Acute brain inflammation, white matter oxidative stress, and myelin deficiency in a model of neonatal intraventricular hemorrhage

OBJECTIVENeonatal intraventricular hemorrhage (IVH) leads to posthemorrhagic hydrocephalus (PHH), brain injury, and long-term disability. Current therapy for IVH is based on treating PHH but does not address the underlying brain injury. In order to develop pharmacological treatment for IVH, there must be a better understanding of the underlying pathology of this disease. This study was designed to determine the time course of the acute inflammation and oxidative stress that may underlie the progressive pathology of IVH. The authors sought to understand the temporal relationships among inflammation, oxidative stress, and white matter pathology in a rat model of IVH.METHODSA rat model of IVH consisting of hemoglobin injection into the lateral ventricle was used. Tissue was analyzed via biochemical and histological methods to map the spatiotemporal distribution of innate immune activation and oxidative stress. White matter was quantified using both immunohistochemistry and Western blot for myelin basic protein (MBP) in the corpus callosum.RESULTSIVH led to acute induction of inflammatory cytokines, followed by oxidative stress. Oxidative stress was concentrated in white matter, adjacent to the lateral ventricles. Animals with IVH initially gained weight at a lower rate than control animals and had larger ventricles and less MBP than control animals.CONCLUSIONSExperimental IVH induces global inflammation throughout the brain and oxidative stress concentrated in the white matter. Both of these phenomena occur early after IVH. This has implications for human neonates with immature white matter that is exquisitely sensitive to inflammation and oxidative stress. Antiinflammatory or antioxidant therapy for IVH may need to be initiated early in order to protect developing white matter.

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Protective effects of epifriedelinol in a rat model of traumatic brain injury assessed with histological and hematological markers

Translational Neuroscience ◽

10.1515/tnsci-2018-0008 ◽

2018 ◽

Vol 9 (1) ◽

pp. 38-42 ◽

Cited By ~ 1

Author(s):

Shiping Li ◽

Qiaoying Zhang ◽

Peiwu Li

Keyword(s):

Oxidative Stress ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Water Content ◽

Rat Model ◽

Protective Effects ◽

Hematological Markers ◽

Cytokine Levels ◽

Factor Α ◽

And Oxidative Stress

Abstract Background This study evaluated the protective effects of epifriedelinol (EFD) in a rat model of traumatic brain injury (TBI). Methodology TBI was induced by dropping a weight from a specific height. The animals were separated into control, TBI, and EFD 100 and 200 mg/kg groups. The latter received 100 and 200 mg/kg EFD, respectively, for 2 days beginning 30 min after inducing TBI. The neurological examination score, permeability of the blood–brain barrier (BBB), water content of the brain, cytokine levels, and oxidative stress parameters were measured in the rats. The effects of EFD on glial fibrillary acidic protein (GFAP)-positive cells were evaluated using immunohistochemistry. ResultThe EFD treatment significantly decreased the neurological score, permeability of the BBB, and water content of brain compared with the TBI group. The levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and oxidative stress were significantly decreased in the EFD-treated groups. The number of GFAP-positive cells was also significantly reduced in the EFD-treated groups. ConclusionEFD attenuates the secondary injury in TBI rats by reducing the serum cytokine levels and oxidative stress.

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GPR18 Agonist Resolvin D2 Reduces the Early Brain Injury in A Rat Model of Subarachnoid Hemorrhage by Multi-Mechanisms of Protection

10.21203/rs.3.rs-398477/v1 ◽

2021 ◽

Author(s):

Tongyu Zhang ◽

Gang Zuo ◽

Hongqi Zhang

Keyword(s):

Subarachnoid Hemorrhage ◽

Brain Injury ◽

White Matter ◽

Western Blot ◽

Rat Model ◽

Time Course ◽

Early Brain Injury ◽

Brain Regions ◽

White Matter Injury ◽

Tnf Α

Abstract Background Early brain injury (EBI) is the early phase of secondary complications resulted in poor prognosis of subarachnoid hemorrhage (SAH). GPR18 is a G protein-coupled receptor which has been reported for neuroprotection in ischemia. In this study, we aimed to use resolvin D2 (RvD2) as an agonist to investigate the roles of GPR18 in different brain regions during EBI. Methods Location and time course of GPR18 after SAH were measured with immunofluorescence and western blot in endovascular perforation rat model. RvD2 was given one hour intranasally post-SAH, and SAH grades, neurobehavior and brain water content tests were performed after 24 hours. TUNEL and DHE staining were measured 24 hours post-SAH in cortex. Immunofluorescence, western blot and immunohistochemistry of proteins related to EBI in different brain regions were also performed. Results We found GPR18 mainly located in meninges, hypothalamus, cortex and white matter. And GPR18 expression increased in meninges and hypothalamus after EBI, however, it decreased in cortex and white matter. RvD2 could improve neurological scores and brain edema. Mast cell degranulation was attenuated, Chymase and Typtase expression decreased after RvD2 administration in meninges. RvD2 attenuated inflammation with increase of POMC, IL-10 and decrease of NPY, TNF-α in hypothalamus. In cortex, RvD2 alleviated oxidative stress and apoptosis, protected blood-brain barrier. RvD2 also ameliorated white matter injury by MBP elevation and APP depression. Conclusions Current results emphasized the importance of GPR18 in the whole brain during EBI. Upregulation of GPR18 with RvD2 may improve neurological functions with multi-mechanisms in different brain regions.

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Short-term Diesel Exhaust Exposure Results in Neuroinflammation and White Matter Injury

Innovation in Aging ◽

10.1093/geroni/igab046.2415 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 640-640

Author(s):

Krista Lamorie-Foote ◽

Kristina Shkirkova ◽

Qinghai Liu ◽

Constantinos Sioutas ◽

Todd Morgan ◽

...

Keyword(s):

Oxidative Stress ◽

White Matter ◽

Corpus Callosum ◽

Diesel Exhaust ◽

Time Course ◽

Ambient Air ◽

White Matter Injury ◽

Ambient Air Pollution ◽

Diesel Exhaust Particulate ◽

And Oxidative Stress

Abstract Ambient air pollution (AAP) exposure is associated with white matter injury and cognitive decline in older adults(Chen et al. 2020,Erickson et al. 2020). Neuroinflammation and oxidative stress may contribute to this white matter injury. Diesel exhaust particulate matter (DEP) is a neurotoxic component of AAP.This study characterizes the time course by which neuroinflammation/oxidative stress occurs and results in white matter injury following DE exposure in a murine model. DEP (Sigma) was re-aerosolized for exposure. Mice were exposed to 100 µg/m3 DEP or filtered air (FA) for 5 hours (n=8/group), 100 hours (n=6/group), or 200 hours (n=6/group). Immunohistochemical analysis of degraded myelin basic protein (dMBP), a marker of myelin damage, was performed. Neuroinflammation and oxidative stress were assessed by histological analysis of complement C5a, an anaphylatoxin, and 4-Hydroxynonenal (4-HNE), a marker of lipid peroxidation.dMBP integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.01), 100 (p<0.01), and 200 hours (p<0.001) compared to FA mice.C5a integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.01), 100 (p<0.01), and 200 hours (p<0.01) compared to FA mice. 4-HNE integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.001), 100 (p=0.001), and 200 hours (p<0.001) compared to FA mice. Neuroinflammation and oxidative stress are upregulated with associated white matter injury in the corpus callosum after 5 hours of DEP exposure.Short-term DEP exposure activates inflammatory/oxidative stress pathways, which may contribute to the pathogenesis of white matter injury.Erickson et al. 2020,PMID:32182984; Chen et al. 2020,PMID:32669395.

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Effects of β-Adrenergic Blockade on Metabolic and Inflammatory Responses in a Rat Model of Ischemic Stroke

Cells ◽

10.3390/cells9061373 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1373 ◽

Cited By ~ 1

Author(s):

Shih-Yi Lin ◽

Ya-Yu Wang ◽

Cheng-Yi Chang ◽

Chih-Cheng Wu ◽

Wen-Ying Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Ischemic Stroke ◽

Brain Injury ◽

Cerebral Ischemia ◽

Rat Model ◽

Inflammatory Responses ◽

Brain Infarction ◽

Brain Inflammation ◽

Adrenergic Blockade ◽

Anti Inflammatory

Ischemic stroke provokes an inflammatory response concurrent with both sympathetic nervous system activation and hyperglycemia. Currently, their crosstalk and consequences in stroke outcomes are of clinical attraction. We have provided experimental evidence showing the suppressive effects of the nonselective β-adrenoreceptor antagonist propranolol on hyperglycemia, inflammation, and brain injury in a rat model experiencing cerebral ischemia. Pretreatment with propranolol protected against postischemic brain infarction, edema, and apoptosis. The neuroprotection caused by propranolol was accompanied by a reduction in fasting glucose, fasting insulin, glucose tolerance impairment, plasma C-reactive protein, plasma free fatty acids, plasma corticosterone, brain oxidative stress, and brain inflammation. Pretreatment with insulin alleviated—while glucose augmented—postischemic brain injury and inflammation. Additionally, the impairment of insulin signaling in the gastrocnemius muscles was noted in rats with cerebral ischemia, with propranolol improving the impairment by reducing oxidative stress and tumor necrosis factor-α signaling. The anti-inflammatory effects of propranolol were further demonstrated in isoproterenol-stimulated BV2 and RAW264.7 cells through its ability to decrease cytokine production. Despite their potential benefits, stroke-associated hyperglycemia and inflammation are commonly linked with harmful consequences. Our findings provide new insight into the anti-inflammatory, neuroprotective, and hypoglycemic mechanisms of propranolol in combating neurodegenerative diseases, such as stroke.

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Fetuin-A exerts a protective effect against experimentally induced intestinal ischemia/reperfusion by suppressing autophagic cell death

Experimental Biology and Medicine ◽

10.1177/1535370221995207 ◽

2021 ◽

pp. 153537022199520

Author(s):

Nanees F El-Malkey ◽

Amira E Alsemeh ◽

Wesam MR Ashour ◽

Nancy H Hassan ◽

Husam M Edrees

Keyword(s):

Oxidative Stress ◽

Rat Model ◽

Intestinal Ischemia ◽

Ischemia Reperfusion ◽

Protective Role ◽

Beclin 1 ◽

Male Rats ◽

Fetuin A ◽

Intestinal Ischemia Reperfusion ◽

And Oxidative Stress

Intestinal tissue is highly susceptible to ischemia/reperfusion injury in many hazardous health conditions. The anti-inflammatory and antioxidant glycoprotein fetuin-A showed efficacy in cerebral ischemic injury; however, its protective role against intestinal ischemia/reperfusion remains elusive. Therefore, this study investigated the protective role of fetuin-A supplementation against intestinal structural changes and dysfunction in a rat model of intestinal ischemia/reperfusion. We equally divided 72 male rats into control, sham, ischemia/reperfusion, and fetuin-A-pretreated ischemia/reperfusion (100 mg/kg/day fetuin-A intraperitoneally for three days prior to surgery and a third dose 1 h prior to the experiment) groups. After 2 h of reperfusion, the jejunum was dissected and examined for spontaneous contractility. A jejunal homogenate was used to assess inflammatory and oxidative stress enzymes. Staining of histological sections was carried out with hematoxylin, eosin and Masson’s trichrome stain for evaluation. Immunohistochemistry was performed to detect autophagy proteins beclin-1, LC3, and p62. This study found that fetuin-A significantly improved ischemia/reperfusion-induced mucosal injury by reducing the percentage of areas of collagen deposition, increasing the amplitude of spontaneous contraction, decreasing inflammation and oxidative stress, and upregulating p62 expression, which was accompanied by beclin-1 and LC3 downregulation. Our findings suggest that fetuin-A treatment can prevent ischemia/reperfusion-induced jejunal structural and functional changes by increasing antioxidant activity and regulating autophagy disturbances observed in the ischemia/reperfusion rat model. Furthermore, fetuin-A may provide a protective influence against intestinal ischemia/reperfusion complications.

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