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

Decreased blood flow in the brain leads to a rapid increase in reactive oxygen species (ROS). NADPH oxidase (NOX) is an enzyme family that has the physiological function to produce ROS. NOX2 and NOX4 overexpression is associated with aggravated ischemic injury, while NOX2/4-deficient mice had reduced stroke size. Dysregulation of matrix metalloproteinases (MMPs) contributes to tissue damage. The active form of vitamin D3 expresses neuroprotective, immunomodulatory, and anti-inflammatory effects in the CNS. The present study examines the effects of the vitamin D3 pretreatment on the oxidative stress parameters and the expression of NOX subunits, MMP9, microglial marker Iba1, and vitamin D receptor (VDR), in the cortex and hippocampus of Mongolian gerbils subjected to ten minutes of global cerebral ischemia, followed by 24 hours of reperfusion. The ischemia/reperfusion procedure has induced oxidative stress, changes in the expression of NOX2 subunits and MMP9 in the brain, and increased MMP9 activity in the serum of experimental animals. Pretreatment with vitamin D3 was especially effective on NOX2 subunits, MMP9, and the level of malondialdehyde and superoxide anion. These results outline the significance of the NOX and MMP9 investigation in brain ischemia and the importance of adequate vitamin D supplementation in ameliorating the injury caused by I/R.

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Bradykinin Antagonists Reduce Leukocyte–Endothelium Interactions after Global Cerebral Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/01.wcb.0000052280.23292.35 ◽

2003 ◽

Vol 23 (4) ◽

pp. 441-448 ◽

Cited By ~ 13

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.

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Neuroprotectionby MK-801 following cerebral ischemia in Mongolian gerbils

Archives of Biological Sciences ◽

10.2298/abs0803341r ◽

2008 ◽

Vol 60 (3) ◽

pp. 341-346 ◽

Cited By ~ 2

Author(s):

Lidija Radenovic ◽

Vesna Selakovic ◽

P.R. Andjus

Keyword(s):

Cerebral Ischemia ◽

Neuronal Damage ◽

Neuronal Loss ◽

Brain Structures ◽

Cell Loss ◽

Global Cerebral Ischemia ◽

Mongolian Gerbils ◽

Nissl Staining ◽

Neuroprotective Effects ◽

Mk 801

Global cerebral ischemia in Mongolian gerbils is an established model in experimental research on cerebral ischemia, which is characterized morphologically by selective neuronal damage in the hippocampus, striatum, and cortex. Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of dizocilpine malate (MK-801), a non-competitive glutamate antagonist, in the model of 10-min gerbil cerebral ischemia. Gerbils were given MK-801(3 mg/kg i.p.)or saline immediately after the occlusion. On day 4 after reperfusion, neuronal damage was examined in the hippocampus (30 ?m)and striatum slices (5 ?m)stained with hematoxylin/eosin, fluorescent Nissl staining and membrane tracer DiI. The striatum and C3 regions of the hippocampus were analyzed by confocal microscopy. Neuroprotection was determined by quantifying the degree of cell loss, reduction of morphologically damaged cells, and the degree of preservation of recog?nizable neuroanatomical pathways after the ischemic insult. Our results demonstrate that the neuronal damage induced by sustained ischemia is related to abnormalities in glutamatergic function associated with NMDA receptors. MK-801significantly prevented neuronal loss in the tested brain structures. All of this contributes to a better understanding of the given pathophysiological process causing ischemic neuronal damage. This article has been corrected. Link to the correction <a href="http://dx.doi.org/10.2298/ABS160524054E">10.2298/ABS160524054E</a>

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Influence of electromagnetic field (0,5mT, 50 Hz) on motor behaviour, oxidative stress parameters and morphological characteristics of brain after global cerebral ischemia in mongolian gerbils

10.2298/bg20121107raus ◽

2012 ◽

Author(s):

Snezana Raus

Keyword(s):

Oxidative Stress ◽

Electromagnetic Field ◽

Cerebral Ischemia ◽

Morphological Characteristics ◽

Global Cerebral Ischemia ◽

Mongolian Gerbils ◽

Motor Behaviour ◽

Oxidative Stress Parameters ◽

Stress Parameters

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Leukocyte-Endothelium Interactions in Pial Venules during the Early and Late Reperfusion Period after Global Cerebral Ischemia in Gerbils

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200006000-00010 ◽

2000 ◽

Vol 20 (6) ◽

pp. 979-987 ◽

Cited By ~ 37

Author(s):

Eberhard Uhl ◽

Jürgen Beck ◽

Walter Stummer ◽

Jens Lehmberg ◽

Alexander Baethmann

Keyword(s):

Blood Flow ◽

Cerebral Ischemia ◽

Brain Damage ◽

Capillary Density ◽

Global Cerebral Ischemia ◽

Microvascular Blood Flow ◽

Mongolian Gerbils ◽

Secondary Brain Damage ◽

Reperfusion Period ◽

Late Reperfusion

The contribution of leukocytes to secondary brain damage after cerebral ischemia is still under discussion. The purpose of the present study was to examine the pial microcirculation after global cerebral ischemia while focusing on leukocyte–endothelium interactions during the early and late reperfusion period of up to 4 days. A closed cranial window technique that leaves the dura mater intact was used. Global cerebral ischemia of 15 minutes' duration was induced in male Mongolian gerbils (n = 91). Pial microcirculation was observed by intravital fluorescence microscopy. Leukocyte–endothelium interactions (LEIs) in pial venules, vessel diameters, capillary density, and regional microvascular blood flow measured by laser Doppler flowmetry were quantified during 3 hours of reperfusion and in intervals up to 4 days after ischemia. Within 3 hours of reperfusion, the number of leukocytes (cells/100 μm × minute) rolling along or adhering to the venular endothelium increased from 0.1 ± 0.2 to 28.4 ± 17.4 ( P < 0.01 vs. control) and from 0.2 ± 0.2 to 4.0 ± 3.8 ( P < 0.05), respectively. There was no capillary plugging by leukocytes; capillary density remained unchanged. In the late reperfusion period, at 7 hours after ischemia, LEIs had returned to baseline values. Furthermore, from 12 hours to 4 days after ischemia, no LEIs were observed. Changes in regional microvascular blood flow did not correlate with LEIs. Global cerebral ischemia of 15 minutes' duration induces transient LEIs that reach a maximum within 3 hours of reperfusion and return to baseline at 7 hours after ischemia. LEIs are not related to changes in microvascular perfusion, which suggests mainly that the expression of adhesion receptors is necessary to induce LEIs rather than rheologic factors. It seems unlikely that this short-lasting activation of leukocytes can play a role in the development of secondary brain damage.

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Ultrastorcture of Cerebellar Purkinje Cells in Rats Subjected To Partial Global Cerebral Ischemia

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120060 ◽

1985 ◽

Vol 43 ◽

pp. 674-675

Author(s):

R.V.W. Dimlich ◽

M.H. Biros

Keyword(s):

Cerebral Ischemia ◽

Purkinje Cells ◽

Cell Types ◽

Microscopic Level ◽

Global Cerebral Ischemia ◽

Light Microscopic Level ◽

Cerebellar Damage ◽

Cerebellar Injury ◽

Cerebellar Purkinje Cells ◽

Cell Changes

In severe cerebral ischemia, Purkinje cells of the cerebellum are one of the cell types most vulnerable to anoxic damage. In the partial (forebrain) global ischemic (PGI) model of the rat, Paljärvi noted at the light microscopic level that cerebellar damage is inconsistant and when present, milder than in the telencephalon, diencephalon and rostral brain stem. Cerebellar injury was observed in 3 of 4 PGI rats following 5 minutes of reperfusion but in none of the rats after 90 min of reperfusion. To evaluate a time between these two extremes (5 and 90 min), the present investigation used the PGI model to study the effects of ischemia on the ultrastructure of cerebellar Purkinje cells in rats that were sacrificed after 30 min of reperfusion. This time also was chosen because lactic acid that is thought to contribute to ischemic cell changes in PGI is at a maximum after 30 min of reperfusion.

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