Dataset Information

Myelin loss associated with neuroinflammation in hypertensive rats.

ABSTRACT: Small vessel disease is the major cause of white matter injury in patients with vascular cognitive impairment. Matrix metalloproteinase (MMP)-mediated inflammation may be involved in the white matter damage with oligodendrocyte (Ol) death. Therefore, we used spontaneously hypertensive stroke-prone rats to study the role of neuroinflammation in white matter damage.Permanent unilateral carotid artery occlusion was performed at 12 weeks of age in spontaneously hypertensive stroke-prone rats. Following surgery, rats were placed on a Japanese permissive diet and received 1% NaCl in drinking water. MRI, histology, biochemistry, and ELISA characterized white matter lesions, and cognitive impairment was tested by Morris water maze.White matter damage was observed 4 to 5 weeks following permanent unilateral carotid artery occlusion/Japanese permissive diet. Immunoblotting showed marked reduction in myelin basic protein and upregulation of immature Ols. Mature Ols underwent caspase-3-mediated apoptosis. Morris water maze showed cognitive impairment. Abnormally appearing vessels were observed and surrounded by inflammatory-like cells. IgG extravasation and hemorrhage, indicating blood-brain barrier (BBB) disruption, was closely associated with MMP-9 expression. Lesions in white matter showed reactive astrocytosis and activated microglia that expressed tumor necrosis factor-?. MMP-3 and MMP-9 were significantly increased, and MMP-2 was reduced in both astrocytes and Ol.We found apoptosis of mature Ols with an increase in immature Ols. Increased MMP-3, MMP-9, and tumor necrosis factor-? were associated with myelin breakdown and BBB disruption. Neuroinflammation is an important factor in white matter damage and Ol death, and studies using this new model can be performed to assess agents to block inflammation.

SUBMITTER: Jalal FY

PROVIDER: S-EPMC3598597 | biostudies-other | 2012 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Myelin loss associated with neuroinflammation in hypertensive rats.

Jalal Fakhreya Y FY Yang Yi Y Thompson Jeffrey J Lopez Anita C AC Rosenberg Gary A GA

Stroke 20120223 4

<h4>Background and purpose</h4>Small vessel disease is the major cause of white matter injury in patients with vascular cognitive impairment. Matrix metalloproteinase (MMP)-mediated inflammation may be involved in the white matter damage with oligodendrocyte (Ol) death. Therefore, we used spontaneously hypertensive stroke-prone rats to study the role of neuroinflammation in white matter damage.<h4>Methods</h4>Permanent unilateral carotid artery occlusion was performed at 12 weeks of age in spont ...[more]

PMID: 22363061

Similar Datasets

Project description:Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt-Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased the mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, the mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications.

Dataset Information

Myelin loss associated with neuroinflammation in hypertensive rats.

Publications

Myelin loss associated with neuroinflammation in hypertensive rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets