3 results on '"Dennis W. Simon"'
Search Results
2. Quantitative and qualitative assessment of glymphatic flux using Evans blue albumin
- Author
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Miora D. Manole, Gregory A. Gibson, Yaming Chen, Patrick M. Kochanek, Robert S. B. Clark, Dennis W. Simon, Hülya Bayır, Mark A. Ross, Henry Alexander, and Michael S. Wolf
- Subjects
Serum ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Blood–brain barrier ,Article ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,parasitic diseases ,medicine ,Animals ,Cerebrospinal Fluid ,Intracranial pressure ,Evans Blue ,Brain Chemistry ,Chemistry ,General Neuroscience ,Albumin ,Brain ,Immunohistochemistry ,030104 developmental biology ,medicine.anatomical_structure ,Spectrophotometry ,Glymphatic system ,Glymphatic System ,Artificial cerebrospinal fluid ,Flux (metabolism) ,030217 neurology & neurosurgery - Abstract
Background The glymphatic system is a proposed pathway for clearance of proteins and macromolecules from brain, and disrupted glymphatic flux is implicated in neurological disease. We capitalized on colorimetric, fluorescent, and protein-binding properties of Evans blue to evaluate glymphatic flux. New method Twenty-five μL of 1% Evans blue-labeled albumin (EBA) in artificial cerebrospinal fluid (aCSF) was injected into the intracisternal space of anesthetized postnatal day 17 rats. Serum was collected at various time points after injection (n = 37) and EBA was measured spectrophotometrically. In separate rats (n = 3), a cranial window was placed over the parietal cortex and EBA transit was evaluated using in vivo multiphoton microscopy. Separate rats (n = 6) were processed for immunohistochemistry to examine localization of EBA. In some rats, intracranial pressure (ICP) was increased via intracisternal injection of aCSF. Results EBA was detected in serum as early as 30 min, was maximal at 4 h, and was undetectable at 72 h after intracisternal injection. Using intra-vital microscopy and immunohistochemistry EBA could be tracked from CSF to perivascular locations. Consistent with removal via glymphatic flux, increasing ICP to 40 mmHg accelerated transit of EBA from CSF to blood. Comparison with existing methods Transit of EBA from CSF to serum could be quantified spectrophotometrically without radioactive labeling. Glymphatic flux could also be qualitatively evaluated using EBA fluorescence. Conclusion We present a novel technique for simultaneous quantitative and qualitative evaluation of glymphatic flux in rats.
- Published
- 2019
3. Rationale for Adjunctive Therapies for Pediatric Sepsis Induced Multiple Organ Failure
- Author
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Andrew J. Nowalk, Dennis W. Simon, Bradley Podd, Santiago Manuel Cayetano Lopez, Joseph A. Carcillo, and Rajesh K. Aneja
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Critical Care ,Multiple Organ Failure ,Inflammation ,030204 cardiovascular system & hematology ,Article ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Pediatric sepsis ,medicine ,Humans ,Combined Modality Therapy ,Precision Medicine ,Personalized therapy ,Child ,Intensive care medicine ,business.industry ,fungi ,Immune modulation ,medicine.disease ,Precision medicine ,030104 developmental biology ,Macrophage activation syndrome ,Pediatrics, Perinatology and Child Health ,medicine.symptom ,business - Abstract
Adjunctive therapies have been proposed for use in at least 5 inflammation pathobiology phenotypes in pediatric sepsis-induced multiple organ failure (MOF). Here, we provide host-pathogen interaction prototypes to facilitate understanding of the rationale for personalized therapy in these phenotypes. Meningococcemic sepsis and Shiga-like toxin-associated atypical Hemolytic Uremic Syndrome sepsis result in thrombocytopenia and MOF due to endothelial dysfunction and formation of small vessel thromboses that can respond to plasma exchange and C5a monoclonal antibody therapy. H1N1 Influenza A sepsis is associated with immune paralysis that can result in opportunistic secondary infection with invasive methicillin resistant Staphylococcus aureus (MRSA) and MOF that can respond to Granulocyte Macrophage Colony Stimulating Factor therapy. Hyperleukocytosis-associated MOF is associated with critical Bordetella Pertussis pulmonary hypertension and cardiovascular collapse which can respond to leukoreduction therapy. Epstein Barr Virus lymphoproliferative disease-associated sequential MOF has high levels of soluble-Fas Ligand that cause liver failure, and can respond to anti-CD20 monoclonal antibody therapy. Viral hemorrhagic fevers such as Ebola or Dengue can lead to macrophage activation syndrome characterized by hyperferritinemia, hepatobiliary dysfunction and disseminated intravascular coagulation (DIC)-related MOF that can theoretically respond to anti-inflammatory therapies. We discuss the literature on adjunctive anti-inflammatory and immune modulation therapies that, in addition to traditional organ support and infection source control, might be part of a personalized precision medicine approach to reverse of each of these inflammatory pathobiology phenotypes.
- Published
- 2017
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