вход по аккаунту


Cellular activity underlying altered brain metabolism during focal epileptic activity.

код для вставкиСкачать
Cellular Activity Underlying Altered Brain
Metabolism During Focal Epileptic Activity
Claus Bruehl, PhD, and Otto W. Witte, M D
Demonstration of focal alterations of brain metabolism with positron emission tomography has become a widely used
method for identifying epileptic foci. Here we investigated how neuronal and glial cell activity relates to alterations
of brain metabolism. Acutely induced epileptic activity in the motor cortex of rat brain increased metabolism in the
focus and homotopic contralateral areas, and decreased metabolism in the ipsilateral somatosensory area. Increases
and decreases of deoxyglucose uptake did not directly correlate with excitations and inhibitions; instead, deoxyglucose
uptake was related to the overall strength of synaptic activity, and both strong excitations and strong inhibitions
increased brain metabolism. Reduction of metabolism below normal values was associated with reduced synaptic
activity and with tonic hyperpolarization of the cells. Our results show that in the absence of structural abnormalities,
hypometabolism indicates functional disturbances which may be both reversible and remote from the epileptogenic
Bruehl C, Witte OW. Cellular activity underlying altered brain metabolism
during focal epileptic activity. A n n Neurol 1995;38:414-420
In patients with focal epilepsy, in between the seizures
a focal reduction of brain metabolism as measured with
positron emission tomography (PET) and deoxyglucose is often found [I-51. In temporal lobe epilepsy,
this reduction is most pronounced in the area of the
diseased mesiotemporal lobe that shows cell loss and
astrocytosis. Demonstration both of unilateral hippocampal atrophy by magnetic resonance tomography
and of unilateral mesiotempor:d hypometabolism helps
to guide surgery for epilepsy and increase its success
rate [b, 77. However, the hypometabolism in temporal
lobe epilepsy may extend well beyond the area with
hippocampal sclerosis [S, 91. Furthermore, in extratemporal epilepsy, focal hypometabolism has been
considerably less helpful in delineating the focus 110,
1I]. Though it assists in localization or lateralization
of the focus [121, the hypometabolism may be more
extended than the focus. Thus, focal hypometabolism
in patients with epilepsy is not necessarily linked to
cell loss and gliosis, and it is possible that it can be
spatially separate from the epileptogenic focus.
Here we investigated how epileptically induced neuronal and glial cell activity is related to alterations of
brain metabolism. The experiments disprove the intuitive assumption that an increase of deoxyglucose uptake indicates increased excitation, and a decrease indicates enhanced inhibition. Measurements of brain
metabolism by deoxyglucose autoradiography during
acutely induced interictal epileptic activity in the rat
brain show that strong excitations as well as strong inhibitions increase brain metabolism. An evaluation of the
duration of neuronal inhibitions and the amplitude of
glial cell depolarizations shows that the deoxyglucose
uptake is related to the overall strength of synaptic
activity. In this model, which is not associated with any
structural lesions. the hypometabolic brain areas are
remote from the focus and are not epileptically active.
However, the function of these brain areas is disturbed
by transient neuronal hyperpolarizations associated
with the focal spikes and by a tonic increase of the
resting membrane potential in this area, which also
explains the reduction of metabolism below normal
From the Neurologische Klinik, Heinrich-Heine-Universitat, Diisseldorf, Germany.
Address correspondence ro Dr Witte. Neurologische Klinik, Heinrich-Heine-Universitat, Moorenstr. 5, D-40225 Diisseldorf, Germany.
Received Mar 31, 1095, and in revised form May 31. Accepted for
publication Jun 1. 1995.
Materials and Methods
Male Wistar rats (n = 16;weight, 300 gm) were anesthetized
with 1.5% halothane during preparation, and 0.457 during
the experiments. After tracheotomy the animals were ventilated (70% N 2 0 and 30%' oxygen) and restrained (dtubocurarine). For administration of '"C-deoxyglucose and
monitoring of blood gases, the femoral vein and artery were
cannulated with fine plastic rubes. One or two holes (internal
diameter, 1.8 mm) were drilled into the skull, and the dura
mater was removed. Electrocardiogram, blood pressure,
blood pH, carbon dioxide (Pco,) and oxygen (Po?)tensions,
and body temperature (37°C) were monitored throughout
the experiment. The electrocorticogram (ECoG) was recorded by a glass electrode filled with artificial cerebrospinal fluid (sodium chloride [NaCl], 125; NaHC03. 25;
414 Copyright 0 1995 by the American Neurological Association
Na,HP04, 0.5; calcium chloride ICaCI,], 1.1; magnesium
chloride [MgCI,], 0.8; potassium chloride [KCI), 3 mmol/
liter; p I i 7.3) located 0.5 mm lateral to the midline and 0.5
mm frontal to the bregma. Focal epilepsy was induced by
replacing this recording electrode with an electrode containing 50,000 IU/ml of sodium penicillin (with NaCl adjusted for osmolarity).
The regional cerebral metabolic rate of glucose
(rCMRGlc) was determined according to the ‘‘C-deoxyglucose method [ 131. “C-Deoxyglucose (40 pCi) dissolved in
0.4 ml of artificial cerebrospinal fluid was injected through
the femoral vein as a bolus. Thereafter blood samples were
taken for the following 45 minutes to determine the glucose
content and the remaining radioactivity. Immediately after
the last sample was taken, the rat brain was frozen in vivo
with liquid nitrogen (“freeze funnel technique”) and then
stored at - 70°C for further preparation. Following brain
dissection in a -20°C freezing chamber, the brain was cut
into 20-wm-thick slices with a cryotome ( - 20°C). These
slices and an isotope standard were exposed to highresolution autoradiography film (Amersham, hyperfilmpmax, RPN9) for 9 to 14 days.
The optical densities of the film were recorded with a
charge coupled device camera (CCD) that was connected to
an online videometry processor for background subtraction
and offset correction. This signal was digitized and analyzed
by an imaging program. To obtain tissue glucose utilization
rates, the data were calibrated according to the isotope standards and blood glucose concentrations. Since the overall
glucose utilization rates of animals varied considerably, independent from the experimental conditions, the data were
normalized with respect to the glucose utilization rates in
the parietal areas contralateral to the focus. This procedure
emphasized the alterations in brain metabolism caused by the
epileptic focus. Data are given as means i_ standard error of
means (SEM). All mentioned alterations in metabolism were
statistically significant within at leastp < 0.05 (Student’s t test).
The reference electrode for intracellular and extracellular
ECoG recordings was positioned onto the frontal nasal bone
of the animal. Intracellular recordings were carried out after a stable focus had developed (> 20 minutes). The glass
microelectrodes, filled with 2 mol/liter of potassiummethylsulfate (70-120 MO), were inserted into the cortex
perpendicularly to its surface, at stereotactically determined
positions, by a microstepper device. Recordings were obtained from neurons of almost all cortical layers, with a predominance in depths of 400 to 600 p m and 1,100 to 1,300
pm. No obvious difference was found between cells obtained
from different cortical depths. Only cells with stable resting
membrane potentials exceeding - 45 mV were included in
the study. The average membrane potential a few hundred
milliseconds (-200-500 msec) before the occurrence of a
spike in the ECoG was used for determining the resting
membrane potential. After successful registration, cell penetration-induced changes of tip potential and the field potential were subtracted by withdrawing the electrode from the
cell and recording of the remaining extracellular potential.
Extracellular single-unit recordings were obtained by using
Teflon-coated tungsten electrodes (exposed tip length, 10
pm). All electrical signals were stored on magnetic tape (upper frequency limit, 5 kHz) and evaluated offline. With extra-
cellular and intracellular recording techniques, a total of 152
neurons were recorded from four different areas of the brain.
Neuronal excitations were clearly detectable as typical paroxysmal depolaritations with strong decreases of the resting
potential of the neurons, while in extracellular recordings a
high frequence burst of action potentials was visible. Inhibitions of neurons were observed either in isolation or as inhibitory afterpotentials following the excitations. They appeared
as a temporary increased resting potential or a cessation of
action potentials within the intracellular recordings and as
an interruption of spontaneous action potential firing in the
extracellular recordings.
Five to 10 minutes after penicillin application, typical
epileptic spikes were seen on ECoG with a frequency
of about 0.5 per second C14) (Fig IA). This was associated with a hypermetabolism in the motor cortex directly beneath the penicillin application site. In this
area, increases in glucose uptake of 55
9% (SEM,
n = 8) were observed in comparison to the contralateral parietal areas, which showed the same metabolism
in experimental and control groups tl5). In the motor
cortex behind the epileptic focus, glucose metabolism
also remained normal. However, in the cortex lateral
to the epileptic area, glucose consumption was reduced
by 28 k 7% (n = 7). This hypometabolism was not
restricted to the vicinity of the hypermetabolic focus,
but occupied wide parts of the ipsilateral hemisphere.
A moderate increase of glucose uptake was observed
in the contralateral hemisphere in an area homotopic
to the focus (22 ? 495, n = 7). All other regions of
the contralateral brain hemisphere were normometabolic.
To examine the neuronal activity underlying the
aforementioned metabolic changes, electrophysiological recordings were done within the focus, the adjacent
cortical areas (i.e., motor cortex caudal to the focus
and the lateral sensory cortex), as well as from the
homotopic contralateral side of the brain.
Neurons directly within the focus displayed paroxysmal depolarization shifts (PDSs), followed by strong
inhibitory afterpotentials (630 2 22 rnsec, n = 38)
Cl6, 171: After an initial series of action potentials,
these neurons were rapidly depolarized and action potential firing ceased. These depolarizations had a mean
duration of 87.0 5 22 msec (n = 62) and an amplitude
of 44.2 k 16 mV (n = 62). In between the PDSs the
neurons usually were silent, giving the typical interictal
discharges pattern described by Matsumoto and Ajrnone-Marsan 118) and Dorn and Witte C191.
During the epileptic discharges of the focus, neurons
outside the focus usually displayed short inhibitions,
with durations of 202 -i- 26 msec (n = 20) in the
ipsilateral and 239.9 5 19 msec (n = 25) in the contralateral motor cortex (Fig 2 , significantly different from
values in the focus, with p < 0.001).Within the ipsilat-
Bruehl and Witte: Cellular Activity and Metabolism
Fig 1 . ''C-Deoxyglucose autoradiogram of rat brain. This slice
is through the epilepticfocus indued by epicortical application
of penicillin in an anesthetized an,d relaxed rat. Not6 the strong
increase of metabolism in the focus (A), the moderate increase in
contralateral homotopic area (B), and the decrease of metabolism
lateral to the focus (D). Scale is in pmo1lgm"min. The recording
on top shows a typical electrocorticogramfrom epileptic focus
with repetitive occurring spikes. Horizontal bar = 1 second; vertical bar = 1 mV.
eral somatosensory cortex, the inhibitory episode was
about half as long (123 i 21 msec, n = 22, significantly different from values in ipsilateral and contralateral motor cortex, withp < 0.05 and] < 0.001). PDSlike discharges were never seen in the hypometabolic
sensory cortex nor were they seen in the normometabolic ipsilateral motor cortex; they were observed in
4 of 48 neurons recorded within the hypermetabolic
contralateral motor cortex. Hence, although there was
some tendency for stronger excitations in areas with a
higher metabolism, the main difference relates to the
duration of the inhibitions: 'These were shortest in hypometabolic areas and longest in hypermetabolic areas,
indicating that the energy demand caused by release
and reuptake of transmitter differed considerably in
these brain areas [20).
As a further indicator of the neuronal activity, the
membrane potential changes of glial cells were recorded: The glial cell membrane potential within the
central nervous system is known to be affected mainly
by the extracellular potassium ion concentration 12 11.
The extracellular potassium ion activity is related to
the activity of the neurons (i.e., potassium efflux after
excitations and during inhibitions). Glial cells within
the epileptic focus showed strong transient depolarizations of 23 t 2.3 mV (n = 17) concomitant with
the spikes in the electroencephalogram (EEG) (Fig 3).
These depolarizations reached their maximum value
within 100 msec and repolarized over a period lasting
between 1.5 and 7.0 seconds. Similar, though smaller,
depolarizations were recorded in glial cells from the
contralateral hypermetabolic cortex (10.4 _t 2.7 mV,
n = 6) and from the normometabolic cortex behind
the focus (6.5 2 0.5 mV, n = 4). In contrast, glial
cells within the (hypometabolic) sensory cortex showed
smaller or no depolarizations associated with the epileptic discharges in the EEG (2.3 f. 1.0 mV, n = 4)
indicating a low activity level of the neurons in this
area. These data show that the amplitude of the transient depolarizations correlates to brain metabolism
(Fig 4B).The resting membrane potential of the glial
cells also pointed toward a lower activity level in hypometabolic brain areas: Resting membrane potential
amounted to -93.8 & 2.7 mV (n = 17) in the focus,
- 76.1 t 3.8 mV (n = 6) in the hypermetabolic contralateral motor cortex, - 78.3 ? 10.0 mV (n = 4 ) in
the normometabolic cortex behind the focus, and
- 107.3 -+ 6.2 mV (n = 4)in the hypometabolic cortex lateral to the focus.
416 Annals of Neurology Vol 38 No 3 September 1975
300 ms
300 ms
Fig 2. Neuronal activity in different brain areas during epileptic discharge of an epileptic focus. Epileptic activity was induced
by epicortical application of penicillin in an anesthetized and relaxed rat. Recordings with intracellular microelectrodes are from
the epileptic focus (A),contralateral bypermetabolic brain area
(B), ipsilateral normometabolic brain area (C),and ipsilateral
hypometabolic brain area (0).
Recordings in (‘A)
through (0)
were obtained from different animals.
The hypometabolism in the somatosensory brain
area is not associated with any structural alterations,
depends on the activity of the focus, and ceases when
the focal epileptic activity ends 122, 2.31. To explain
the reduction of metabolism below normal values by
cellular activity, a reduction of synaptic activity or a
tonic hyperpolarization associated with reduced activity
has to be assumed. Therefore, we evaluated the neuronal membrane potential in metabolically different
areas. This revealed that neurons within the hypometabolic brain areas displayed a tonically increased
Fig 3. Glial cell activio in d i f f e n t brain areas during epileptic discharge of an epileptic focus. Epileptic actidy was induced
by epicortical application of penicillin in an anesthetized and relaxed rat. Recordings with intracellular microelectrodes were
from the epileptic focus (A),
contralateral hypermetabolic brain
area ( B ) ,ipsilateral normometabolic brain area (C),and ipsilatera1 hypometabolic brain area (0).
Recordings in (A)through
(Di were obtained from different animals.
membrane potential. Neurons in the normometabolic
area located caudally to the focus had a mean membrane potential of -55.8 -+ 2 mV (n = 11). This
potential did not differ from that measured in neurons
within the contralateral and slightly hypermetabolic
motor cortex ( - 53.9 k 1.5 mV, n = 25). In contrast,
neurons from the hypometabolic sensory cortex
showed a membrane potential of -64.3 5 3.5 mV
(n = 16).This mean value differs statistically from that
in the normometabolic brain ( p < 0.01) and from that
in the contralateral hypermetabolic brain ( p < 0.01).
Thus hypometabolism correlated to an increase of
membrane potential compared to normometabolic or
hypermetabolic extrafocal areas. However, the resting
membrane potential of neurons within the epileptic
focus was even higher ( - 70.1 & 14 mV, n = 62,
different from hypometabolic area, with p < 0.01).
This is due to the fact that the PDSs in the focus are
associated with strong calcium influxes that elicit calcium-dependent potassium currents; the latter have
Bruehl and Witte: Cellular Activity and Metabolism
4. (A) Correlation of duration of inhibition with changes
of brain metabolism. IB) Correlation of glial cell depolarizations
with changes of brain metabolism. Data are from the epileptic
focus in motor cortex (open square), moto+cortex homotopic and
contralateral to the focus (closed c:riangle), ipsilateral motor cortex behind focus (open circle), and ipsilateval somatosensory cortex lateral from focus (closed diamond).
such a long duration that in a focus discharging at a
rate of 0.5 to 1.0 per second, they considerably contribute to the apparent resting membrane potential of
the neurons C24-263.
The present results do not allow us to determine
whether the alterations of brain metabolism are mainly
due to changes of glucose uptake in neurons or glial
cells. However, since the behavior of the glial cells
reflects the neuronal activity, the metabolism is either
directly or indirectly coupled to the neuronal behavior.
Obviously, an increase or decrease in metabolism does
not directly relate to excitation and inhibition. The
metabolic changes are best fitted when the cellular behavior is expressed in terms of increased or decreased
transmitter release.
The hypermetabolism within the focus is easily explained by the strong excitations during the PDSs associated with massive release of glutamate, and the following long-lasting inhibitions involving release of
gamma-aminobutyric acid (GABA). The hypermetabolism in the contralateral homotopic brain area in
which the vast majority of neurons only displayed inhibitions shows that inhibitory interactions can increase
the metabolism, as was suggested previously by Ackermann and colleagues [27, 28). Reduction of metabolism below normal values was associated with a tonic
hyperpolarization of the neurons. A previous study
showed that the hypometabolism is confined to cytoarchitectonic areas, affects mainly somatosensory parts of
the brain 1151, and is associated with an activation of
thalamic nuclei. Consistent with this, the motor cortex
close behind the epileptic focus is not hypometabolic.
It is conceivable that activation of the thalamus tonically disfacilitates the somatosensory cortex. By means
of such corticothalamic circuitry, the motor cortex
could modulate the characteristics of the somatosensory cortex. Under physiological conditions, such a circuit may prevent an excessive input to the sensory cortex during motor activity 129, 303. This modulation in
turn could reduce the energy demand of the somatosensory cortical areas. This assumption is supported by
the observation that lesioning of the thalamus prevents
the hypometabolism in the somatosensory cortex (unpublished observations, 1995). How an increase of activity in the thalamus conveys such a modulation of the
somatosensory cortex during focal epileptic activity is
not known.
It was previously shown that within the vicinity of
an epileptic focus, strong inhibitions appear in the neurons concomitant with the spikes in the ECoG {31331. The neurons displaying these inhibitions constitute the so-called “inhibitory surround.” Collins and
coauthors [23] reported a small boundary of hypometabolic area surrounding the epileptic focus, and suggested that this hypometabolism resembles the inhibitory surround. This is at variance with the observation
that strong inhibitions are hypermetabolic, as shown
by Ackermann and colleagues [27] and by the present
study. There was no hypometabolic rim surrounding
the focus in the present experiments, and the motor
cortex immediately behind the focus was normometabolic. Furthermore, the neuronal inhibitions within the
inhibitory surround have a longer duration than do
those observed in the remote hypometabolic areas described in the present study. Altogether, these observa-
418 Annals of Neurology Vol 38 No 3 September 1995
tions suggest that the inhibitory surround is included
within the region of hypermetabolism.
Clinical measurements of brain metabolism with
PET and {"F ldeoxyglucose in patients with epilepsy
usually show a focal hypometabolism [34, 351. However, hypermetabolic spots become visible within such
hypometabolic regions when epileptic activity increases, as occurs, for example, in the transition from
interictal to ictal states [22, 23}. Generally, stronger
epileptic activity is needed to produce a focal hypermetabolism in measurements with PET than in experimental autoradiographic investigations { 361. This
difference between animal experiments and patient
measurements may be largely due to a resolution limit
of the modern PET cameras, that is, the so-called partial volume effects f37-391, which prevent detection
of small hypermetabolic spots. It is also conceivable
that cell loss and a reduction of inhibitory activity as
well as chronic disturbances like the alteration of receptor expression C40-42) contribute to the hypometabolism in chronic epilepsy. Furthermore, it has been
shown that epileptic foci in humans niay be considerably less active than acute penicillin-induced epileptic
foci 114, 18, 431.
The present data suggest that in patients, hypometabolism without structural alterations may represent
functionally disturbed brain areas surrounding the epileptogenic focus or remote from it. In extratemporal
epilepsy, in the absence of structural abnormalities focal hypometabolism may help to identify the functional
circuit involved in epileptic activity, but it should not
be regarded as a secure guide for surgery of epilepsy.
Instead, focal hypometabolism may actually indicate
brain areas that are functionally disturbed but may regain normal function after excision of a remote focus
The investigation was supported by SFB 194 B2.
The authors thank H.-J. Freund, T. U. Heinemann, K.-A. Hossmann, T. Neumann-Haefelin, and E.-J. Speckmann for helpful comments and discussion.
1. Theodore WH, Sato S, Kufta C, et al. Temporal lobectomy for
uncontrolled seizures: the role of positron emission tomography. Ann Neurol 1992;32:789-794
Swartz BE, Tomiyasu U, Delgado-Escueta AV, et al. Neuroimaging in temporal lobe epilepsy: test sensitivity and relationships to pathology and postoperative outcome. Epilepsia 1992;
Theodore WH, Newmark ME, Sato S, et a]. C18F]Fluorodeoxyglucose positron emission tomography in refractory complex
partial seizures. Ann Neurol 1983;14:429-437
Abou-Khalil BW, Siege1 GJ, SackellaresJC, et al. Positron emission tomography studies of cerebral glucose metabolism in
chronic partial epilepsy. Ann Neurol 1987;22:480-486
Engel J Jr, Kuhl DE, Phelps ME, Mazziotra JC. Interictal cere-
bra1 glucose metabolism in partial epilepsy and its relation to
EEG changes. Ann Neurol 1982;12:510-5 17
6 . Jack CR Jr, Sharbrough FW,Cascino GD, et al. Magnetic resonance image-based hippocampal volumetry: correlation with
outcome after temporal lobectomy. Ann Neurol 1792;31:138146
7. Theodore WH, Sato S, Kufta C. Strategy for surgical selection
of patients with partial seizures: the role of positron emission
tomography. Ann Neurol 1987;22:133
8. Engel J Jr, Brown WJ. Kuhl DE, et al. Pathological findings
underlying focal temporal lobe hypometabolism in partial epilepsy. Ann Neurol 1982;12:518-528
9. Henry TR, Mazziotta JC, Engel J Jr. Interictal metabolic anatomy of mesial temporal lobe epilepsy. Arch Neurol 1993;50:
10. Franck G, Maquet P, Sadzot B, et al. Contribution of positron
emission tomography to the investigation of epilepsies of frontal
lobe origin. Adv Neurol 1992;57:471-485
1 1 . Henry TR, Sutherling WW, Engel J Jr, et al. The role of positron
emission tomography in presurgical evaluation of partial epilepsies of neocortical origin. In: Luders HO, ed. Epilepsy surgery.
New York: Raven, 1991:243-250
12. Chugani HT, Shewmon DA, Shields WD, et al. Surgery for
intractable infantile spasms: neuroimaging perspectives. Epilepsia 1993;34:764-771
13. Sokoloff L, Reivich M, Kennedy C, et al. The (14C)deoxyglucose method for the measurement of local cerebral glucose urilization: theory, procedure, and normal values in conscious and
anesthetized albino rat. J Neurochem 1977;28:897-916
14. Dorn T, Witte OW. Separation of different interictal discharge
patterns in acute experimentally induced epileptic foci of the rat
in vivo. Brain Res 1993;616:303-306
15. Bruehl C, Kloiber 0, Hossmann KA, et al. Regional hypomerabolism in an acute model of focal epileptic acriviry in the rat.
Eur J Neurosci 1995;7:192-197
16. Witte OW. Afterpotentials of penicillin-induced epileptiform
neuronal discharges in the motor cortex of the rat in vivo. Epilepsy Res 1994;18:45-55
17. Domann R, Uhlig S, Dorn T, Witte OW. Participation of interneurons in penicillin-induced epileptic discharges. Exp Brain
Res 1991;83:681-686
18. Matsumoto H, Ajmone-Marsan C. Cortical cellular phenomena
in experimental epilepsy: intericral manifestations. Exp Neurol
19. Dorn T, Witte OW. Refractory periods following interictal
spikes in acute experimentally induced epileptic foci. Electroencephalogr Clin Neurophysiol 1995;94:80-85
20. Siesio BK. Brain energy metabolism. Chichester: Wiley 8r Sons,
21 Sugaya E, Serikiya Y,Kobori T, Noda Y.Glial membrane potential and extracellular potassium concentration in cultured glial
cells. Exp Neurol 1979;66:403-408
22 Witte OW, Bruehl C, Schlaug G, et al. Dynamic changes of
focal hypometabolism in relation to epileptic activity. J Neurol
Sci 1994;124:188-197
23. Collins RC, Kennedy C, Sokoloff L, Plum F. Metabolic anatomy
of focal motor seizures. Arch Neurol 1976;33:536-542
24. Domann R, Dorn T, Witte OW. Afterpotentials following penicillin-induced paroxysmal depolarizations in rat hippocampal
CA1 pyramidal cells in vitro. Pflugers Arch 1991;417:469-478
2 5 . Mitre OW, Uhlig S, Valle E. Separation of different types of
afterpotentials following penicillin-induced paroxysmal depolarization shifts of neurons in the motor correx of the rat. Neurosci
Lett 1989;101 :51-56
26. Domann R, Dorn T, Witte OW. Calcium-dependent potassium
current following pencillin-induced epileptiform discharges in
the hippocampal slice. Exp Brain Res 1989;78:646-648
Bruehl and Witte: Cellular Activity and Metabolism
27. Ackermann RF, Finch DM, Babb TL, Engel J Jr. Increased glucose metabolism during long-duration recurrent inhibition of
hippocampal pyramidal cells. J Neurosci 1984;4:251-264
28. Ackermann RF, Engel J Jr. Baxter L. Positron emission tomography and autoradiographic studies of glucose utilization following
electroconvulsive seizures in humans and rats. Ann N Y Acad
Sci 1986;462:263-269
29. Chapin JK, Woodward DJ. Modulation of sensory responsiveness of single somatosensory cortical cells during movement
and arousal behaviors. Exp Neurol 1981;72:164-178
30. Chapin JK, Woodward DJ. Somatic sensory transmission to the
cortex during movement: gating of single cell respoilses to
touch. Exp Neurol 1982;78:654--669
3 1. Prince DA, Wilder BJ. Control niechanisms in cortical epileptogenic foci: ‘surround’inhibition. Arch Neurol 1967; 16: 194-202
32. Speckmann EJ, Elger C. Penicillin induced epileptic foci in the
motor cortex: vertical inhibition. Electroencephalogr Clin Neurophysiol 1983;56:604-622
3 3. Goldcnsohn ES, Salazar AM. Temporal and spatial distribution
of intracellular potentials during, generation and spread of epileptogenic discharges. In: Delgado Escueta AV, Ward AA Jr,
Woodhury DM, Porter RJ, eds. Advances in neurology, 44.
New York: Raven, 1986:559-582
34. Chugani HT, Shewmon DA, K.hanna S, Phelps ME. Interictal
and postictal focal hypermetabolism on positron emission tomography. Pediatr Neurol l993;9:10- I 5
35. Henry TR, Sutherling WW, EngelJ Jr, et al. lnterictal cerebral
metabolism in partial epilepsies of neocortical origin. Epilepsy
Res 1991;10:174-182
Annals of Neurology
Vol 38
No 3
36. Handforth A, Finch DM, Peters R, et al. Lnterictal spiking increases 2-deoxy( 14C)glucose uptake and c-fos-like reactivity.
Ann Neurol 1994;35:724-731
37. Knorr U, Weder B, Kleinschmidt A, et al. Identification of
task-specific rCBF changes in individual subjects: validation and
application for PET. J Comput Assist Tomogr 1993;17:517528
38. Hoffman EJ, Huang SC, Phelps ME. Quantification in positron
emission computed tomography. 1. Effects of object size. J
Coniput Assist Tomogr 1979;3:299-308
39. Goochee C, Rasband W, Sokoloff L. Computerized densitometry and color coding of (14C)-deoxyglucose autoradiographs.
Ann Neurol 1980;7:359-370
40. Frost JJ, Mayberg HS, Fisher RS, et al. Muopiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy. Ann Neurol 1988;23:231237
41. Frost JJ. Imaging muopiate receptors in epilepsy by positron
emission tomography. Semin Neurol 1989;9:317-322
42. Savic I, Widen L, Thorell J O , et al. Cortical benzodiazepine
receptor binding in patients with generalized and partial epilepsy. Epilepsia 1990;31:724-730
43. Bahb TL, Wilson CL, Isokawa-Akesson M. Firing patterns of
human limbic neurons during stereoencephalography (SEEG)
and clinical temporal lobe seizures. Electroencephalogr Clin
Neurophysiol 1987;66:467-482
44. Hajek M, Wieser HG, Khan N , et al. Preoperative and postoperative glucose consumption in mesiobasal and lateral temporal
lobe epilepsy. Neurology 1994;44:2125-2 132
September 1995
Без категории
Размер файла
677 Кб
epileptic, metabolico, underlying, focal, activity, brain, alteren, cellular
Пожаловаться на содержимое документа