Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury

Abstract Traumatic brain injury (TBI) is a common phenomenon, accounting for significant cost and adverse health effects. While there is information about focal pathologies following TBI, knowledge of more diffuse processes is lacking, particularly regarding how analgesics affect this pathology. As...

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Autores principales:	Jane Ryu, Phillip Stone, Sabrina Lee, Brighton Payne, Karen Gorse, Audrey Lafrenaye
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6f30f17ca78a4fa3b2219916b41a21c0
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spelling	oai:doaj.org-article:6f30f17ca78a4fa3b2219916b41a21c02021-12-02T17:32:56ZBuprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury10.1038/s41598-021-88030-z2045-2322https://doaj.org/article/6f30f17ca78a4fa3b2219916b41a21c02021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88030-zhttps://doaj.org/toc/2045-2322Abstract Traumatic brain injury (TBI) is a common phenomenon, accounting for significant cost and adverse health effects. While there is information about focal pathologies following TBI, knowledge of more diffuse processes is lacking, particularly regarding how analgesics affect this pathology. As buprenorphine is the most commonly used analgesic in experimental TBI models, this study investigated the acute effects of the opioid analgesic buprenorphine (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. We utilized a model of central fluid percussion injury (CFPI) in adult male rats treated with a single subcutaneous bolus of Bup-SR-Lab or saline 15 min post-injury. Microscopic assessments were performed at 1 day post-injury. Cell impermeable dextran was infused intraventricularly prior to sacrifice to assess neuronal membrane disruption. Axonal injury was assessed by investigating labeling of the anterogradely transported amyloid precursor protein. Neuroinflammation was assessed by analyzing Iba-1 + microglial and GFAP + astrocyte histological/morphological features as well as cytokine levels in both regions of interest (ROIs). Myelin pathology was assessed by evaluating the expression of myelin basic protein (MBP) and the propensity of MBP + myelin debris. Acute physiologic data showed no difference between groups except for reduction in weight loss following cFPI in Bup treated animals compared to saline. There were no discernable differences in axonal injury or membrane disruption between treatment groups. Cytokine levels were consistent between Bup and saline treated animals, however, microglia and astrocytes revealed region specific histological changes at 1d following Bup treatment. Myelin integrity and overall MBP expression showed no differences between Bup and saline treated animals, but there were significant regional differences in MBP expression between the cortex and thalamus. These data suggest effects of Bup treatment on weight following CFPI and potential regional specificity of Bup-associated microglial and astrocyte alterations, but very little change in other acute pathology at 1-day post-injury. Overall, this preliminary study indicates that use of Bup-SR-Lab in preclinical work does have effects on acute glial pathology, however, longer term studies will be needed to assess potential effects of Bup treatment on more chronic pathological progressions.Jane RyuPhillip StoneSabrina LeeBrighton PayneKaren GorseAudrey LafrenayeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jane Ryu Phillip Stone Sabrina Lee Brighton Payne Karen Gorse Audrey Lafrenaye Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury
description	Abstract Traumatic brain injury (TBI) is a common phenomenon, accounting for significant cost and adverse health effects. While there is information about focal pathologies following TBI, knowledge of more diffuse processes is lacking, particularly regarding how analgesics affect this pathology. As buprenorphine is the most commonly used analgesic in experimental TBI models, this study investigated the acute effects of the opioid analgesic buprenorphine (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. We utilized a model of central fluid percussion injury (CFPI) in adult male rats treated with a single subcutaneous bolus of Bup-SR-Lab or saline 15 min post-injury. Microscopic assessments were performed at 1 day post-injury. Cell impermeable dextran was infused intraventricularly prior to sacrifice to assess neuronal membrane disruption. Axonal injury was assessed by investigating labeling of the anterogradely transported amyloid precursor protein. Neuroinflammation was assessed by analyzing Iba-1 + microglial and GFAP + astrocyte histological/morphological features as well as cytokine levels in both regions of interest (ROIs). Myelin pathology was assessed by evaluating the expression of myelin basic protein (MBP) and the propensity of MBP + myelin debris. Acute physiologic data showed no difference between groups except for reduction in weight loss following cFPI in Bup treated animals compared to saline. There were no discernable differences in axonal injury or membrane disruption between treatment groups. Cytokine levels were consistent between Bup and saline treated animals, however, microglia and astrocytes revealed region specific histological changes at 1d following Bup treatment. Myelin integrity and overall MBP expression showed no differences between Bup and saline treated animals, but there were significant regional differences in MBP expression between the cortex and thalamus. These data suggest effects of Bup treatment on weight following CFPI and potential regional specificity of Bup-associated microglial and astrocyte alterations, but very little change in other acute pathology at 1-day post-injury. Overall, this preliminary study indicates that use of Bup-SR-Lab in preclinical work does have effects on acute glial pathology, however, longer term studies will be needed to assess potential effects of Bup treatment on more chronic pathological progressions.
format	article
author	Jane Ryu Phillip Stone Sabrina Lee Brighton Payne Karen Gorse Audrey Lafrenaye
author_facet	Jane Ryu Phillip Stone Sabrina Lee Brighton Payne Karen Gorse Audrey Lafrenaye
author_sort	Jane Ryu
title	Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury
title_short	Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury
title_full	Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury
title_fullStr	Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury
title_full_unstemmed	Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury
title_sort	buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6f30f17ca78a4fa3b2219916b41a21c0
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Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury

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