Medical Tourism - Spreading Brain/Spinning Hypnosis
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1 SPREADING DEPRESSION AS A HOLISTIC PROCESS: A HISTORICAL PERSPECTIVE Bernice Grafstein, Ph.D. Professor of Physiology & Biophysics Professor of Neuroscience Vincent & Brooke Astor Distinguished Professor in Neuroscience Weill Cornell Medical College New York, NY I do not have a financial interest in commercial products or services related to the subject of this lecture.
2 Why we are here Aristides A.P. Leão ( ) Leão, A.P., 1944a. SPREADING DEPRESSION OF ACTIVITY IN THE CEREBRAL CORTEX. J. Neurophysiol. 3, Leão, A.P., 1944b. PIAL CIRCULATION AND SPREADING DEPRESSION OF ACTIVITY IN THE CEREBAL CORTEX. J. Neurophysiol. 7, Leão, A.P., FURTHER OBSERVATIONS ON THE SPREADING OF DEPRESSION OF ACTIVITY IN THE CEREBRAL CORTEX. J. Neurophysiol. 7, Leão, A.P., THE SLOW VOLTAGE VARIATION OF CORTICAL SPREADING DEPRESSION OF ACTIVITY. EEG Clin. Neurophyiol. 3: /Aristides_Leao_1914_1993.html Leão, A.P., Morison, R.A., PROPAGATION OF SPREADING CORTICAL DEPRESSION. J. Neurophysiol. 8,
3 Characteristics of spreading cortical depression Sequential disappearance of electrical activity, advancing over cortex several mm/min Modified from Leão, 1944 Slow surface depolarization From Leño,
4 SD invalidates the concept of the suppressor strip J.G. Dusser de Barenne ne/founders/page0027.html Warren S. McCulloch BEFORE STRYCHNINE 7 min. AFTER 11.5 min. AFTER b05/photos.html J. Neurophysiol. 1: (1938) 4
5 Significance of spreading depression/depolarization Initiating conditions: strong electrical stimulation/activity depolarization KCl mechanical impact trauma anoxia/ ischemia hypoglycemia Relevant clinical conditions: migraine aura epilepsy/postictal symptoms head injury/ concussion/ chronic traumatic encephalopathy stroke subarachnoid hemorrhage 5
6 Characteristics of spreading cortical depression (cont.) Bernice Grafstein Benedict Delisle Burns MECHANISM OF SPREADING CORTICAL DEPRESSION B. Grafstein J. Neurophysiol. 19: (1956) Onset of slow surface depolarization is accompanied by neuronal excitation Modified from Grafstein,
7 The hypothesis J. Neurophysiol. 19: (1956) 7
8 Some uneasiness? 8
9 Some high-quality support 9
10 Some vindication POTASSIUM OUTFLUX FROM RABBIT CORTEX DURING SPREADING DEPRESSION F. J. Brinley, Jr., E. R. Kandel, and Wade H. Marshall J. Neurophysiol. 23: (1960) 10
11 50 years later -- still grumbling! 11
12 White knights to the rescue REPLY (condensed): The release of K + is an essential factor giving SD its all-or-none characteristic... It was Grafstein (1956) who first suggested a critical role for K +. George Somjen Departments of Cell Biology and Neurobiology Duke University Medical Center Durham, North Carolina g.somjen@cellbio.duke.edu Anthony Strong Departments of Cell Biology and Neurobiology Department of Clinical Neuroscience King s College London, United Kingdom anthony.strong@kcl.ac.uk 12
13 More features of SD 13
14 In SD there is increased tissue resistance, cell swelling and decreased extracellular space EVOKED RESPONSE DC POTENTIAL Saline RESISTIVITY KCl J. Cell Comp. Physiol. 45: (1955) J. Neurophysiol. 30: (1967) * 14
15 Spreading depression can be visualized in retina by change in light scattering H. Martins-Ferreira ltado.php3?codigo=hiss Figure modified from Martins-Ferreira et al., 2000 J. Neurophysiol. 29: (1966) 15
16 SD is accompanied by glutamate release and can be initiated by glutamate Antonie van Harreveld KCl 1 min. TRANSPARENCY RELEASED GLUTAMATE J. Neurobiol. 2: (1970) J. Neurochemistry 3: (1959) 16
17 Spreading depression as a tool to study brain function Jan Bures ndex.php?skript=prezentace.php 17
18 SD involves ionic changes in addition to K + Richard P. Kraig Voltage Na + Cl - Charles Nicholson Voltage Ca ++ Neuroscience 3: (1978) 18
19 Vascular changes 19
20 Vascular changes during SD in mouse cortex Takahiro Takano Maiken Nedergaard CORTICAL SPREADING DEPRESSION CAUSES AND COINCIDES WITH TISSUE HYPOXIA T. Takano, G.-F. Tian., W. Peng, N. Lou1, D. Lovatt, A.J. Hansen, K.A. Kasischke1 and M. Nedergaard Nature Neuroscience 10, (2007) 20
21 Hypoxia during SD, even during vasodilation phase CORTICAL SPREADING DEPRESSION CAUSES AND COINCIDES WITH TISSUE HYPOXIA T. Takano, G.-F. Tian., W. Peng, N. Lou1, D. Lovatt, A.J. Hansen, K.A. Kasischke1 and M. Nedergaard Nature Neuroscience 10, (2007) 21
22 The role of astrocytes 22
23 Astrocytes depolarize during SD Cortical surface potential K + Intracellular astrocyte potential Modified from Sugaya et al., 1974 NEURONAL AND GLIAL ACTIVITY DURING SPREADING DEPRESSION IN CEREBRAL CORTEX OF CAT Sugaya, E., Takato, M., and Noda, Y. J. NeurophysioI. 38: (1974) 23
24 Calcium waves in astrocytes (mediated by gap junctions and ATP diffusion) spread at the same rate as SD Astrocytes in culture filled with Ca ++ -sensitive dye (stimulated at arrow) Modified from Martins-Ferreira et al.,
25 Do astrocyte Ca 2 + waves contribute to SD? YES GAP JUNCTIONS ARE REQUIRED FOR THE PROPAGATION OF SPREADING DEPRESSION M. Nedergaard, A.J.L.Cooper and S.A. Goldman J. Neurobiol. 28: (1995) NO DIFFERENT MECHANISMS PROMOTE ASTROCYTE Ca 2+ WAVES AND SPREADING DEPRESSION IN THE MOUSE NEOCORTEX O. Peters, C. G. Schipke, Y. Hashimoto, and H. Kettenmann J. Neurosci. 23: (2003) 25
26 The role of microglia 26
27 SD activates microglia in cerebral cortex Normal 24 hr after SD MICROGLIAL REACTION IN THE RAT CEREBRAL CORTEX INDUCED BY CORTICAL SPREADING DEPRESSION J. Gehrmann, G. Mies, P. Bonnekoh, R. Banati, T. lijima, G.W. Kreutzberg and K.-A. Hossmann Brain Pathology 3: (1 993) 27
28 Initiation of spreading depression requires microglia Drug (clodronate) that depletes microglia blocks initiation of SD by K + in hippocampal slice cultures Adapted from Pusic et al., 2014 SPREADING DEPRESSION REQUIRES MICROGLIA AND IS DECREASED BY THEIR M2A POLARIZATION FROM ENVIRONMENTAL ENRICHMENT K.M. Pusic, A.D. Pusic, J. Kemme and R.P. Kraig. Glia 62: (2014) 28
29 The migraine connection 29
30 Spread of SD = spread of visual aura activity on the cortex From Lashley, 1947 NOTE ON A POSSIBLE CORRESPONDENCE BETWEEN THE SCOTOMAS OF MIGRAINE AND SPREADING DEPRESSION OF LEÃO P.M. Milner, Ph.D. EEG Clin. Neurophysiol. 10: 705 (1958) 30
31 First demonstration of spreading depression during migraine using PET BILATERAL SPREADING HYPOPERFUSION DURING SPONTANEOUS MIGRAINE HEADACHE R.P. Woods, M. Iacoboni and J.C. Mazziotta New Eng. J. Med. 331: (1994) 31
32 Typical course of cerebral blood flow changes in migraine Modified from Tfelt-Hansen, 2010, after original from Olesen et al., 1990 TIMING AND TOPOGRAPHY OF CEREBRAL BLOOD FLOW, AURA, AND HEADACHE DURING MIGRAINE ATTACKS J. Olesen, L. Friberg, T. Skyhøj Olsen, H.K. Iversen, N.A. Lassen, A.R. Andersen and A.Karle Ann. Neurol. 28: (1990) 32
33 Why women are more susceptible to migraine? Brain Research 1370: (2011) 8.0 +/- 0.6 mm K + vs /- 0.4 mm K + 33
34 How do SD events cause headache? 34
35 Trigeminovascular hypothesis of migraine headache ATP SD Modified from Pietrobon & Moskowitz, 2014 CHAOS AND COMMOTION IN THE WAKE OF CORTICAL SPREADING DEPRESSION AND SPREADING DEPOLARIZATIONS D. Pietrobon and M. Moskowitz Nature Rev. Neurosci. 15: (2014) 35
36 The message 36
37 Mechanisms participating in spreading depression K + release by neuronal activity and depolarization internalization of Na +, Cl - and Ca 2+ and cell swelling glutamate release from neurons and astrocytes astrocytic Ca ++ waves via gap junctions and ATP release vasodilation/vasoconstriction microglial activation (inflammation) anoxia NO generation blood-brain barrier disruption 37
38 The neurovascular unit: multiple participants in spreading depression Modified from Del Zoppo,
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