NDLI: Predicting Neuroinflammation in Morphine Tolerance for Tolerance Therapy from Immunostaining Images of Rat Spinal Cord

Content Provider	PubMed Central
Author	Lin, Shinn-long Chang, Fang-lin Ho, Shinn-ying Charoenkwan, Phasit Wang, Kuan-wei Huang, Hui-ling
Editor	Dang, Yong-hui
Copyright Year	2015
Abstract	Long-term morphine treatment leads to tolerance which attenuates analgesic effect and hampers clinical utilization. Recent studies have sought to reveal the mechanism of opioid receptors and neuroinflammation by observing morphological changes of cells in the rat spinal cord. This work proposes a high-content screening (HCS) based computational method, HCS-Morph, for predicting neuroinflammation in morphine tolerance to facilitate the development of tolerance therapy using immunostaining images for astrocytes, microglia, and neurons in the spinal cord. HCS-Morph first extracts numerous HCS-based features of cellular phenotypes. Next, an inheritable bi-objective genetic algorithm is used to identify a minimal set of features by maximizing the prediction accuracy of neuroinflammation. Finally, a mathematic model using a support vector machine with the identified features is established to predict drug-treated images to assess the effects of tolerance therapy. The dataset consists of 15 saline controls (1 μl/h), 15 morphine-tolerant rats (15 μg/h), and 10 rats receiving a co-infusion of morphine (15 μg/h) and gabapentin (15 μg/h, Sigma). The three individual models of astrocytes, microglia, and neurons for predicting neuroinflammation yielded respective Jackknife test accuracies of 96.67%, 90.00%, and 86.67% on the 30 rats, and respective independent test accuracies of 100%, 90%, and 60% on the 10 co-infused rats. The experimental results suggest that neuroinflammation activity expresses more predominantly in astrocytes and microglia than in neuron cells. The set of features for predicting neuroinflammation from images of astrocytes comprises mean cell intensity, total cell area, and second-order geometric moment (relating to cell distribution), relevant to cell communication, cell extension, and cell migration, respectively. The present investigation provides the first evidence for the role of gabapentin in the attenuation of morphine tolerance from phenotypic changes of astrocytes and microglia. Based on neuroinflammation prediction, the proposed computer-aided image diagnosis system can greatly facilitate the development of tolerance therapy with anti-inflammatory drugs.
Related Links	http://dx.doi.org/10.1371/journal.pone.0139806
Starting Page	139806
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	10
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2015-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
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