Does Metoprolol Inhibit the Cortical Spreading Depression? Acute Effects of Systematic Metropol on CSD in Rats

Cephalalgia ◽  
2007 ◽  
Vol 27 (9) ◽  
pp. 1010-1013 ◽  
Author(s):  
M Alemdar ◽  
Ö Akman ◽  
HM Selekler ◽  
SŞ Komsuoğlu ◽  
N Ateş
Keyword(s):  
Dura Mater ◽  
Cortical Spreading Depression ◽  
Wistar Rats ◽  
Spreading Depression ◽  
Migraine Prophylaxis ◽  
Migraine Aura ◽  
Direct Effects ◽  
Acute Effects ◽  
Before And After ◽  
Induction Model

Cortical spreading depression (CSD) is supposed to be the underlying biological basis of the migraine aura. Metoprolol was proven to be effective in migraine prophylaxis in clinical trials, but its mechanism of action has not been clarified yet. We studied direct effects of metoprolol on a continuous CSD induction model in rats. Six adult Wistar rats were anaesthetized with intraperitoneal thiopental (50 mg/kg). CSD was induced with application of 1 M KCL through a burr hole into the left frontal dura-mater, and recorded by an Ag/AgCl DC electrode on the left parietal dura-mater. After a basal recording of CSD induction during the first 40-min period, metoprolol (5 mg/kg) was infused within 4 min. Then DC recordings were maintained for a further 120 min. Any significant differences in total number and duration of CSDs before and after metoprolol administration were not detected. This study suggests that the mode of action of metoprolol in prophylaxis is not via direct CSD inhibition.

Oxcarbazepine does not suppress cortical spreading depression

Cephalalgia ◽  
2010 ◽  
Vol 31 (5) ◽  
pp. 537-542 ◽  
Author(s):  
Ulrike Hoffmann ◽  
Ergin Dileköz ◽  
Chiho Kudo ◽  
Cenk Ayata
Keyword(s):  
Single Dose ◽  
Cortical Spreading Depression ◽  
Chronic Treatment ◽  
Spreading Depression ◽  
Screening Tool ◽  
Positive Control ◽  
Migraine Prophylaxis ◽  
Migraine Aura ◽  
Predictive Utility ◽  
Prophylactic Drugs

Background: Cortical spreading depression is the electrophysiological substrate of migraine aura, and may trigger headache. Recently, chronic treatment with five migraine prophylactic drugs was shown to suppress cortical spreading depression, implicating spreading depression as a common therapeutic target in migraine prophylaxis. Materials and methods: In order to assess the negative predictive value of spreading depression susceptibility as a preclinical drug screening tool, we tested oxcarbazepine, an anti-epileptic ineffective in migraine prophylaxis. Valproate served as the positive control. Cortical spreading depression susceptibility was measured in rats using topical KCl or electrical stimulation. Results: Oxcarbazepine did not suppress spreading depression either after a single dose or after daily treatment for 5 weeks. As previously shown, valproate suppressed spreading depression susceptibility after chronic dosing, while a single dose was ineffective. Conclusions: These data provide further support for spreading depression as a relevant target in migraine prophylaxis, and demonstrate the predictive utility of employed spreading depression models.

scholarly journals MR Detection of Cortical Spreading Depression Immediately after Focal Ischemia in the Rat

1996 ◽  
Vol 16 (2) ◽  
pp. 214-220 ◽  
Author(s):  
Joachim Röther ◽  
Alexander J. de Crespigny ◽  
Helen D'Arceuil ◽  
Michael E. Moseley
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Tissue Perfusion ◽  
Artery Occlusion ◽  
Acute Ischemia ◽  
Planar Imaging ◽  
Mr Perfusion Imaging ◽  
Before And After ◽  
Apparent Diffusion ◽  
Cortical Regions

The suture model for middle cerebral artery occlusion (MCAO) was used to induce acute ischemia in rats remotely within a magnetic resonance (MRI) scanner. Serial MR diffusion weighted imaging (DWI) was performed during remote MCAO using an echo planar imaging technique. MR perfusion imaging was performed before and after occlusion using the bolus tracking technique. Transient apparent diffusion coefficient (ADC) changes were detected in six of seven rats as early as 2.7 ± 1.5 min post MCAO. ADC values declined transiently to 70.1 ± 6.0% of control and recovered to 95.5 ± 6.8% of control within 3.3 ± 2.9 min. These ADC changes propagated bidirectionally away from the ischemic core with a speed of 3.0 ± 1.1 mm/min. Transient ADC decreases only occurred in ischemic areas characterized by moderately decreased tissue perfusion. Propagation toward cortical regions with severe tissue perfusion deficits was not detected. DWI can detect the earliest dynamic, reversible ADC changes in the ischemic tissue. The speed of propagation of the decreasing ADC wave, the waveform characteristics, and the occurrence in moderately perturbated tissue are compatible with cortical spreading depression.

Migraine

2020 ◽  
pp. 213-224
Author(s):  
Julio R Vieira ◽  
Richard B Lipton
Keyword(s):  
Chronic Migraine ◽  
Migraine With Aura ◽  
Cortical Spreading Depression ◽  
Migraine Without Aura ◽  
Spreading Depression ◽  
Headache Frequency ◽  
Motor Symptoms ◽  
Migraine Aura ◽  
Younger Age ◽  
Psychiatric Conditions

This chapter examines migraine. The incidence of migraine varies depending on multiple aspects, including age, sex, and the presence of aura. At an earlier age (younger than age ten), migraine initially affects more boys than girls, with migraine with aura (MA) occurring at a younger age than migraine without aura (MO). Later in life, when puberty starts, this relationship changes and it becomes more common in women than men. Migraine aura are focal neurological symptoms that typically occur prior to the onset of a headache due to a phenomenon called cortical spreading depression. The prevalence of migraine with aura vary between visual, sensory, or motor symptoms. It can also present as diplopia, slurred speech, aphasia, dizziness, vertigo, and hemiparesis. Moreover, the prevalence of migraine varies according to headache frequency. The chapter then looks at chronic migraine and menstrual migraine. It also explores several comorbidities associated with migraine, including many neurologic, medical, and psychiatric conditions.

scholarly journals Cerebral cortex does not modulate “regulated” decrease in core temperature during hypoxemia in rats

1998 ◽  
Vol 274 (4) ◽  
pp. R1158-R1161
Author(s):  
Evvi-Lynn M. Rollins ◽  
James E. Fewell
Keyword(s):  
Cerebral Cortex ◽  
Core Temperature ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Temperature Response ◽  
Sprague Dawley ◽  
Adult Rats ◽  
The Core ◽  
Sprague Dawley Rats ◽  
Before And After

In newborns and adults of a number of species including humans, exposure to acute hypoxemia produces a “regulated” decease in core temperature, the mechanism of which is unknown. Considering that various cortical areas participate in autonomic regulation including thermoregulation, the present experiments were carried out to test the hypothesis that the cerebral cortex plays a role in modulating the regulated decrease in core temperature during acute hypoxemia. This hypothesis was tested by determining the core temperature response to acute hypoxemia in chronically instrumented adult Sprague-Dawley rats before and after cortical spreading depression (i.e., functional decortication) was produced by the local application of potassium chloride to the dura overlying the cerebral hemispheres. There was no effect of cortical spreading depression on baseline core temperature. Core temperature decreased during acute hypoxemia in a similar fashion when the cerebral cortex was intact as well as during functional decortication. Thus our data do not support the hypothesis that the cerebral cortex modulates the regulated decrease in core temperature that occurs in adult rats during acute hypoxemia.

scholarly journals High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression

2016 ◽  
Vol 37 (3) ◽  
pp. 890-901 ◽  
Author(s):  
Tsubasa Takizawa ◽  
Mamoru Shibata ◽  
Yohei Kayama ◽  
Toshihiko Shimizu ◽  
Haruki Toriumi ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Cortical Spreading Depression ◽  
Microglial Activation ◽  
Spreading Depression ◽  
High Mobility ◽  
High Mobility Group ◽  
Migraine Aura ◽  
Double Knockout ◽  
Activated Microglia ◽  
Important Mediator

Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CSD inductions caused microglial hypertrophy (activation) accompanied by a greater impact on the transcription activity of the HMGB1 receptor genes, TLR2 and TLR4, while the total number of cortical microglia was not affected. Both an HMGB1-neurtalizing antibody and the HMGB1 inhibitor glycyrrhizin abrogated multiple CSD-induced microglial hypertrophy. Moreover, multiple CSD inductions failed to induce microglial hypertrophy in TLR2/4 double knockout mice. These results strongly implicate the HMGB1–TLR2/4 axis in the activation of microglia following multiple CSD inductions. Increased expression of the lysosomal acid hydrolase cathepsin D was detected in activated microglia by immunostaining, suggesting that lysosomal phagocytic activity may be enhanced in multiple CSD-activated microglia.

scholarly journals Cerebral Blood Flow Changes during Cortical Spreading Depression are Not Altered by Inhibition of Nitric Oxide Synthesis

1994 ◽  
Vol 14 (6) ◽  
pp. 939-943 ◽  
Author(s):  
Zheng Gang Zhang ◽  
Michael Chopp ◽  
Kenneth I. Maynard ◽  
Michael A. Moskowitz
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Arterial Blood ◽  
Nos Inhibitors ◽  
Before And After ◽  
Male Wistar Rats

CBF increases concomitantly with cortical spreading depression (CSD). We tested the hypothesis that CBF changes during CSD are mediated by nitric oxide (NO). Male Wistar rats (n = 23) were subjected to KCl-induced CSD before and after administration of nitric oxide synthase (NOS) inhibitors N-nitro-l-arginine (L-NNA) or N-nitro-l-arginine methyl ester (L-NAME) and in nontreated animals. CBF, CSD, and mean arterial blood pressure were recorded. Brain NOS activity was measured in vitro in control, L-NNA, and L-NAME-treated rats by the conversion of [3H]arginine to [3H]citrulline. Our data show that the NOS inhibitors did not significantly change regional CBF (rCBF) during CSD, even though cortical NOS activity was profoundly depressed and systemic arterial blood pressure was significantly increased. Our data suggest that rCBF during CSD in rats is not regulated by NO.

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