a cellular level, making surgical margins more accurate than ever before. The applications of CLE-assisted neurosurgery help to accurate the therapy by extending the resection borders and protecting the functionality of normal brain tissue in critical eloquent areas.

Gelatinized Copper–Capillary Alginate Gel Functions as an Injectable Tissue Scaffolding System for Stem Cell Transplants

PubMed Central

Willenberg, Bradley Jay; Zheng, Tong; Meng, Fan-Wei; Meneses, Juan Carlos; Rossignol, Candace; Batich, Christopher D.; Terada, Naohiro; Steindler, Dennis A.; Weiss, Michael D.

2013-01-01

In severe hypoxic–ischemic brain injury, cellular components such as neurons and astrocytes are injured or destroyed along with the supporting extracellular matrix. This presents a challenge to the field of regenerative medicine since the lack of extracellular matrix and supporting structures makes the transplant milieu inhospitable to the transplanted cells. A potential solution to this problem is the use of a biomaterial to provide the extracellular components needed to keep cells localized in cystic brain regions, allowing the cells to form connections and repair lost brain tissue. Ideally, this biomaterial would be combined with stem cells, which have been proven to have therapeutic potentials, and could be delivered via an injection. To study this approach, we derived a hydrogel biomaterial tissue scaffold from oligomeric gelatin and copper–capillary alginate gel (GCCAG). We then demonstrated that our multipotent astrocytic stem cells (MASCs) could be maintained in GCCAG scaffolds for up to 2 weeks in vitro and that the cells retained their multipotency. We next performed a pilot transplant study in which GCCAG was mixed with MASCs and injected into the brain of a neonatal rat pup. After a week in vivo, our results showed that: the GCCAG biomaterial did not cause a significant reactive gliosis; viable cells were retained within the injected scaffolds; and some delivered cells migrated into the surrounding brain tissue. Therefore, GCCAG tissue scaffolds are a promising, novel injectable system for transplantation of stem cells to the brain. PMID:20699061

Postnatal brain and skull growth in an Apert syndrome mouse model

PubMed Central

Hill, Cheryl A.; Martínez-Abadías, Neus; Motch, Susan M.; Austin, Jordan R.; Wang, Yingli; Jabs, Ethylin Wang; Richtsmeier, Joan T.; Aldridge, Kristina

2012-01-01

Craniofacial and neural tissues develop in concert throughout pre- and postnatal growth. FGFR-related craniosynostosis syndromes, such as Apert syndrome (AS), are associated with specific phenotypes involving both the skull and the brain. We analyzed the effects of the FGFR P253R mutation for Apert syndrome using the Fgfr2+/P253R mouse to evaluate the effects of this mutation on these two tissues over the course of development from day of birth (P0) to postnatal day 2 (P2). Three-dimensional magnetic resonance microscopy and computed tomography images were acquired from Fgfr2+/P253R mice and unaffected littermates at P0 (N=28) and P2 (N=23). 3D coordinate data for 23 skull and 15 brain landmarks were statistically compared between groups. Results demonstrate that the Fgfr2+/P253R mice show reduced growth in the facial skeleton and the cerebrum, while the height and width of the neurocranium and caudal regions of the brain show increased growth relative to unaffected littermates. This localized correspondence of differential growth patterns in skull and brain point to their continued interaction through development and suggest that both tissues display divergent postnatal growth patterns relative to unaffected littermates. However, the change in the skull-brain relationship from P0 to P2 implies that each tissue affected by the mutation retains a degree of independence, rather than one tissue directing the development of the other. PMID:23495236

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues

PubMed Central

2013-01-01

Background Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. Results In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed “sleep specific” changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Conclusion Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a ubiquitous role in reducing cellular metabolic stress in both brain and peripheral tissues. Finally, our data suggest a novel role for sleep in synchronizing transcription in peripheral tissues. PMID:23721503

Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions.

PubMed

Dubey, Jitender P; Ferreira, Leandra R; Alsaad, Mohammad; Verma, Shiv K; Alves, Derron A; Holland, Gary N; McConkey, Glenn A

2016-01-01

The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse. Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains) of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection) of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i.) to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25%) of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle. This study reevaluated in depth the rat model of toxoplasmosis visualizing cyst rupture and clarified many aspects of the biology of the parasite useful for future investigations.

Brain tissue stiffness is a sensitive marker for acidosis.

PubMed

Holtzmann, Kathrin; Gautier, Hélène O B; Christ, Andreas F; Guck, Jochen; Káradóttir, Ragnhildur Thóra; Franze, Kristian

2016-09-15

Carbon dioxide overdose is frequently used to cull rodents for tissue harvesting. However, this treatment may lead to respiratory acidosis, which potentially could change the properties of the investigated tissue. Mechanical tissue properties often change in pathological conditions and may thus offer a sensitive generic readout for changes in biological tissues with clinical relevance. In this study, we performed force-indentation measurements with an atomic force microscope on acute cerebellar slices from adult rats to test if brain tissue undergoes changes following overexposure to CO2 compared to other methods of euthanasia. The pH significantly decreased in brain tissue of animals exposed to CO2. Concomitant with the drop in pH, cerebellar grey matter significantly stiffened. Tissue stiffening was reproduced by incubation of acute cerebellar slices in acidic medium. Tissue stiffness provides an early, generic indicator for pathophysiological changes in the CNS. Atomic force microscopy offers unprecedented high spatial resolution to detect such changes. Our results indicate that the stiffness particularly of grey matter strongly correlates with changes of the pH in the cerebellum. Furthermore, the method of tissue harvesting and preparation may not only change tissue stiffness but very likely also other physiologically relevant parameters, highlighting the importance of appropriate sample preparation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Mechanical characterization of human brain tissue.

PubMed

Budday, S; Sommer, G; Birkl, C; Langkammer, C; Haybaeck, J; Kohnert, J; Bauer, M; Paulsen, F; Steinmann, P; Kuhl, E; Holzapfel, G A

2017-01-15

Mechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed compression but not tension. Our results demonstrate that material parameters identified for a single loading mode fail to predict the response under arbitrary loading conditions. Our systematic characterization of human brain tissue will lead to more accurate computational simulations, which will allow us to determine criteria for injury, to develop smart protection systems, and to predict brain development and disease progression. There is a pressing need to characterize the mechanical behavior of human brain tissue under multiple loading conditions, and to identify constitutive models that are able to capture the tissue response under these conditions. We perform a sequence of experimental tests on the same brain specimen to characterize the regional and directional behavior, and we supplement our tests with DTI and histology to explore to which extent the macrostructural response is a result of the underlying microstructure. Results demonstrate that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry, and we show that the multiaxial data can best be captured by a modified version of the one-term Ogden model. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A rapid approach to high-resolution fluorescence imaging in semi-thick brain slices.

PubMed

Selever, Jennifer; Kong, Jian-Qiang; Arenkiel, Benjamin R

2011-07-26

A fundamental goal to both basic and clinical neuroscience is to better understand the identities, molecular makeup, and patterns of connectivity that are characteristic to neurons in both normal and diseased brain. Towards this, a great deal of effort has been placed on building high-resolution neuroanatomical maps(1-3). With the expansion of molecular genetics and advances in light microscopy has come the ability to query not only neuronal morphologies, but also the molecular and cellular makeup of individual neurons and their associated networks(4). Major advances in the ability to mark and manipulate neurons through transgenic and gene targeting technologies in the rodent now allow investigators to 'program' neuronal subsets at will(5-6). Arguably, one of the most influential contributions to contemporary neuroscience has been the discovery and cloning of genes encoding fluorescent proteins (FPs) in marine invertebrates(7-8), alongside their subsequent engineering to yield an ever-expanding toolbox of vital reporters(9). Exploiting cell type-specific promoter activity to drive targeted FP expression in discrete neuronal populations now affords neuroanatomical investigation with genetic precision. Engineering FP expression in neurons has vastly improved our understanding of brain structure and function. However, imaging individual neurons and their associated networks in deep brain tissues, or in three dimensions, has remained a challenge. Due to high lipid content, nervous tissue is rather opaque and exhibits auto fluorescence. These inherent biophysical properties make it difficult to visualize and image fluorescently labelled neurons at high resolution using standard epifluorescent or confocal microscopy beyond depths of tens of microns. To circumvent this challenge investigators often employ serial thin-section imaging and reconstruction methods(10), or 2-photon laser scanning microscopy(11). Current drawbacks to these approaches are the associated labor-intensive tissue preparation, or cost-prohibitive instrumentation respectively. Here, we present a relatively rapid and simple method to visualize fluorescently labelled cells in fixed semi-thick mouse brain slices by optical clearing and imaging. In the attached protocol we describe the methods of: 1) fixing brain tissue in situ via intracardial perfusion, 2) dissection and removal of whole brain, 3) stationary brain embedding in agarose, 4) precision semi-thick slice preparation using new vibratome instrumentation, 5) clearing brain tissue through a glycerol gradient, and 6) mounting on glass slides for light microscopy and z-stack reconstruction (Figure 1). For preparing brain slices we implemented a relatively new piece of instrumentation called the 'Compresstome' VF-200 (http://www.precisionary.com/products_vf200.html). This instrument is a semi-automated microtome equipped with a motorized advance and blade vibration system with features similar in function to other vibratomes. Unlike other vibratomes, the tissue to be sliced is mounted in an agarose plug within a stainless steel cylinder. The tissue is extruded at desired thicknesses from the cylinder, and cut by the forward advancing vibrating blade. The agarose plug/cylinder system allows for reproducible tissue mounting, alignment, and precision cutting. In our hands, the 'Compresstome' yields high quality tissue slices for electrophysiology, immunohistochemistry, and direct fixed-tissue mounting and imaging. Combined with optical clearing, here we demonstrate the preparation of semi-thick fixed brain slices for high-resolution fluorescent imaging.

Precursors to radiopharmaceutical agents for tissue imaging

DOEpatents

Srivastava, Prem C.; Knapp, Jr., Furn F.

1988-01-01

A class of radiolabeled compounds to be used in tissue imaging that exhibits rapid brain uptake, good brain:blood radioactivity ratios, and long retention times. The imaging agents are more specifically radioiodinated aromatic amines attached to dihydropyridine carriers, that exhibit heart as well as brain specificity. In addition to the radiolabeled compounds, classes of compounds are also described that are used as precursors and intermediates in the preparation of the imaging agents.

Light-scattering signal may indicate critical time zone to rescue brain tissue after hypoxia

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

2011-02-01

A light-scattering signal, which is sensitive to cellular/subcellular structural integrity, is a potential indicator of brain tissue viability because metabolic energy is used in part to maintain the structure of cells. We previously observed a unique triphasic scattering change (TSC) at a certain time after oxygen/glucose deprivation for blood-free rat brains; TSC almost coincided with the cerebral adenosine triphosphate (ATP) depletion. We examine whether such TSC can be observed in the presence of blood in vivo, for which transcranial diffuse reflectance measurement is performed for rat brains during hypoxia induced by nitrogen gas inhalation. At a certain time after hypoxia, diffuse reflectance intensity in the near-infrared region changes in three phases, which is shown by spectroscopic analysis to be due to scattering change in the tissue. During hypoxia, rats are reoxygenated at various time points. When the oxygen supply is started before TSC, all rats survive, whereas no rats survive when the oxygen supply is started after TSC. Survival is probabilistic when the oxygen supply is started during TSC, indicating that the period of TSC can be regarded as a critical time zone for rescuing the brain. The results demonstrate that light scattering signal can be an indicator of brain tissue reversibility.

Quantitative comparison of 3D third harmonic generation and fluorescence microscopy images.

PubMed

Zhang, Zhiqing; Kuzmin, Nikolay V; Groot, Marie Louise; de Munck, Jan C

2018-01-01

Third harmonic generation (THG) microscopy is a label-free imaging technique that shows great potential for rapid pathology of brain tissue during brain tumor surgery. However, the interpretation of THG brain images should be quantitatively linked to images of more standard imaging techniques, which so far has been done qualitatively only. We establish here such a quantitative link between THG images of mouse brain tissue and all-nuclei-highlighted fluorescence images, acquired simultaneously from the same tissue area. For quantitative comparison of a substantial pair of images, we present here a segmentation workflow that is applicable for both THG and fluorescence images, with a precision of 91.3 % and 95.8 % achieved respectively. We find that the correspondence between the main features of the two imaging modalities amounts to 88.9 %, providing quantitative evidence of the interpretation of dark holes as brain cells. Moreover, 80 % bright objects in THG images overlap with nuclei highlighted in the fluorescence images, and they are 2 times smaller than the dark holes, showing that cells of different morphologies can be recognized in THG images. We expect that the described quantitative comparison is applicable to other types of brain tissue and with more specific staining experiments for cell type identification. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pathological changes in Alzheimer"s brain evaluated with fluorescence emission analysis (FEA)

NASA Astrophysics Data System (ADS)

Christov, Alexander; Ottman, Todd; Grammas, Paula

2004-07-01

Development of AD is associated with cerebrovascular deposition of amyloid beta (Aβ) as well as a progressive increase in vasular collagen content. Both AΒ and collagen are naturally fluorescent compounds when exposed to UV light. We analyzed autofluorescence emitted from brain tissue samples and isolated brain resistance vessels harvested postmortem from patients with Alzheimer's disease (AD) and age-matched controls. Fluorescence emission, excited at 355 nm with an Nd:YAG laser, was measured using a fiber-optic based fluorescence spectroscopic system for tissue analysis. Significantly higher values of fluorescence emission intensity (P<0.001) in the spectral region from 465 to 490 nm were detected in brain resistance vessel samples from AD patients compared to the normal individuals. Results from western blot analysis showed elevated levels of type I and type III collagen, and reduced levels of type IV collagen in resistance vessels from AD patients, compared to control samples. In addition, using direct scanning of the cortical suface for fluoresxcence emission by the laser-induced fluorescence spectroscopy system we detected a significantly (P<0.05) higher level of apoptosis in AD brain tissue compared to age-matched controls. Fluorescence emission analysis (FEA) appears to be a sensitive technique for detecting structural changes in AD brain tissue.

Dual Sarcocystis neurona and Toxoplasma gondii infection in a northern sea otter from Washington state, USA

USGS Publications Warehouse

Lindsay, D.S.; Thomas, N.J.; Rosypal, A.C.; Dubey, J.P.

2001-01-01

Dual Sarcocystis neurona and Toxoplasma gondii infection was observed in a Northern sea otter from Washington, USA. The animal was found stranded, convulsed, and died shortly thereafter. Encephalitis caused by both S. neurona and T. gondii was demonstrated in histological sections of brain. Immunohistochemical examination of sections with S. neurona specific antisera demonstrated developmental stages that divided by endopolygeny and produced numerous merozoites. PCR of brain tissue from the sea otter using primer pairs JNB33/JNB54 resulted in amplification of a 1100 bp product. This PCR product was cut in to 884 and 216 bp products by Dra I but was not cut by Hinf I indicating that it was S. neurona [J. Parasitol. 85 (1999) 221]. No PCR product was detected in the brain of a sea otter which had no lesions of encephalitis. Examination of brain sections using T. gondii specific antisera demonstrated tachyzoites and tissue cysts of T. gondii. The lesions induced by T. gondii suggested that the sea otter was suffering from reactivated toxoplasmosis. T. gondii was isolated in mice inoculated with brain tissue. A cat that was fed infected mouse brain tissue excreted T. gondii oocysts which were infective for mice. This is apparently the first report of dual S. neurona and T. gondii in a marine mammal.

Miniature standoff Raman probe for neurosurgical applications

NASA Astrophysics Data System (ADS)

Stevens, Oliver A. C.; Hutchings, Joanne; Gray, William; Vincent, Rosa Louise; Day, John C.

2016-08-01

Removal of intrinsic brain tumors is a delicate process, where a high degree of specificity is required to remove all of the tumor tissue without damaging healthy brain. The accuracy of this process can be greatly enhanced by intraoperative guidance. Optical biopsies using Raman spectroscopy are a minimally invasive and lower-cost alternative to current guidance methods. A miniature Raman probe for performing optical biopsies of human brain tissue is presented. The probe allows sampling inside a conventional stereotactic brain biopsy system: a needle of length 200 mm and inner diameter of 1.8 mm. By employing a miniature stand-off Raman design, the probe removes the need for any additional components to be inserted into the brain. Additionally, the probe achieves a very low internal silica background while maintaining good collection of Raman signal. To illustrate this, the probe is compared with a Raman probe that uses a pair of optical fibers for collection. The miniature stand-off Raman probe is shown to collect a comparable number of Raman scattered photons, but the Raman signal to background ratio is improved by a factor of five at Raman shifts below ˜500 cm-1. The probe's suitability for use on tissue is demonstrated by discriminating between different types of healthy porcine brain tissue.

A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5×-familial Alzheimer's disease mice.

PubMed

Maiti, Panchanan; Hall, Tia C; Paladugu, Leela; Kolli, Nivya; Learman, Cameron; Rossignol, Julien; Dunbar, Gary L

2016-11-01

Deposition of amyloid beta protein (Aβ) is a key component in the pathogenesis of Alzheimer's disease (AD). As an anti-amyloid natural polyphenol, curcumin (Cur) has been used as a therapy for AD. Its fluorescent activity, preferential binding to Aβ, as well as structural similarities with other traditional amyloid-binding dyes, make it a promising candidate for labeling and imaging of Aβ plaques in vivo. The present study was designed to test whether dietary Cur and nanocurcumin (NC) provide more sensitivity for labeling and imaging of Aβ plaques in brain tissues from the 5×-familial AD (5×FAD) mice than the classical Aβ-binding dyes, such as Congo red and Thioflavin-S. These comparisons were made in postmortem brain tissues from the 5×FAD mice. We observed that Cur and NC labeled Aβ plaques to the same degree as Aβ-specific antibody and to a greater extent than those of the classical amyloid-binding dyes. Cur and NC also labeled Aβ plaques in 5×FAD brain tissues when injected intraperitoneally. Nanomolar concentrations of Cur or NC are sufficient for labeling and imaging of Aβ plaques in 5×FAD brain tissue. Cur and NC also labeled different types of Aβ plaques, including core, neuritic, diffuse, and burned-out, to a greater degree than other amyloid-binding dyes. Therefore, Cur and or NC can be used as an alternative to Aβ-specific antibody for labeling and imaging of Aβ plaques ex vivo and in vivo. It can provide an easy and inexpensive means of detecting Aβ-plaque load in postmortem brain tissue of animal models of AD after anti-amyloid therapy.

Regional muscle tissue saturation is an indicator of global inadequate circulation during cardiopulmonary bypass: a randomized porcine study using muscle, intestinal and brain tissue metabolomics.

PubMed

Thomassen, Sisse Anette; Kjærgaard, Benedict; Sørensen, Preben; Andreasen, Jan Jesper; Larsson, Anders; Rasmussen, Bodil Steen

2017-04-01

Muscle tissue saturation (StO 2 ) measured with near-infrared spectroscopy has generally been considered a measurement of the tissue microcirculatory condition. However, we hypothesized that StO 2 could be more regarded as a fast and reliable measure of global than of regional circulatory adequacy and tested this with muscle, intestinal and brain metabolomics at normal and two levels of low cardiopulmonary bypass blood flow rates in a porcine model. Twelve 80 kg pigs were connected to normothermic cardiopulmonary bypass with a blood flow of 60 mL/kg/min for one hour, reduced randomly to 47.5 mL/kg/min (Group I) or 35 mL/kg/min (Group II) for one hour followed by one hour of 60 mL/kg/min in both groups. Regional StO 2 was measured continuously above the musculus gracilis (non-cannulated leg). Metabolomics were obtained by brain tissue oxygen monitoring system (Licox) measurements of the brain and microdialysis perfusate from the muscle, intestinal mucosa and brain. A non-parametric statistical method was used. The systemic parameters showed profound systemic ischaemia during low CPB blood flow. StO 2 did not change markedly in Group I, but in Group II, StO 2 decreased immediately when blood flow was reduced and, furthermore, was not restored despite blood flow being normalized. Changes in the metabolomics from the muscle, colon and brain followed the changes in StO 2 . We found, in this experimental cardiopulmonary bypass model, that StO 2 reacted rapidly when the systemic circulation became inadequate and, furthermore, reliably indicate insufficient global tissue perfusion even when the systemic circulation was restored after a period of systemic hypoperfusion.

Cerebral Apolipoprotein-D Is Hypoglycosylated Compared to Peripheral Tissues and Is Variably Expressed in Mouse and Human Brain Regions.

PubMed

Li, Hongyun; Ruberu, Kalani; Karl, Tim; Garner, Brett

2016-01-01

Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in the mouse increases sensitivity to lipid peroxidation and accelerates AD pathology. Very little data are available, however, regarding the expression of apoD protein levels in different brain regions. This is important as both brain lipid peroxidation and neurodegeneration occur in a region-specific manner. Here we addressed this using western blotting of seven different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain regions, the hippocampus is deficient in apoD. In comparison to other major organs and tissues (liver, spleen, kidney, adrenal gland, heart and skeletal muscle), brain apoD was approximately 10-fold higher (corrected for total protein levels). Our analysis also revealed that brain apoD was present at a lower apparent molecular weight than tissue and plasma apoD. Utilising peptide N-glycosidase-F and neuraminidase to remove N-glycans and sialic acids, respectively, we found that N-glycan composition (but not sialylation alone) were responsible for this reduction in molecular weight. We extended the studies to an analysis of human brain regions (hippocampus, frontal cortex, temporal cortex and cerebellum) where we found that the hippocampus had the lowest levels of apoD. We also confirmed that human brain apoD was present at a lower molecular weight than in plasma. In conclusion, we demonstrate apoD protein levels are variable across different brain regions, that apoD levels are much higher in the brain compared to other tissues and organs, and that cerebral apoD has a lower molecular weight than peripheral apoD; a phenomenon that is due to the N-glycan content of the protein.

Breaking ignorance: the case of the brain.

PubMed

Wekerle, H

2006-01-01

Immunological self-tolerance is maintained through diverse mechanisms, including deletion of autoreactive immune cells following confrontation with autoantigen in the thymus or in the periphery and active suppression by regulatory cells. A third way to prevent autoimmunity is by hiding self tissues behind a tissue barrier impermeable for circulating immune cells. The latter mechanism has been held responsible for self-tolerance within the nervous tissue. Indeed, the nervous tissues enjoy a conditionally privileged immune status: they are normally unreachable for self-reactive T and B cells, they lack lymphatic drainage, and they are deficient in local antigen-presenting cells. Yet the immune system is by no means fully ignorant of the nervous structures. An ever-growing number of brain specific autoantigens is expressed within the thymus, which ensures an early confrontation with the unfolding T cell repertoire, and there is evidence that B cells also contact CNS-like structures outside of the brain. Then pathological processes such as neurodegeneration commonly lift the brain's immune privilege, shifting the local milieus from immune-hostile to immune-friendly. Finally, brain-reactive T cells, which abound in the healthy immune repertoire, but remain innocuous throughout life, can be activated and gain access to their target tissues. On their way, they take an ordered migration through peripheral lymphoid tissues and blood circulation, and undergo a profound reprogramming of their gene expression profile, which renders them fit to enter the nervous system and to interact with local cellule elements.

Study of intracranial pressure in human brain during transcranial magnetic stimulation.

PubMed

Honrath, Marc; Sabouni, Abas

2015-01-01

This paper presents the results of cranial force in human brain due to electromagnetic pulse during transcranial magnetic stimulation. To model the force in a realistic brain, we used three dimensional magnetic resonance image of the 26 years old female subject. Simulation results show that during TMS procedure, there is a small force generated within the cranial tissue layers along with a torque value in different layers of brain tissues. The force depends on the magnitude of the magnetic field generated by the TMS coil.

Reexpression of a developmentally regulated antigen in Down syndrome and Alzheimer disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolozin, B.; Scicutella, A.; Davies, P.

1988-08-01

ALZ-50 is a monoclonal antibody that recognizes a protein of apparent molecular mass 68 kilodaltons (A68). The protein is present in the brains of patients with Alzheimer disease but is not detectable in normal adult brain tissue. The authors report that ALZ-50-reactive neurons are found in normal fetal and neonatal human brain and in brain tissue from neonatal individuals with Down syndrome. Reactive neurons decrease sharply in number after age 2 and reappear in older individuals with Down syndrome and in patients with Alzheimer disease.

Elastic light single-scattering spectroscopy for detection of dysplastic tissues

NASA Astrophysics Data System (ADS)

Canpolat, Murat; Denkçeken, Tuba; Akman, Ayşe.; Alpsoy, Erkan; Tuncer, Recai; Akyüz, Mahmut; Baykara, Mehmet; Yücel, Selçuk; Başsorgun, Ibrahim; ćiftçioǧlu, M. Akif; Gökhan, Güzide Ayşe.; Gürer, ElifInanç; Peştereli, Elif; Karaveli, Šeyda

2013-11-01

Elastic light single-scattering spectroscopy (ELSSS) system has been developed and tested in diagnosis of cancerous tissues of different organs. ELSSS system consists of a miniature visible light spectrometer, a single fiber optical probe, a halogen tungsten light source and a laptop. Measurements were performed on excised brain, skin, cervix and prostate tumor specimens and surrounding normal tissues. Single fiber optical probe with a core diameter of 100 μm was used to deliver white light to and from tissue. Single optical fiber probe mostly detects singly scattered light from tissue rather than diffused light. Therefore, measured spectra are sensitive to size of scatters in tissue such as cells, nuclei, mitochondria and other organelles of cells. Usually, nuclei of tumor cells are larger than nuclei of normal cells. Therefore, spectrum of singly scattered light of tumor tissue is different than normal tissue. The spectral slopes were shown to be positive for normal brain, skin and prostate and cervix tissues and negative for the tumors of the same tissues. Signs of the spectral slopes were used as a discrimination parameter to differentiate tumor from normal tissues for the three organ tissues. Sensitivity and specificity of the system in differentiation between tumors from normal tissues were 93% and %100 for brain, 87% and 85% for skin, 93.7% and 46.1% for cervix and 98% and 100% for prostate.

Quantification and Segmentation of Brain Tissues from MR Images: A Probabilistic Neural Network Approach

PubMed Central

Wang, Yue; Adalý, Tülay; Kung, Sun-Yuan; Szabo, Zsolt

2007-01-01

This paper presents a probabilistic neural network based technique for unsupervised quantification and segmentation of brain tissues from magnetic resonance images. It is shown that this problem can be solved by distribution learning and relaxation labeling, resulting in an efficient method that may be particularly useful in quantifying and segmenting abnormal brain tissues where the number of tissue types is unknown and the distributions of tissue types heavily overlap. The new technique uses suitable statistical models for both the pixel and context images and formulates the problem in terms of model-histogram fitting and global consistency labeling. The quantification is achieved by probabilistic self-organizing mixtures and the segmentation by a probabilistic constraint relaxation network. The experimental results show the efficient and robust performance of the new algorithm and that it outperforms the conventional classification based approaches. PMID:18172510

In Vivo Investigation of the Effectiveness of a Hyper-viscoelastic Model in Simulating Brain Retraction

PubMed Central

Li, Ping; Wang, Weiwei; Zhang, Chenxi; An, Yong; Song, Zhijian

2016-01-01

Intraoperative brain retraction leads to a misalignment between the intraoperative positions of the brain structures and their previous positions, as determined from preoperative images. In vitro swine brain sample uniaxial tests showed that the mechanical response of brain tissue to compression and extension could be described by the hyper-viscoelasticity theory. The brain retraction caused by the mechanical process is a combination of brain tissue compression and extension. In this paper, we first constructed a hyper-viscoelastic framework based on the extended finite element method (XFEM) to simulate intraoperative brain retraction. To explore its effectiveness, we then applied this framework to an in vivo brain retraction simulation. The simulation strictly followed the clinical scenario, in which seven swine were subjected to brain retraction. Our experimental results showed that the hyper-viscoelastic XFEM framework is capable of simulating intraoperative brain retraction and improving the navigation accuracy of an image-guided neurosurgery system (IGNS). PMID:27387301

Importance of Multimodal MRI in Characterizing Brain Tissue and Its Potential Application for Individual Age Prediction.

PubMed

Cherubini, Andrea; Caligiuri, Maria Eugenia; Peran, Patrice; Sabatini, Umberto; Cosentino, Carlo; Amato, Francesco

2016-09-01

This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2(*) relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. The results of the linear model were used to predict apparent age in different regions of individual brain. This approach pointed to a number of novel applications that could potentially help highlighting areas particularly vulnerable to disease.

Reproducibility of Ultrasound-Guided High Intensity Focused Ultrasound (HIFU) Thermal Lesions in Minimally-Invasive Brain Surgery

NASA Astrophysics Data System (ADS)

Zahedi, Sulmaz

This study aims to prove the feasibility of using Ultrasound-Guided High Intensity Focused Ultrasound (USg-HIFU) to create thermal lesions in neurosurgical applications, allowing for precise ablation of brain tissue, while simultaneously providing real time imaging. To test the feasibility of the system, an optically transparent HIFU compatible tissue-mimicking phantom model was produced. USg-HIFU was then used for ablation of the phantom, with and without targets. Finally, ex vivo lamb brain tissue was imaged and ablated using the USg-HIFU system. Real-time ultrasound images and videos obtained throughout the ablation process showing clear lesion formation at the focal point of the HIFU transducer. Post-ablation gross and histopathology examinations were conducted to verify thermal and mechanical damage in the ex vivo lamb brain tissue. Finally, thermocouple readings were obtained, and HIFU field computer simulations were conducted to verify findings. Results of the study concluded reproducibility of USg-HIFU thermal lesions for neurosurgical applications.

Pathophysiological changes of the cerebellum and brain stem in a rabbit model after superior petrosal vein sacrifice.

PubMed

Cheng, Lei; Guo, Pin; Liao, Yi-Wei; Zhang, Hong-Liang; Li, Huan-Ting; Yuan, Xianrui

2017-11-13

In certain surgical procedures sacrifice of the superior petrosal vein (SPV) is required. Previous studies have reported transient cerebellar edema, venous infarction or hemorrhage might occur after sectioning of the SPV. This study investigated the pathophysiological changes of cerebellum and brain stem after SPV sacrifice. Rabbits were divided into the operation group where the SPV was sacrificed and the control group where the SPV remained intact. Each group was further subdivided into 4, 8, 12, 24, 48 and 72 hours groups which represented the time period from sacrifice of the SPV to sacrifice of the rabbits. The water content (WC), Na + content, K + content and pathophysiological changes of cerebellum and brain stem tissue were measured. In comparison to the control, the WC and Na + content of cerebellar tissue were increased in the 4h, 8h, 12h and 24h operation subgroups (p<0.05), but only increased in the 4h subgroup of the brain stem tissue (p<0.05). The K + content of the cerebellar tissue decreased in the 4h, 8h, 12h and 24h operation subgroups (p<0.05) but only decreased in the 4h subgroup of brain stem tissue (p<0.05). Nissl staining and transmission electron microscopy demonstrated that cerebellar edema occurred in the 4h, 8h, 12h and 24h operation subgroups but not in the 48h and 72h subgroups. Brain stem edema occurred in the 4h operation subgroup. In summary, cerebellum and brain stem edema can be observed at different time points after sacrifice of the SPV in the rabbit model. ©2017 The Author(s).

Characterization of cortical neuronal and glial alterations during culture of organotypic whole brain slices from neonatal and mature mice.

PubMed

Staal, Jerome A; Alexander, Samuel R; Liu, Yao; Dickson, Tracey D; Vickers, James C

2011-01-01

Organotypic brain slice culturing techniques are extensively used in a wide range of experimental procedures and are particularly useful in providing mechanistic insights into neurological disorders or injury. The cellular and morphological alterations associated with hippocampal brain slice cultures has been well established, however, the neuronal response of mouse cortical neurons to culture is not well documented. In the current study, we compared the cell viability, as well as phenotypic and protein expression changes in cortical neurons, in whole brain slice cultures from mouse neonates (P4-6), adolescent animals (P25-28) and mature adults (P50+). Cultures were prepared using the membrane interface method. Propidium iodide labeling of nuclei (due to compromised cell membrane) and AlamarBlue™ (cell respiration) analysis demonstrated that neonatal tissue was significantly less vulnerable to long-term culture in comparison to the more mature brain tissues. Cultures from P6 animals showed a significant increase in the expression of synaptic markers and a decrease in growth-associated proteins over the entire culture period. However, morphological analysis of organotypic brain slices cultured from neonatal tissue demonstrated that there were substantial changes to neuronal and glial organization within the neocortex, with a distinct loss of cytoarchitectural stratification and increased GFAP expression (p<0.05). Additionally, cultures from neonatal tissue had no glial limitans and, after 14 DIV, displayed substantial cellular protrusions from slice edges, including cells that expressed both glial and neuronal markers. In summary, we present a substantial evaluation of the viability and morphological changes that occur in the neocortex of whole brain tissue cultures, from different ages, over an extended period of culture.

Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

NASA Astrophysics Data System (ADS)

Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

2015-03-01

Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

Lack of effect of moderate hypothermia on brain tissue oxygenation after acute intracranial hypertension in pigs.

PubMed

Bao, Ying-Hui; Liang, Yu-Min; Gao, Guo-Yi; Jiang, Ji-Yao

2010-02-01

In this study, we explored the effect of moderate hypothermia on brain tissue oxygenation following acute intracranial hypertension in micropigs. Twenty healthy juvenile micropigs weighting 4-6 kg were randomized into two groups: a normothermia group (n = 10) and a moderate hypothermia group (n = 10). The animals were intravenously anesthetized with propofol (4 mg/kg), an endotracheal tube was inserted, and mechanical ventilation was begun. Autologous arterial blood was injected into the left frontal lobe to establish acute intracerebral hematoma and intracranial hypertension (intracranial pressure [ICP] >40 mm Hg) in all animals. Cooling was initiated at 30 min after injection of the blood, and was achieved via the use of an ice bath and ice packs. In the hypothermia group, the brain temperature decreased to 33-34 degrees C. Brain temperature was maintained at 37 +/- 0.3 degrees C in the normothermia group. The ICP, cerebral perfusion pressure (CPP), brain tissue oxygen pressure (P(br)O(2)), brain tissue carbon dioxide pressure (P(br)CO(2)), and brain tissue pH value (pH(br)) were continuously monitored for 3 h in all animals. Compared to normothermia group, ICP values significantly decreased and CPP markedly improved in the hypothermia group (p < 0.05). Further, pH(br) also markedly increased and P(br)CO(2) decreased significantly in the hypothermia group (p < 0.05). However, P(br)O(2) did not statistically significantly improve in the hypothermia group (p > 0.05). In sum, moderate hypothermia significantly decreased ICP, reduced P(br)CO(2), and increased pH(br) values, but did not improve cerebral oxygenation following acute intracranial hypertension.

[Burning Vulva: Significance of Surgery in Inflammatory and Precancerous Vulvar Pathologies].

PubMed

Ghisu, Gian-Piero; Fink, Daniel

2015-06-17

Vuval pathologies manifested by allodynia and burning sensations can be due to infection, inflammatory dermatoses or other causes. Infective as well as certain inflammatory diseases, e.g. drug eruptions, allergic eczemas, irritative dermatitis/vulvitis, Behcet's Syndrome and pemphigus/pemphigoid usually respond well to conservative treatment. The category of inflammatory diseases also contains pathologies that in certain circumstances do require a surgical intervention, e.g. Lichen ruber planus/Lichen sclerosus, Condyloma, scars, premalignant lesions (VIN, genital M. Paget) and cancer. Vulodynia also can cause some stinging to the vulvar skin. The surgical aspects relating to the treatment of the benign and premalignant pathologies indicated above are mentioned in this mini-review.

[Report on the 34th meeting of the German Clinical Immunology Workgroup, Frankfurt, 03.-04.11.2006].

PubMed

Aries, P M; Witte, T; Lamprecht, P

2007-02-01

The annual meeting of the Clinical Immunology Workgroup focused on autoimmune vasculitides. The role of innate immunity, T- and B-cells, and innovative therapies for autoimmune vasculitides was discussed. Further topics of the meeting were the role of endothelial microparticles, ghrelin and leptin, regulatory and effector-memory T-cells in ANCA-associated vasculitides, as well as the lethal midline granuloma, intracytoplasmic cytokine-profile in Behcet's disease, autoantibodies in rheumatoid arthritis, polyarteritis nodosa with cranial manifestation, ILT6 as genetic marker in multiple sclerosis and Sjögren's syndrome, alpha-fodrin autoantibodies in multiple sclerosis, interferon-g autoantibodies in a patient with atypical mycobacteriosis, and autoreactive T-cells in murine lupus.

Real time analysis of brain tissue by direct combination of ultrasonic surgical aspiration and sonic spray mass spectrometry.

PubMed

Schäfer, Karl-Christian; Balog, Júlia; Szaniszló, Tamás; Szalay, Dániel; Mezey, Géza; Dénes, Júlia; Bognár, László; Oertel, Matthias; Takáts, Zoltán

2011-10-15

Direct combination of cavitron ultrasonic surgical aspirator (CUSA) and sonic spray ionization mass spectrometry is presented. A commercially available ultrasonic surgical device was coupled to a Venturi easy ambient sonic-spray ionization (V-EASI) source by directly introducing liquified tissue debris into the Venturi air jet pump. The Venturi air jet pump was found to efficiently nebulize the suspended tissue material for gas phase ion production. The ionization mechanism involving solely pneumatic spraying was associated with that of sonic spray ionization. Positive and negative ionization spectra were obtained from brain and liver samples reflecting the primary application areas of the surgical device. Mass spectra were found to feature predominantly complex lipid-type constituents of tissues in both ion polarity modes. Multiply charged peptide anions were also detected. The influence of instrumental settings was characterized in detail. Venturi pump geometry and flow parameters were found to be critically important in ionization efficiency. Standard solutions of phospholipids and peptides were analyzed in order to test the dynamic range, sensitivity, and suppression effects. The spectra of the intact tissue specimens were found to be highly specific to the histological tissue type. The principal component analysis (PCA) and linear discriminant analysis (LDA) based data analysis method was developed for real-time tissue identification in a surgical environment. The method has been successfully tested on post-mortem and ex vivo human samples including astrocytomas, meningeomas, metastatic brain tumors, and healthy brain tissue. © 2011 American Chemical Society

Quantitative brain tissue oximetry, phase spectroscopy and imaging the range of homeostasis in piglet brain.

PubMed

Chance, Britton; Ma, Hong Yan; Nioka, Shoko

2003-01-01

The quantification of tissue oxygen by frequency or time domain methods has been discussed in a number of prior publications where the meaning of the tissue hemoglobin oxygen saturation was unclear and where the CW instruments were unsuitable for proper quantitative measurements [1, 2]. The development of the IQ Phase Meter has greatly simplified and made reliable the difficult determination of precise phase and amplitude signals from brain. This contribution reports on the calibration of the instrument in model systems and the use of the instrument to measure tissue saturation (StO2) in a small animal model. In addition, a global interpretation of the meaning of tissue oxygen has been formulated based on the idea that autoregulation will maintain tissue oxygen at a fixed value over a range of arterial and venous oxygen values over the range of autoregulation. Beyond that range, the tissue oxygen is still correctly measured but, as expected, approaches the arterial saturation at low metabolic rates and the venous saturation at high metabolic rates of mitochondria.

Improving the modelling of irradiation-induced brain activation for in vivo PET verification of proton therapy.

PubMed

Bauer, Julia; Chen, Wenjing; Nischwitz, Sebastian; Liebl, Jakob; Rieken, Stefan; Welzel, Thomas; Debus, Juergen; Parodi, Katia

2018-04-24

A reliable Monte Carlo prediction of proton-induced brain tissue activation used for comparison to particle therapy positron-emission-tomography (PT-PET) measurements is crucial for in vivo treatment verification. Major limitations of current approaches to overcome include the CT-based patient model and the description of activity washout due to tissue perfusion. Two approaches were studied to improve the activity prediction for brain irradiation: (i) a refined patient model using tissue classification based on MR information and (ii) a PT-PET data-driven refinement of washout model parameters. Improvements of the activity predictions compared to post-treatment PT-PET measurements were assessed in terms of activity profile similarity for six patients treated with a single or two almost parallel fields delivered by active proton beam scanning. The refined patient model yields a generally higher similarity for most of the patients, except in highly pathological areas leading to tissue misclassification. Using washout model parameters deduced from clinical patient data could considerably improve the activity profile similarity for all patients. Current methods used to predict proton-induced brain tissue activation can be improved with MR-based tissue classification and data-driven washout parameters, thus providing a more reliable basis for PT-PET verification. Copyright © 2018 Elsevier B.V. All rights reserved.

Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects

ClinicalTrials.gov

2018-06-20

Brain Cancer; Brain Neoplasm; Glioma; Glioblastoma; Gliosarcoma; Malignant Brain Tumor; Neoplasm, Neuroepithelial; Neuroectodermal Tumors; Neoplasm by Histologic Type; Neoplasm, Nerve Tissue; Nervous System Diseases

Validation and quantification of [18F]altanserin binding in the rat brain using blood input and reference tissue modeling

PubMed Central

Riss, Patrick J; Hong, Young T; Williamson, David; Caprioli, Daniele; Sitnikov, Sergey; Ferrari, Valentina; Sawiak, Steve J; Baron, Jean-Claude; Dalley, Jeffrey W; Fryer, Tim D; Aigbirhio, Franklin I

2011-01-01

The 5-hydroxytryptamine type 2a (5-HT2A) selective radiotracer [18F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats. Metabolite-corrected plasma input modeling was compared with reference tissue modeling using the cerebellum as reference tissue. [18F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT2A receptors. Full binding saturation and displacement was documented, and no significant uptake of radioactive metabolites was detected in the brain. Blood input as well as reference tissue models were equally appropriate to describe the radiotracer kinetics. [18F]altanserin is suitable for quantification of 5-HT2A receptor availability in rats. PMID:21750562

Shear wave propagation in anisotropic soft tissues and gels

PubMed Central

Namani, Ravi; Bayly, Philip V.

2013-01-01

The propagation of shear waves in soft tissue can be visualized by magnetic resonance elastography (MRE) [1] to characterize tissue mechanical properties. Dynamic deformation of brain tissue arising from shear wave propagation may underlie the pathology of blast-induced traumatic brain injury. White matter in the brain, like other biological materials, exhibits a transversely isotropic structure, due to the arrangement of parallel fibers. Appropriate mathematical models and well-characterized experimental systems are needed to understand wave propagation in these structures. In this paper we review the theory behind waves in anisotropic, soft materials, including small-amplitude waves superimposed on finite deformation of a nonlinear hyperelastic material. Some predictions of this theory are confirmed in experimental studies of a soft material with controlled anisotropy: magnetically-aligned fibrin gel. PMID:19963987

Colchicine induced intraneuronal free zinc accumulation and dentate granule cell degeneration.

PubMed

Choi, Bo Young; Lee, Bo Eun; Kim, Jin Hee; Kim, Hyun Jung; Sohn, Min; Song, Hong Ki; Chung, Tae Nyoung; Suh, Sang Won

2014-08-01

Colchicine has been discovered to inhibit many inflammatory processes such as gout, familial Mediterranean fever, pericarditis and Behcet disease. Other than these beneficial anti-inflammatory effects, colchicine blocks microtubule-assisted axonal transport, which results in the selective loss of dentate granule cells of the hippocampus. The mechanism of the colchicine-induced dentate granule cell death and depletion of mossy fiber terminals still remains unclear. In the present study, we hypothesized that colchicine-induced dentate granule cell death may be caused by accumulation of labile intracellular zinc. 10 μg kg(-1) of colchicine was injected into the adult rat hippocampus and then brain sections were evaluated at 1 day or 1 week later. Neuronal cell death was evaluated by H&E staining or Fluoro-Jade B. Zinc accumulation and vesicular zinc were detected by N-(6-methoxy-8-quinolyl)-para-toluene sulfonamide (TSQ) staining. To test whether an extracellular zinc chelator can prevent this process, CaEDTA was injected into the hippocampus over a 5 min period with colchicine. To test whether other microtubule toxins also produce similar effects as colchicine, vincristine was injected into the hippocampus. The present study found that colchicine injection induced intracellular zinc accumulation in the dentate granule cells and depleted vesicular zinc from mossy fiber terminals. Injection of a zinc chelator, CaEDTA, did not block the zinc accumulation and neuronal death. Vincristine also produced intracellular zinc accumulation and neuronal death. These results suggest that colchicine-induced dentate granule cell death is caused by blocking axonal zinc flow and accumulation of intracellular labile zinc.

The tissue-type plasminogen activator–plasminogen activator inhibitor 1 complex promotes neurovascular injury in brain trauma: evidence from mice and humans

PubMed Central

Sashindranath, Maithili; Sales, Eunice; Daglas, Maria; Freeman, Roxann; Samson, Andre L.; Cops, Elisa J.; Beckham, Simone; Galle, Adam; McLean, Catriona; Morganti-Kossmann, Cristina; Rosenfeld, Jeffrey V.; Madani, Rime; Vassalli, Jean-Dominique; Su, Enming J.; Lawrence, Daniel A.

2012-01-01

The neurovascular unit provides a dynamic interface between the circulation and central nervous system. Disruption of neurovascular integrity occurs in numerous brain pathologies including neurotrauma and ischaemic stroke. Tissue plasminogen activator is a serine protease that converts plasminogen to plasmin, a protease that dissolves blood clots. Besides its role in fibrinolysis, tissue plasminogen activator is abundantly expressed in the brain where it mediates extracellular proteolysis. However, proteolytically active tissue plasminogen activator also promotes neurovascular disruption after ischaemic stroke; the molecular mechanisms of this process are still unclear. Tissue plasminogen activator is naturally inhibited by serine protease inhibitors (serpins): plasminogen activator inhibitor-1, neuroserpin or protease nexin-1 that results in the formation of serpin:protease complexes. Proteases and serpin:protease complexes are cleared through high-affinity binding to low-density lipoprotein receptors, but their binding to these receptors can also transmit extracellular signals across the plasma membrane. The matrix metalloproteinases are the second major proteolytic system in the mammalian brain, and like tissue plasminogen activators are pivotal to neurological function but can also degrade structures of the neurovascular unit after injury. Herein, we show that tissue plasminogen activator potentiates neurovascular damage in a dose-dependent manner in a mouse model of neurotrauma. Surprisingly, inhibition of activity following administration of plasminogen activator inhibitor-1 significantly increased cerebrovascular permeability. This led to our finding that formation of complexes between tissue plasminogen activator and plasminogen activator inhibitor-1 in the brain parenchyma facilitates post-traumatic cerebrovascular damage. We demonstrate that following trauma, the complex binds to low-density lipoprotein receptors, triggering the induction of matrix metalloproteinase-3. Accordingly, pharmacological inhibition of matrix metalloproteinase-3 attenuates neurovascular permeability and improves neurological function in injured mice. Our results are clinically relevant, because concentrations of tissue plasminogen activator: plasminogen activator inhibitor-1 complex and matrix metalloproteinase-3 are significantly elevated in cerebrospinal fluid of trauma patients and correlate with neurological outcome. In a separate study, we found that matrix metalloproteinase-3 and albumin, a marker of cerebrovascular damage, were significantly increased in brain tissue of patients with neurotrauma. Perturbation of neurovascular homeostasis causing oedema, inflammation and cell death is an important cause of acute and long-term neurological dysfunction after trauma. A role for the tissue plasminogen activator–matrix metalloproteinase axis in promoting neurovascular disruption after neurotrauma has not been described thus far. Targeting tissue plasminogen activator: plasminogen activator inhibitor-1 complex signalling or downstream matrix metalloproteinase-3 induction may provide viable therapeutic strategies to reduce cerebrovascular permeability after neurotrauma. PMID:22822039

Iron biomineralization of brain tissue and neurodegenerative disorders

NASA Astrophysics Data System (ADS)

Mikhaylova (Mikhailova), Albina

The brain is an organ with a high concentration of iron in specific areas, particularly in the globus pallidus, the substantia nigra, and the red nucleus. In certain pathological states, such as iron overload disease and neurodegenerative disorders, a disturbed iron metabolism can lead to increased accumulation of iron not only in these areas, but also in the brain regions that are typically low in iron content. Recent studies of the physical and magnetic properties of metalloproteins, and in particular the discovery of biogenic magnetite in human brain tissue, have raised new questions about the role of biogenic iron formations in living organisms. Further investigations revealed the presence of magnetite-like crystalline structures in human ferritin, and indicated that released ferritin iron might act as promoter of oxidative damage to tissue, therefore contributing to pathogenesis of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. The purpose of this work was to examine the elemental composition and structure of iron deposits in normal brain tissue as well as tissue affected by neurodegenerative disorders. Employing the methods of X-ray microfocus fluorescence mapping, X-ray Absorption Near Edge Structure (XANES), X-ray Absorption Fine Structure spectroscopy (XAFS), and light and electron microscopic examinations allows one to obtain qualitative as well as quantitative data with respect to the cellular distribution and chemical state of iron at levels not detected previously. The described tissue preparation technique allows not only satisfactory XAS iron elemental imaging in situ but also multimodal examination with light and electron microscopes of the same samples. The developed protocol has assured consistent and reproducible results on relatively large sections of flat-embedded tissue. The resulting tissue samples were adequate for XAS examination as well as sufficiently well-preserved for future microscopy studies. The continued development of this technique should lead to major advances in mapping iron anomalies and the related chemical and structural information directly to cells and tissue structures in human brain tissue. At present this is done primarily by iron staining methods and any information on the relationship between iron distribution and cellular structures obtained this way is limited. Iron staining also offers no information on the specific compounds of iron that are present. This can be vitally important as the form of iron [including its oxidation state] in the human body can determine whether it plays a detrimental or beneficial role in neurophysiological processes.

Examination of Physiological Function and Biochemical Disorders in a Rat Model of Prolonged Asphyxia-Induced Cardiac Arrest followed by Cardio Pulmonary Bypass Resuscitation

PubMed Central

Kim, Junhwan; Yin, Tai; Yin, Ming; Zhang, Wei; Shinozaki, Koichiro; Selak, Mary A.; Pappan, Kirk L.; Lampe, Joshua W.; Becker, Lance B.

2014-01-01

Background Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion. Method A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition. Results After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue. Conclusion The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage. PMID:25383962

Examination of physiological function and biochemical disorders in a rat model of prolonged asphyxia-induced cardiac arrest followed by cardio pulmonary bypass resuscitation.

PubMed

Kim, Junhwan; Yin, Tai; Yin, Ming; Zhang, Wei; Shinozaki, Koichiro; Selak, Mary A; Pappan, Kirk L; Lampe, Joshua W; Becker, Lance B

2014-01-01

Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion. A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition. After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue. The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage.

Development and Implementation of a Transversely Isotropic Hyperelastic Constitutive Model With Two Fiber Families to Represent Anisotropic Soft Biological Tissues

DTIC Science & Technology

2014-06-01

brain tissue and skeletal muscles , is also discussed. transversely isotropic hyperelastic, two fiber families, nearly incompressible, anisotropic...comprised of fibrous structures, such as muscles , ligaments, tendons, intervertebral discs and the brain, often exhibit strong anisotropy along these fiber ...directions, e.g., collagen fibers of the cornea, striated muscle fibers in skeletal muscles , multiple axonal directions within the brain. In each case

Contribution of Brain Tissue Oxidative Damage in Hypothyroidism-associated Learning and Memory Impairments

PubMed Central

Baghcheghi, Yousef; Salmani, Hossein; Beheshti, Farimah; Hosseini, Mahmoud

2017-01-01

The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments. PMID:28584813

Magnetic Resonance Elastography Demonstrating Low Brain Stiffness in a Patient with Low-Pressure Hydrocephalus: Case Report.

PubMed

Olivero, William C; Wszalek, Tracey; Wang, Huan; Farahvar, Arash; Rieth, Sandra M; Johnson, Curtis L

2016-01-01

The authors describe the case of a 19-year-old female with shunted aqueductal stenosis who presented with low-pressure hydrocephalus that responded to negative pressure drainage. A magnetic resonance elastography scan performed 3 weeks later demonstrated very low brain tissue stiffness (high brain tissue compliance). An analysis of the importance of this finding in understanding this rare condition is discussed. © 2016 S. Karger AG, Basel.

Prediction of brain tissue temperature using near-infrared spectroscopy

PubMed Central

Holper, Lisa; Mitra, Subhabrata; Bale, Gemma; Robertson, Nicola; Tachtsidis, Ilias

2017-01-01

Abstract. Broadband near-infrared spectroscopy (NIRS) can provide an endogenous indicator of tissue temperature based on the temperature dependence of the water absorption spectrum. We describe a first evaluation of the calibration and prediction of brain tissue temperature obtained during hypothermia in newborn piglets (animal dataset) and rewarming in newborn infants (human dataset) based on measured body (rectal) temperature. The calibration using partial least squares regression proved to be a reliable method to predict brain tissue temperature with respect to core body temperature in the wavelength interval of 720 to 880 nm with a strong mean predictive power of R2=0.713±0.157 (animal dataset) and R2=0.798±0.087 (human dataset). In addition, we applied regression receiver operating characteristic curves for the first time to evaluate the temperature prediction, which provided an overall mean error bias between NIRS predicted brain temperature and body temperature of 0.436±0.283°C (animal dataset) and 0.162±0.149°C (human dataset). We discuss main methodological aspects, particularly the well-known aspect of over- versus underestimation between brain and body temperature, which is relevant for potential clinical applications. PMID:28630878

Expression Profile of DNA Damage Signaling Genes in Proton Exposed Mouse Brain

NASA Astrophysics Data System (ADS)

Ramesh, Govindarajan; Wu, Honglu

Exposure of living systems to radiation results in a wide assortment of lesions, the most signif-icant of is damage to genomic DNA which induce several cellular functions such as cell cycle arrest, repair, apoptosis etc. The radiation induced DNA damage investigation is one of the im-portant area in biology, but still the information available regarding the effects of proton is very limited. In this report, we investigated the differential gene expression pattern of DNA damage signaling genes particularly, damaged DNA binding, repair, cell cycle arrest, checkpoints and apoptosis using quantitative real-time RT-PCR array in proton exposed mouse brain tissues. The expression profiles showed significant changes in DNA damage related genes in 2Gy proton exposed mouse brain tissues as compared with control brain tissues. Furthermore, we also show that significantly increased levels of apoptotic related genes, caspase-3 and 8 activities in these cells, suggesting that in addition to differential expression of DNA damage genes, the alteration of apoptosis related genes may also contribute to the radiation induced DNA damage followed by programmed cell death. In summary, our findings suggest that proton exposed brain tissue undergo severe DNA damage which in turn destabilize the chromatin stability.

THE EFFECT OF POLIOMYELITIS VIRUS ON HUMAN BRAIN CELLS IN TISSUE CULTURE

PubMed Central

Hogue, M. J.; McAllister, R.; Greene, A. E.; Coriell, L. L.

1955-01-01

Poliomyelitis virus I, Mahoney strain, affected human brain cells grown in tissue cultures usually causing death of the cells in 3 days. The neurons reacted in different ways to the virus, some died with their neurites extended, others contracted one or more of their neurites. Terminal bulbs were frequently formed at the tips of the neurites when they were being drawn into the cell body. The final contraction of the cell body and the change into a mass of granules were often very sudden. Vacuoles often developed in the neuron. There was no recovery. Astrocytes, oligodendroglia, and macrophages were affected by the virus but not as quickly as the neurons. The age of the tissue culture was not a factor when the cells were in good condition. The age of the individual donor of the brain tissue was a factor; the fetal brain cells appeared to be more sensitive to the virus than the adult brain cells. The fetal neurons often reacted ½ hour after inoculation while the adult neurons reacted more slowly, 2 to 24 hours after inoculation. All these changes seemed to be caused by virus infection because they were prevented by specific antiserum or by preheating the virus. PMID:14392238

[From Brownian motion to mind imaging: diffusion MRI].

PubMed

Le Bihan, Denis

2006-11-01

The success of diffusion MRI, which was introduced in the mid 1980s is deeply rooted in the powerful concept that during their random, diffusion-driven movements water molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. The observation of these movements thus provides valuable information on the structure and the geometric organization of tissues. The most successful application of diffusion MRI has been in brain ischemia, following the discovery that water diffusion drops at a very early stage of the ischemic event. Diffusion MRI provides some patients with the opportunity to receive suitable treatment at a very acute stage when brain tissue might still be salvageable. On the other hand, diffusion is modulated by the spatial orientation of large bundles of myelinated axons running in parallel through in brain white matter. This feature can be exploited to map out the orientation in space of the white matter tracks and to visualize the connections between different parts of the brain on an individual basis. Furthermore, recent data suggest that diffusion MRI may also be used to visualize rapid dynamic tissue changes, such as neuronal swelling, associated with cortical activation, offering a new and direct approach to brain functional imaging.

Regional pressure and temperature variations across the injured human brain: comparisons between paired intraparenchymal and ventricular measurements.

PubMed

Childs, Charmaine; Shen, Liang

2015-06-23

Intraparenchymal, multimodality sensors are commonly used in the management of patients with severe traumatic brain injury (TBI). The 'gold standard', based on accuracy, reliability and cost for intracranial pressure (ICP) monitoring is within the cerebral ventricle (external strain gauge). There are no standards yet for intracerebral temperature monitoring and little is known of temperature differences between brain tissue and ventricle. The aim of the study therefore was to determine pressure and temperature differences at intraparenchymal and ventricular sites during five days of continuous neuromonitoring. Patients with severe TBI requiring emergency surgery. patients who required ICP monitoring were eligible for recruitment. Two intracerebral probe types were used: a) intraventricular, dual parameter sensor (measuring pressure, temperature) with inbuilt catheter for CSF drainage: b) multiparameter intraparenchymal sensor measuring pressure, temperature and oxygen partial pressure. All sensors were inserted during surgery and under aseptic conditions. Seventeen patients, 12 undergoing neurosurgery (decompressive craniectomy n = 8, craniotomy n = 4) aged 21-78 years were studied. Agreement of measures for 9540 brain tissue-ventricular temperature 'pairs' and 10,291 brain tissue-ventricular pressure 'pairs' were determined using mixed model to compare mean temperature and pressure for longitudinal data. There was no significant overall difference for mean temperature (p = 0.92) or mean pressure readings (p = 0.379) between tissue and ventricular sites. With 95.8 % of paired temperature readings within 2SD (-0.4 to 0.4 °C) differences in temperature between brain tissue and ventricle were clinically insignificant. For pressure, 93.5 % of readings pairs fell within the 2SD range (-9.4756 to 7.8112 mmHg). However, for individual patients, agreement for mean tissue-ventricular pressure differences was poor on occasions. There is good overall agreement between paired temperature measurements obtained from deep white matter and brain ventricle in patients with and without early neurosurgery. For paired ICP measurements, 93.5 % of readings were within 2SD of mean difference. Whilst the majority of paired readings were comparable (within 10 mmHg) clinically relevant tissue-ventricular dissociations were noted. Further work is required to unravel the events responsible for short intervals of pressure dissociation before tissue pressure readings can be definitively accepted as a reliable surrogate for ventricular pressure.

A method for monitoring of oxygen saturation changes in brain tissue using diffuse reflectance spectroscopy.

PubMed

Rejmstad, Peter; Johansson, Johannes D; Haj-Hosseini, Neda; Wårdell, Karin

2017-03-01

Continuous measurement of local brain oxygen saturation (SO 2 ) can be used to monitor the status of brain trauma patients in the neurocritical care unit. Currently, micro-oxygen-electrodes are considered as the "gold standard" in measuring cerebral oxygen pressure (pO 2 ), which is closely related to SO 2 through the oxygen dissociation curve (ODC) of hemoglobin, but with the drawback of slow in response time. The present study suggests estimation of SO 2 in brain tissue using diffuse reflectance spectroscopy (DRS) for finding an analytical relation between measured spectra and the SO 2 for different blood concentrations. The P 3 diffusion approximation is used to generate a set of spectra simulating brain tissue for various levels of blood concentrations in order to estimate SO 2 . The algorithm is evaluated on optical phantoms mimicking white brain matter (blood volume of 0.5-2%) where pO 2 and temperature is controlled and on clinical data collected during brain surgery. The suggested method is capable of estimating the blood fraction and oxygen saturation changes from the spectroscopic signal and the hemoglobin absorption profile. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prevalence of Toxoplasma gondii infection in brain and heart by Immunohistochemistry in a hospital-based autopsy series in Durango, Mexico.

PubMed

Alvarado-Esquivel, Cosme; Sánchez-Anguiano, Luis Francisco; Mendoza-Larios, Alejandra; Hernández-Tinoco, Jesús; Pérez-Ochoa, José Francisco; Antuna-Salcido, Elizabeth Irasema; Rábago-Sánchez, Elizabeth; Liesenfeld, Oliver

2015-06-01

The presence of tissue cysts of Toxoplasma gondii has only poorly been investigated in autopsy series. We determined the presence of T. gondii cysts in a series of 51 autopsies in a public hospital using immunohistochemistry of brain and heart tissues. The association of tissue cysts with the general characteristics of the autopsy cases was also investigated. Of the 51 cases studied, five (9.8%) were positive by immunohistochemistry for T. gondii cysts in the brain. None of the heart specimens was positive for T. gondii cysts. The presence of T. gondii cysts in brains did not vary with age, sex, birthplace, residence, education, occupation, or the presence of pathology in the brain. In contrast, multivariate analysis showed that the presence of T. gondii cysts was associated with undernourishment (OR = 33.90; 95% CI: 2.82-406.32; P = 0.005). We demonstrated cerebral T. gondii cysts in an autopsy series in Durango City, Mexico. Results suggest that T. gondii can be more readily found in brain than in heart of infected individuals. This is the first report of an association between the presence of T. gondii in brains and undernourishment.

Prevalence of Toxoplasma gondii infection in brain and heart by Immunohistochemistry in a hospital-based autopsy series in Durango, Mexico

PubMed Central

Alvarado-Esquivel, Cosme; Sánchez-Anguiano, Luis Francisco; Mendoza-Larios, Alejandra; Hernández-Tinoco, Jesús; Pérez-Ochoa, José Francisco; Antuna-Salcido, Elizabeth Irasema; Rábago-Sánchez, Elizabeth; Liesenfeld, Oliver

2015-01-01

The presence of tissue cysts of Toxoplasma gondii has only poorly been investigated in autopsy series. We determined the presence of T. gondii cysts in a series of 51 autopsies in a public hospital using immunohistochemistry of brain and heart tissues. The association of tissue cysts with the general characteristics of the autopsy cases was also investigated. Of the 51 cases studied, five (9.8%) were positive by immunohistochemistry for T. gondii cysts in the brain. None of the heart specimens was positive for T. gondii cysts. The presence of T. gondii cysts in brains did not vary with age, sex, birthplace, residence, education, occupation, or the presence of pathology in the brain. In contrast, multivariate analysis showed that the presence of T. gondii cysts was associated with undernourishment (OR = 33.90; 95% CI: 2.82–406.32; P = 0.005). We demonstrated cerebral T. gondii cysts in an autopsy series in Durango City, Mexico. Results suggest that T. gondii can be more readily found in brain than in heart of infected individuals. This is the first report of an association between the presence of T. gondii in brains and undernourishment. PMID:26185682

State of the art survey on MRI brain tumor segmentation.

PubMed

Gordillo, Nelly; Montseny, Eduard; Sobrevilla, Pilar

2013-10-01

Brain tumor segmentation consists of separating the different tumor tissues (solid or active tumor, edema, and necrosis) from normal brain tissues: gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). In brain tumor studies, the existence of abnormal tissues may be easily detectable most of the time. However, accurate and reproducible segmentation and characterization of abnormalities are not straightforward. In the past, many researchers in the field of medical imaging and soft computing have made significant survey in the field of brain tumor segmentation. Both semiautomatic and fully automatic methods have been proposed. Clinical acceptance of segmentation techniques has depended on the simplicity of the segmentation, and the degree of user supervision. Interactive or semiautomatic methods are likely to remain dominant in practice for some time, especially in these applications where erroneous interpretations are unacceptable. This article presents an overview of the most relevant brain tumor segmentation methods, conducted after the acquisition of the image. Given the advantages of magnetic resonance imaging over other diagnostic imaging, this survey is focused on MRI brain tumor segmentation. Semiautomatic and fully automatic techniques are emphasized. Copyright © 2013 Elsevier Inc. All rights reserved.

Prospective multi-centre Voxel Based Morphometry study employing scanner specific segmentations: Procedure development using CaliBrain structural MRI data

PubMed Central

2009-01-01

Background Structural Magnetic Resonance Imaging (sMRI) of the brain is employed in the assessment of a wide range of neuropsychiatric disorders. In order to improve statistical power in such studies it is desirable to pool scanning resources from multiple centres. The CaliBrain project was designed to provide for an assessment of scanner differences at three centres in Scotland, and to assess the practicality of pooling scans from multiple-centres. Methods We scanned healthy subjects twice on each of the 3 scanners in the CaliBrain project with T1-weighted sequences. The tissue classifier supplied within the Statistical Parametric Mapping (SPM5) application was used to map the grey and white tissue for each scan. We were thus able to assess within scanner variability and between scanner differences. We have sought to correct for between scanner differences by adjusting the probability mappings of tissue occupancy (tissue priors) used in SPM5 for tissue classification. The adjustment procedure resulted in separate sets of tissue priors being developed for each scanner and we refer to these as scanner specific priors. Results Voxel Based Morphometry (VBM) analyses and metric tests indicated that the use of scanner specific priors reduced tissue classification differences between scanners. However, the metric results also demonstrated that the between scanner differences were not reduced to the level of within scanner variability, the ideal for scanner harmonisation. Conclusion Our results indicate the development of scanner specific priors for SPM can assist in pooling of scan resources from different research centres. This can facilitate improvements in the statistical power of quantitative brain imaging studies. PMID:19445668

Distribution of AAV-TK following intracranial convection-enhanced delivery into rats.

PubMed

Cunningham, J; Oiwa, Y; Nagy, D; Podsakoff, G; Colosi, P; Bankiewicz, K S

2000-01-01

Adeno-associated virus (AAV)-based vectors are being tested in animal models as viable treatments for glioma and neurodegenerative disease and could potentially be employed to target a variety of central nervous system disorders. The relationship between dose of injected vector and its resulting distribution in brain tissue has not been previously reported nor has the most efficient method of delivery been determined. Here we report that convection-enhanced delivery (CED) of 2.5 x 10(8), 2.5 x 10(9), or 2.5 x 10(10) particles of AAV-thymidine kinase (AAV-TK) into rat brain revealed a clear dose response. In the high-dose group, a volume of 300 mm3 of brain tissue was partially transduced. Results showed that infusion pump and subcutaneous osmotic pumps were both capable of delivering vector via CED and that total particle number was the most important determining factor in obtaining efficient expression. Results further showed differences in histopathology between the delivery groups. While administration of vector using infusion pump had relatively benign effects, the use of osmotic pumps resulted in notable toxicity to the surrounding brain tissue. To determine tissue distribution of vector following intracranial delivery, PCR analysis was performed on tissues from rats that received high doses of AAV-TK. Three weeks following CED, vector could be detected in both hemispheres of the brain, spinal cord, spleen, and kidney.

Effects of dietary selenium of organic form against lead toxicity on the antioxidant system in Cyprinus carpio.

PubMed

Özkan-Yilmaz, Ferbal; Özlüer-Hunt, Arzu; Gündüz, Suna Gül; Berköz, Mehmet; Yalin, Serap

2014-04-01

In this study was evaluated potential protective effect of organic selenium (Se) on heavy metal stress induced by lead (Pb) in Cyprinus carpio. For this reason, C. carpio was exposed to sublethal concentration of Pb (1.5 mg/L Pb(NO3)2) for 14 days. The fish were fed a basal (control; measured 0.55 mg/kg Se) diet or a basal diet supplemented with 2.50 mg/kg (measured 2.92 mg/kg Se) organic Se (Sel-Plex(®)) during the experiment period. The variations in glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) activities, and levels of reduced glutathione (GSH) with malondialdehyde (MDA) in liver and brain tissues of C. carpio were investigated in experimental groups. GSH levels in liver and brain tissues were significantly decreased by exposure to Pb. GST activity was significantly increased (p < 0.05) in liver tissue, but decreased in brain of treated fish by exposure to Pb. Also, GSH-Px activity was significantly increased in liver tissue, but decreased in brain of Pb-treated fish. Levels of MDA were increased in liver and brain of Pb-treated fish. The organic Se treatment for Pb-intoxicated animals improved activities of GSH-Px, GST and levels of MDA within normal limits. Supplemented Se could be able to improve Pb-induced oxidative stress by decreasing lipid peroxidation and regulating antioxidant defense system in tissues.

Considerations in establishing a post-mortem brain and tissue bank for the study of myalgic encephalomyelitis/chronic fatigue syndrome: a proposed protocol.

PubMed

Nacul, Luis; O'Donovan, Dominic G; Lacerda, Eliana M; Gveric, Djordje; Goldring, Kirstin; Hall, Alison; Bowman, Erinna; Pheby, Derek

2014-06-18

Our aim, having previously investigated through a qualitative study involving extensive discussions with experts and patients the issues involved in establishing and maintaining a disease specific brain and tissue bank for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), was to develop a protocol for a UK ME/CFS repository of high quality human tissue from well characterised subjects with ME/CFS and controls suitable for a broad range of research applications. This would involve a specific donor program coupled with rapid tissue collection and processing, supplemented by comprehensive prospectively collected clinical, laboratory and self-assessment data from cases and controls. We reviewed the operations of existing tissue banks from published literature and from their internal protocols and standard operating procedures (SOPs). On this basis, we developed the protocol presented here, which was designed to meet high technical and ethical standards and legal requirements and was based on recommendations of the MRC UK Brain Banks Network. The facility would be most efficient and cost-effective if incorporated into an existing tissue bank. Tissue collection would be rapid and follow robust protocols to ensure preservation sufficient for a wide range of research uses. A central tissue bank would have resources both for wide-scale donor recruitment and rapid response to donor death for prompt harvesting and processing of tissue. An ME/CFS brain and tissue bank could be established using this protocol. Success would depend on careful consideration of logistic, technical, legal and ethical issues, continuous consultation with patients and the donor population, and a sustainable model of funding ideally involving research councils, health services, and patient charities. This initiative could revolutionise the understanding of this still poorly-understood disease and enhance development of diagnostic biomarkers and treatments.

Expansion of Multipotent Stem Cells from the Adult Human Brain

PubMed Central

Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

2013-01-01

The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

A Novel Application for the Cavalieri Principle: A Stereological and Methodological Study

PubMed Central

Altunkaynak, Berrin Zuhal; Altunkaynak, Eyup; Unal, Deniz; Unal, Bunyamin

2009-01-01

Objective The Cavalieri principle was applied to consecutive pathology sections that were photographed at the same magnification and used to estimate tissue volumes via superimposing a point counting grid on these images. The goal of this study was to perform the Cavalieri method quickly and practically. Materials and Methods In this study, 10 adult female Sprague Dawley rats were used. Brain tissue was removed and sampled both systematically and randomly. Brain volumes were estimated using two different methods. First, all brain slices were scanned with an HP ScanJet 3400C scanner, and their images were shown on a PC monitor. Brain volume was then calculated based on these images. Second, all brain slices were photographed in 10× magnification with a microscope camera, and brain volumes were estimated based on these micrographs. Results There was no statistically significant difference between the volume measurements of the two techniques (P>0.05; Paired Samples t Test). Conclusion This study demonstrates that personal computer scanning of serial tissue sections allows for easy and reliable volume determination based on the Cavalieri method. PMID:25610077

A novel application for the cavalieri principle: a stereological and methodological study.

PubMed

Altunkaynak, Berrin Zuhal; Altunkaynak, Eyup; Unal, Deniz; Unal, Bunyamin

2009-08-01

The Cavalieri principle was applied to consecutive pathology sections that were photographed at the same magnification and used to estimate tissue volumes via superimposing a point counting grid on these images. The goal of this study was to perform the Cavalieri method quickly and practically. In this study, 10 adult female Sprague Dawley rats were used. Brain tissue was removed and sampled both systematically and randomly. Brain volumes were estimated using two different methods. First, all brain slices were scanned with an HP ScanJet 3400C scanner, and their images were shown on a PC monitor. Brain volume was then calculated based on these images. Second, all brain slices were photographed in 10× magnification with a microscope camera, and brain volumes were estimated based on these micrographs. There was no statistically significant difference between the volume measurements of the two techniques (P>0.05; Paired Samples t Test). This study demonstrates that personal computer scanning of serial tissue sections allows for easy and reliable volume determination based on the Cavalieri method.

Cross-linked polyhemoglobin-superoxide dismutase-catalase supplies oxygen without causing blood-brain barrier disruption or brain edema in a rat model of transient global brain ischemia-reperfusion.

PubMed

Powanda, D Douglas; Chang, Thomas M S

2002-01-01

In strokes, myocardial infarctions, severe sustained hemorrhagic shock, and donor organs, inadequate blood supply results in lack of oxygen to the tissue (ischemia). If ischemia is sustained, reperfusion with the needed oxygen can result in tissue injury (ischemia-reperfusion injury) due to formation of reactive oxygen species. We are studying an oxygen-carrying solution with anitoxidant activity formed by cross-linking hemoglobin, superoxide dismutase, and catalase to form PolyHb-SOD-CAT. The present report studies its effect on the blood-brain barrier and cerebral edema when used in a transient global brain ischemia-reperfusion rat model. We compare this solution to sham-control, oxygenated saline, stroma-free hemoglobin (SF-Hb), polymerized hemoglobin (PolyHb), and a mixture of SF-Hb, SOD, and CAT in free solution. The results show that the cross-linked PolyHb-SOD-CAT solution, unlike the other solutions, can supply oxygen to ischemic tissues without causing reperfusion injury in the transient global brain ischemia-reperfusion model.

PD-1 immune checkpoint blockade promotes brain leukocyte infiltration and diminishes cyst burden in a mouse model of Toxoplasma infection.

PubMed

Xiao, Jianchun; Li, Ye; Yolken, Robert H; Viscidi, Raphael P

2018-06-15

Tissue cysts, the hallmark of chronic Toxoplasma gondii infection, are predominantly located in the brain making clearance of the parasite difficult. Currently available anti-T. gondii drugs are ineffective on cysts and fail to prevent reactivation of latent toxoplasmosis. We examined whether abrogation of inhibitory signaling pathways that maintain T cells in an exhausted state can be exploited for treating T. gondii tissue cysts. By using a mouse model of chronic toxoplasmosis, we showed immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway results in a significant reduction in brain cyst number (77% lower). We showed leukocyte infiltration (CD3+ T cells, CD8+ T cells, and CD11b + cells) in the leptomeninges, choroid plexus, and subependymal tissue, which are known routes of entry of immune cells into the brain, and in proximal brain parenchyma. Our study provides proof of concept for blockade of immune checkpoint inhibitors as a therapy for chronic toxoplasmosis and potentially for other brain pathogens. Copyright © 2018 Elsevier B.V. All rights reserved.

Statistical model of laminar structure for atlas-based segmentation of the fetal brain from in utero MR images

NASA Astrophysics Data System (ADS)

Habas, Piotr A.; Kim, Kio; Chandramohan, Dharshan; Rousseau, Francois; Glenn, Orit A.; Studholme, Colin

2009-02-01

Recent advances in MR and image analysis allow for reconstruction of high-resolution 3D images from clinical in utero scans of the human fetal brain. Automated segmentation of tissue types from MR images (MRI) is a key step in the quantitative analysis of brain development. Conventional atlas-based methods for adult brain segmentation are limited in their ability to accurately delineate complex structures of developing tissues from fetal MRI. In this paper, we formulate a novel geometric representation of the fetal brain aimed at capturing the laminar structure of developing anatomy. The proposed model uses a depth-based encoding of tissue occurrence within the fetal brain and provides an additional anatomical constraint in a form of a laminar prior that can be incorporated into conventional atlas-based EM segmentation. Validation experiments are performed using clinical in utero scans of 5 fetal subjects at gestational ages ranging from 20.5 to 22.5 weeks. Experimental results are evaluated against reference manual segmentations and quantified in terms of Dice similarity coefficient (DSC). The study demonstrates that the use of laminar depth-encoded tissue priors improves both the overall accuracy and precision of fetal brain segmentation. Particular refinement is observed in regions of the parietal and occipital lobes where the DSC index is improved from 0.81 to 0.82 for cortical grey matter, from 0.71 to 0.73 for the germinal matrix, and from 0.81 to 0.87 for white matter.

A combined MR and CT study for precise quantitative analysis of the avian brain

NASA Astrophysics Data System (ADS)

Jirak, Daniel; Janacek, Jiri; Kear, Benjamin P.

2015-10-01

Brain size is widely used as a measure of behavioural complexity and sensory-locomotive capacity in avians but has largely relied upon laborious dissections, endoneurocranial tissue displacement, and physical measurement to derive comparative volumes. As an alternative, we present a new precise calculation method based upon coupled magnetic resonance (MR) imaging and computed tomography (CT). Our approach utilizes a novel interactive Fakir probe cross-referenced with an automated CT protocol to efficiently generate total volumes and surface areas of the brain tissue and endoneurocranial space, as well as the discrete cephalic compartments. We also complemented our procedures by using sodium polytungstate (SPT) as a contrast agent. This greatly enhanced CT applications but did not degrade MR quality and is therefore practical for virtual brain tissue reconstructions employing multiple imaging modalities. To demonstrate our technique, we visualized sex-based brain size differentiation in a sample set of Ring-necked pheasants (Phasianus colchicus). This revealed no significant variance in relative volume or surface areas of the primary brain regions. Rather, a trend towards isometric enlargement of the total brain and endoneurocranial space was evidenced in males versus females, thus advocating a non-differential sexually dimorphic pattern of brain size increase amongst these facultatively flying birds.

RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

PubMed Central

Hosonaga, Mari; Koya, Ikuko

2017-01-01

Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients. PMID:28210624

Intra-Arterial Delivery of AAV Vectors to the Mouse Brain After Mannitol Mediated Blood Brain Barrier Disruption

PubMed Central

Santillan, Alejandro; Sondhi, Dolan; Dyke, Jonathan P.; Crystal, Ronald G.; Gobin, Y. Pierre; Ballon, Douglas J.

2014-01-01

The delivery of therapeutics to neural tissue is greatly hindered by the blood brain barrier (BBB). Direct local delivery via diffusive release from degradable implants or direct intra-cerebral injection can bypass the BBB and obtain high concentrations of the therapeutic in the targeted tissue, however the total volume of tissue that can be treated using these techniques is limited. One treatment modality that can potentially access large volumes of neural tissue in a single treatment is intra-arterial (IA) injection after osmotic blood brain barrier disruption. In this technique, the therapeutic of interest is injected directly into the arteries that feed the target tissue after the blood brain barrier has been disrupted by exposure to a hyperosmolar mannitol solution, permitting the transluminal transport of the therapy. In this work we used contrast enhanced magnetic resonance imaging (MRI) studies of IA injections in mice to establish parameters that allow for extensive and reproducible BBB disruption. We found that the volume but not the flow rate of the mannitol injection has a significant effect on the degree of disruption. To determine whether the degree of disruption we observed with this method was sufficient for delivery of nanoscale therapeutics, we performed IA injections of an adeno-associated viral vector containing the CLN2 gene (AAVrh.10CLN2), which is mutated in the lysosomal storage disorder Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL). We demonstrated that IA injection of AAVrh.10CLN2 after BBB disruption can achieve widespread transgene production in the mouse brain after a single administration. Further, we showed that there exists a minimum threshold of BBB disruption necessary to permit the AAV.rh10 vector to pass into the brain parenchyma from the vascular system. These results suggest that IA administration may be used to obtain widespread delivery of nanoscale therapeutics throughout the murine brain after a single administration. PMID:25270115

Keratin 13 expression reprograms bone and brain metastases of human prostate cancer cells.

PubMed

Li, Qinlong; Yin, Lijuan; Jones, Lawrence W; Chu, Gina C-Y; Wu, Jason B-Y; Huang, Jen-Ming; Li, Quanlin; You, Sungyong; Kim, Jayoung; Lu, Yi-Tsung; Mrdenovic, Stefan; Wang, Ruoxiang; Freeman, Michael R; Garraway, Isla; Lewis, Michael S; Chung, Leland W K; Zhau, Haiyen E

2016-12-20

Lethal progression of prostate cancer metastasis can be improved by developing animal models that recapitulate the clinical conditions. We report here that cytokeratin 13 (KRT13), an intermediate filament protein, plays a directive role in prostate cancer bone, brain, and soft tissue metastases. KRT13 expression was elevated in bone, brain, and soft tissue metastatic prostate cancer cell lines and in primary and metastatic clinical prostate, lung, and breast cancer specimens. When KRT13 expression was determined at a single cell level in primary tumor tissues of 44 prostate cancer cases, KRT13 level predicted bone metastasis and the overall survival of prostate cancer patients. Genetically enforced KRT13 expression in human prostate cancer cell lines drove metastases toward mouse bone, brain and soft tissues through a RANKL-independent mechanism, as KRT13 altered the expression of genes associated with EMT, stemness, neuroendocrine/neuromimicry, osteomimicry, development, and extracellular matrices, but not receptor activator NF-κB ligand (RANKL) signaling networks in prostate cancer cells. Our results suggest new inhibitors targeting RANKL-independent pathways should be developed for the treatment of prostate cancer bone and soft tissue metastases.

Aronia melanocarpa Treatment and Antioxidant Status in Selected Tissues in Wistar Rats

PubMed Central

Krośniak, Mirosław; Sanocka, Ilona; Bartoń, Henryk; Hebda, Tomasz; Francik, Sławomir

2014-01-01

Aronia juice is considered to be a source of compounds with high antioxidative potential. We conducted a study on the impact of compounds in the Aronia juice on oxidative stress in plasma and brain tissues. The influence of Aronia juice on oxidative stress parameters was tested with the use of a model with a high content of fructose and nonsaturated fats. Therefore, the activity of enzymatic (catalase, CAT, and paraoxonase, PON) and nonenzymatic (thiol groups, SH, and protein carbonyl groups, PCG) oxidative stress markers, which indicate changes in the carbohydrate and protein profiles, was marked in brain tissue homogenates. Adding Aronia caused statistically significant increase in the CAT activity in plasma in all tested diets, while the PON activity showed a statistically significant increase only in case of high fat diet. In animals fed with Aronia juice supplemented with carbohydrates or fat, statistically significant increase in the PON activity and the decrease in the CAT activity in brain tissue were observed. In case of the high fat diet, an increase in the number of SH groups and a decrease in the number of PCG groups in brain tissue were observed. PMID:25057488

Aronia melanocarpa treatment and antioxidant status in selected tissues in Wistar rats.

PubMed

Francik, Renata; Krośniak, Mirosław; Sanocka, Ilona; Bartoń, Henryk; Hebda, Tomasz; Francik, Sławomir

2014-01-01

Aronia juice is considered to be a source of compounds with high antioxidative potential. We conducted a study on the impact of compounds in the Aronia juice on oxidative stress in plasma and brain tissues. The influence of Aronia juice on oxidative stress parameters was tested with the use of a model with a high content of fructose and nonsaturated fats. Therefore, the activity of enzymatic (catalase, CAT, and paraoxonase, PON) and nonenzymatic (thiol groups, SH, and protein carbonyl groups, PCG) oxidative stress markers, which indicate changes in the carbohydrate and protein profiles, was marked in brain tissue homogenates. Adding Aronia caused statistically significant increase in the CAT activity in plasma in all tested diets, while the PON activity showed a statistically significant increase only in case of high fat diet. In animals fed with Aronia juice supplemented with carbohydrates or fat, statistically significant increase in the PON activity and the decrease in the CAT activity in brain tissue were observed. In case of the high fat diet, an increase in the number of SH groups and a decrease in the number of PCG groups in brain tissue were observed.

Optimization of immunolabeling and clearing techniques for indelibly-labeled memory traces.

PubMed

Pavlova, Ina P; Shipley, Shannon C; Lanio, Marcos; Hen, René; Denny, Christine A

2018-04-16

Recent genetic tools have allowed researchers to visualize and manipulate memory traces (i.e. engrams) in small brain regions. However, the ultimate goal is to visualize memory traces across the entire brain in order to better understand how memories are stored in neural networks and how multiple memories may coexist. Intact tissue clearing and imaging is a new and rapidly growing area of focus that could accomplish this task. Here, we utilized the leading protocols for whole-brain clearing and applied them to the ArcCreER T2 mice, a murine line that allows for the indelible labeling of memory traces. We found that CLARITY and PACT greatly distorted the tissue, and iDISCO quenched enhanced yellow fluorescent protein (EYFP) fluorescence and hindered immunolabeling. Alternative clearing solutions, such as tert-Butanol, circumvented these harmful effects, but still did not permit whole-brain immunolabeling. CUBIC and CUBIC with Reagent 1A produced improved antibody penetration and preserved EYFP fluorescence, but also did not allow for whole-brain memory trace visualization. Modification of CUBIC with Reagent-1A resulted in EYFP fluorescence preservation and immunolabeling of the immediate early gene (IEG) Arc in deep brain areas; however, optimized memory trace labeling still required tissue slicing into mm-thick tissue sections. In summary, our data show that CUBIC with Reagent-1A* is the ideal method for reproducible clearing and immunolabeling for the visualization of memory traces in mm-thick tissue sections from ArcCreER T2 mice. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Deep Convolutional Neural Networks for Multi-Modality Isointense Infant Brain Image Segmentation

PubMed Central

Zhang, Wenlu; Li, Rongjian; Deng, Houtao; Wang, Li; Lin, Weili; Ji, Shuiwang; Shen, Dinggang

2015-01-01

The segmentation of infant brain tissue images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying early brain development in health and disease. In the isointense stage (approximately 6–8 months of age), WM and GM exhibit similar levels of intensity in both T1 and T2 MR images, making the tissue segmentation very challenging. Only a small number of existing methods have been designed for tissue segmentation in this isointense stage; however, they only used a single T1 or T2 images, or the combination of T1 and T2 images. In this paper, we propose to use deep convolutional neural networks (CNNs) for segmenting isointense stage brain tissues using multi-modality MR images. CNNs are a type of deep models in which trainable filters and local neighborhood pooling operations are applied alternatingly on the raw input images, resulting in a hierarchy of increasingly complex features. Specifically, we used multimodality information from T1, T2, and fractional anisotropy (FA) images as inputs and then generated the segmentation maps as outputs. The multiple intermediate layers applied convolution, pooling, normalization, and other operations to capture the highly nonlinear mappings between inputs and outputs. We compared the performance of our approach with that of the commonly used segmentation methods on a set of manually segmented isointense stage brain images. Results showed that our proposed model significantly outperformed prior methods on infant brain tissue segmentation. In addition, our results indicated that integration of multi-modality images led to significant performance improvement. PMID:25562829

Evaluation of a deep learning approach for the segmentation of brain tissues and white matter hyperintensities of presumed vascular origin in MRI.

PubMed

Moeskops, Pim; de Bresser, Jeroen; Kuijf, Hugo J; Mendrik, Adriënne M; Biessels, Geert Jan; Pluim, Josien P W; Išgum, Ivana

2018-01-01

Automatic segmentation of brain tissues and white matter hyperintensities of presumed vascular origin (WMH) in MRI of older patients is widely described in the literature. Although brain abnormalities and motion artefacts are common in this age group, most segmentation methods are not evaluated in a setting that includes these items. In the present study, our tissue segmentation method for brain MRI was extended and evaluated for additional WMH segmentation. Furthermore, our method was evaluated in two large cohorts with a realistic variation in brain abnormalities and motion artefacts. The method uses a multi-scale convolutional neural network with a T 1 -weighted image, a T 2 -weighted fluid attenuated inversion recovery (FLAIR) image and a T 1 -weighted inversion recovery (IR) image as input. The method automatically segments white matter (WM), cortical grey matter (cGM), basal ganglia and thalami (BGT), cerebellum (CB), brain stem (BS), lateral ventricular cerebrospinal fluid (lvCSF), peripheral cerebrospinal fluid (pCSF), and WMH. Our method was evaluated quantitatively with images publicly available from the MRBrainS13 challenge ( n  = 20), quantitatively and qualitatively in relatively healthy older subjects ( n  = 96), and qualitatively in patients from a memory clinic ( n  = 110). The method can accurately segment WMH (Overall Dice coefficient in the MRBrainS13 data of 0.67) without compromising performance for tissue segmentations (Overall Dice coefficients in the MRBrainS13 data of 0.87 for WM, 0.85 for cGM, 0.82 for BGT, 0.93 for CB, 0.92 for BS, 0.93 for lvCSF, 0.76 for pCSF). Furthermore, the automatic WMH volumes showed a high correlation with manual WMH volumes (Spearman's ρ  = 0.83 for relatively healthy older subjects). In both cohorts, our method produced reliable segmentations (as determined by a human observer) in most images (relatively healthy/memory clinic: tissues 88%/77% reliable, WMH 85%/84% reliable) despite various degrees of brain abnormalities and motion artefacts. In conclusion, this study shows that a convolutional neural network-based segmentation method can accurately segment brain tissues and WMH in MR images of older patients with varying degrees of brain abnormalities and motion artefacts.

A comparison of head dynamic response and brain tissue stress and strain using accident reconstructions for concussion, concussion with persistent postconcussive symptoms, and subdural hematoma.

PubMed

Oeur, R Anna; Karton, Clara; Post, Andrew; Rousseau, Philippe; Hoshizaki, T Blaine; Marshall, Shawn; Brien, Susan E; Smith, Aynsley; Cusimano, Michael D; Gilchrist, Michael D

2015-08-01

Concussions typically resolve within several days, but in a few cases the symptoms last for a month or longer and are termed persistent postconcussive symptoms (PPCS). These persisting symptoms may also be associated with more serious brain trauma similar to subdural hematoma (SDH). The objective of this study was to investigate the head dynamic and brain tissue responses of injury reconstructions resulting in concussion, PPCS, and SDH. Reconstruction cases were obtained from sports medicine clinics and hospitals. All subjects received a direct blow to the head resulting in symptoms. Those symptoms that resolved in 9 days or fewer were defined as concussions (n = 3). Those with symptoms lasting longer than 18 months were defined as PPCS (n = 3), and 3 patients presented with SDHs (n = 3). A Hybrid III headform was used in reconstruction to obtain linear and rotational accelerations of the head. These dynamic response data were then input into the University College Dublin Brain Trauma Model to calculate maximum principal strain and von Mises stress. A Kruskal-Wallis test followed by Tukey post hoc tests were used to compare head dynamic and brain tissue responses between injury groups. Statistical significance was set at p < 0.05. A significant difference was identified for peak resultant linear and rotational acceleration between injury groups. Post hoc analyses revealed the SDH group had higher linear and rotational acceleration responses (316 g and 23,181 rad/sec(2), respectively) than the concussion group (149 g and 8111 rad/sec(2), respectively; p < 0.05). No significant differences were found between groups for either brain tissue measures of maximum principal strain or von Mises stress. The reconstruction of accidents resulting in a concussion with transient symptoms (low severity) and SDHs revealed a positive relationship between an increase in head dynamic response and the risk for more serious brain injury. This type of relationship was not found for brain tissue stress and strain results derived by finite element analysis. Future research should be undertaken using a larger sample size to confirm these initial findings. Understanding the relationship between the head dynamic and brain tissue response and the nature of the injury provides important information for developing strategies for injury prevention.

Voluntary exercise confers protection against age-related deficits in brain oxygenation in awake mice model of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Lu, Xuecong; Moeini, Mohammad; Li, Baoqiang; Sakadžić, Sava; Lesage, Frédéric

2018-02-01

Alzheimer's disease (AD) is a neurodegenerative disease characterized by short-term memory loss and cognitive inabilities. This work seeks to study the effects of voluntary exercise on the change in oxygen delivery in awake mice models of Alzheimer's disease by monitoring brain tissue oxygenation. Experiments were performed on Young (AD_Y, 3-4 months, n=8), Old (AD_O, 6-7 months, n=8), and Old with exercise (AD_OEX, 6-7 months, n=8) transgenic APPPS1 mice and their controls. Brain tissue oxygenation was measured by two photon phosphorescence lifetime microscopy on the left sensory motor cortex. We found that the average tissue PO2 decreased with age but were regulated by exercise. The results suggest a potential for exercise to improve brain function with age and AD.

Dynamical properties of the brain tissue under oscillatory shear stresses at large strain range

NASA Astrophysics Data System (ADS)

Boudjema, F.; Khelidj, B.; Lounis, M.

2017-01-01

In this experimental work, we study the viscoelastic behaviour of in vitro brain tissue, particularly the white matter, under oscillatory shear strain. The selective vulnerability of this tissue is the anisotropic mechanical properties of theirs different regions lead to a sensitivity to the angular shear rate and magnitude of strain. For this aim, shear storage modulus (G‧) and loss modulus (G″) were measured over a range of frequencies (1 to 100 Hz), for different levels of strain (1 %, to 50 %). The mechanical responses of the brain matter samples showed a viscoelastic behaviour that depend on the correlated strain level and frequency range and old age sample. The samples have been showed evolution behaviour by increasing then decreasing the strain level. Also, the stiffness anisotropy of brain matter was showed between regions and species.

Simultaneous two-photon imaging of cerebral oxygenation and capillary blood flow in atherosclerotic mice

NASA Astrophysics Data System (ADS)

Lu, Xuecong; Li, Baoqiang; Moeini, Mohammad; Lesage, Frédéric

2017-02-01

Gradual changes in brain microvasculature and cerebral capillary blood flow occurring with atherosclerosis may significantly contribute to cognition decline due to their role in brain tissue oxygenation. However, previous stud- ies of the relationship between cerebral capillary blood flow and brain tissue oxygenation are limited. This study aimed to investigate vascular and concomitant changes in brain tissue pO2 with atherosclerosis. Experiments in young healthy C57B1/6 mice (n=6 , WT), young atherosclerotic mice (n=6 , ATX Y) and old atherosclerotic mice (n=6 , ATX O) were performed imaging on the left sensory-motor cortex at resting state under urethane (1.5 g/kg) anesthesia using two-photon fluorescence microscopy. The results showed that pO2 around capillaries, correlated with red blood cell (RBC) flux, increased with atherosclerosis.

Thioesters for the in vitro evaluation of agents to image brain cholinesterases.

PubMed

Macdonald, Ian R; Jollymore, Courtney T; Reid, G Andrew; Pottie, Ian R; Martin, Earl; Darvesh, Sultan

2013-06-01

Cholinesterases are associated with pathology characteristic of conditions such as Alzheimer's disease and are therefore, considered targets for neuroimaging. Ester derivatives of N-methylpiperidinol are promising potential imaging agents; however, methodology is lacking for evaluating these compounds in vitro. Here, we report the synthesis and evaluation of a series of N-methylpiperidinyl thioesters, possessing comparable properties to their corresponding esters, which can be directly evaluated for cholinesterase kinetics and histochemical distribution in human brain tissue. N-methylpiperidinyl esters and thioesters were synthesized and they demonstrated comparable cholinesterase kinetics. Furthermore, thioesters were capable, using histochemical method, to visualize cholinesterase activity in human brain tissue. N-methylpiperidinyl thioesters can be rapidly evaluated for cholinesterase kinetics and visualization of enzyme distribution in brain tissue which may facilitate development of cholinesterase imaging agents for application to conditions such as Alzheimer's disease.

OFF-CENTER SPHERICAL MODEL FOR DOSIMETRY CALCULATIONS IN CHICK BRAIN TISSUE

EPA Science Inventory

The paper presents calculations for the electric field and absorbed power density distribution in chick brain tissue inside a test tube, using an off-center spherical model. It is shown that the off-center spherical model overcomes many of the limitations of the concentric spheri...

Alzheimer's Disease. LC Science Tracer Bullet 87-2.

ERIC Educational Resources Information Center

Sammons, Vivian O., Comp.

Alzheimer's disease is characterized by a degeneration and shrinkage of brain tissue; the symptoms include progressive memory loss, bizarre behavior, difficulty in speaking and walking, incontinence, and confusion. Positive diagnosis is possible only upon examination of brain tissue at autopsy. The disease affects not only the patient but also the…

Epidemiology of rheumatic diseases in Iran from analysis of four COPCORD studies.

PubMed

Davatchi, Fereydoun; Sandoughi, Mahnaz; Moghimi, Nasrin; Jamshidi, Ahmad-Reza; Tehrani Banihashemi, Arash; Zakeri, Zahra; Sadeghi Abdollahi, Bahar

2016-11-01

To calculate the epidemiology of Rheumatic Diseases in Iran. The data of Tehran, Zahedan, Sanandaj (urban) and Tuyserkan (rural) stage Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) studies were gathered. The data were adjusted to the population number of the studied areas to represent Iran. The population of Iran is 75 149 669 (71.5% urban areas, males 50.4%) and of the mentioned area were respectively 10 000 000, 580 071, 311 444 and 109 262. The interviewed subjects were 10 291, 1565, 2100 and 5830. Male/female ratio was 0.9/1, 0.8/1, 08/1 and 0.8/1. Musculoskeletal complaints during the past 7 days (people aged ≥ 15 years) were detected in 44.7% of subjects. They were: shoulder 15.6%, wrist 10.4%, hands and fingers 10.2%, hip 8.3%, knee 27.4%, ankle 12.3%, toes 6.2%, cervical spine 14.2% and dorsolumbar spine 23.7%. Osteoarthritis (OA) was detected in 16.9%: knee 15.5%, hands 2.9% and hip 0.32%. Low back pain was found in 15.7%, sciatica in 0.94%, and soft tissue rheumatism in 4.6% (shoulder tenosynovitis 2.5%, frozen shoulder 0.56%, tennis elbow 1.2%, golf elbow 0.48%, de Quervain tenosynovitis 0.24%, trigger finger 0.2%, carpal tunnel syndrome 1.3%). Rheumatoid arthritis was detected in 0.37%, seronegative spondyloarthropathy in 0.24%, ankylosing spondylitis in 0.12%, systemic lupus erythematosus in 0.06%, Behcet's disease in 0.08%, fibromyalgia in 0.79% and gout in 0.13%. Compared to other COPCORD reports (17 countries), Iran gets the following rank: musculoskeletal complaints second, low back pain fourth, osteoarthritis second, knee osteoarthritis third, soft tissue rheumatism sixth, rheumatoid arthritis tenth, seronegative spondyloarthropathies fifth, gout eleventh and fibromyalgia fifth. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Wnt/Notum spatial feedback inhibition controls neoblast differentiation to regulate reversible growth of the planarian brain

PubMed Central

Hill, Eric M.; Petersen, Christian P.

2015-01-01

Mechanisms determining final organ size are poorly understood. Animals undergoing regeneration or ongoing adult growth are likely to require sustained and robust mechanisms to achieve and maintain appropriate sizes. Planarians, well known for their ability to undergo whole-body regeneration using pluripotent adult stem cells of the neoblast population, can reversibly scale body size over an order of magnitude by controlling cell number. Using quantitative analysis, we showed that after injury planarians perfectly restored brain:body proportion by increasing brain cell number through epimorphosis or decreasing brain cell number through tissue remodeling (morphallaxis), as appropriate. We identified a pathway controlling a brain size set-point that involves feedback inhibition between wnt11-6/wntA/wnt4a and notum, encoding conserved antagonistic signaling factors expressed at opposite brain poles. wnt11-6/wntA/wnt4a undergoes feedback inhibition through canonical Wnt signaling but is likely to regulate brain size in a non-canonical pathway independently of beta-catenin-1 and APC. Wnt/Notum signaling tunes numbers of differentiated brain cells in regenerative growth and tissue remodeling by influencing the abundance of brain progenitors descended from pluripotent stem cells, as opposed to regulating cell death. These results suggest that the attainment of final organ size might be accomplished by achieving a balance of positional signaling inputs that regulate the rates of tissue production. PMID:26525673

Brain tissue pulsatility mediates cognitive and electrophysiological changes in normal aging: Evidence from ultrasound tissue pulsatility imaging (TPI).

PubMed

Angel, Lucie; Bouazzaoui, Badiâa; Isingrini, Michel; Fay, Séverine; Taconnat, Laurence; Vanneste, Sandrine; Ledoux, Moïse; Gissot, Valérie; Hommet, Caroline; Andersson, Fréderic; Barantin, Laurent; Cottier, Jean-Philippe; Pasco, Jérémy; Desmidt, Thomas; Patat, Frédéric; Camus, Vincent; Remenieras, Jean-Pierre

2018-06-01

Aging is characterized by a cognitive decline of fluid abilities and is also associated with electrophysiological changes. The vascular hypothesis proposes that brain is sensitive to vascular dysfunction which may accelerate age-related brain modifications and thus explain age-related neurocognitive decline. To test this hypothesis, cognitive performance was measured in 39 healthy participants from 20 to 80 years, using tests assessing inhibition, fluid intelligence, attention and crystallized abilities. Brain functioning associated with attentional abilities was assessed by measuring the P3b ERP component elicited through an auditory oddball paradigm. To assess vascular health, we used an innovative measure of the pulsatility of deep brain tissue, due to variations in cerebral blood flow over the cardiac cycle. Results showed (1) a classical effect of age on fluid neurocognitive measures (inhibition, fluid intelligence, magnitude and latency of the P3b) but not on crystallized measures, (2) that brain pulsatility decreases with advancing age, (3) that brain pulsatility is positively correlated with fluid neurocognitive measures and (4) that brain pulsatility strongly mediated the age-related variance in cognitive performance and the magnitude of the P3b component. The mediating role of the brain pulsatility in age-related effect on neurocognitive measures supports the vascular hypothesis of cognitive aging. Copyright © 2018 Elsevier Inc. All rights reserved.

Development of an autofluorescent probe designed to help brain tumor removal: study on an animal model

NASA Astrophysics Data System (ADS)

Siebert, R.; Leh, B.; Charon, Y.; Collado-Hilly, M.; Duval, M.-A.; Menard, L.; Monnet, F. P.; Varlet, P.

2010-02-01

The complete resection of the brain tumour is crucial to the patient life quality and prognosis. An autofluorescence probe aiming at helping the surgeon to improve the completeness of the removal is being developed. Autofluorescence spectroscopy is a promising approach to define whether the tissue is cancerous or not. First ex vivo measurements have been realised on an animal model. After tumorous cell injection in rat brain, autofluorescence intensity is revealed from the extracted brain. These autofluorescence data are compared to results from a histological analysis of same brains. First indicators are identified that may have the ability to differentiate tumorous and healthy tissues.

Delta-aminolevulinic acid dehydratase enzyme activity in blood, brain, and liver of lead-dosed ducks

USGS Publications Warehouse

Dieter, M.P.; Finley, M.T.

1979-01-01

Mallard ducks were dosed with a single shotgun pellet (ca. 200 mg lead). After 1 month there was about 1 ppm lead in blood, 2.5 in liver, and 0.5 in brain. Lead-induced inhibition of delta-aminolevulinic acid dehydratase enzyme in blood and cerebellum was much greater than in cerebral hemisphere or liver and was strongly correlated with the lead concentration in these tissues. The cerebellar portion of the brain was more sensitive to delta-aminolevulinic acid dehydratase enzyme inhibition by lead than were the other tissues examined. There was also a greater increase in the glial cell marker enzyme, butyrylcholinesterase, in cerebellum than in cerebral hemisphere, suggesting that nonregenerating neuronal cells were destroyed by lead and replaced by glial cells in that portion of the brain. Even partial loss of cerebellar tissue is severely debilitating in waterfowl, because functions critical to survival such as visual, auditory, motor, and reflex responses are integrated at this brain center.

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

NASA Astrophysics Data System (ADS)

Xie, Chong; Liu, Jia; Fu, Tian-Ming; Dai, Xiaochuan; Zhou, Wei; Lieber, Charles M.

2015-12-01

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.

CT Perfusion in Acute Stroke: "Black Holes" on Time-to-Peak Image Maps Indicate Unsalvageable Brain.

PubMed

Meagher, Ruairi; Shankar, Jai Jai Shiva

2016-11-01

CT perfusion is becoming important in acute stroke imaging to determine optimal patient-management strategies. The purpose of this study was to examine the predictive value of time-to-peak image maps and, specifically, a phenomenon coined a "black hole" for assessing infarcted brain tissue at the time of scan. Acute stroke patients were screened for the presence of black holes and their follow-up imaging (noncontrast CT or MR) was reviewed to assess for infarcted brain tissue. Of the 23 patients with signs of acute ischemia on CT perfusion, all had black holes. The black holes corresponded with areas of infarcted brain on follow-up imaging (specificity 100%). Black holes demonstrated significantly lower cerebral blood volumes (P < .001) and cerebral blood flow (P < .001) compared to immediately adjacent tissue. Black holes on time-to-peak image maps represent areas of unsalvageable brain. Copyright © 2016 by the American Society of Neuroimaging.

Distribution of opiate alkaloids in brain tissue of experimental animals

PubMed Central

Pilija, Vladimir; Mimica-Dukic, Neda; Budakov, Branislav; Cvjeticanin, Stanko

2012-01-01

The present study examined regional distribution of opiate alkaloids from seized heroin in brain regions of experimental animals in order to select parts with the highest content of opiates. Their analysis should contribute to resolve causes of death due to heroin intake. The tests were performed at different time periods (5, 15, 45 and 120 min) after male and female Wistar rats were treated with seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6-acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain regions known for their high concentration of µ-opiate receptors: cortex, brainstem, amygdala and basal ganglia, by using gas chromatography–mass spectrometry (GC–MS). The highest content of opiate alkaloids in the brain tissue of female animals was found 15 min and in male animals 45 min after treatment. The highest content of opiates was determined in the basal ganglia of the animals of both genders, indicating that this part of brain tissue presents a reliable sample for identifying and assessing contents of opiates after heroin intake. PMID:23554560

The NSW brain tissue resource centre: Banking for alcohol and major neuropsychiatric disorders research.

PubMed

Sutherland, G T; Sheedy, D; Stevens, J; McCrossin, T; Smith, C C; van Roijen, M; Kril, J J

2016-05-01

The New South Wales Brain Tissue Resource Centre (NSWBTRC) at the University of Sydney (Australia) is an established human brain bank providing tissue to the neuroscience research community for investigations on alcohol-related brain damage and major psychiatric illnesses such as schizophrenia. The NSWBTRC relies on wide community engagement to encourage those with and without neuropsychiatric illness to consent to donation through its allied research programs. The subsequent provision of high-quality samples relies on standardized operational protocols, associated clinical data, quality control measures, integrated information systems, robust infrastructure, and governance. These processes are continually augmented to complement the changes in internal and external governance as well as the complexity and diversity of advanced investigation techniques. This report provides an overview of the dynamic process of brain banking and discusses the challenges of meeting the future needs of researchers, including synchronicity with other disease-focus collections. Copyright © 2016 Elsevier Inc. All rights reserved.

Roles of elevated 20‑HETE in the breakdown of blood brain barrier and the severity of brain edema in experimental traumatic brain injury.

PubMed

Lu, Liyan; Wang, Mingliang; Yuan, Fang; Wei, Xiaoer; Li, Wenbin

2018-05-01

Breakdown of the blood brain barrier (BBB) is a secondary injury following traumatic brain injury (TBI) and can lead to the development of brain edema. However, the factors that contribute to the disruption of the BBB and increase the severity of brain edema in TBI remain to be elucidated. 20‑hydroxyeicosatetraenoic acid (20‑HETE) is a metabolite of arachidonic acid. The inhibition of 20‑HETEsynthesis by HET0016 has been suggested as a strategy to decrease brain edema. The present study aimed to investigate whether the elevated production of 20‑HETE in cerebral tissue may contribute to BBB breakdown and increase the severity of brain edema in rats with TBI. BBB permeability was quantified using dynamic contrast‑enhanced magnetic resonance imaging and brain edema was measured according to brain water content. Superoxide production in injured tissue was also assessed. Liquid chromatography‑mass spectrometry was used to evaluate 20‑HETE production in injured tissue. Western blot analysis was used to assess the expression of occludin, zonula occludens (ZO)‑1, matrix metalloproteinase (MMP)‑9, and proteins of the c‑Jun N‑terminal kinase (JNK) pathway. A total of 3, 24 and 72 h following the induction of TBI, 20‑HETE levels, BBB permeability and brain edema were identified to be increased, accompanied by an increase in superoxide production. Conversely, superoxide dismutase levels, in addition to the total antioxidative capability were decreased. In addition, the expression of MMP‑9 and proteins of the JNK pathway was upregulated, whereas the expression of occludin and ZO‑1 was observed to be suppressed. These results suggested that 20‑HETE may aggravate BBB disruption following TBI, via enhancing the expression of MMP‑9 and tight junction proteins. Furthermore, oxidative stress and the JNK signaling pathway may be involved in BBB dysregulation. In conclusion, the results of the present demonstrated that the production of 20‑HETE was increased in cerebral tissue following traumatic injury, thus suggesting that it may contribute to the compromise of BBB integrity and the development of brain edema.

3D surface rendered MR images of the brain and its vasculature.

PubMed

Cline, H E; Lorensen, W E; Souza, S P; Jolesz, F A; Kikinis, R; Gerig, G; Kennedy, T E

1991-01-01

Both time-of-flight and phase contrast magnetic resonance angiography images are combined with stationary tissue images to provide data depicting two contrast relationships yielding intrinsic discrimination of brain matter and flowing blood. A computer analysis is based on nearest neighbor segmentation and the connection between anatomical structures to partition the images into different tissue categories: from which, high resolution brain parenchymal and vascular surfaces are constructed and rendered in juxtaposition, aiding in surgical planning.

Detection of brain tumor margins using optical coherence tomography

NASA Astrophysics Data System (ADS)

Juarez-Chambi, Ronald M.; Kut, Carmen; Rico-Jimenez, Jesus; Campos-Delgado, Daniel U.; Quinones-Hinojosa, Alfredo; Li, Xingde; Jo, Javier

2018-02-01

In brain cancer surgery, it is critical to achieve extensive resection without compromising adjacent healthy, noncancerous regions. Various technological advances have made major contributions in imaging, including intraoperative magnetic imaging (MRI) and computed tomography (CT). However, these technologies have pros and cons in providing quantitative, real-time and three-dimensional (3D) continuous guidance in brain cancer detection. Optical Coherence Tomography (OCT) is a non-invasive, label-free, cost-effective technique capable of imaging tissue in three dimensions and real time. The purpose of this study is to reliably and efficiently discriminate between non-cancer and cancerinfiltrated brain regions using OCT images. To this end, a mathematical model for quantitative evaluation known as the Blind End-Member and Abundances Extraction method (BEAE). This BEAE method is a constrained optimization technique which extracts spatial information from volumetric OCT images. Using this novel method, we are able to discriminate between cancerous and non-cancerous tissues and using logistic regression as a classifier for automatic brain tumor margin detection. Using this technique, we are able to achieve excellent performance using an extensive cross-validation of the training dataset (sensitivity 92.91% and specificity 98.15%) and again using an independent, blinded validation dataset (sensitivity 92.91% and specificity 86.36%). In summary, BEAE is well-suited to differentiate brain tissue which could support the guiding surgery process for tissue resection.

Detection of brain tumor margins using optical coherence tomography

NASA Astrophysics Data System (ADS)

Juarez-Chambi, Ronald M.; Kut, Carmen; Rico-Jimenez, Jesus; Campos-Delgado, Daniel U.; Quinones-Hinojosa, Alfredo; Li, Xingde; Jo, Javier

2018-02-01

In brain cancer surgery, it is critical to achieve extensive resection without compromising adjacent healthy, non-cancerous regions. Various technological advances have made major contributions in imaging, including intraoperative magnetic imaging (MRI) and computed tomography (CT). However, these technologies have pros and cons in providing quantitative, real-time and three-dimensional (3D) continuous guidance in brain cancer detection. Optical Coherence Tomography (OCT) is a non-invasive, label-free, cost-effective technique capable of imaging tissue in three dimensions and real time. The purpose of this study is to reliably and efficiently discriminate between non-cancer and cancer-infiltrated brain regions using OCT images. To this end, a mathematical model for quantitative evaluation known as the Blind End- Member and Abundances Extraction method (BEAE). This BEAE method is a constrained optimization technique which extracts spatial information from volumetric OCT images. Using this novel method, we are able to discriminate between cancerous and non-cancerous tissues and using logistic regression as a classifier for automatic brain tumor margin detection. Using this technique, we are able to achieve excellent performance using an extensive cross-validation of the training dataset (sensitivity 92.91% and specificity 98.15%) and again using an independent, blinded validation dataset (sensitivity 92.91% and specificity 86.36%). In summary, BEAE is well-suited to differentiate brain tissue which could support the guiding surgery process for tissue resection.

Red and NIR light dosimetry in the human deep brain

NASA Astrophysics Data System (ADS)

Pitzschke, A.; Lovisa, B.; Seydoux, O.; Zellweger, M.; Pfleiderer, M.; Tardy, Y.; Wagnières, G.

2015-04-01

Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson’s Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 × 201 × 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated μeff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.

Quantitative Susceptibility Mapping of Human Brain Reflects Spatial Variation in Tissue Composition

PubMed Central

Li, Wei; Wu, Bing; Liu, Chunlei

2011-01-01

Image phase from gradient echo MRI provides a unique contrast that reflects brain tissue composition variations, such as iron and myelin distribution. Phase imaging is emerging as a powerful tool for the investigation of functional brain anatomy and disease diagnosis. However, the quantitative value of phase is compromised by its nonlocal and orientation dependent properties. There is an increasing need for reliable quantification of magnetic susceptibility, the intrinsic property of tissue. In this study, we developed a novel and accurate susceptibility mapping method that is also phase-wrap insensitive. The proposed susceptibility mapping method utilized two complementary equations: (1) the Fourier relationship of phase and magnetic susceptibility; and (2) the first-order partial derivative of the first equation in the spatial frequency domain. In numerical simulation, this method reconstructed the susceptibility map almost free of streaking artifact. Further, the iterative implementation of this method allowed for high quality reconstruction of susceptibility maps of human brain in vivo. The reconstructed susceptibility map provided excellent contrast of iron-rich deep nuclei and white matter bundles from surrounding tissues. Further, it also revealed anisotropic magnetic susceptibility in brain white matter. Hence, the proposed susceptibility mapping method may provide a powerful tool for the study of brain physiology and pathophysiology. Further elucidation of anisotropic magnetic susceptibility in vivo may allow us to gain more insight into the white matter microarchitectures. PMID:21224002

Optical properties of mouse brain tissue after optical clearing with FocusClear™

NASA Astrophysics Data System (ADS)

Moy, Austin J.; Capulong, Bernard V.; Saager, Rolf B.; Wiersma, Matthew P.; Lo, Patrick C.; Durkin, Anthony J.; Choi, Bernard

2015-09-01

Fluorescence microscopy is commonly used to investigate disease progression in biological tissues. Biological tissues, however, are strongly scattering in the visible wavelengths, limiting the application of fluorescence microscopy to superficial (<200 μm) regions. Optical clearing, which involves incubation of the tissue in a chemical bath, reduces the optical scattering in tissue, resulting in increased tissue transparency and optical imaging depth. The goal of this study was to determine the time- and wavelength-resolved dynamics of the optical scattering properties of rodent brain after optical clearing with FocusClear™. Light transmittance and reflectance of 1-mm mouse brain sections were measured using an integrating sphere before and after optical clearing and the inverse adding doubling algorithm used to determine tissue optical scattering. The degree of optical clearing was quantified by calculating the optical clearing potential (OCP), and the effects of differing OCP were demonstrated using the optical histology method, which combines tissue optical clearing with optical imaging to visualize the microvasculature. We observed increased tissue transparency with longer optical clearing time and an analogous increase in OCP. Furthermore, OCP did not vary substantially between 400 and 1000 nm for increasing optical clearing durations, suggesting that optical histology can improve ex vivo visualization of several fluorescent probes.

A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats☆

PubMed Central

Jin, Minghua; Song, Peilin; Li, Na; Li, Xuejun; Chen, Jiajun

2012-01-01

Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and demonstrated that the poisoning was dose-dependent. PMID:25538742

In-vivo imaging of the morphology and blood perfusion of brain tumours in rats with UHR-OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Bizheva, Kostadinka; Tan, Bingyao; Fisher, Carl J.; Mason, Erik; Lilge, Lothar D.

2017-02-01

Brain tumors are characterized with morphological changes at cellular level such as enlarged, non-spherical nuclei, microcalcifications, cysts, etc., and are highly vascularized. In this study, two research-grade optical coherence tomography (OCT) systems operating at 800 nm and 1060 nm with axial resolution of 0.95 µm and 3.5 µm in biological tissue respectively, were used to image in vivo and ex vivo the structure of brain tumours in rats. Female Fischer 344 rats were used for this study, which has received ethics clearance by the Animal Research Ethics Committees of the University of Waterloo and the University Health Network, Toronto. Brain tumours were induced by injection of rat brain cancer cell line (RG2 glioma) through a small craniotomy. Presence of brain tumours was verified by MRI imaging on day 7 post tumour cells injection. The in vivo OCT imaging session was conducted on day 14 of the study with the 1060 nm OCT system and both morphological OCT, Doppler OCT and OMAG images were acquired from the brain tumour and the surrounding healthy brain tissue. After completion of the imaging procedure, the brains were harvested, fixed in formalin and reimaged after 2 weeks with the 800 nm OCT system. The in vivo and ex vivo OCT morphological images were correlated with H and E histology. Results from this study demonstrate that UHR-OCT can distinguish between healthy and cancerous brain tissue based on differences in structural and vascular pattern.

Interleukin-10 gene polymorphisms are associated with Behcet's disease but not with Vogt-Koyanagi-Harada syndrome in the Chinese Han population.

PubMed

Hu, Jianmin; Hou, Shengping; Zhu, Xueping; Fang, Jing; Zhou, Yan; Liu, Yunjia; Bai, Lin; Kijlstra, Aize; Yang, Peizeng

2015-01-01

This study aimed to investigate the association of interleukin (IL)-10 gene polymorphisms with Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in the Chinese Han population. A two-stage association study was performed on 718 BD patients, 300 VKH patients, and 1,753 controls. Genotyping of the IL-10 gene was performed for six single nucleotide polymorphisms (SNPs), including rs1800871, rs1800872, rs1800896, rs3021094, rs3790622, and rs1554286 using PCR-restricted fragment length polymorphism or TaqMan SNP assays. Real-time PCR was performed to test the IL-10 mRNA expression of the associated polymorphisms. The first-stage result showed significantly increased frequencies of the rs1800871 T allele, rs1800872 A allele, and rs1554286 T allele in BD patients compared with controls (Pcorrected (Pcorr)=1.82×10(-5), OR=1.837; Pcorr=6.1×10(-5), OR=1.780; Pcorr=3.15×10(-5), OR=1.794, respectively). There was no association of the tested six SNPs with VKH syndrome. A second-stage study was therefore performed in BD patients to validate the result of the first stage, showing a significantly increased frequency of the rs1800871 T allele (Second stage, Pcorr=5.59×10(-5), OR=1.493; Combined data, Pcorr=3.65×10(-11), OR=1.632). Compared to the controls, an increased frequency of the rs1800871 T allele was observed in BD patients with extraocular findings, including genital ulcers, skin lesions, and a positive pathergy test. No difference was found among the mRNA expressions of IL-10 in the peripheral blood mononuclear cells (PBMCs) of controls with different genotypes of rs1800871 after stimulation of lipopolysaccharide (LPS) or anti-CD3/CD28 antibodies. The findings showed that IL-10 is a risk gene for BD but not for VKH syndrome.

Vascular endothelial function and oxidative stress mechanisms in patients with Behçet's syndrome.

PubMed

Chambers, J C; Haskard, D O; Kooner, J S

2001-02-01

We sought to test the hypothesis that vascular endothelial function is impaired in Behçet's syndrome and reflects increased levels of oxidative stress. Behçet's syndrome is a multisystem inflammatory disorder commonly complicated by vascular thrombosis and arterial aneurysm formation. The precise mechanisms underlying vascular disease in Behçet's syndrome are not known. We studied 19 patients with Behçet's syndrome (18 to 50 years old, 9 men) and 21 healthy volunteers (18 to 50 years old, 10 men). Brachial artery flow-mediated dilation (endothelium-dependent), and nitroglycerin (NTG)-induced dilation (endothelium-independent) were measured. To investigate oxidative stress mechanisms, vascular studies were repeated 1 h after administration of vitamin C (1 g, intravenous) in 12 patients and 12 control subjects. Flow-mediated dilation was reduced in patients with Behcet's syndrome as compared with control subjects (0.7 +/- 0.9% vs. 5.7 +/- 0.9%, p = 0.001). In contrast, there were no significant differences in the brachial artery diameter (4.2 +/- 0.2 vs. 4.0 +/- 0.2 mm, p = 0.47) or NTG-induced dilation (19.7 +/- 1.9% vs. 19.7 +/- 1.2%, p = 0.98). In regression analysis, Behçet's syndrome was associated with impaired flow-mediated dilation independent of age, gender, brachial artery diameter, blood pressure, cholesterol and glucose. Vitamin C increased flow-mediated dilation in Behçet's syndrome (0.2 +/- 0.7% to 3.5 +/- 1.0%, p = 0.002), but not in control subjects (4.3 +/- 0.6% to 4.7 +/- 0.4%, p = 0.51). In both groups, NTG-induced dilation and brachial artery diameter were unchanged after vitamin C treatment. Vascular endothelial function is impaired in Behcet's syndrome and can be rapidly improved by vitamin C treatment. Our results support a role for oxidative stress in the pathophysiology of Behçet's syndrome and provide a rationale for therapeutic studies aimed at reducing vascular complications in this disorder.

Time-frequency analyses of fluid-solid interaction under sinusoidal translational shear deformation of the viscoelastic rat cerebrum

NASA Astrophysics Data System (ADS)

Leahy, Lauren N.; Haslach, Henry W.

2018-02-01

During normal extracellular fluid (ECF) flow in the brain glymphatic system or during pathological flow induced by trauma resulting from impacts and blast waves, ECF-solid matter interactions result from sinusoidal shear waves in the brain and cranial arterial tissue, both heterogeneous biological tissues with high fluid content. The flow in the glymphatic system is known to be forced by pulsations of the cranial arteries at about 1 Hz. The experimental shear stress response to sinusoidal translational shear deformation at 1 Hz and 25% strain amplitude and either 0% or 33% compression is compared for rat cerebrum and bovine aortic tissue. Time-frequency analyses aim to correlate the shear stress signal frequency components over time with the behavior of brain tissue constituents to identify the physical source of the shear nonlinear viscoelastic response. Discrete fast Fourier transformation analysis and the novel application to the shear stress signal of harmonic wavelet decomposition both show significant 1 Hz and 3 Hz components. The 3 Hz component in brain tissue, whose magnitude is much larger than in aortic tissue, may result from interstitial fluid induced drag forces. The harmonic wavelet decomposition locates 3 Hz harmonics whose magnitudes decrease on subsequent cycles perhaps because of bond breaking that results in easier fluid movement. Both tissues exhibit transient shear stress softening similar to the Mullins effect in rubber. The form of a new mathematical model for the drag force produced by ECF-solid matter interactions captures the third harmonic seen experimentally.

[Chromogranin A derived peptide CGA47-66 inhibits hyper-permeability of blood brain barrier in mice with sepsis].

PubMed

Zeng, Yan; Zhang, Dan; Jiang, Liping; Wei, Fu; Xu, Shan

2016-02-01

To explore the effect of chromofungin (CHR), a chromogranin A (CGA) derived peptide CGA47-66, on hyper-permeability of blood brain barrier in septic mice. 120 healthy male C57BL/6 mice were randomly divided into groups, with 12 mice in each group. Seventy-two mice were used for dynamic observation of the contents of water and Evan blue (EB) in brain tissue after being treated with lipopolysaccharide (LPS). Another 48 mice were divided into normal saline control group (NS group), LPS induced sepsis model group (LPS group), low-dose CHR pretreatment group (CL+LPS group), and high-dose CHR pretreatment group (CH+LPS group). The septic model was reproduced by intraperitoneal injection of 10 mg/kg LPS 0.1 mL, and the mice in NS group was given equal volume of normal saline. The mice in CL+LPS group and CH+LPS group were intraperitoneally injected with 15.5 μg/kg and 77.5 μg/kg CHR 10 minutes before LPS injection. Six hours after LPS injection, 4 mL/kg of 2% EB was injected via caudal vein, the contents of water and EB in brain tissue were determined, and EB immune fluorescence in brain tissue was determined to assess the changes in permeability of blood brain barrier. Brain pathology was observed with hematoxylin and eosin (HE) staining. With the extension of time after LPS injection, the contents of water and EB in brain tissue were gradually increased, and the time of difference with statistical significance appeared earlier when compared with that of control group in the contents of water than that in EB contents (3 hours and 6 hours, respectively). The contents of water and EB in brain tissue in LPS group were significantly increased as compared with NS group [water content: (79.77±0.62)% vs. (78.28±0.44)%, P < 0.01; EB content (μg/g): 13.87±4.50 vs. 7.13±1.76, P < 0.05]. CHR pretreatment with either of two dosages could reverse the increase in water and EB contents in brain tissue induced by LPS, and the effect was more significant in CH+LPS group [water content: (78.15±0.73)% vs. (79.77±0.62)%, EB (μg/g): 7.09±2.59 vs. 13.87±4.50, both P < 0.05]. It was shown by EB fluorescence observation that the fluorescence signal displayed only in the meninges in NS group, and EB fluorescence was widely distributed in brain parenchyma in LPS group, indicating that the EB leakage in LPS group was more marked than that of NS group. In CHR pretreatment groups, EB fluorescence was decreased in brain parenchyma, indicating that EB leakage was significantly less marked, while it was more obvious in high dose CHR group. It was shown by HE staining that cerebral blood vessel structure was intact in NS group, and the gap around blood vessel was not significant increased. On the other hand, brain structure in LPS group appeared loose, with widening of small perivascular spaces and obvious edema. Brain edema in CHR pretreatment groups was improved as compared with that of the LPS group, and it was more apparent in high dose CHR group. LPS induced change in blood brain barrier permeability in mice in a time-dependent manner. Exogenous CGA derived peptides CHR can inhibit LPS induced hyper-permeability of blood brain barrier in septic mice, thus reduces brain edema, protects the brain tissue, and the effect is more obvious with a high dose of CHR (77.5 μg/kg).

Synthesis and Preliminary Evaluation of Phenyl 4-123I-Iodophenylcarbamate for Visualization of Cholinesterases Associated with Alzheimer Disease Pathology.

PubMed

Macdonald, Ian R; Reid, G Andrew; Pottie, Ian R; Martin, Earl; Darvesh, Sultan

2016-02-01

Acetylcholinesterase and butyrylcholinesterase accumulate with brain β-amyloid (Aβ) plaques in Alzheimer disease (AD). The overall activity of acetylcholinesterase is found to decline in AD, whereas butyrylcholinesterase has been found to either increase or remain the same. Although some cognitively normal older adults also have Aβ plaques within the brain, cholinesterase-associated plaques are generally less abundant in such individuals. Thus, brain imaging of cholinesterase activity associated with Aβ plaques has the potential to distinguish AD from cognitively normal older adults, with or without Aβ accumulation, during life. Current Aβ imaging agents are not able to provide this distinction. To address this unmet need, synthesis and evaluation of a cholinesterase-binding ligand, phenyl 4-(123)I-iodophenylcarbamate ((123)I-PIP), is described. Phenyl 4-iodophenylcarbamate was synthesized and evaluated for binding potency toward acetylcholinesterase and butyrylcholinesterase using enzyme kinetic analysis. This compound was subsequently rapidly radiolabeled with (123)I and purified by high-performance liquid chromatography. Autoradiographic analyses were performed with (123)I-PIP using postmortem orbitofrontal cortex from cognitively normal and AD human brains. Comparisons were made with an Aβ imaging agent, 2-(4'-dimethylaminophenyl)-6-(123)I-iodo-imidazo[1,2-a]pyridine ((123)I-IMPY), in adjacent brain sections. Tissues were also stained for Aβ and cholinesterase activity to visualize Aβ plaque load for comparison with radioligand uptake. Synthesized and purified PIP exhibited binding to cholinesterases. (123)I was successfully incorporated into this ligand. (123)I-PIP autoradiography with human tissue revealed accumulation of radioactivity only in AD brain tissues in which Aβ plaques had cholinesterase activity. (123)I-IMPY accumulated in brain tissues with Aβ plaques from both AD and cognitively normal individuals. Radiolabeled ligands specific for cholinesterases have potential for use in neuroimaging AD plaques during life. The compound herein described, (123)I-PIP, can detect cholinesterases associated with Aβ plaques and can distinguish AD brain tissues from those of cognitively normal older adults with Aβ plaques. Imaging cholinesterase activity associated with Aβ plaques in the living brain may contribute to the definitive diagnosis of AD during life. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Postmortem Brain and Blood Reference Concentrations of Alprazolam, Bromazepam, Chlordiazepoxide, Diazepam, and their Metabolites and a Review of the Literature.

PubMed

Skov, Louise; Holm, Karen Marie Dollerup; Johansen, Sys Stybe; Linnet, Kristian

2016-09-01

To interpret postmortem toxicology results, reference concentrations for non-toxic and toxic levels are needed. Usually, measurements are performed in blood, but because of postmortem redistribution phenomena this may not be optimal. Rather, measurement in the target organ of psychoactive drugs, the brain, might be considered. Here we present reference concentrations of femoral blood and brain tissue of selected benzodiazepines (BZDs). Using LC-MS/MS, we quantified alprazolam, bromazepam, chlordiazepoxide, diazepam, and the metabolites desmethyldiazepam, oxazepam and temazepam in postmortem femoral blood and brain tissue in 104 cases. BZDs were judged to be unrelated to the cause of death in 88 cases and contributing to death in 16 cases. No cases were found with cause of death solely attributed to BZD poisoning. All BZDs investigated tended to have higher concentrations in brain than in blood with median brain-blood ratios ranging from 1.1 to 2.3. A positive correlation between brain and blood concentrations was found with R(2) values from 0.51 to 0.95. Our reported femoral blood concentrations concur with literature values, but sparse information on brain concentration was available. Drug-metabolite ratios were similar in brain and blood for most compounds. Duplicate measurements of brain samples showed that the pre-analytical variation in brain (5.9%) was relatively low, supporting the notion that brain tissue is a suitable postmortem specimen. The reported concentrations in both brain and blood can be used as reference values when evaluating postmortem cases. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Biological and molecular characterizations of Toxoplasma gondii strains obtained from Southern sea otters (Enhydra lutris nereis)

USGS Publications Warehouse

Cole, Rebecca A.; Lindsay, D.S.; Howe, D.K.; Roderick, Constance L.; Dubey, J.P.; Thomas, N.J.; Baeten, L.A.

2000-01-01

Toxoplasma gondii was isolated from brain or heart tissue from 15 southern sea otters (Enhydra lutris nereis) in cell cultures. These strains were used to infect mice that developed antibodies to T. gondii as detected in the modified direct agglutination test and had T. gondii tissue cysts in their brains at necropsy. Mouse brains containing tissue cysts from 4 of the strains were fed to 4 cats. Two of the cats excreted T. gondii oocysts in their feces that were infectious for mice. Molecular analyses of 13 strains indicated that they were all type II strains, but that they were genetically distinct from one another.

Large-scale Scanning Transmission Electron Microscopy (Nanotomy) of Healthy and Injured Zebrafish Brain.

PubMed

Kuipers, Jeroen; Kalicharan, Ruby D; Wolters, Anouk H G; van Ham, Tjakko J; Giepmans, Ben N G

2016-05-25

Large-scale 2D electron microscopy (EM), or nanotomy, is the tissue-wide application of nanoscale resolution electron microscopy. Others and we previously applied large scale EM to human skin pancreatic islets, tissue culture and whole zebrafish larvae(1-7). Here we describe a universally applicable method for tissue-scale scanning EM for unbiased detection of sub-cellular and molecular features. Nanotomy was applied to investigate the healthy and a neurodegenerative zebrafish brain. Our method is based on standardized EM sample preparation protocols: Fixation with glutaraldehyde and osmium, followed by epoxy-resin embedding, ultrathin sectioning and mounting of ultrathin-sections on one-hole grids, followed by post staining with uranyl and lead. Large-scale 2D EM mosaic images are acquired using a scanning EM connected to an external large area scan generator using scanning transmission EM (STEM). Large scale EM images are typically ~ 5 - 50 G pixels in size, and best viewed using zoomable HTML files, which can be opened in any web browser, similar to online geographical HTML maps. This method can be applied to (human) tissue, cross sections of whole animals as well as tissue culture(1-5). Here, zebrafish brains were analyzed in a non-invasive neuronal ablation model. We visualize within a single dataset tissue, cellular and subcellular changes which can be quantified in various cell types including neurons and microglia, the brain's macrophages. In addition, nanotomy facilitates the correlation of EM with light microscopy (CLEM)(8) on the same tissue, as large surface areas previously imaged using fluorescent microscopy, can subsequently be subjected to large area EM, resulting in the nano-anatomy (nanotomy) of tissues. In all, nanotomy allows unbiased detection of features at EM level in a tissue-wide quantifiable manner.

Large-scale Scanning Transmission Electron Microscopy (Nanotomy) of Healthy and Injured Zebrafish Brain

PubMed Central

Kuipers, Jeroen; Kalicharan, Ruby D.; Wolters, Anouk H. G.

2016-01-01

Large-scale 2D electron microscopy (EM), or nanotomy, is the tissue-wide application of nanoscale resolution electron microscopy. Others and we previously applied large scale EM to human skin pancreatic islets, tissue culture and whole zebrafish larvae1-7. Here we describe a universally applicable method for tissue-scale scanning EM for unbiased detection of sub-cellular and molecular features. Nanotomy was applied to investigate the healthy and a neurodegenerative zebrafish brain. Our method is based on standardized EM sample preparation protocols: Fixation with glutaraldehyde and osmium, followed by epoxy-resin embedding, ultrathin sectioning and mounting of ultrathin-sections on one-hole grids, followed by post staining with uranyl and lead. Large-scale 2D EM mosaic images are acquired using a scanning EM connected to an external large area scan generator using scanning transmission EM (STEM). Large scale EM images are typically ~ 5 - 50 G pixels in size, and best viewed using zoomable HTML files, which can be opened in any web browser, similar to online geographical HTML maps. This method can be applied to (human) tissue, cross sections of whole animals as well as tissue culture1-5. Here, zebrafish brains were analyzed in a non-invasive neuronal ablation model. We visualize within a single dataset tissue, cellular and subcellular changes which can be quantified in various cell types including neurons and microglia, the brain's macrophages. In addition, nanotomy facilitates the correlation of EM with light microscopy (CLEM)8 on the same tissue, as large surface areas previously imaged using fluorescent microscopy, can subsequently be subjected to large area EM, resulting in the nano-anatomy (nanotomy) of tissues. In all, nanotomy allows unbiased detection of features at EM level in a tissue-wide quantifiable manner. PMID:27285162

Tissue oxidative metabolism can increase the difference between local temperature and arterial blood temperature by up to 1.3oC: Implications for brain, brown adipose tissue, and muscle physiology.

PubMed

Zaretsky, Dmitry V; Romanovsky, Andrej A; Zaretskaia, Maria V; Molkov, Yaroslav I

2018-01-01

Tissue temperature increases, when oxidative metabolism is boosted. The source of nutrients and oxygen for this metabolism is the blood. The blood also cools down the tissue, and this is the only cooling mechanism, when direct dissipation of heat from the tissue to the environment is insignificant, e.g. , in the brain. While this concept is relatively simple, it has not been described quantitatively. The purpose of the present work was to answer two questions: 1) to what extent can oxidative metabolism make the organ tissue warmer than the body core, and, 2) how quickly are changes in the local metabolism reflected in the temperature of the tissue? Our theoretical analysis demonstrates that, at equilibrium, given that heat exchange with the organ is provided by the blood, the temperature difference between the organ tissue and the arterial blood is proportional to the arteriovenous difference in oxygen content, does not depend on the blood flow, and cannot exceed 1.3 o C. Unlike the equilibrium temperature difference, the rate of change of the local temperature, with respect to time, does depend on the blood flow. In organs with high perfusion rates, such as the brain and muscles, temperature changes occur on a time scale of a few minutes. In organs with low perfusion rates, such changes may have characteristic time constants of tens or hundreds of minutes. Our analysis explains, why arterial blood temperature is the main determinant of the temperature of tissues with limited heat exchange, such as the brain.

Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions

PubMed Central

Dubey, Jitender P.; Ferreira, Leandra R.; Alsaad, Mohammad; Verma, Shiv K.; Alves, Derron A.; Holland, Gary N.; McConkey, Glenn A.

2016-01-01

Background The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse. Methodology/Principal Findings Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains) of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection) of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i.) to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25%) of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle. Conclusion/Significance This study reevaluated in depth the rat model of toxoplasmosis visualizing cyst rupture and clarified many aspects of the biology of the parasite useful for future investigations. PMID:27228262

The Brain.

ERIC Educational Resources Information Center

Hubel, David H.

1979-01-01

This article on the brain is part of an entire issue about neurobiology and the question of how the human brain works. The brain as an intricate tissue composed of cells is discussed based on the current knowledge and understanding of its composition and structure. (SA)

Identification of Insulin Receptor Splice Variant B in Neurons by in situ Detection in Human Brain Samples.

PubMed

Spencer, Brian; Rank, Logan; Metcalf, Jeff; Desplats, Paula

2018-03-06

Insulin and its receptor are widely expressed in a variety of tissues throughout the body including liver, adipose tissue, liver and brain. The insulin receptor is expressed as two functionally distinct isoforms, differentiated by a single 12 amino acid exon. The two receptor isoforms, designated IR/A and IR/B, are expressed in a highly tissue and cell specific manner and relative proportions of the different isoforms vary during development, aging and disease states. The high degree of similarity between the two isoforms has prevented detailed studies as differentiation of the two isoforms by traditional immunological methods cannot be achieved. We describe here a new in situ RT-PCR/ FISH assay that allows for the visualization of IR/A and IR/B in tissue along with tissue specific markers. We used this new method to show for the first time that IR/A and IR/B are both expressed in neurons in the adult human brain. Thus, we present a method that enables the investigation of IR/A and IR/B insulin receptor isoform expression in situ in various tissues.

A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes

PubMed Central

Nitzsche, Björn; Frey, Stephen; Collins, Louis D.; Seeger, Johannes; Lobsien, Donald; Dreyer, Antje; Kirsten, Holger; Stoffel, Michael H.; Fonov, Vladimir S.; Boltze, Johannes

2015-01-01

Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs, and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM) that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams) were acquired on a 1.5 T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight (BW), age, and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM) and white (WM) matter as well as cerebrospinal fluid (CSF) classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM). Overall, a positive correlation of GM volume and BW explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species. PMID:26089780

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue.

PubMed

Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Lenhard, Diana Constanze; Naganawa, Shinji; Pietsch, Hubertus

2017-07-01

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. • Gadolinium-based contrast agents can cross the blood-CSF barrier. • Fluid-attenuated MRI shows GBCA distribution with CSF flow. • GBCA structure and physicochemical properties do not impact CSF penetration and distribution. • GBCA clearance from CSF was almost complete within 24 h in rats. • CSF is a potential pathway of GBCA entry into the brain.

Estrogen synthesis and signaling pathways during ageing: from periphery to brain

PubMed Central

Cui, Jie; Shen, Yong; Li, Rena

2012-01-01

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissue as liver, heart, muscle, bone and brain. The tissue-specific estrogen synthesis is consistent with a diversity of estrogen actions. Here, we will focus on tissue and cell-specific estrogen synthesis and estrogen receptor signaling. This review will include three parts: (I) tissue and cell-specific estrogen synthesis and metabolism, (II) tissue and cell-specific distribution of estrogen receptors and signaling and (III) tissue-specific estrogen function and related disorders, including cardiovascular diseases, osteoporosis, Alzheimer's disease and Parkinson disease. This comprehensive review provides new insights into estrogens by giving a better understanding of the tissue-specific estrogen effects and their roles in various diseases. PMID:23348042