Publications by authors named "Jeffrey D Hepburn"

2 Publications

  • Page 1 of 1

Increased Expression of Simple Ganglioside Species GM2 and GM3 Detected by MALDI Imaging Mass Spectrometry in a Combined Rat Model of Aβ Toxicity and Stroke.

PLoS One 2015 18;10(6):e0130364. Epub 2015 Jun 18.

Dept. Anatomy and Cell Biology, Western University, London, ON, N6A 5C1, Canada; Dept. Clinical Neurological Sciences, London Health Sciences Centre, University of Western Ontario, London, ON, N6A 5A5, Canada.

The aging brain is often characterized by the presence of multiple comorbidities resulting in synergistic damaging effects in the brain as demonstrated through the interaction of Alzheimer's disease (AD) and stroke. Gangliosides, a family of membrane lipids enriched in the central nervous system, may have a mechanistic role in mediating the brain's response to injury as their expression is altered in a number of disease and injury states. Matrix-Assisted Laser Desorption Ionization (MALDI) Imaging Mass Spectrometry (IMS) was used to study the expression of A-series ganglioside species GD1a, GM1, GM2, and GM3 to determine alteration of their expression profiles in the presence of beta-amyloid (Aβ) toxicity in addition to ischemic injury. To model a stroke, rats received a unilateral striatal injection of endothelin-1 (ET-1) (stroke alone group). To model Aβ toxicity, rats received intracerebralventricular (i.c.v.) injections of the toxic 25-35 fragment of the Aβ peptide (Aβ alone group). To model the combination of Aβ toxicity with stroke, rats received both the unilateral ET-1 injection and the bilateral icv injections of Aβ25-35 (combined Aβ/ET-1 group). By 3 d, a significant increase in the simple ganglioside species GM2 was observed in the ischemic brain region of rats who received a stroke (ET-1), with or without Aβ. By 21 d, GM2 levels only remained elevated in the combined Aβ/ET-1 group. GM3 levels however demonstrated a different pattern of expression. By 3 d GM3 was elevated in the ischemic brain region only in the combined Aβ/ET-1 group. By 21 d, GM3 was elevated in the ischemic brain region in both stroke alone and Aβ/ET-1 groups. Overall, results indicate that the accumulation of simple ganglioside species GM2 and GM3 may be indicative of a mechanism of interaction between AD and stroke.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130364PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4473074PMC
April 2016

Protein markers of cerebrovascular disruption of neurovascular unit: immunohistochemical and imaging approaches.

Rev Neurosci 2014 ;25(4):481-507

Currently, there is great interest in the assembly and function of cerebral endothelial, glial and neuronal cells that form the anatomical basis of the neurovascular unit (NVU) to maintain blood-brain barrier (BBB) and cerebral blood flow. Recent studies have provided considerable insight into the assembly of the components of the NVU. However, there is still paucity of data regarding the identification and expression pattern of these components in various pathologies of the central nervous system. Here, we provide a brief overview of the histological and imaging methods to study BBB disruption in various experimental settings especially the ischemia models associated with necrosis. Emphasis is on the immunohistochemistry of various protein markers of NVU. An understanding of the alterations in the expression pattern of these markers in various neurodegenerative disorders could lead to a better understanding of the conditions that cause BBB disruption as well as to the development of new restorative and protective treatments.
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http://dx.doi.org/10.1515/revneuro-2013-0041DOI Listing
May 2015