scholarly journals Regulation of Body Temperature and Neuroprotection by Endogenous Interleukin-6 in Cerebral Ischemia

2003 ◽  
Vol 23 (4) ◽  
pp. 406-415 ◽  
Author(s):  
Oliver Herrmann ◽  
Victoria Tarabin ◽  
Shigeaki Suzuki ◽  
Nicolas Attigah ◽  
Irinel Coserea ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Body Temperature ◽  
Interleukin 6 ◽  
Neuroprotective Effect ◽  
Treatment Options ◽  
Artery Occlusion ◽  
Endogenous Pyrogen ◽  
Cerebral Artery Occlusion ◽  
Deficient Mice ◽  
Elevated Body Temperature

Although the function of fever is still unclear, it is now beyond doubt that body temperature influences the outcome of brain damage. An elevated body temperature is often found in stroke patients and denotes a bad prognosis. However, the pathophysiologic basis and treatment options of elevated body temperature after stroke are still unknown. Cerebral ischemia rapidly induced neuronal interleukin-6 (IL-6) expression in mice. In IL-6–deficient mice, body temperature was markedly decreased after middle cerebral artery occlusion (MCAO), but infarct size was comparable to that in control mice. If body temperature was controlled by external warming after MCAO, IL-6–deficient mice had a reduced survival, worse neurologic status, and larger infarcts than control animals. In cell culture, IL-6 exerted an antiapoptotic and neuroprotective effect. These data suggest that IL-6 is a key regulator of body temperature and an endogenous neuroprotectant in cerebral ischemia. Neuroprotective properties apparently compensate for its pyretic action after MCAO and enhance the safety of this endogenous pyrogen.

scholarly journals Oxytocin Mediates Social Neuroprotection After Cerebral Ischemia

Stroke ◽  
2011 ◽  
Vol 42 (12) ◽  
pp. 3606-3611 ◽  
Author(s):  
Kate Karelina ◽  
Kathleen A. Stuller ◽  
Brant Jarrett ◽  
Ning Zhang ◽  
Jackie Wells ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Receptor Antagonist ◽  
Social Housing ◽  
Neuroprotective Effect ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Stroke Outcome ◽  
Socially Isolated ◽  
Cerebral Artery Occlusion ◽  
And Oxidative Stress

Background and Purpose— The reduced incidence, morbidity, and mortality of stroke among humans with strong social support have been well-documented; however, the mechanisms underlying these socially mediated phenomena remain unknown, but may involve oxytocin (OT), a hormone that modulates some aspects of social behavior in humans and other animals. Methods— In the present study, adult male mice were socially isolated (housed individually) or socially paired (housed with an ovariectomized female); social pairing increased hypothalamic OT gene expression. To determine whether a causal relationship exists between increased OT and improved stroke outcome, mice were treated with exogenous OT or OT receptor antagonist beginning 1 week before induction of experimental stroke via middle cerebral artery occlusion. Results— Relative to social isolation, social housing attenuated infarct size, neuroinflammation, and oxidative stress following experimental stroke; the neuroprotective effect of social housing was eliminated by receptor antagonist treatment. In contrast, administration of OT to socially isolated mice reproduced the neuroprotection conferred by social housing. We further report evidence for a direct suppressive action of OT on cultured microglia, which is a key instigator in the development of neuroinflammation after cerebral ischemia. Conclusions— These findings support the hypothesis that OT mediates the neuroprotective effect of social interaction on stroke outcome.

Contributions of LFA-1 and Mac-1 to brain injury and microvascular dysfunction induced by transient middle cerebral artery occlusion

2004 ◽  
Vol 287 (6) ◽  
pp. H2555-H2560 ◽  
Author(s):  
Thiruma V. Arumugam ◽  
James W. Salter ◽  
John H. Chidlow ◽  
Christie M. Ballantyne ◽  
Christopher G. Kevil ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Blood Cell ◽  
Vessel Wall ◽  
Leukocyte Adhesion ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Wild Type ◽  
Cerebral Artery Occlusion ◽  
Deficient Mice ◽  
Α Subunits

Although the β2-integrins have been implicated in the pathogenesis of cerebral ischemia-reperfusion (I/R) injury, the relative contributions of the α-subunits to the pathogenesis of ischemic stroke remains unclear. The objective of this study was to determine whether and how genetic deficiency of either lymphocyte function-associated antigen-1 (LFA-1) or macrophage-1 (Mac-1) alters the blood cell-endothelial cell interactions, tissue injury, and organ dysfunction in the mouse brain exposed to focal I/R. Middle cerebral artery occlusion was induced for 1 h (followed by either 4 or 24 h of reperfusion) in wild-type mice and in mice with null mutations for either LFA-1 or Mac-1. Neurological deficit and infarct volume were monitored for 24 h after reperfusion. Platelet- and leukocyte-vessel wall adhesive interactions were monitored in cortical venules by intravital microscopy. Mice with null mutations for LFA-1 or Mac-1 exhibited significant reductions in infarct volume. This was associated with a significant improvement in the I/R-induced neurological deficit. Leukocyte adhesion in cerebral venules did not differ between wild-type and mutant mice at 4 h after reperfusion. However, after 24 h of reperfusion, leukocyte adhesion was reduced in both LFA-1- and Mac-1-deficient mice compared with their wild-type counterparts. Platelet adhesion was also reduced at both 4 and 24 h after reperfusion in the LFA-1- and Mac-1-deficient mice. These findings indicate that both α-subunits of the β2-integrins contribute to the brain injury and blood cell-vessel wall interactions that are associated with transient focal cerebral ischemia.

scholarly journals Neuroprotective effect ofPanax ginsengextract against cerebral ischemia–reperfusion-injury-induced oxidative stress in middle cerebral artery occlusion models

FACETS ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 52-68 ◽  
Author(s):  
Mufzala Shamim ◽  
Nazish Iqbal Khan
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Lipid Profile ◽  
Liver Enzymes ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Liver And Kidney ◽  
Cerebral Artery Occlusion

The present study investigated the in vivo neuroprotective role of Panax ginseng extract (PGE) pretreatment against transient cerebral ischemia in a middle cerebral artery occlusion (MCAO) model. Rats were randomly divided as follows: group I, control; group II, sham-operated; group III, where animals were subjected to MCAO surgery; and group IV, where animals were orally administered 10 mL PGE per day (200 mg/kg of body weight per day) for 30 d followed by MCAO induction at day 31. Following 24 h of reperfusion, blood and tissue (brain, liver, and kidney) samples were collected for biochemical and histopathological examination. Biochemical testing included lipid profile, liver enzymes, kidney function tests, C-reactive protein (CRP), lactate dehydrogenase (LDH), glucose, and total protein estimation. Tissue antioxidants (catalase, superoxide dismutase, and glutathione) were assessed in brain, liver, and kidney tissues. MCAO-induced histopathological changes were also examined in the tissues. Pretreatment with PGE showed significant improvement in tissue antioxidant status in brain, liver and kidney tissues. PGE treatment maintains plasma lipid profile, liver enzymes, kidney function, and CRP, LDH, and glucose levels. Histologically, monocytes and macrophage infiltration were observed in the tissues of MCAO animals, whereas PGE treatment preserved tissue architecture and minimal monocyte infiltration. PGE supplementation showed a neuroprotective effect against ischemia–reperfusion injury by effectively increasing endogenous antioxidant enzyme activity.

Abstract TP109: Impact of ATP-Induced Mild Hypothermia on Focal Cerebral Ischemia in Rats

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Meijuan Zhang ◽  
Wenjin Li ◽  
Rehana K Leak ◽  
Jun Chen ◽  
Feng Zhang
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Body Temperature ◽  
Mild Hypothermia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Core Body Temperature ◽  
Artery Occlusion ◽  
Dependent Manner

Brain ischemia is a devastating disorder without effective therapies. One of the most promising approaches to attenuate ischemic brain injury is mild hypothermia. Recent studies show that adenosine nucleotides can induce hypothermia in mice. The purpose of the present study was to test the hypothesis that ATP, a common form of energy currency, induces mild hypothermia in rats and reduces brain injury following focal cerebral ischemia. ATP solution was dissolved in water and intraperitoneally injected; and focal stroke was induced by a suture model of middle cerebral artery occlusion and ischemic outcomes were evaluated within 24 hr. We found that injections of ATP lowered core body temperature in a dose-dependent manner; the dose appropriate for subsequent experiments was 2 g/kg as it reduced temperature to the range of mild hypothermia for approximately 7 hours. While intravenous injection of ATP was less effective in lowering body temperature. However, when ATP-induced hypothermia was applied to stroke, a neuroprotective effect was not observed. In contrast, the infarct volume grew even larger in ATP-treated rats. Not surprisingly, this was accompanied by an increased rate of seizure events, hemorrhagic transformation, and higher mortality. Continuous monitoring of physiological parameters revealed that ATP severely reduced heartbeat rate and blood pressure. ATP also raised blood glucose to dangerous levels and this was accompanied by severe acidosis and hypocalcemia. Western blotting showed that ATP treatment decreased levels of both phospho-Akt and total-Akt in the ischemic cortex. Our results reveal that, despite inducing hypothermia, ATP is not appropriate for protecting the brain against stroke, as it is associated with exaggerated ischemic outcomes and dangerous systemic side effects.

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