Article

Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression.

Headache Research and Treatment Program, Department of Neurology, David Geffen School of Medicine at UCLA, 635 Charles E. Young Drive South, Neuroscience Research Building 1, Room 555a, Los Angeles, CA 90095, USA.
Brain (Impact Factor: 10.23). 03/2010; 133(Pt 4):996-1012. DOI: 10.1093/brain/awp338
Source: PubMed

ABSTRACT Cortical spreading depression is a propagating wave of depolarization that plays important roles in migraine, stroke, subarachnoid haemorrhage and brain injury. Cortical spreading depression is associated with profound vascular changes that may be a significant factor in the clinical response to cortical spreading depression events. We used a combination of optical intrinsic signal imaging, electro-physiology, potassium sensitive electrodes and spectroscopy to investigate neurovascular changes associated with cortical spreading depression in the mouse. We identified two distinct phases of altered neurovascular function, one during the propagating cortical spreading depression wave and a second much longer phase after passage of the wave. The direct current shift associated with the cortical spreading depression wave was accompanied by marked arterial constriction and desaturation of cortical haemoglobin. After recovery from the initial cortical spreading depression wave, we observed a second phase of prolonged, negative direct current shift, arterial constriction and haemoglobin desaturation, lasting at least an hour. Persistent disruption of neurovascular coupling was demonstrated by a loss of coherence between electro-physiological activity and perfusion. Extracellular potassium concentration increased during the cortical spreading depression wave, but recovered and remained at baseline after passage of the wave, consistent with different mechanisms underlying the first and second phases of neurovascular dysfunction. These findings indicate that cortical spreading depression is associated with a multiphasic alteration in neurovascular function, including a novel second direct current shift accompanied by arterial constriction and decrease in tissue oxygen supply, that is temporally and mechanistically distinct from the initial propagated cortical spreading depression wave. Vascular/metabolic uncoupling with cortical spreading depression may have important clinical consequences, and the different phases of dysfunction may represent separate therapeutic targets in the disorders where cortical spreading depression occurs.

Download full-text

Full-text

Available from: Joshua C Chang, Feb 03, 2014
0 Followers
 · 
124 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Changes in cerebral blood flow are one of the main features of migraine attack and have inspired the vascular theory of migraine. This traditional view has been reshaped with recent experimental data, which gave rise to the neural theory of migraine. In this review, we speculate that there might be an important link between the two theories, that is, the dysfunction of neurovascular coupling.
    01/2015; 2015:1-11. DOI:10.1155/2015/574186
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aneurysmal subarachnoid hemorrhage (SAH) has devastating consequences on brain function including profound effects on communication between neurons and the vasculature leading to cerebral ischemia. Physiologically, neurovascular coupling represents a focal increase in cerebral blood flow to meet increased metabolic demand of neurons within active regions of the brain. Neurovascular coupling is an ongoing process involving coordinated activity of the neurovascular unit-neurons, astrocytes, and parenchymal arterioles. Neuronal activity can also influence cerebral blood flow on a larger scale. Spreading depolarizations (SD) are self-propagating waves of neuronal depolarization and are observed during migraine, traumatic brain injury, and stroke. Typically, SD is associated with increased cerebral blood flow. Emerging evidence indicates that SAH causes inversion of neurovascular communication on both the local and global level. In contrast to other events causing SD, SAH-induced SD decreases rather than increases cerebral blood flow. Further, at the level of the neurovascular unit, SAH causes an inversion of neurovascular coupling from vasodilation to vasoconstriction. Global ischemia can also adversely affect the neurovascular response. Here, we summarize current knowledge regarding the impact of SAH and global ischemia on neurovascular communication. A mechanistic understanding of these events should provide novel strategies to treat these neurovascular disorders.
    03/2013; 2013:819340. DOI:10.1155/2013/819340
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A rat cortical spreading depression (CSD) model was established to explore whether cerebral mitochondria injury was induced by CSD under both normoxic and hypoxic conditions and whether flunarizine had a protective effect on cerebral mitochondria. SD rats, which were divided into seven groups, received treatment as follows: no intervention (control Group I); 1 M NaCl injections (Group II); 1 M KCl injections (Group III); intraperitoneal flunarizine (3 mg/kg) 30 min before KCl injections (Group IV); 14% O(2) inhalation before NaCl injections (Group V); 14% O(2) inhalation followed by KCl injections (Group VI); 14% O(2) inhalation and intraperitoneal flunarizine followed by KCl injections (Group VII). Following treatment, brains were removed for the analysis of mitochondria transmembrane potential (MMP) and oxidative respiratory function after recording the number, amplitude and duration of CSD. The duration of CSD was significantly longer in Group VI than that in Group III. The number and duration of CSD in Group VII was significantly lower than that in Group VI. MMP in Group VI was significantly lower than that in Group III, and MMP in Group VII was significantly higher than that in Group VI. State 4 respiration in Group VI was significantly higher than that in Group III, and state 3 respiration in Group VII was significantly higher than that in Group VI. Respiration control of rate in Group VII was also significantly higher than that in Group VI. Thus, we concluded that aggravated cerebral mitochondria injury might be attributed to CSD under hypoxic conditions. Flunarizine can alleviate such cerebral mitochondria injury under both normoxic and hypoxic conditions.
    The Journal of Headache and Pain 02/2011; 12(1):47-53. DOI:10.1007/s10194-011-0300-1 · 3.28 Impact Factor