Estrogen status affects sensitivity to focal cerebral ischemia in stroke-prone spontaneously hypertensive rats

2000 ◽  
Vol 278 (1) ◽  
pp. H290-H294 ◽  
Author(s):  
H. V. O. Carswell ◽  
A. F. Dominiczak ◽  
I. M. Macrae
Keyword(s):  
Estrous Cycle ◽  
Brain Damage ◽  
Spontaneously Hypertensive Rats ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Hypertensive Rats ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Spontaneously Hypertensive ◽  
Estradiol Levels

Estrogen treatment has been shown to reduce ischemic brain damage. Because endogenous estrogen levels fluctuate markedly during the estrous cycle, we investigated the effect of stage of estrous cycle on ischemic brain damage. Halothane anesthetized 3- to 5-mo-old female Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) in proestrus (high estradiol levels) or metestrus (low estradiol levels) underwent permanent middle cerebral artery occlusion. In SHRSP, infarct volume at 24 h postocclusion was 24% smaller in proestrus compared with metestrus [208.6 ± 9.5 mm3 ( n = 7) vs. 272.7 ± 23.8 mm3 ( n = 7), respectively, means ± SE; P = 0.0278, unpaired t-test]. In WKY, infarct volumes were similar in proestrus and metestrus [157.0 ± 5.4 mm3 ( n= 5) and 131.5 ± 16.5 mm3 ( n = 8), respectively; P = not significant (NS)]. Brain swelling (ipsilateral minus contralateral hemispheric volumes) was similar in proestrus and metestrus for SHRSP [138 ± 9 mm3 ( n = 6) and 136 ± 10 mm3 ( n = 7), respectively] and for WKY [103 ± 15 mm3 ( n = 5) and 90 ± 11 mm3 ( n = 8), respectively]. Thus the reduction in infarct size in SHRSP is caused by a true attenuation of the infarct volume and not simply by a reduction in brain edema.

scholarly journals Continuous Nimodipine Treatment Attenuates Cortical Infarction in Rats Subjected to 24 Hours of Focal Cerebral Ischemia

1990 ◽  
Vol 10 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Michael Jacewicz ◽  
Steve Brint ◽  
Jody Tanabe ◽  
William A. Pulsinelli
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Spontaneously Hypertensive ◽  
Cortical Infarction ◽  
Cortical Edema ◽  
Tandem Occlusion

Focal cerebral infarction and edema were measured in rats (Wistar, Fisher 344, and spontaneously hypertensive strains) pretreated with nimodipine (2 μg/kg/min i.v.) or its vehicle and subjected to the tandem occlusion of the middle cerebral and common carotid arteries. Animals awoke from anesthesia 10–15 min after onset of ischemia and continued to receive treatment over a 24-h survival period. Cortical infarction and edema were quantified by image analysis of frozen brain sections processed for histology. Nimodipine-treated rats developed 20–60% smaller cortical infarct volumes than controls (p < 0.002). Cortical edema was reduced proportionately to the decrease in infarct volume and constituted ∼36% of the infarct volume. Nimodipine caused a mild hypotensive response that did not aggravate ischemic brain damage. The results indicate that continuous nimodipine treatment, started before induction of focal cerebral ischemia, can attenuate ischemic brain damage and edema as late as 24 h after the onset of ischemia.

scholarly journals Mito-Tempo prevents nicotine-induced exacerbation of ischemic brain damage

2018 ◽  
Vol 125 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Chun Li ◽  
Hong Sun ◽  
Guodong Xu ◽  
Kimberly D. McCarter ◽  
Jiyu Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neutrophil Infiltration ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Ischemic Brain Damage ◽  
Mitochondrial Oxidative Stress ◽  
Ischemic Brain

Nicotine may contribute to the pathogenesis of cerebrovascular disease via the generation of reactive oxygen species (ROS). Overproduction of ROS leads to brain damage by intensifying postischemic inflammation. Our goal was to determine the effect of Mito-Tempo, a mitochondria-targeted antioxidant, on ischemic brain damage and postischemic inflammation during chronic exposure to nicotine. Male Sprague-Dawley rats were divided into four groups: control, nicotine, Mito-Tempo-treated control, and Mito-Tempo-treated nicotine. Nicotine (2 mg·kg−1·day−1) was administered via an osmotic minipump for 4 wk. Mito-Tempo (0.7 mg·kg−1·day−1ip) was given for 7 days before cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of the middle cerebral artery for 2 h. Brain damage and inflammation were evaluated after 24 h of reperfusion by measuring infarct volume, expression of adhesion molecules, activity of matrix metalloproteinase, brain edema, microglial activation, and neutrophil infiltration. Nicotine exacerbated infarct volume and worsened neurological deficits. Nicotine did not alter baseline ICAM-1 expression, matrix metallopeptidase-2 activity, microglia activation, or neutrophil infiltration but increased these parameters after cerebral ischemia. Mito-Tempo did not have an effect in control rats but prevented the chronic nicotine-induced augmentation of ischemic brain damage and postischemic inflammation. We suggest that nicotine increases brain damage following cerebral ischemia via an increase in mitochondrial oxidative stress, which, in turn, contributes to postischemic inflammation.NEW & NOTEWORTHY Our findings have important implications for the understanding of mechanisms contributing to increased susceptibility of the brain to damage in smokers and users of nicotine-containing tobacco products.

scholarly journals WNK-Cab39-NKCC1 signaling increases the susceptibility to ischemic brain damage in hypertensive rats

2016 ◽  
Vol 37 (8) ◽  
pp. 2780-2794 ◽  
Author(s):  
Mohammad Iqbal H Bhuiyan ◽  
Shanshan Song ◽  
Hui Yuan ◽  
Gulnaz Begum ◽  
Julia Kofler ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Hypertensive Rats ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
Novel Target

With-no-lysine kinase (WNK) and Na+-K+-2Cl− cotransporter 1 (NKCC1) are involved in the pathogenesis of hypertension. In this study, we investigated the WNK-NKCC1 signaling pathway in spontaneously hypertensive rats (SHR) and their associated susceptibility to stroke injury. Basal NKCC1 protein levels were higher in SHR than in normotensive Wistar Kyoto (WKY) rat brains. After inducing ischemic stroke, adult male WKY and SHR received either saline or NKCC1 inhibitor bumetanide (10 mg/kg/day, i.p.) starting at 3-h post-reperfusion. NKCC1 inhibition blunted the extent of ischemic infarction in SHR and improved their neurobehavioral functions. Interestingly, ischemia led to increased NKCC1 phosphorylation in SHR but not in WKY rats. Pronounced elevation of WNK1, WNK2 and WNK4 protein and downregulation of WNK3 were detected in ischemic SHR, but not in ischemic WKY rats. Upregulation of WNK-NKCC1 complex in ischemic SHR brain was associated with increased Ca2+-binding protein 39 (Cab39), without increases in Ste20-related proline alanine-rich kinase or oxidative stress-responsive kinase-1. Moreover, subacute middle cerebral artery stroke human brain autopsy exhibited increased expression of NKCC1 protein. We conclude that augmented WNK-Cab39-NKCC1 signaling in SHR is associated with an increased susceptibility to ischemic brain damage and may serve as a novel target for anti-hypertensive and anti-ischemic stroke therapy.

scholarly journals Protective Role for Type 4 Metabotropic Glutamate Receptors against Ischemic Brain Damage

2010 ◽  
Vol 31 (4) ◽  
pp. 1107-1118 ◽  
Author(s):  
Slavianka G Moyanova ◽  
Federica Mastroiacovo ◽  
Lidia V Kortenska ◽  
Rumiana G Mitreva ◽  
Erminia Fardone ◽  
...  
Keyword(s):  
Brain Damage ◽  
Metabotropic Glutamate Receptors ◽  
Infarct Volume ◽  
Focal Ischemia ◽  
Protective Role ◽  
Ischemic Brain Damage ◽  
Systemic Injection ◽  
Ischemic Brain ◽  
Metabotropic Glutamate ◽  
Transient Focal Ischemia

We examined the influence of type 4 metabotropic glutamate (mGlu4) receptors on ischemic brain damage using the permanent middle cerebral artery occlusion (MCAO) model in mice and the endothelin-1 (Et-1) model of transient focal ischemia in rats. Mice lacking mGlu4 receptors showed a 25% to 30% increase in infarct volume after MCAO as compared with wild-type littermates. In normal mice, systemic injection of the selective mGlu4 receptor enhancer, N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-caboxamide (PHCCC; 10 mg/kg, subcutaneous, administered once 30 minutes before MCAO), reduced the extent of ischemic brain damage by 35% to 45%. The drug was inactive in mGlu4 receptor knockout mice. In the Et-1 model, PHCCC administered only once 20 minutes after ischemia reduced the infarct volume to a larger extent in the caudate/putamen than in the cerebral cortex. Ischemic rats treated with PHCCC showed a faster recovery of neuronal function, as shown by electrocorticographic recording and by a battery of specific tests, which assess sensorimotor deficits. These data indicate that activation of mGlu4 receptors limit the development of brain damage after permanent or transient focal ischemia. These findings are promising because selective mGlu4 receptor enhancers are under clinical development for the treatment of Parkinson's disease and other central nervous system disorders.

scholarly journals Cilostazol, Not Aspirin, Reduces Ischemic Brain Injury via Endothelial Protection in Spontaneously Hypertensive Rats

Stroke ◽  
2011 ◽  
Vol 42 (9) ◽  
pp. 2571-2577 ◽  
Author(s):  
Naoki Oyama ◽  
Yoshiki Yagita ◽  
Miki Kawamura ◽  
Yukio Sugiyama ◽  
Yasukazu Terasaki ◽  
...  
Keyword(s):  
Brain Injury ◽  
Spontaneously Hypertensive Rats ◽  
Ischemic Brain Injury ◽  
Hypertensive Rats ◽  
Ischemic Brain ◽  
Spontaneously Hypertensive
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