Spreading depolarization remarkably exacerbates ischemia-induced tissue acidosis in the young and aged rat brain.

Spreading depolarizations (SDs) occur spontaneously in the cerebral cortex of subarachnoid hemorrhage, stroke or traumatic brain injury patients. Accumulating evidence prove that SDs exacerbate focal ischemic injury by converting zones of the viable but non-functional ischemic penumbra to the core region beyond rescue. Yet the SD-related mechanisms to mediate neurodegeneration remain poorly understood.

Imaging reveals the focal area of spreading depolarizations and a variety of hemodynamic responses in a rat microembolic stroke model.

Spreading depolarizations (SDs) occur in stroke, but the spatial association between SDs and the corresponding hemodynamic changes is incompletely understood. We applied multimodal imaging to visualize the focal area of selected SDs, and hemodynamic responses with SDs propagating over the ischemic cortex. The intracarotid infusion of polyethylene microspheres (d=45 to 53 μm) produced multifocal ischemia in anesthetized rats (n=7).

Effects of NMDA receptor antagonists with different subtype selectivities on retinal spreading depression.

Background And Purpose: Spreading depression (SD) is a local, temporary disruption of cellular ionic homeostasis that propagates slowly across the cerebral cortex and other neural tissues such as the retina. Spreading depolarization associated with SD occurs in different types of stroke, and this phenomenon correlates also with the initiation of classical migraine aura. The aim of this study was to investigate how NMDA receptor antagonists with different subtype selectivity alter SD.

Multi-modal imaging of anoxic depolarization and hemodynamic changes induced by cardiac arrest in the rat cerebral cortex.

We have reported previously that, in otherwise physiological conditions, spreading depression (SD) can be visualized directly by using a fluorescent, voltage-sensitive (VS) dye. However, in stroke models, where depolarizations occur spontaneously near the ischemic core, marked hemodynamic changes interfere significantly with VS dye imaging. This study provides the scientific basis necessary for accurate interpretation of VS dye images captured from ischemic brains.

Effects of early aging and cerebral hypoperfusion on spreading depression in rats.

Cortical spreading depression (CSD) is a feature of stroke pathophysiology. As stroke incidence increases with age, we have examined the effects of early aging and chronic cerebral hypoperfusion on CSD in rats. Three groups were studied: Young, 2-month-old animals; Middle-aged-2VO, subjected to 8 months of bilateral carotid occlusion from 2-month-of-age; and Middle-aged-SHAM, sham-operated.

Simultaneous, live imaging of cortical spreading depression and associated cerebral blood flow changes, by combining voltage-sensitive dye and laser speckle contrast methods.

Cortical spreading depression (i.e. waves of cellular depolarization, CSD) causes the aura symptoms in classical migraine, and may contribute to delayed cellular damage after an ischemic or traumatic insult to the brain.

Molecular physiology of preconditioning-induced brain tolerance to ischemia.

Ischemic tolerance describes the adaptive biological response of cells and organs that is initiated by preconditioning (i.e., exposure to stressor of mild severity) and the associated period during which their resistance to ischemia is markedly increased.

Direct, live imaging of cortical spreading depression and anoxic depolarisation using a fluorescent, voltage-sensitive dye.

Perilesion depolarisations, whether transient anoxic depolarisation (AD) or spreading depression (SD), occur in stroke models and in patients with acute brain ischaemia, but their contribution to lesion progression remains unclear. As these phenomena correspond to waves of cellular depolarisation, we have developed a technique for their live imaging with a fluorescent voltage-sensitive (VS) dye (RH-1838). Method development and validation were performed in two different preparations: chicken retina, to avoid any vascular interference; and cranial window exposing the cortical surface of anaesthetised rats.

Is anoxic depolarisation associated with an ADC threshold? A Markov chain Monte Carlo analysis.

A Bayesian nonlinear hierarchical random coefficients model was used in a reanalysis of a previously published longitudinal study of the extracellular direct current (DC)-potential and apparent diffusion coefficient (ADC) responses to focal ischaemia. The main purpose was to examine the data for evidence of an ADC threshold for anoxic depolarisation. A Markov chain Monte Carlo simulation approach was adopted.

Effects of phosphodiesterase inhibition on cortical spreading depression and associated changes in extracellular cyclic GMP.

Cortical spreading depression (CSD) is a temporary disruption of local ionic homeostasis that propagates slowly across the cerebral cortex, and may contribute to the pathophysiology of stroke and migraine. Previous studies demonstrated that nitric oxide (NO) formation promotes the repolarisation phase of CSD, and this effect may be cyclic GMP (cGMP)-mediated. Here, we have examined how phosphodiesterase (PDE) inhibition, either alone or superimposed on NO synthase (NOS) inhibition, alters CSD and the associated changes in extracellular cGMP.

Oxygen-induced DNA damage in freshly isolated brain cells compared with cultured astrocytes in the Comet assay.

Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defence mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important, therefore, to identify tools for the quantitative analysis of DNA damage in models of neurological disorders.

Temporal relation between the ADC and DC potential responses to transient focal ischemia in the rat: a Markov chain Monte Carlo simulation analysis.

Markov chain Monte Carlo simulation was used in a reanalysis of the longitudinal data obtained by Harris et al. (J Cereb Blood Flow Metab 20:28-36) in a study of the direct current (DC) potential and apparent diffusion coefficient (ADC) responses to focal ischemia. The main purpose was to provide a formal analysis of the temporal relationship between the ADC and DC responses, to explore the possible involvement of a common latent (driving) process.

Nitric oxide formation during cortical spreading depression is critical for rapid subsequent recovery of ionic homeostasis.

Cortical spreading depression (CSD) is a temporary disruption of local ionic homeostasis that propagates slowly across the cerebral cortex. Cortical spreading depression promotes lesion progression in experimental stroke, and may contribute to the initiation of migraine attacks. The purpose of this study was to investigate the roles of the marked increase of nitric oxide (NO) formation that occurs with CSD.

Repetitive spreading depression induces nestin protein expression in the cortex of rats and mice. Is this upregulation initiated by N-methyl-D-aspartate receptors?

In the November issue (2001) of Neuroscience Letters, Holmin et al. (Neurosci. Lett.