Molecular Neurobiology Copyright 2006 Humana Press Inc All rights of any nature whatsoever reserved ISSN 0893 7648 06 33 3 000 000 30 00 ISSN Online 1559 1182 Neurovascular Coupling and Oximetry During Epileptic Events Minah Suh Hongtao Ma Mingrui Zhao Saadat Sharif and Theodore H Schwartz Department of Neurological Surgery Weill Cornell Medical College New York Presbyterian Hospital New York NY Abstract Epilepsy is an abnormal brain state in which a large population of neurons is synchronously active causing an enormous increase in metabolic demand Recent investigations using highresolution imaging techniques such as optical recording of intrinsic signals and voltagesensitive dyes as well as measurements with oxygen sensitive electrodes have elucidated the spatiotemporal relationship between neuronal activity cerebral blood volume and oximetry in vivo A focal decrease in tissue oxygenation and a focal increase in deoxygenated hemoglobin occurs following both interictal and ictal events This epileptic dip in oxygenation can persist for the duration of an ictal event suggesting that cerebral blood flow is inadequate to meet metabolic demand A rapid focal increase in cerebral blood flow and cerebral blood volume also accompanies epileptic events however this increase in perfusion soon 2 s spreads to a larger area of the cortex than the excitatory change in membrane potential Investigations in humans during neurosurgical operations have confirmed the laboratory data derived from animal studies These data not only have clinical implications for the interpretation of noninvasive imaging studies such as positron emission tomography single photon emission tomography and functional magnetic resonance imaging but also provide a mechanism for the cognitive decline in patients with chronic epilepsy Index Entries Epilepsy ictal interictal intrinsic signal optical imaging voltage sensitive dye oxygen sensitive electrodes neurovascular coupling oximetry initial dip BOLD rat seizure human AU Please provide accepted date Author to whom all correspondence and reprint requests should be addressed E mail mis2032 med cornell edu Received August 25 2005 Accepted Molecular Neurobiology 1 Volume 33 2006 2 Introduction The study of neurovascular coupling examines the relationship between neuronal activity metabolism tissue and blood oxygenation and blood flow It has been generally accepted that increases in neuronal activity increase the cerebral metabolic rate of oxygen consumption CMRO2 leading to an increase in cerebral blood flow CBF and cerebral blood volume CBV as the brain attempts to perfuse the active neurons with oxygenated hemoglobin 1 It was then shown using positron emission tomography PET of glucose metabolism a technique with a slow temporal resolution approximately seconds ref 2 that increases in CBF occurring 1 to 2 s after the onset of neuronal activity provide an oversupply of oxygenated hemoglobin HbO2 Therefore CMRO2 and CBF are uncoupled causing relative increases in the concentration of HbO2 compared with deoxygenated hemoglobin Hbr which forms the basis of the blood oxygenlevel dependent BOLD signal that can be imaged with functional magnetic resonance imaging fMRI ref 3 More recently using techniques with higher spatial and temporal resolution such as optical recording of intrinsic signals ORIS refs 4 and5 imaging spectroscopy 6 7 oxygen dependent phospherescence quenching 8 oxygen sensitive electrodes 9 10 and fMRI at 1 5 and 4 Tesla 11 12 investigators have examined changes in tissue and blood oxygenation that occur within the first few hundred milliseconds after neurons become active These studies have demonstrated a rapid decrease in tissue oxygenation or an increase in Hbr that precedes the increase in CBF This initial dip although questioned by some studies 13 15 implies that for a brief period of time after neurons discharge the brain is mildly ischemic until cerebrovascular autoregulation dilates arterioles to increase CBF Epilepsy is an abnormal physiological state that unlike normal somatosensory processing places supranormal demands on the brain s autoregulatory mechanisms because of an Molecular Neurobiology Suh et al enormous increase in CMRO2 16 Therefore the neurovascular coupling mechanisms that apply in the normal situation may not be relevant Epilepsy is a disease involving recurrent seizures that consist of the paroxysmal synchronous rhythmic firing of a population of pathologically interconnected neurons capable of demonstrating high frequency oscillatory activity 17 Between these ictal events brief paroxysmal short duration 100 ms events occur called interictal spikes 18 Prior investigations into neurovascular coupling during epileptic events have demonstrated contradictory results in both animals and humans using autoradiography PET and fMRI all of which are techniques with limited temporal and spatial resolution 19 25 Although an increase in perfusion is universally demonstrated some studies have shown that perfusion oversupplies metabolism 24 27 whereas others have demonstrated the opposite namely inadequate perfusion to meet metabolic demand 19 21 23 Therefore the relationship between perfusion and oxygenation during the first few seconds after an epileptiform event has remained elusive This article reviews recent data on neurovascular coupling during epilepsy obtained in vivo using techniques that have high temporal and spatial resolution such as ORIS oxygen sensitive electrodes and voltage sensitive dyes VSDs Optical Recording of Intrinsic Signals The intrinsic optical signal IOS is a small change in the absorption or reflection of light that occurs in neuronal tissue when neurons are activated These changes can be recorded from various preparations ranging from a single neuron preserved in vitro 28 to the human brain in the neurosurgical operating room 29 ORIS has been used extensively to map static functional architecture such as orientation and ocular dominance columns in visual cortex which has led to discoveries such as the pinwheel organization of orientation Volume 33 2006 Neurovascular Coupling During Epileptic Events AU Please define IIS at first use columns 30 The origins of the IOS are multiple because neuronal activity induces a cascade of events in the surrounding tissues each of which can influence the reflection of light The real power of the IOS arises from the fact that depending on the wavelength of light the IOS can separately
View Full Document
Unlocking...