Development of a rapid autopsy program for studies of brain immunity

Ghorpade, Anuja; Bruch, Leslie A.; Persidsky, Yuri; Chin, Betty; Brown, William; Borgmann, Kathleen; Persidsky, Raisa; Wu, Li; Holter, Spring; Cotter, Robin L.; Faraci, Jill; Heilman, David; Meyer, V.S.E.; Potter, Jane; Swindells, Susan; Gendelman, Howard E.

doi:10.1016/j.jneuroim.2005.01.021

Cited by 18 publications

(12 citation statements)

References 30 publications

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“…17 The brain tissue is obtained following the rapid autopsy protocol. 20 Plaques (outside neurons) and neurofibrillary tangles (inside neurons) are clearly visible here, confirming the anatomopathological diagnosis of the disease. From Figure 1, it is clear that in the advanced stage of the disease, a substantial part of the brain is affected.…”

Section: Beta Amyloid Peptide and Alzheimer's Diseasesupporting

confidence: 77%

Electroacupuncture Effects on the Disintegration of Beta Amyloid Sheets: Its Application to Alzheimer's Disease

Joshi

Páez

Araque

2012

Medical Acupuncture

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Recent research indicates that electroacupuncture could help patients suffering from Alzheimer's disease. Indeed, certain acupoints, when stimulated by electric pulses, activate particular parts of the brain, the details of which have been revealed by magnetic resonance imaging and positron emission tomography. Observed stimulated regions of the brain of Alzheimer's patients can be compared with the images obtained by fluorescence technique with a proper dye in Alzheimer's brain sections. This article provides support based on Western medical science for the treatment of Alzheimer's with electroacupuncture. Electroacupuncture acts in different and efficient ways. First, the positive charge of the electric pulses helps to detach from the neuron or the neuron membranes b amyloid peptides, which have been associated with the pathogenesis of the disease. In addition to this, the presence of the carboxyl group of b amyloids suffers a torque in the presence of an electric field and creates a serious deformation. Lastly, the moderate shaking originating from the electric pulses facilitates the partial disintegration of the b sheet, a frequent conformational change of the b amyloid peptide.

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Section: Beta Amyloid Peptide and Alzheimer's Diseasesupporting

confidence: 77%

Electroacupuncture Effects on the Disintegration of Beta Amyloid Sheets: Its Application to Alzheimer's Disease

Joshi

Páez

Araque

2012

Medical Acupuncture

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“…HIVE and HAD diagnoses were performed by neuropathologists and neuropsychologists of the NNTC and the CNND rapid autopsy program. 44,45 Plasma and cerebrospinal fluid (CSF) viral load (VL) and CD4 counts were available for donors P1 and P4, HAD1, HAD2, and HAD5. For patient P1, plasma VL was 684 444 copies/mL, CD4 ϩ T-cell count was 13/mm 3 , and CSF VL was 2300 copies/mL.…”

Section: Activation and Overexpression Of Stat1 And Proinflammatory Mmentioning

confidence: 99%

STAT1 signaling modulates HIV-1–induced inflammatory responses and leukocyte transmigration across the blood-brain barrier

Chaudhuri

Yang

Gendelman

et al. 2008

Blood

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129

156

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The relationship among neuroinflammation, blood-brain barrier (BBB) dysfunction, and progressive HIV-1 infection as they affect the onset and development of neuroAIDS is incompletely understood. IntroductionHuman immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) commonly results in behavioral, motor, and cognitive impairments. [1][2][3] Although disease severity and progression has slowed, in part, as a result of antiretroviral therapy, 76% to 83% of brain autopsies continue to show observable neuropathological abnormalities. [4][5][6] Disease pathology ranges from mild brain atrophy and gliosis to robust viral replication, multinucleated giant cell formation, astrogliosis and microgliosis, myelin pallor, and neuronal loss. 7,8 These pathological findings are collectively termed HIV-1 encephalitis (HIVE). HIVE is a common correlate to the later stages of behavioral, motor, neuropsychiatric, and neurologic consequences of disease termed HIV-1-associated dementia (HAD) (for recent reviews, see McArthur 1 ; Grant et al 2 ; Ghafouri 3 ). HIVE is fueled by viral infection and immune activation of brain mononuclear phagocytes (MPs: blood-derived perivascular macrophages and microglia). 9 Such MP-and virus-associated neuroinflammation promotes monocyte trafficking across the bloodbrain barrier (BBB), MP infiltration into the CNS, and neurodegeneration. [10][11][12] Thus, dysfunction of the BBB is one critical feature of HIV-1 neuropathogenesis.Brain microvascular endothelial cells, a major component of BBB function and integrity, are connected by tight junctions (TJs) that limit paracellular flux and restrict permeability. 13 Indeed, under normal physiologic conditions, the brain endothelium functions as an interface between the blood and the brain parenchyma, strictly regulating influx of ions, molecules, and leukocytes into the CNS. Nonetheless, in disease, a variety of environmental, toxic, degenerative, and microbial insults could cause BBB breakdown. 12,14 Such a breakdown occurs during progressive HIV-1 infection 12,[15][16][17] and was documented in laboratory, animal models, human clinical observations, and autopsy studies. 10,[16][17][18][19][20] Underlying mechanisms of BBB dysfunction and how it affects ongoing disease are incompletely understood. 1,12,14 Dysfunction of the BBB enhances penetration of cell-free virus, ingress of activated HIV-1-infected monocytes across the BBB, accumulation of MP in the CNS, and spread of the virus to neighboring microglia and astrocytes. 15,21 Thus, BBB breech is commonly associated with accelerated disease and the development of behavioral and cognitive deficits that are signatures of HAD. 1,16 Based on these observations, the elucidation of the signaling pathways mediating BBB compromise can prove important for understanding disease mechanisms and development of new therapies.Signal transducers and activators of transcription (STATs) proteins are latent cytoplasmic transcription factors that are phosphorylated by Janus kinases (JAKs) in...

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“…The most commonly reported barriers were: distressed relatives who did not wish to support patients’ RTD consent;8 the drain on institutional staff time to consent and retrieve the tissue; and the inability to recruit sufficient numbers of patients to create a viable programme/database. Institutions with RTD programmes reported obtaining the best results when relying on experts and partnering with patient family groups;1 9 and working with hospice 10. Physicians and nurses have been identified as the gatekeepers in organ donation programmes;11 therefore, gaining a better understanding of how their roles influence acceptance rates has been the focus of many organ donation studies 8…”

Section: Discussionmentioning

confidence: 99%

“…These institutions report that the decision to participate is based upon a strong patient-physician relationship and on the clinical assessment of the patient's emotional state 16. Literature recognises the complexity of these programmes and success is contingent upon infrastructure, time commitment and buy-in from all physicians involved 10. The results of this survey suggested more training is needed for HCP to learn about RTD prior to the initiation of a research programme.…”

Section: Discussionmentioning

confidence: 99%

Healthcare providers’ knowledge and attitudes about rapid tissue donation (RTD): phase one of establishing a rapid tissue donation programme in thoracic oncology

et al. 2013

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In preparation for the development of a Rapid Tissue Donation (RTD) program, we surveyed health care providers (HCP) in our institution about knowledge and attitudes related to RTD with lung cancer patients. A 31-item web based survey was developed collecting data on demographics, knowledge and attitudes about RTD. The survey contained 3 items measuring participants’ knowledge about RTD, 5 items assessed attitudes about RTD recruitment, and 6 items assessed HCPs’ level of agreement with factors influencing decisions to discuss RTD. Response options were presented on a 5-point Likert scale. Ninety-one HCPs participated in the study. 66% indicated they had never heard of RTD prior to the survey, 78% rated knowledge of RTD as none or limited, and 95.6% reported not having ethical or religious concerns about discussing RTD with patients. The majority were either not comfortable (17.8%) or not sure if they felt comfortable discussing RTD with cancer patients (42.2%). 56.1% indicated their knowledge of RTD would plays an integral role in their decision to discuss RTD with patients. 71.4% reported concerns with RTD discussion and the emotional state of the patient. Physicians and nurses play an important role in initiating conversations about recruitment and donation to research that can ultimately influence uptake. Increasing HCP knowledge about RTD is a necessary step towards building and RTD program. Our study provides important information about characteristics associated with low levels of knowledge and practice related to RTD where additional education and training may be warranted.

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Development of a rapid autopsy program for studies of brain immunity

Cited by 18 publications

References 30 publications

Electroacupuncture Effects on the Disintegration of Beta Amyloid Sheets: Its Application to Alzheimer's Disease

Electroacupuncture Effects on the Disintegration of Beta Amyloid Sheets: Its Application to Alzheimer's Disease

STAT1 signaling modulates HIV-1–induced inflammatory responses and leukocyte transmigration across the blood-brain barrier

Healthcare providers’ knowledge and attitudes about rapid tissue donation (RTD): phase one of establishing a rapid tissue donation programme in thoracic oncology

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