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Spreading Depression (spreading + depression)

Distribution by Scientific Domains
Medical Sciences72%
Distribution within Medical Sciences
Neurology75%
Pathology25%

Kinds of Spreading Depression

  • cortical spreading depression
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    Selected Abstracts

    Injury-induced neurogenesis in Bax-deficient mice: evidence for regulation by voltage-gated potassium channels

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007
    Jian Shi
    Abstract Adult neural stem and progenitor cells may help remodel the brain in response to injury. The pro-apoptotic molecule Bax has recently been identified as a key player in adult neural stem cell survival. In Bax-deficient mice that have undergone traumatic brain injury, we find increased numbers of neural progenitor cells in the dentate gyrus and improved remodeling of the hippocampus. Exogenous potassium chloride mimics spreading depression (SD)-like events in vitro, and Bax-deficient neural stem cells proliferate in response to these events more robustly than wild-type neural stem cells. Selective potassium channel blockers interrupt SD-mediated stimulation of stem cells. In addition, the potassium channel Kv4.1 is expressed within neural stem and progenitor cells in the dentate gyrus and is increased in Bax-deficiency. These data suggest that the neuroprotection observed after injury in Bax-deficiency may be due to increased neurogenesis via activation of the Kv4 family of potassium channels. [source]

    Effect of cortical spreading depression on synaptic transmission of rat hippocampal tissues

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2006
    Brigitta Wernsmann
    Abstract Cortical spreading depression (CSD) is believed to be a putative neuronal mechanism underlying migraine aura and subsequent pain. In vitro and ex vivo/in vitro brain slice techniques were used to investigate CSD effects on the field excitatory postsynaptic potentials (fEPSP) and tetanus-induced long-term potentiation (LTP) in combined rat hippocampus,cortex slices. Induction of CSD in combined hippocampus,cortex slices in which DC negative deflections did not propagate from neocortex to hippocampus significantly augmented fEPSP amplitude and LTP in the hippocampus. Propagation of CSD to the hippocampus resulted in a transient suppression followed by reinstatement of fEPSP with amplitude of pre-CSD levels. LTP was inhibited when DC potential shifts were recorded in the hippocampus. Furthermore, CSD was induced in anaesthetized rats and, thereafter, hippocampal tissues were examined in vitro. LTP was significantly enhanced in hippocampal slices obtained from ipsilateral site to the hemisphere in which CSD was evoked. The results indicate the disturbances of hippocampal synaptic transmission triggered by propagation of CSD. This perturbation of hippocampal synaptic transmission induced by CSD may relate to some symptoms occurring during migraine attacks, such as amnesia and hyperactivity. [source]

    Recurrent Wernicke's Aphasia: Migraine and Not Stroke!

    HEADACHE, Issue 5 2009
    Nishant Kumar Mishra MBBS
    We report the clinical findings of a 40-year-old woman with recurrent migraine presenting with Wernicke's aphasia in accordance with the results of a standardized battery for language assessment (Boston Aphasia Diagnostic Examination). The patient had no evidence of parenchymal or vascular lesions on MRI and showed delta and theta slowing over the left posterior temporal leads on the EEG. Although the acute onset of a fluent aphasia suggested stroke as a likely etiology, the recurrence of aphasia as the initial symptom of migraine was related to cortical spreading depression and not to stroke. [source]

    Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement

    NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2006
    J. Betts
    Mitochondrial DNA (mtDNA) disease is an important genetic cause of neurological disability. A variety of different clinical features are observed and one of the most common phenotypes is MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes). The majority of patients with MELAS have the 3243A>G mtDNA mutation. The neuropathology is dominated by multifocal infarct-like lesions in the posterior cortex, thought to underlie the stroke-like episodes seen in patients. To investigate the relationship between mtDNA mutation load, mitochondrial dysfunction and neuropathological features in MELAS, we studied individual neurones from several brain regions of two individuals with the 3243A>G mutation using dual cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) histochemistry, and Polymerase Chain Reaction Restriction Fragment Lenght Polymorphism (PCR-RFLP) analysis. We found a low number of COX-deficient neurones in all brain regions. There appeared to be no correlation between the threshold level for the 3243A>G mutation to cause COX deficiency within single neurones and the degree of pathology in affected brain regions. The most severe COX deficiency associated with the highest proportion of mutated mtDNA was present in the walls of the leptomeningeal and cortical blood vessels in all brain regions. We conclude that vascular mitochondrial dysfunction is important in the pathogenesis of the stroke-like episodes in MELAS patients. As migraine is a commonly encountered feature in MELAS, we propose that coupling of the vascular mitochondrial dysfunction with cortical spreading depression (CSD) might underlie the selective distribution of ischaemic lesions in the posterior cortex in these patients. [source]

    Microemboli may link spreading depression, migraine aura, and patent foramen ovale

    ANNALS OF NEUROLOGY, Issue 2 2010
    Ala Nozari MD
    Objective Patent foramen ovale and pulmonary arteriovenous shunts are associated with serious complications such as cerebral emboli, stroke, and migraine with aura. The pathophysiological mechanisms that link these conditions are unknown. We aimed to establish a mechanism linking microembolization to migraine aura in an experimental animal model. Methods We introduced particulate or air microemboli into the carotid circulation in mice to determine whether transient microvascular occlusion, insufficient to cause infarcts, triggered cortical spreading depression (CSD), a propagating slow depolarization that underlies migraine aura. Results Air microemboli reliably triggered CSD without causing infarction. Polystyrene microspheres (10,m) or cholesterol crystals (<70,m) triggered CSD in 16 of 28 mice, with 60% of the mice (40% of those with CSD) showing no infarcts or inflammation on detailed histological analysis of serial brain sections. No evidence of injury was detected on magnetic resonance imaging examination (9.4T; T2 weighted) in 14 of 15 selected animals. The occurrence of CSD appeared to be related to the magnitude and duration of flow reduction, with a triggering mechanism that depended on decreased brain perfusion but not sustained tissue damage. Interpretation In a mouse model, microemboli triggered CSD, often without causing microinfarction. Paradoxical embolization then may link cardiac and extracardiac right-to-left shunts to migraine aura. If translatable to humans, a subset of migraine auras may belong to a spectrum of hypoperfusion disorders along with transient ischemic attacks and silent infarcts. ANN NEUROL 2010;67:221,229 [source]

    High cortical spreading depression susceptibility and migraine-associated symptoms in Cav2.1 S218L mice

    ANNALS OF NEUROLOGY, Issue 1 2010
    Arn M. J. M. van den Maagdenberg PhD
    Objective The CACNA1A gene encodes the pore-forming subunit of neuronal CaV2.1 Ca2+ channels. In patients, the S218L CACNA1A mutation causes a dramatic hemiplegic migraine syndrome that is associated with ataxia, seizures, and severe, sometimes fatal, brain edema often triggered by only a mild head trauma. Methods We introduced the S218L mutation into the mouse Cacna1a gene and studied the mechanisms for the S218L syndrome by analyzing the phenotypic, molecular, and electrophysiological consequences. Results Cacna1aS218L mice faithfully mimic the associated clinical features of the human S218L syndrome. S218L neurons exhibit a gene dosage,dependent negative shift in voltage dependence of CaV2.1 channel activation, resulting in enhanced neurotransmitter release at the neuromuscular junction. Cacna1aS218L mice also display an exquisite sensitivity to cortical spreading depression (CSD), with a vastly reduced triggering threshold, an increased propagation velocity, and frequently multiple CSD events after a single stimulus. In contrast, mice bearing the R192Q CACNA1A mutation, which in humans causes a milder form of hemiplegic migraine, typically exhibit only a single CSD event after one triggering stimulus. Interpretation The particularly low CSD threshold and the strong tendency to respond with multiple CSD events make the S218L cortex highly vulnerable to weak stimuli and may provide a mechanistic basis for the dramatic phenotype seen in S218L mice and patients. Thus, the S218L mouse model may prove a valuable tool to further elucidate mechanisms underlying migraine, seizures, ataxia, and trauma-triggered cerebral edema. ANN NEUROL 2010;67:85,98 [source]

    Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice,

    ANNALS OF NEUROLOGY, Issue 4 2009
    Katharina Eikermann-Haerter MD
    Familial hemiplegic migraine type 1 (FHM1), a severe migraine with aura variant, is caused by mutations in the CACNA1A gene. Mutant mice carrying the FHM1 R192Q mutation exhibit increased propensity for cortical spreading depression (CSD), a propagating wave of neuroglial depolarization implicated in migraine aura. The CSD phenotype is stronger in female R192Q mutants and diminishes after ovariectomy. Here, we show that orchiectomy reciprocally increases CSD susceptibility in R192Q mutant mice. Chronic testosterone replacement restores CSD susceptibility by an androgen receptor-dependent mechanism. Hence, androgens modulate genetically-enhanced CSD susceptibility and may provide a novel prophylactic target for migraine. Ann Neurol 2009;66:564,568 [source]

    Propagation of spreading depression inversely correlates with cortical myelin content,

    ANNALS OF NEUROLOGY, Issue 3 2009
    Doron Merkler MD
    Objective Cortical myelin can be severely affected in patients with demyelinating disorders of the central nervous system. However, the functional implication of cortical demyelination remains elusive. In this study, we investigated whether cortical myelin influences cortical spreading depression (CSD). Methods CSD measurements were performed in rodent models of toxic and autoimmune induced cortical demyelination, in neuregulin-1 type I transgenic mice displaying cortical hypermyelination, and in glial fibrillary acidic protein,transgenic mice exhibiting pronounced astrogliosis. Results Cortical demyelination, but not astrogliosis or inflammation per se, was associated with accelerated CSD. In contrast, hypermyelinated neuregulin-1 type I transgenic mice displayed a decelerated CSD propagation. Interpretation Cortical myelin may be crucially involved in the stabilization and buffering of extracellular ion content that is decisive for CSD propagation velocity and cortical excitability, respectively. Our data thus indicate that cortical involvement in human demyelinating diseases may lead to relevant alterations of cortical function. Ann Neurol 2009;66:355,365 [source]

    The Initiation of the Microglial Response

    BRAIN PATHOLOGY, Issue 1 2000
    Hiroyuki Kato
    The initial response of microglia to ischemia and ischemia-like conditions was analyzed in situ and in vitro. After sublethal ischemia in situ, microglia appear activated morphologically, but do not express macrophage-like antigens. In contrast, neuronal damage induces full expression of immunomolecules in microglia. Additionally, blood-borne cells readily infiltrate the region of the ischemic core and constitute another source of cells with macrophage-like expression. Thus, it appears that the microglia are the earliest cells to respond to injury, but their response is graded and complicated by the presence of blood-borne immune cells. In vitro ischemia-like conditions caused an irreversible depolarization, ion channel shutdown, and blebbing, indicating that microglia are not equipped to withstand an ischemic insult. Application of ATP alone to microglia produced outward currents and calcium transients and these calcium transients increased when ATP was applied in combination with high potassium. It is known that both outward currents and calcium transients are induced during spreading depression, a feature of focal injury, and this suggests that spreading depression might be one of the initial activators of microglia. [source]