Abstract:Objective:The objective of this study is to characterize the effects of the sleep-wake cycle on neurovascular and behavioral characteristics of cortical spreading depression
(CSD).Background: There is an important bi-directional relationship between migraine and the sleep-wake cycle, but the basic mechanisms of this relationship are poorly understood.
Methods:We have developed a minimally invasive microchip system to continuously monitor cerebral blood volume (CBV) with optical intrinsic signal (OIS), head mov… Show more
“…Together, these motor activity patterns suggest that SD episodes significantly suppress voluntary motor behaviors as was previously observed in optogenetically evoked SD 40,41 .…”
Section: Resultssupporting
confidence: 79%
“…SD was preceded by prodromal activation and this motor behavior is later suppressed when SD invades the frontal cortex (Figure 5). The latter is generally consistent with findings from optogeneticallyevoked SD in awake animals 40,41 . The seizure+SD complex also showed prolonged motor behavior suppression which was occasionally detected as continuous immobility following PGES.…”
Section: Behavioral Consequences Of Spontaneous Sdsupporting
confidence: 89%
“…It will be important to examine whether the presence of postictal SD also modifies the cardiorespiratory consequences of seizure. Optogenetically evoked cortical SD can significantly modify the heart rhythm in a sleep/awake status-dependent manner ( 40 and our unpublished observation).…”
Objective: Spreading depolarization (SD) is a massive wave of cellular depolarization that slowly migrates across brain gray matter. SD is frequently generated following brain injury and is associated with various acute and chronic neurological deficits. Here we report that spontaneous cortical SD waves are a common EEG abnormality in the Scn1a deficient mouse model (Scn1a+/R1407X). Method: Chronic DC-band EEG recording detected SDs, seizures, and seizure-SD complexes during prolonged monitoring in awake adult Scn1a+/R1407X mice. The effect of hyperthermic seizure and memantine was tested. Results: The spontaneous incidence of events is low and varied among animals, but SDs outnumber seizures. SD waves almost always spread unilaterally from parietal to frontal cortex. On average, spontaneous SD frequency robustly increased by 4.2-fold following a single hyperthermia-evoked seizure, persisting for days to a week without altering the kinetics of individual events. Combined video image and electromyogram analyses revealed that a single interictal SD is associated with prodromal motor activation followed by minutes-lasting immobility upon invasion of frontal cortex. Similar behavioral sequelae also appeared during postictal SD. Memantine treatment was effective in preventing SD exacerbation when given before and after the hyperthermic seizure, suggesting chronic activation of NMDA-receptor contributed to the prolonged SD aftermath. Interpretation: Our results reveal that cortical SD is a prominent electro-behavioral phenotype in this Scn1a deficient mouse model, and SD frequency is robustly sensitive to hyperthermic seizure induced mechanisms likely involving excess NMDAR signaling. The high susceptibility to SD may contribute to co-morbid pathophysiology in developmental epileptic encephalopathy.
“…Together, these motor activity patterns suggest that SD episodes significantly suppress voluntary motor behaviors as was previously observed in optogenetically evoked SD 40,41 .…”
Section: Resultssupporting
confidence: 79%
“…SD was preceded by prodromal activation and this motor behavior is later suppressed when SD invades the frontal cortex (Figure 5). The latter is generally consistent with findings from optogeneticallyevoked SD in awake animals 40,41 . The seizure+SD complex also showed prolonged motor behavior suppression which was occasionally detected as continuous immobility following PGES.…”
Section: Behavioral Consequences Of Spontaneous Sdsupporting
confidence: 89%
“…It will be important to examine whether the presence of postictal SD also modifies the cardiorespiratory consequences of seizure. Optogenetically evoked cortical SD can significantly modify the heart rhythm in a sleep/awake status-dependent manner ( 40 and our unpublished observation).…”
Objective: Spreading depolarization (SD) is a massive wave of cellular depolarization that slowly migrates across brain gray matter. SD is frequently generated following brain injury and is associated with various acute and chronic neurological deficits. Here we report that spontaneous cortical SD waves are a common EEG abnormality in the Scn1a deficient mouse model (Scn1a+/R1407X). Method: Chronic DC-band EEG recording detected SDs, seizures, and seizure-SD complexes during prolonged monitoring in awake adult Scn1a+/R1407X mice. The effect of hyperthermic seizure and memantine was tested. Results: The spontaneous incidence of events is low and varied among animals, but SDs outnumber seizures. SD waves almost always spread unilaterally from parietal to frontal cortex. On average, spontaneous SD frequency robustly increased by 4.2-fold following a single hyperthermia-evoked seizure, persisting for days to a week without altering the kinetics of individual events. Combined video image and electromyogram analyses revealed that a single interictal SD is associated with prodromal motor activation followed by minutes-lasting immobility upon invasion of frontal cortex. Similar behavioral sequelae also appeared during postictal SD. Memantine treatment was effective in preventing SD exacerbation when given before and after the hyperthermic seizure, suggesting chronic activation of NMDA-receptor contributed to the prolonged SD aftermath. Interpretation: Our results reveal that cortical SD is a prominent electro-behavioral phenotype in this Scn1a deficient mouse model, and SD frequency is robustly sensitive to hyperthermic seizure induced mechanisms likely involving excess NMDAR signaling. The high susceptibility to SD may contribute to co-morbid pathophysiology in developmental epileptic encephalopathy.
“…Dr. Yousef Yengej is currently applying these techniques to study mechanisms of migraine, the sleep–wake cycle, and a variety of neurological and systemic disorders and pain. He plans to continue working to develop these unique methods further in the future 4 …”
“…The next runner‐up for this prize is Dr. Yousef Yengej and colleagues for the paper entitled “Different characteristics of cortical spreading depression in the sleep and wake states”, 4 with work conducted at the Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, California, USA, in the laboratory of Dr. Andrew Charles. The authors briefly explain their contribution here.There is a bi‐directional relationship between migraine and the sleep–wake cycle, but the mechanisms of this relationship are poorly understood.…”
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