Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats.

Lin, Teng Nan; He, Yong; Wu, Guangjie; Khan, Myrna M.; Hsu, Chung Y.

doi:10.1161/01.str.24.1.117

Cited by 659 publications

(443 citation statements)

References 14 publications

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“…Infarct volume of six slices of 2-mm coronal sections of each brain was calculated in a blinded manner by capturing the images with a digital camera and then performing computerized analysis using National Institutes of Health IMAGE 1.61 software. Infarct volume determination was corrected for edema by subtracting the volume of normal tissue in the ischemic hemisphere from the volume of the contralateral hemisphere, essentially as described (12). Rats showing tremor and seizure were excluded from studies of brain infarction and neurological deficits.…”

Section: Methodsmentioning

confidence: 99%

Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model

Ren

Senatorov

Chen

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

191

165

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Lithium has long been a primary drug used to treat bipolar mood disorder, even though the drug's therapeutic mechanisms remain obscure. Recent studies demonstrate that lithium has neuroprotective effects against glutamate-induced excitotoxicity in cultured neurons and in vivo. The present study was undertaken to examine whether postinsult treatment with lithium reduces brain damage induced by cerebral ischemia. We found that s.c. injection of lithium dose dependently (0.5-3 mEq͞kg) reduced infarct volume in the rat model of middle cerebral artery occlusion͞reperfusion. Infarct volume was reduced at a therapeutic dose of 1 mEq͞kg even when administered up to 3 h after the onset of ischemia. Neurological deficits induced by ischemia were also reduced by daily administration of lithium over 1 week. Moreover, lithium treatment decreased the number of neurons showing DNA damage in the ischemic brain. These neuroprotective effects were associated with an up-regulation of cytoprotective heat shock protein 70 (HSP70) in the ischemic brain hemisphere as determined by immunohistochemistry and Western blotting analysis. Lithium-induced HSP70 up-regulation in the ischemic hemisphere was preceded by an increase in the DNA binding activity of heat shock factor 1, which regulates the transcription of HSP70. Physical variables and cerebral blood flow were unchanged by lithium treatment. Our results suggest that postinsult lithium treatment reduces both ischemia-induced brain damage and associated neurological deficits. Moreover, the heat shock response is likely to be involved in lithium's neuroprotective actions. Additionally, our studies indicate that lithium may have clinical utility for the treatment of patients with acute stroke. cerebral ischemia ͉ heat shock factor 1 ͉ heat shock protein ͉ neuroprotection ͉ DNA damage L ithium has been extensively used in the treatment of bipolar mood disorder, although the mechanisms underlying the drug's therapeutic action remain unclear. There is growing evidence that lithium is neuroprotective against a variety of insults, such as glutamate-induced excitotoxicity, in cultured cells and animal models of diseases (1-3). The mechanisms underlying lithium-induced neuroprotection are complex and may include inactivation of N-methyl-D-aspartate receptors (4), activation of the phosphatidylinositol 3-kinase͞Akt cell survival pathway (5), enhanced expression of cytoprotective Bcl-2 (6, 7), and inhibition of glycogen synthase kinase-3␤ (8).The brain is extremely sensitive to ischemic insult, and the resulting brain damage is related to excitotoxicity. Development of neuroprotective agents against ischemia-induced brain damage has been a therapeutic strategy to reduce the mortality and morbidity associated with stroke. Animal models of brain focal ischemia primarily involve middle cerebral artery occlusion (MCAO). We previously found that lithium pretreatment decreased the infarct volume and neurological deficits in a permanent MCAO model of rats (9). The present study was undertaken to explor...

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Section: Methodsmentioning

confidence: 99%

Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model

Ren

Senatorov

Chen

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

191

165

View full text Add to dashboard Cite

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“…The infarction areas were quantified using the iSolution full image analysis software (Image & Microscope Technology, Vancouver, Canada). To account for and eliminate the effects of swelling/edema, the infarction volume was calculated via an indirect measure produced by summing the volumes of each section according to the following formula: contralateral hemisphere (mm 3 ) -undamaged ipsilateral hemisphere (mm 3 ) [29] .…”

Section: Focal Cerebral Ischemiamentioning

confidence: 99%

Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice

et al. 2016

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Aim: Increasing evidence suggests that probucol, a lipid-lowering agent with anti-oxidant activities, may be useful for the treatment of ischemic stroke with hyperlipidemia via reduction in cholesterol and neuroinflammation. In this study we examined whether probucol could protect against brain ischemic injury via anti-neuroinflammatory action in normal and hyperlipidemic mice. Methods: Primary mouse microglia and murine BV2 microglia were exposed to lipopolysaccharide (LPS) for 3 h, and the release NO, PGE2, IL-1β and IL-6, as well as the changes in NF-κB, MAPK and AP-1 signaling pathways were assessed. ApoE KO mice were fed a high-fat diet containing 0.004%, 0.02%, 0.1% (wt/wt) probucol for 10 weeks, whereas normal C57BL/6J mice received probucol (3, 10, 30 mg·kg -1 ·d -1 , po) for 4 d. Then all the mice were subjected to focal cerebral ischemia through middle cerebral artery occlusion (MCAO). The neurological deficits were scored 24 h after the surgery, and then brains were removed for measuring the cerebral infarct size and the production of pro-inflammatory mediators. Results: In LPS-treated BV2 cells and primary microglial cells, pretreatment with probucol (1, 5, 10 μmol/L) dose-dependently inhibited the release of NO, PGE2, IL-1β and IL-6, which occurred at the transcription levels. Furthermore, the inhibitory actions of probucol were associated with the downregulation of the NF-κB, MAPK and AP-1 signaling pathways. In the normal mice with MCAO, preadministration of probucol dose-dependently decreased the infarct volume and improved neurological function. These effects were accompanied by the decreased production of pro-inflammatory mediators (iNOS, COX-2, IL-1, IL-6). In ApoE KO mice fed a high-fat diet, pre-administration of 0.1% probucol significantly reduced the infarct volume, improved the neurological deficits following MCAO, and decreased the total-and LDL-cholesterol levels. Conclusion: Probucol inhibits LPS-induced microglia activation and ameliorates cerebral ischemic injury in normal and hyperlipidemic mice via its anti-neuroinflammatory actions, suggesting that probucol has potential for the treatment of patients with or at risk for ischemic stroke and hyperlipidemia.

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“…To correct for the effects of the cerebral edema and of differential shrinkage resulting from tissue processing, the infarction area in each section was calculated by subtracting the area of the healthy, uninfarcted (TTC-or hematoxylin-stained) tissue in the ipsilateral hemisphere from the area of the contralateral hemisphere as described previously. 35 Infarction volume was determined by summing the infarction areas of all sections and multiplying by the slice thicknesses.…”

Section: Quantification Of Infarct Volumementioning

confidence: 99%

Adeno-associated virus-mediated delivery of BCL-w gene improves outcome after transient focal cerebral ischemia

et al. 2003

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A recombinant adeno-associated virus (rAAV) vector was used to overexpress the anti-apoptotic Bcl-2-family protein, BCL-w, in rat brain. Three weeks after injecting the vector into cerebral cortex and striatum on one side, temporary focal ischemia was induced by occlusion of the ipsilateral middle cerebral artery for 90 min, followed by reperfusion for 24 h. BCL-w expression was increased in cerebral cortex and striatum -and in neurons, astroglia and endothelial cells -in the brains of rats that received the rAAV-BCL-w vector, compared to rats given phosphate-buffered saline or a control vector containing the gene for green fluorescent protein. Recipients of the rAAV-BCL-w vector also showed a 30% reduction in infarct size and a 33-40% improvement in neurological function, compared to the control groups. These results provide evidence for a role of BCL-w in regulating histological and functional outcome after focal cerebral ischemia.

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Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats.

Cited by 659 publications

References 14 publications

Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model

Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model

Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice

Adeno-associated virus-mediated delivery of BCL-w gene improves outcome after transient focal cerebral ischemia

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