Introduction: The brain is one of the first organs affected clinically in sepsis. Microcirculatory alterations are suggested to be a critical component in the pathophysiology of sepsis. The aim of this study was to investigate the effects of recombinant human activated protein C (rhAPC) on the pial microcirculation in experimental endotoxemia using intravital microscopy. Our hypothesis is rhAPC protects pial microcirculation in endotoxemia.
Methods: Endotoxemia was generated in Lewis rats with intravenous injection of lipopolysaccharide (LPS, 5 mg/kg i.v.). Dura mater was removed through a cranial window to expose pial vessels on the brain surface. The microcirculation, including leukocyte-endothelial interaction, functional capillary density (FCD) and plasma extravasation of pial vessels was examined by fluorescent intravital microscopy (IVM) 2 h after administration of LPS, LPS and rhAPC or equivalent amount of saline (used as Control group). Plasma cytokine levels of interleukin 1 alpha (IL1-α), tumor necrosis factor-α (TNF-α), interferon γ (IFN-γ), Monocyte chemotactic protein-1 (MCP-1) and Granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated after IVM.
Results: LPS challenge significantly increased leukocyte adhesion (773±190 vs. 592±152 n/mm(2) Control), decreased FCD (218±54 vs. 418±74 cm/cm(2) Control) and increased proinflammatory cytokine levels (IL-1α: 5032±1502 vs. 8±21 pg/ml; TNF-α: 1823±1007 vs. 168±228 pg/ml; IFN-γ: 785±434 vs. 0 pg/ml; GM-CSF: 54±52 vs. 1±3 pg/ml) compared to control animals. rhAPC treatment significantly reduced leukocyte adhesion (599±111 n/mm(2)), increased FCD (516±118 cm/cm(2)) and reduced IL-1α levels (2134±937 pg/ml) in the endotoxemic rats.
Conclusion: APC treatment significantly improves pial microcirculation by reducing leukocyte adhesion and increasing FCD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.mvr.2012.03.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
L-Arginine and Taurisolo Effects on Brain Hypoperfusion-Reperfusion Damage in Hypertensive Rats.
Int J Mol Sci
October 2024
Department of Translational Medicine and New Technologies in Medicine and Surgery, University of Pisa, 56127 Pisa, Italy.
Acute and chronic hypertension causes cerebral vasculopathy, increasing the risk of ischemia and stroke. Our study aimed to compare the effects of arterial pressure reduction on the pial microvascular responses induced by hypoperfusion and reperfusion in spontaneously hypertensive Wistar rats, desamethasone-induced hypertensive Wistar rats and age-matched normotensive Wistar rats fed for 3 months with a normal diet or normal diet supplemented with L-arginine or Taurisolo or L-arginine plus Taurisolo. At the end of treatments, the rats were submitted to bilateral occlusion of common carotid arteries for 30 min and reperfusion.
View Article and Find Full Text PDFNinjin'yoeito Modulates Baseline and Reperfusion-Induced Changes in the Arteriole Diameter and Blood Flow in the Cerebral Cortex of Anesthetized Mice.
Microcirculation
October 2024
Department of Autonomic Neuroscience, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
Objective: Intragastric administration of ninjin'yoeito (NYT), a traditional Japanese herbal medicine, reportedly prevents the decrease in baseline cerebral blood flow (CBF) in the cortex following gastric administration of water. We investigated the effect of NYT on baseline and dynamic changes in cerebral cortical arteriole diameter.
Methods: Urethane-anesthetized mice were intragastrically administered 1 g/kg NYT or distilled water (DW).
Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion.
Neurosurgery
August 2024
Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei , Taiwan.
Background And Objectives: Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF).
Methods: On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline.
Impact of stalling events on microcirculatory hemodynamics in the aged brain.
Microcirculation
April 2024
Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, Illinois, USA.
Objective: The role of cerebral microvasculature in cognitive dysfunction can be investigated by identifying the impact of blood flow on cortical tissue oxygenation. In this paper, the impact of capillary stalls on microcirculatory characteristics such as flow and hematocrit (Ht) in the cortical angioarchitecture is studied.
Methods: Using a deterministic mathematical model to simulate blood flow in a realistic mouse cortex, hemodynamics parameters, including pressure, flow, vessel diameter-adjustable hematocrit, and transit time are calculated as a function of stalling events.
NO Deficiency Compromises Inter- and Intrahemispheric Blood Flow Adaptation to Unilateral Carotid Artery Occlusion.
Int J Mol Sci
January 2024
Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary.
Carotid artery stenosis (CAS) affects approximately 5-7.5% of older adults and is recognized as a significant risk factor for vascular cognitive impairment (VCI). The impact of CAS on cerebral blood flow (CBF) within the ipsilateral hemisphere relies on the adaptive capabilities of the cerebral microcirculation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!