Effect Of Cortical Spreading Depression Research Articles

Characteristics of cortical spreading depression and c-Fos expression in transgenic mice having a mutation associated with familial hemiplegic migraine 2.

Cortical spreading depression is thought to be the underlying mechanism of migraine aura. In 2006, three relatives having the point mutation E700K in ATP1A2 exon 15 were diagnosed with familial hemiplegic migraine 2 characterized by complicated forms of aura. Here, we generated a transgenic mouse model having the human E700K mutation in the Atp1a2 orthologous gene. To investigate the characteristics of cortical spreading depression in a mouse model with E700K mutation in the Atp1a2. Cortical spreading depression was induced by applying stepwise increases of KCl concentration or electrical stimulation intensity to C57BL/6J-Tg(Atp1a2*E700K)9151Kwk mice (Tg, both sexes) and corresponding wild-type animals. Under urethane anesthesia, the responsiveness and threshold to cortical spreading depression were examined and the distribution of c-Fos expression, a neuronal activity marker, was immunohistochemically determined. Overall, Tg mice showed significantly faster propagation velocity (p < 0.01) and longer full-width-at-half-maximum (p < 0.01) than wild-type animals, representing a slower recovery from direct current potential deflection. The cortical spreading depression threshold tended to be lower in Tg, especially in females. c-Fos-positive cells were significantly enhanced in the ipsilateral somatosensory cortex, piriform cortex, amygdala and striatum (each p < 0.05 vs. contralateral side). Numbers of c-Fos positive cells were significantly higher in the ipsilateral amygdala of Tg, as compared with wild-type animals (p < 0.01). The effect of cortical spreading depression may be greater in E700K transgenic mice than that in wild-type animals, while the threshold for cortical spreading depression shows little change. Higher c-Fos expression in the amygdala may indicate alterations of the limbic system in Tg, suggesting an enhanced linkage between cortical spreading depression and amygdala connectivity in familial hemiplegic migraine 2 patients.

PSD-95 uncoupling from NMDA receptors by Tat-N-dimer ameliorates neuronal depolarization in cortical spreading depression

Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA receptor complex formation by anti-ischemic compound, UCCB01-144 (Tat-N-dimer) ameliorates the persistent effects of cortical spreading depression on cortical function. Using in vivo two-photon microscopy in somatosensory cortex in mice, we show that fluorescently labelled Tat-N-dimer readily crosses blood-brain barrier and accumulates in nerve cells during the first hour after i.v. injection. The Tat-N-dimer suppressed stimulation-evoked synaptic activity by 2–20%, while cortical blood flow and cerebral oxygen metabolic (CMRO2) responses were preserved. During cortical spreading depression, the Tat-N-dimer reduced the average amplitude of the negative shift in direct current potential by 33% (4.1 mV). Furthermore, the compound diminished the average depression of spontaneous electrocorticographic activity by 11% during first 40 min of post-cortical spreading depression recovery, but did not mitigate the suppressing effect of cortical spreading depression on cortical blood flow and CMRO2. We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarization wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling in stroke.

The Effect of Cortical Spreading Depression on Glutamate Receptors in Rat Brain

E-mail: Fariba_karimzade@yahoo.com ABSTRACT Article info: Received: 25 Jun. 2013 Accepted: 23 Jul. 2013 هلاقم تاعلاطا 1392 ريت 4 :تفایرد 1392 دادرم 1 :شریذپ یمهم شقن هك دشاب یم یزكرم یبصع متسيس رد یتاذ یکيرتکلاويب تيلاعف کي هدنوشرشتنم راهم همدقم یراميب و ارذگ رشتنم یاه یشومارف ،عرص ،اروا اب نرگيم هلمج زا یکيژولورون یاه یراميب یژولويزيفوتاپ رد وراد قيرزت تهج( لوناك و هدش یحارج ناوجون یاه تر ادتبا هعلاطم نيا رد اه شور و داوم .دراد یعاخن یاه KCl قيرزت اب SD هورگ رد یرشق ي هدنوشرشتنم راهم .دندش هتشاك یزغم رشق یور تابث یاهدورتکلا و )اه هورگ لماش اه تر ی همه زغم .دش قيرزت رگنير لولحم ،مش هورگ رد .ديدرگ اقلا یلاوتم هتفه راهچ تدم هب اه هتفاي .ديدرگ ماجنا یميشوتسيهونوميا هعلاطم یارب یزاس هدامآ لحارم و هدش جراخ SD و مش ،لرتنك یاه شيازفا مش و لرتنك هورگ اب هسياقم رد SD هورگ رد یريگمشچ روط هب CA1 ی هيحان رد NR2B هدنريگ نايب هدهاشم SD هورگ رد CA3 و CA1 یحاون رد GluR1 ي هدنريگ نايب رد یراد ینعم شيازفا نينچمه .تفاي ي هدنريگ و NMDA یاه هدنريگ یاهدحاوريز زا NR2B هدنريگ نايب ،هدنوش رشتنم راهم یريگ هجيتن .ديدرگ .دهد یم شيازفا ناوجون یاه تر پمكوپيه فلتخم قطانم رد ار AMPA یاه هدنريگ یاهدحاو ريز زا GluR1

Responses to Cortical Spreading Depression under Oxygen Deficiency.

Objectives:Objectives: The effect of cortical spreading depression (CSD) on extracellular K+ concentrations ([K+]e), cerebral blood flow (CBF), mitochondrial NADH redox state and direct current (DC) potential was studied during normoxia and three pathological conditions: hypoxia, after NOS inhibition by L-NAME and partial ischemia.Methods:A special device (MPA) was used for monitoring CSD wave propagation, containing: mitochondrial NADH redox state and reflected light, by a fluorometry technique; DC potential by Ag/AgCl electrodes; CBF by laser Doppler flowmetry; and [K+]e by a mini-electrode.Results and Discussion:CSD under the 3 pathological conditions caused an initial increase in NADH and a further decrease in CBF during the first phase of CSD, indicating an imbalance between oxygen supply and demand as a result of the increase in oxygen requirements. The hyperperfusion phase in CBF was significantly reduced during hypoxia and ischemia showing a further decline in oxygen supply during CSD. CSD wave duration increased during the pathological conditions, showing a disturbance in energy production.Extracellular K+ levels during CSD, increased to identical levels during normoxia and during the three pathological groups, indicating correspondingly increase in oxygen demand. 5. The special design of the MPA enabled identifying differences in the simultaneous responses of the measured parameters, which may indicate changes in the interrelation between oxygen demand, oxygen supply and oxygen balance during CSD propagation, under the conditions tested. 6. In conclusion, brain oxygenation was found to be a critical factor in the responses of the brain to CSD.

The trigeminovascular system does not require a peripheral sensory input to be activated – migraine is a central disorder Focus on ‘Effect of cortical spreading depression on basal and evoked traffic in the trigeminovascular sensory system’

The trigeminovascular system does not require a peripheral sensory input to be activated – migraine is a central disorder Focus on ‘Effect of cortical spreading depression on basal and evoked traffic in the trigeminovascular sensory system’

Effect of cortical spreading depression on basal and evoked traffic in the trigeminovascular sensory system

To use an animal model to test whether migraine pain arises peripherally or centrally. We monitored the spontaneous and evoked activity of second-order trigeminovascular neurons in rats to test whether traffic increased following a potential migraine trigger (cortical spreading depression, CSD) and by what mechanism any such change was mediated. Neurons (n = 33) responded to stimulation of the dura mater and facial skin with A-δ latencies. They were spontaneously active with a discharge rate of 6.1 ± 6.4 discharges s(-1). Injection of 10 µg lignocaine into the trigeminal ganglion produced a fully reversible reduction of the spontaneous discharge rate of neurons. Neuronal discharge rate returned to normal by 90 min. Lignocaine reduced the evoked responses of neurons to dural stimulation to 37% and to facial skin stimulation to 53% of control. Induction of CSD by cortical injection of KCl increased the spontaneous discharge rate of neurons from 2.9 to 16.3 discharges s(-1) at 20 min post CSD. Injection of 10 µg lignocaine into the trigeminal ganglion at this time failed to arrest or reverse this increase. Injection of lignocaine prior to the initiation of CSD failed to prevent the subsequent development of CSD-induced increases in discharge rates. These results suggest that there is a continuous baseline traffic in primary trigeminovascular fibres and that CSD does not act to increase this traffic by a peripheral action alone - rather, it must produce some of its effect by a mechanism intrinsic to the central nervous system. Thus the pain of migraine may not always be the result of peripheral sensory stimulation, but may also arise by a central mechanism.

CSD as a Therapeutic Target for Migraine

To explore the effects of cortical spreading depression (CSD), an intrinsic brain event underlying migraine aura, on the excitability of the human neocortex, the authors conducted in vitro electrophysiological studies on slices from human temporal lobe that were obtained during epilepsy surgery. Neocortical slices were prepared from 13 different patients with intractable temporal lobe epilepsy. CSD was induced by KCl application to the sixth layer of neocortical tissue, and evoked extracellular field potentials and long-term potentiation (LTP) were induced by single or tetanic stimulation of white matter substance. Local application of KCl consistently induced spreading depressions (SDs). Baseline field excitatory postsynaptic potentials (EPSPs) temporarily disappeared during CSD for 3―5 min and recovered completely approximately 20 min later. Further recordings revealed that CSD significantly enhanced the amplitude of EPSPs for the next 90 min and increased the induction of LTP in the third layer of neocortical tissues. The authors concluded that CSD facilitates synaptic excitability and efficacy in human neocortical tissues, which can be assumed to contribute to hyperexcitability of the cerebral cortex in migraineurs.

Effects of anesthesia on the responses to cortical spreading depression in the rat brain in vivo

Objectives: The aim of this study was to evaluate the effect of cortical spreading depression (CSD) on the metabolic, hemodynamic, electrical and ionic properties during anesthesia as compared with the awake state.Methods: The mitochondrial NADH redox state, reflected light, direct current (DC) potential, electrocorticography (ECoG), cerebral blood flow (CBF) and volume (CBV), and extracellular K+ concentrations ([K+]e), were measured continuously and simultaneously in real time using two unique monitoring systems that evaluate brain function. Three consecutive CSD waves were initiated using a KCl solution in both awake and anesthetized rats.Results and discussion: CSD caused typical amplitude changes: biphasic waves in reflectance, oxidation cycles in NADH, an increase in CBF, CBV and in [K+]e, a negative shift in DC potential and depression in ECoG. Anesthesia by equithesin decreased significantly the baseline levels of CBF and [K+]e, showing a reduction in oxygen supply and demand. After anesthesia, CSD significantly decreased [K+]e and NADH oxidation cycles, indicating a reduction in oxygen demand and in oxygen balance, respectively. Furthermore, anesthesia reduced CSD wave frequencies by slowing the recovery period, showing a decline in energy production during brain activation, or by changing electrophysiological properties of the tissue. No changes were found in the propagation rate and in the initiation period of CSD, which may indicate that equithesin does not block CSD initiation. In addition, we found that the whole cerebral cortex reacts homogenously to CSD and that equithesin may reduce oxygen demand and energy production, which may have a protective effect on the brain exposed to pathophysiological conditions.

Effect of cortical spreading depression on synaptic transmission of rat hippocampal tissues

Cortical spreading depression (CSD) is believed to be a putative neuronal mechanism underlying migraine aura and subsequent pain. In vitro and ex vivo/in vitro brain slice techniques were used to investigate CSD effects on the field excitatory postsynaptic potentials (fEPSP) and tetanus-induced long-term potentiation (LTP) in combined rat hippocampus-cortex slices. Induction of CSD in combined hippocampus-cortex slices in which DC negative deflections did not propagate from neocortex to hippocampus significantly augmented fEPSP amplitude and LTP in the hippocampus. Propagation of CSD to the hippocampus resulted in a transient suppression followed by reinstatement of fEPSP with amplitude of pre-CSD levels. LTP was inhibited when DC potential shifts were recorded in the hippocampus. Furthermore, CSD was induced in anaesthetized rats and, thereafter, hippocampal tissues were examined in vitro. LTP was significantly enhanced in hippocampal slices obtained from ipsilateral site to the hemisphere in which CSD was evoked. The results indicate the disturbances of hippocampal synaptic transmission triggered by propagation of CSD. This perturbation of hippocampal synaptic transmission induced by CSD may relate to some symptoms occurring during migraine attacks, such as amnesia and hyperactivity.

Effect of cortical spreading depression on basal forebrain neurons

During natural sleep and anesthesia, rhythmic hypo- and hyperpolarizations alternate in cortical pyramidal cells and are reflected as slow (<1 Hz) cortical rhythm at the level of the electroencephalogram (EEG). Membrane potential changes in pyramidal neurons were initially attributed to the rhythmic fluctuation of the cholinergic input as the basal forebrain (BF) neurons fire in synchrony with cortical waves, but a more recent proposal suggested that the slow rhythm was of cortical origin. In the present experiments, interaction between the cortex and the BF was examined in urethane-anesthetized rats. BF neuronal activity was inhibited by local infusion of lidocaine into the substantia innominata in one group of rats, while in another group, the slow cortical rhythm was blocked by inducing spreading depression (SD) in the cortex. Slow cortical rhythm persisted after unilateral lidocaine injection, but rhythmic firing in BF neurons disappeared following SD induction. These findings support the view that slow cortical rhythm is generated in the cortex and transmitted to the BF through descending fibers. According to anatomical data, these fibers can excite cholinergic cells only indirectly as they terminate on non-cholinergic neurons. Thus, timing of activity changes in BF neurons during the slow cortical rhythm might give some clue regarding their transmitter specificity.

Spreading depression in the cortex differently modulates dopamine release in rat mesolimbic and nigrostriatal terminal fields

The effects of cortical spreading depression (SD) on evoked dopamine release in mesolimbic (nucleus accumbens) and nigrostriatal (nucleus caudatus) terminal fields were studied by in vivo voltammetry in anesthetized rats. Dopamine release was evoked by electrical stimulation of medial forebrain bundle (20 Hz, 100 pulses). Local application of 3 M KCl on the dura initiated SD in the cortex. It was found that SD modulated evoked dopamine release in subcortical structures at the same time when the wave of depression of cortical activity reached reciprocally connected subcortical areas. This cortical depression increased stimulated dopamine release in the nucleus accumbens and decreased dopamine release in the nucleus caudatus. In agreement with these results, electrical stimulation of the prefrontal cortex at 20 Hz, synchronized with medial forebrain bundle stimulation, decreased evoked dopamine release in the nucleus accumbens. Areas of the cortex which modulated dopamine release in these two terminal fields were spatially separated by at least 5 mm from each other. It is proposed that depression and activation of evoked dopamine release in the nucleus caudatus and nucleus accumbens following SD are indicative of tonic activation of the nigrostriatal and tonic inhibition of the mesolimbic dopaminergic terminals by cortex in normal conditions. SD in the cortex, modulating neurotransmitter release in subcortical structures, may have a general impact on redistribution of oxygen supply in these subcortical areas and on behavior associated with brain trauma, migraine, insult or seizures, i.e. the kind of neuropathology which may cause SD type phenomena also in human brain.

Cortical spreading depression blocks the hyperthermic reaction induced by orexin a

This experiment tested the effect of cortical spreading depression on the sympathetic and thermogenic effects induced by orexin A. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures and heart rate were monitored in urethane-anesthetized male Sprague–Dawley rats before and 5 h after an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle. The same variables were monitored in rats with cortical spreading depression, induced by an application of cotton pellets soaked with 2 M KCl to the frontal cortex. The results show that orexin A increases the sympathetic firing rate, IBAT and colonic temperatures and heart rate. The increases in firing rate, IBAT and colonic temperatures are blocked by cortical spreading depression, while the increase in heart rate is not affected by cortical spreading depression. These findings suggest that the cerebral cortex is involved in the control of the orexin A-induced hyperthermia. Furthermore, we suggested the name “hyperthermine A,” as additional denomination of “orexin A.”

Functional decortication lowers ventromedial hypothalamic activation induced by hippocampal neostigmine injection.

This experiment tested the effects of cortical spreading depression (CSD) on the ventromedial hypothalamic activity and on the related thermogenesis, both stimulated by an injection of neostigmine in the hippocampus. The firing rate of the neurons of the ventromedial hypothalamus, and the temperature of the interscapular brown adipose tissue and of the colon (T:(IBAT) and T:(C)) were monitored in 24 urethane-anesthetized male Sprague-Dawley rats divided into four groups. These variables were measured before and after hippocampal injection of neostigmine (5 x 10(-7) mol) in the first and second groups or of saline in the third and fourth groups. The hippocampal injection was preceded by CSD in the first and third groups, while CSD was not induced in the second and fourth groups. The same procedure was carried out in the other four groups of six rats each and oxygen consumption was monitored. The results show an increase in the firing rate, T:(IBAT), T:(C) and oxygen consumption after the neostigmine injection. CSD significantly reduces these enhancements. The findings demonstrate that: (i) the activation of ventromedial hypothalamic neurons are involved in the thermogenic changes due to the effects of a neostigmine injection into the hippocampus; and (ii) integrity of cerebral cortex is required for this activation of thermogenesis.

Effects of brain oxygenation on metabolic, hemodynamic, ionic and electrical responses to spreading depression in the rat

The effect of cortical spreading depression (CSD) on oxygen demand (extracellular K +), oxygen supply (cerebral blood flow – CBF) and oxygen balance (mitochondrial NADH) was studied by a special multiprobe assembly (MPA), during hypoxia and partial ischemia. The MPA was constructed and applied to monitor the CSD wave from its front line until complete recovery, continuously and simultaneously. CSD under hypoxia or partial ischemia led to an initial increase in NADH levels and a further decrease in CBF during the first phase of the CSD wave, indicating a decrease of tissue capability to compensate for an increase in oxygen demand. Furthermore, the special design of the MPA enabled identifying the close interrelation between oxygen demand, supply and balance during CSD propagation. In conclusion, brain oxygenation was shown to have a clear effect on tissue responses to CSD.

Effects of Cortical Spreading Depression on Cortical Blood Flow, Impedance, DC Potential, and Infarct Size in a Rat Venous Infarct Model

A cortical venous infarction model has been evaluated as to the degree of regional flow reduction and by studying effects of cortical spreading depression (CSD). Two adjacent cortical veins were occluded photochemically with rose bengal and fiberoptic illumination. Seven rats served to demonstrate effects on regional cortical blood flow using laser Doppler scanning. In 36 rats local CBF, DC potential, and brain tissue impedance were measured continuously for 75 min after vein occlusion. No, 3, or 10 CSD waves were induced by potassium chloride injection during the initial 75 min. Rats were compared for spontaneous CSDs; baseline local CBF, CBF, and impedance response to CSD; and infarct volume. Seventy-five minutes after vein occlusion regional cortical flow in a 3.5 × 7-mm window was reduced to 34.3 ± 13.2%. At 45% of the 840 measured locations in 7 rats flow was <40% baseline and at 27.3% <30%, indicating a widespread penumbra territory. During the initial 75 min 2.1 ± 1.1 spontaneous CSDs were observed. There was a positive correlation between the number of spontaneous CSDs seen acutely and infarction volume after 5 days. Moreover, brain injury was significantly increased in the group with 10 KCl-induced CSDs. A reduced 1CBF response and an overshooting tissue impedance change during CSD were predictors of ischemic damage. This study demonstrates a CSD-related growth of the venous infarct. Second, the data indicate that flow after two-vein occlusion resembles that seen under penumbra conditions, allowing for studies of damage mechanisms responsible for infarct growth.

Effect of cortical spreading depression on activity of trigeminovascular sensory neurons.

The effect of cortical spreading depression, a proposed initiating event for migraine pain, on cortical blood flow (laser Doppler method) and on the spontaneous firing rate and stimulus-evoked responses of trigemino-cervical neurons with craniovascular input was studied in 17 neurons in 8 cats anesthetized with chloralose. Cortical spreading depression, induced via cortical pinprick injury, produced an initial wave of cortical hyperemia (243+/-57% of control) and a later and smaller phase of oligemia (96+/-4% of control). Neither the basal discharge rate (6.7+/-1.7 sec(-1)) nor the evoked responses to electrical stimulation of the superior sagittal sinus (4.1+/-0.8 discharges per stimulus) of upper cervical spinal cord neurons was altered over periods of up to 2 h following one, two, or three waves of spreading cortical depression. We conclude that a small number of episodes of cortical spreading depression is not capable of activating C2 cervical spinal cord craniovascular sensory neurons in the cat.

Effect of cortical spreading depression on the levels of mRNA coding for putative neuroprotective proteins in rat brain.

Previous studies have demonstrated that cortical spreading depression (CSD) induces neuronal tolerance to a subsequent episode of ischemia. The objective of the present investigation was to determine whether CSD alters levels of mRNA coding for putative neuroprotective proteins. Unilateral CSD was evoked in male Wistar rats by applying 2 mol/L KCl over the frontal cortex for 2 hours. After recovery for 0, 2, or 24 hours, levels of several mRNA coding for neuroprotective proteins were measured bilaterally in parietal cortex using Northern blot analysis. Levels of c-fos mRNA and brain-derived neurotrophic factor (BDNF) mRNA were markedly elevated at 0 and 2 hours, but not 24 hours after CSD. Tissue plasminogen activator (tPA) mRNA levels were also significantly increased at 0 and 2 hours, but not 24 hours after CSD. Levels of the 72-kDa heat-shock protein (hsp72) mRNA were not significantly increased by CSD, except for a small elevation (20%) at 2 hours recovery. Levels of the 73-kDa heat-shock cognate (hsc73) mRNA were slightly, but significantly, increased at 2 and 24 hours of recovery. Finally, levels of mRNA for protease nexin-1 and glutamine synthetase were not significantly altered by CSD at any time studied. The current results support the hypothesis that neuronal tolerance to ischemia after CSD may be mediated by increased expression of FOS, BDNF, or tPA, but not by increased expression of hsp72, hsc73, nexin-1, or glutamine synthetase.

Cerebral cortex does not modulate "regulated" decrease in core temperature during hypoxemia in rats.

In newborns and adults of a number of species including humans, exposure to acute hypoxemia produces a "regulated" decrease in core temperature, the mechanism of which is unknown. Considering that various cortical areas participate in autonomic regulation including thermoregulation, the present experiments were carried out to test the hypothesis that the cerebral cortex plays a role in modulating the regulated decrease in core temperature during acute hypoxemia. This hypothesis was tested by determining the core temperature response to acute hypoxemia in chronically instrumented adult Sprague-Dawley rats before and after cortical spreading depression (i.e., functional decortication) was produced by the local application of potassium chloride to the dura overlying the cerebral hemispheres. There was no effect of cortical spreading depression on baseline core temperature. Core temperature decreased during acute hypoxemia in a similar fashion when the cerebral cortex was intact as well as during functional decortication. Thus our data do not support the hypothesis that the cerebral cortex modulates the regulated decrease in core temperature that occurs in adult rats during acute hypoxemia.

Microdialysis of interstitial amino acids during spreading depression and anoxic depolarization in rat neocortex

We have examined the effect of cortical spreading depression (SD) and anoxic depolarization (AD) on the interstitial concentration changes of amino acids (AA) in the neocortex of anesthetized rats using microdialysis and HPLC. Accompanying SD alanine increased to126±11%, arginine to116±3%, asparate to160±17%, glutamate to163±9%, glycine to158±21%, serine to125±9%, and taurine to172±15% (mean± 1S.E.M.). The increases lasted for about 1 min. Histidine decreased to74%±4% at 1 min following SD, and returned to normal 4 min later. Cardiac arrest triggered AD after approximately 2 min, immediately followed by changes of interstitial AAs. At 5 min after AD alanine had increased to183±13%, aspartate to3,458±656%, GABA to338±35%, glutamate to1,696±546%, glycine to297±37%, serine to153±12%, and taurine to1721±98% as compared to control values (mean± 1S.E.M.). Histidine decreased to78±2% at 3 min following AD while arginine exhibited insignificant variations around the baseline. The increase of glutamate during SD is consistent with activation of NMDA-receptors as an essential requirement for this reaction. The increase of AAs may also contribute to the sequence of events leading to AD, though the exact mechanism remains unknown. SD is an important pathophysiological mechanism of the ischemic penumbra associated with focal cerebral ischemia, while AD reflects the electrophysiological status of the infarct core. The brief duration of the AA increase during SD may explain survival of cells in the penumbra zone in contrast to the cell death in the infarct center in accord with the excitotoxic hypothesis of ischemic cell death.

Inhibition of protein synthesis during repetitive cortical spreading depression.

The effect of cortical spreading depression (CSD) on cerebral protein synthesis (CPS) was examined. CSD was evoked in normal rats with KCl, and CPS was measured autoradiographically with [1-14C]leucine. Average rates (mean +/- SD) of CPS in layers I-IV of cortex decreased significantly from 10.7 +/- 0.6 (sham-operated controls; n = 4) to 6.7 +/- 0.7 nmol/g/min (n = 4; p < 0.01) and in layers V-VI from 10.9 +/- 0.5 to 9.4 +/- 0.4 nmol/g/min (p < 0.05) during 60 min of repetitive CSD. Spreading depression did not affect CPS rates in other subcortical brain regions. These results indicate that KCl-evoked CSD induces inhibition but not suppression of cortical protein synthesis.