scholarly journals Bradykinin Antagonists Reduce Leukocyte–Endothelium Interactions after Global Cerebral Ischemia

2003 ◽  
Vol 23 (4) ◽  
pp. 441-448 ◽  
Author(s):  
Jens Lehmberg ◽  
Jürgen Beck ◽  
Alexander Baethmann ◽  
Eberhard Uhl
Keyword(s):  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Intravital Microscopy ◽  
Global Cerebral Ischemia ◽  
Mongolian Gerbils ◽  
Leukocyte Activation ◽  
Cerebral Microcirculation ◽  
Receptor Antagonists ◽  
Bradykinin Antagonists ◽  
Adherent Leukocytes

The aim of the present study was to evaluate the influence of bradykinin on microcirculatory changes and outcome after global cerebral ischemia (15 minute) in Mongolian gerbils. The cerebral microcirculation was investigated by fluorescent intravital microscopy. Survival and functional outcome was evaluated up to 4 d after ischemia. Animals were treated with the selective B1 and B2 receptor antagonists B 9858 and CP 0597, respectively, and the nonselective B1/B2 receptor antagonist B 9430. Leukocyte activation was significantly reduced by all antagonists as indicated by a significant decrease in the number of rolling (33 ± 20, 6 ± 8, 9 ± 10, and 13 ± 10) and adherent leukocytes (9 ± 7, 3 ± 4, 1 ± 1, and 2 ± 3 · 100 μm–1 · min–1 in controls and in animals treated with B1, B2, and B1/B2 antagonist, respectively). Arteriolar diameters were significantly reduced during reperfusion (35 ± 11 before and 27 ± 8 μm 40 minutes after ischemia) in animals treated with the B2 antagonist. The postischemic hypoperfusion, however, was not affected. Mortality was significantly higher in animals treated with the B1 and the B1/B2 antagonist. The authors concluded that bradykinin is involved in postischemic disturbances of cerebral microcirculation. The therapeutic effect of specific bradykinin receptor antagonists on functional outcome, however, remains unclear.

scholarly journals Capsaicin exhibits neuroprotective effects in a model of transient global cerebral ischemia in Mongolian gerbils

2005 ◽  
Vol 144 (5) ◽  
pp. 727-735 ◽  
Author(s):  
Simona Pegorini ◽  
Daniela Braida ◽  
Chiara Verzoni ◽  
Chiara Guerini-Rocco ◽  
Gian Giacomo Consalez ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Global Cerebral Ischemia ◽  
Mongolian Gerbils ◽  
Neuroprotective Effects ◽  
Transient Global Cerebral Ischemia

scholarly journals Acute Microvascular Changes after Subarachnoid Hemorrhage and Transient Global Cerebral Ischemia

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Michael K. Tso ◽  
R. Loch Macdonald
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Therapeutic Target ◽  
Global Cerebral Ischemia ◽  
Preclinical Studies ◽  
Cerebral Microcirculation ◽  
Blood Brain Barrier Disruption ◽  
Transient Global Cerebral Ischemia ◽  
Microvascular Changes ◽  
Brain Barrier Disruption

Subarachnoid hemorrhage and transient global cerebral ischemia result in similar pathophysiological changes in the cerebral microcirculation. These changes include microvascular constriction, increased leukocyte-endothelial interactions, blood brain barrier disruption, and microthrombus formation. This paper will look at various animal and preclinical studies that investigate these various microvascular changes, perhaps providing insight in how these microvessels can be a therapeutic target in both subarachnoid hemorrhage and transient global cerebral ischemia.

Neuroprotective efficiency of tetanus toxin C fragment in model of global cerebral ischemia in Mongolian gerbils

2014 ◽  
Vol 101 ◽  
pp. 37-44 ◽  
Author(s):  
Lidija Radenovic ◽  
Vesna Selakovic ◽  
Sara Olivan ◽  
Ana Cristina Calvo ◽  
Amaya Rando ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Tetanus Toxin ◽  
Global Cerebral Ischemia ◽  
Mongolian Gerbils

Anti-inflammatory iron chelator, DIBI, reduces leukocyte-endothelial adhesion and clinical symptoms of LPS-induced interstitial cystitis in mice

2021 ◽  
Vol 79 (3) ◽  
pp. 395-406
Author(s):  
Georg Hagn ◽  
Bruce Holbein ◽  
Juan Zhou ◽  
Christian Lehmann
Keyword(s):  
Interstitial Cystitis ◽  
Intravital Microscopy ◽  
Iron Chelator ◽  
Capillary Density ◽  
Control Group ◽  
Pain Response ◽  
Leukocyte Activation ◽  
Gram Negative ◽  
Pain And Suffering ◽  
Adherent Leukocytes

BACKGROUND: Interstitial cystitis (IC) is a prevalent and debilitating chronic inflammatory disease of the urinary bladder. Currently there are no fully effective therapeutic agents available, in part due to the still obscure pathogenesis of IC. Lipopolysaccharide (LPS) also known as endotoxin from Gram negative bacteria elicits IC in mice and has formed the basis of model systems for investigation. Excess free iron plays an important role in inflammation through generation of reactive oxygen species (ROS). The novel iron chelator DIBI has been shown to sequester excess free iron and dampen excess inflammatory responses to systemic LPS administration and also to Gram negative bacterial infections. OBJECTIVE: The overall objective of this study was to evaluate the effects of DIBI on LPS induced IC in mice. Leukocyte activation, endothelial adhesion and functional capillary density were assessed by intravital microscopy of the bladder microcirculation following a single intravesical LPS administration with or without intravesical DIBI treatment. Clinical IC symptoms were also assessed through behavioral and pain threshold force measurements. METHODS: Four groups of female BALB/c mice (n = 5–6/group) were randomized in this study: control group, IC group without therapy, IC group with DIBI therapy and control group with DIBI therapy. The groups were examined using intravital microscopy (IVM) of the bladder for leukocyte-endothelial interactions (adherent leukocytes, temporarily interacting leukocytes) and functional capillary density (FCD). A modified behavioral score by Boucher et al. and Von-Frey-Aesthesiometry were used to evaluate key behavioral indices related to pain and visceral pain perception. RESULTS: LPS introduced intravesically induced an early (≤2h) inflammation of the bladder evidenced by leukocyte activation and adhesion to bladder capillary walls. Intravesical DIBI therapy of mice 30min following LPS administration and assessed after 1.5h treatment showed a significant decrease in the number of adherent leukocytes compared to IC animals without DIBI treatment. DIBI treated mice showed a significantly lowered increase in behavioral distress scores compared to IC mice without therapy. Untreated IC mice exhibited a significantly decreased threshold force value for evoked pain response and DIBI treatment improved the threshold pain response. A significant inverse correlation was found for the two pain and suffering evaluation methods results. CONCLUSION: DIBI reduced inflammatory endothelial leukocyte adhesion and key indices related to pain and suffering over those observed in untreated IC mice. Our findings suggest a potential therapeutic role for DIBI for IC treatment.

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