A novel, rapid, computerised method for quantitation of neuronal damage in a rat model of stroke

Callaway, Jennifer K.; Knight, Melissa J.; Watkins, Dianne J.; Beart, Philip M; Jarrott, Bevyn; Delaney, Peter

doi:10.1016/s0165-0270(00)00278-8

Cited by 39 publications

(31 citation statements)

References 29 publications

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“…The corrected infarct volume to compensate brain edema was calculated by applying the formula: (nonischemic volume/ischemic volume) × infarct volume. 25 Coronal cryosections after TTC staining and fixing were cryostat cut at 10 μm, sections mounted onto gelatinized microscope slides, and stored at − 20°C until next staining with FJ. Sections were air dried and stained with 0.0001% FJ for 20 minutes, washed, dried, and coverslipped with DPX (24).…”

Section: Determination Of Brain Infarct and Histologic Analysismentioning

confidence: 99%

Blockade of P2X7 Receptors or Pannexin-1 Channels Similarly Attenuates Postischemic Damage

Cisneros-Mejorado

Gottlieb

Cavaliere

et al. 2015

J Cereb Blood Flow Metab

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The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise.

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Section: Determination Of Brain Infarct and Histologic Analysismentioning

confidence: 99%

Blockade of P2X7 Receptors or Pannexin-1 Channels Similarly Attenuates Postischemic Damage

Cisneros-Mejorado

Gottlieb

Cavaliere

et al. 2015

J Cereb Blood Flow Metab

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“…The infarct area and volume were calculated using a method developed by Callaway and colleagues. 27 The infarct volume was quantified by integrating the area of damage with the distance between each level. 28 …”

Section: Quantification Of Ischemic Damagementioning

confidence: 99%

Angiotensin AT ₂ Receptor Stimulation Causes Neuroprotection in a Conscious Rat Model of Stroke

McCarthy

Vinh

Callaway

et al. 2009

Stroke

102

100

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Background and Purpose-The angiotensin II type 2 receptor (AT 2 R) is implicated to be neuroprotective in stroke, although this premise has not been directly tested. Therefore, we have examined the neuroprotective effect of AT 2 R stimulation after intracerebroventricular administration of AT 2 R agonist CGP42112 in a conscious rat model of stroke. Methods-Spontaneously hypertensive rats were treated with either CGP42112 (0.1 to 10 ng/kg/min intracerebroventricularly) alone or in combination with the AT 2 R antagonist PD123319 (36 ng/kg/min intracerebroventricularly) beginning 5 days before stroke induction. A focal reperfusion model of stroke was induced in conscious spontaneously hypertensive rats by administering endothelin-1 to the middle cerebral artery through a surgically implanted cannula. Behavioral tests were used to assess the severity of neurological deficit as a result of the ischemic event. Cortical and striatal infarct volumes were measured 72 hours poststroke. Results-Blood pressure was unaffected by treatments. CGP42112 dose-dependently reduced cortical infarct volume poststroke, and PD123319 abolished the neuroprotective effect of CGP42112. PD123319 had no effect on infarct volume alone. These results were consistent with the behavioral findings, indicating that CGP42112 reduced motor deficit on the ledged beam test at 72 hours poststroke and immunohistochemical analyses showing that CGP42112 increased neuronal survival and minimized the loss of AT 2 R expression in the infarcted region. Conclusion-Based on infarct, behavioral, and immunohistochemical data, these results indicate that centrally administered CGP42112 exhibits a neuroprotective effect, which was independent of blood pressure. Thus, for the first time, we have shown that central AT 2 R stimulation is neuroprotective in a conscious rat model of stroke.

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“…Histopathology in sections adjacent to those used for incubation with DHE revealed damage in the parietal, insular, and frontal cortices as well as in the dorsolateral striatum that extended through the corpus striatum (Callaway et al, 2000). Regions of interest were identified in MCID-generated images and defined as the core infarct (ischemic tissue that appears as a dark area when visualized on the image analysis monitor; Callaway et al, 2000) and the penumbra, defined as the tissue directly bordering the core ( Fig.…”

Section: Superoxide Generationmentioning

confidence: 99%

Early increase of Nox4 NADPH oxidase and superoxide generation following endothelin‐1‐induced stroke in conscious rats

McCann

Dusting

Roulston

2008

J of Neuroscience Research

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Oxidative stress contributes to the progression of brain injury following ischemic stroke and reperfusion. NADPH oxidase is a well-established source of superoxide in vascular disease, but its contribution to tissue injury following ischemic stroke has yet to be fully elucidated. Here we show the spatiotemporal profile of NADPH oxidase subunits Nox2 and Nox4 and concurrent superoxide generation following stroke induced by middle cerebral artery constriction in conscious rats. Nox2 mRNA was progressively up-regulated in both the ipsilateral cortex and the striatum from 6 hr to 7 days poststroke and reperfusion. Nox4 mRNA was also up-regulated transiently in the cortex at 6 hr poststroke but returned to control levels after this time. In situ detection of superoxide generation with dihydroethidium fluorescence revealed an increase in superoxide within the ischemic core at 6 hr poststroke that was mostly colocalized with the neuronal marker NeuN. By 24 hr, this increase in superoxide production had spread to the boundary zone of the infarct, whereas it disappeared in the ischemic core as neuronal numbers declined. Subsequently, superoxide within the ischemic core again increased at 7 days and was mostly colocalized with the activated microglia/macrophage marker OX-42. Immunoreactivity to Nox2 followed the same spatiotemporal pattern as that of OX-42 immunostaining poststroke. Clearly, NADPH oxidase is an important mediator of oxidative stress and contributes to the progression of brain damage beyond the infarct core, via the activation of two catalytic subunits, Nox2 and Nox4. Selectively blocking these subunits might be useful for intervening in the progression of stroke brain injury.

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A novel, rapid, computerised method for quantitation of neuronal damage in a rat model of stroke

Cited by 39 publications

References 29 publications

Blockade of P2X7 Receptors or Pannexin-1 Channels Similarly Attenuates Postischemic Damage

Blockade of P2X7 Receptors or Pannexin-1 Channels Similarly Attenuates Postischemic Damage

Angiotensin AT ₂ Receptor Stimulation Causes Neuroprotection in a Conscious Rat Model of Stroke

Early increase of Nox4 NADPH oxidase and superoxide generation following endothelin‐1‐induced stroke in conscious rats

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A novel, rapid, computerised method for quantitation of neuronal damage in a rat model of stroke

Cited by 39 publications

References 29 publications

Blockade of P2X7 Receptors or Pannexin-1 Channels Similarly Attenuates Postischemic Damage

Blockade of P2X7 Receptors or Pannexin-1 Channels Similarly Attenuates Postischemic Damage

Angiotensin AT 2 Receptor Stimulation Causes Neuroprotection in a Conscious Rat Model of Stroke

Early increase of Nox4 NADPH oxidase and superoxide generation following endothelin‐1‐induced stroke in conscious rats

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Angiotensin AT ₂ Receptor Stimulation Causes Neuroprotection in a Conscious Rat Model of Stroke