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Cortical spreading depression (CSD) may be the underlying mechanism of migraine aura. The role of CSD in initiating a migraine headache remains to be determined, but it might involve specific changes in gene expression in the brain. To examine these changes, four episodes of CSD at 5-minute intervals were induced in the mouse brain by application of 300mM KCl, and gene expression was examined 2 hours later using cDNA array and reverse transcriptase-polymerase chain reaction. Controls consisted of groups that received anesthesia only, attachment of recording electrodes only, and application of 0.9% NaCl. Of the over 1,180 genes examined in our experiments, those consistently regulated by CSD included vasoactive peptides; the vasodilator atrial natriuretic peptide was induced by CSD, while the vasoconstrictor neuropeptide Y was downregulated. Other genes specifically regulated by CSD were involved in oxidative stress responses (major prion protein, glutathione-S-transferase-5, and apolipoprotein E). L-type calcium channel mRNA was upregulated. In summary, CSD regulates genes that are intrinsic to its propagation, that identify accompanying vascular responses as a potential source of pain, and that protect against its potential pathological consequences. We believe these observations have strong relevance to the mechanisms of migraine and its outcomes.

We investigate and characterize the magnetoencephalographic waveforms from patients during spontaneous and visually induced migraine aura. Direct current neuromagnetic fields were measured during spontaneous onset of migraine auras in 4 migraine patients, and compared with recordings from 8 migraine-with-aura patients and 6 normal controls during visual stimulation of the occipital cortex. Complex direct current magnetoencephalographic shifts, similar in waveform, were observed in spontaneous and visually induced migraine patients, but not in controls. Two-dimensional inverse imaging showed multiple cortical areas activated in spontaneous and visually induced migraine aura patients. In normal subjects, activation was only observed in the primary visual cortex. Results support a spreading, depression-like neuroelectric event occurring during migraine aura that can arise spontaneously or be visually triggered in widespread regions of hyperexcitable occipital cortex.

Microvessels were isolated by albumin flotation and glass bead filtration from cerebral cortices of gerbils decapitated during pentylenetetrazol (PTZ)-induced seizures and ischemia-induced seizures. The uptake of 2-deoxy-D-glucose (2-DG) into these microvessels was studied in vitro. This uptake was increased during PTZ-induced seizures, in keeping with mechanisms whereby glucose transport into brain is increased to keep pace with the augmented tissue glycolysis provoked by enhanced neuronal activity. Uptake of 2-DG was decreased in microvessels isolated from animals that were decapitated while undergoing a seizure during ischemia and 90 to 120 minutes after ischemia. In contrast to results obtained when seizures are due to other causes, these results suggest that brain glucose transport is decreased during a seizure if the microvasculature has been previously subjected to ischemia. The results are discussed in relation to clinical stroke and Todd's postepileptic paralysis.

Lupus anticoagulants and anticardiolipin antibodies, known collectively as antiphospholipid antibodies, are becoming established as markers for increased risk of thrombosis, including ischemic cerebrovascular disease. In this brief review, we highlight evidence for and against a pathogenetic role of these antibodies in ischemic brain disease and comment on currently available laboratory studies to detect them. Future research on the association of antiphospholipid antibodies with neurological disease should focus on establishing the pathogenicity of these antibodies, identifying groups at high risk for recurrent ischemic cerebrovascular events, and initiating prospective multicenter natural history and treatment protocols.

We report on a patient with a large ischemic hemispherical stroke studied serially by 31P nuclear magnetic resonance spectroscopy. Persistent hyperglycemia was associated with prolonged acidosis in ischemic brain and failure of high-energy phosphate metabolism to recover. These in vivo human data support the concept that hyperglycemia adversely affects ischemic brain metabolism, pH, and clinical outcome.

Seizure activity as a component of the ischemic process possibly responsible for monoamine changes described in the gerbil stroke model was the subject of this study. Abnormal motor activity suggestive of seizures developed one to three hours after unilateral ligation of the common carotid artery in approximately 50% of gerbils that exhibited signs of stroke. Reduction of cortical levels of dopamine and norepinephrine was observed only when seizures occurred in association with stroke. The levels of 5-hydroxytryptamine were reduced bilaterally in animals with and without signs of stroke and were reduced further in animals with stroke plus seizures. Further study is needed to establish whether the catecholamine changes associated with ischemia-induced seizures are primary and causative or secondary to seizure activity itself. In the ischemic brain, 5-hydroxytryptamine metabolism appears disordered independent of seizure activity. Seizure activity must be taken into account when the mechanisms of disordered monoamine metabolism are being examined in the gerbil stroke model.

Twenty-four neurologically normal subjects, 12 in their twenties and 12 in their sixties, were included in a protocol that studied the relationship of resting cerebral blood flow and cerebral blood flow activation by neuropsychological testing to age and stroke risk factors. Both age and a stroke risk index were predictive of a reduced resting cerebral blood flow. Despite this, cerebral blood flow activation relative to resting flow was preserved. Subclinical lesions of deep white matter are proposed to explain the apparently paradoxical result that resting cerebral blood flow is decreased by factors that damage cerebral vessels, while cerebral vascular reactivity is unimpaired.