Cortical Spreading Depression Propagation Research Articles

Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats

The ketogenic diet (KD) is a high fat and low carbohydrate and protein diet. It is used in the clinical treatment of epilepsy, in order to decrease cerebral excitability. KD is usually composed by long-chain triglycerides (LCT) while medium-chain triglycerides (MCT) diet is beginning to be used in some clinical treatment of disorders of pyruvate carboxylase enzyme and long-chain fatty acid oxidation. Our study aimed to analyze the effects of medium- and long-chain KD on cerebral electrical activity, analyzing the propagation of the phenomenon of cortical spreading depression (CSD). Three groups of weaned rats (21 days old) received, for 7 weeks, either a control (AIN-93G diet), or a MCT-KD (rich in triheptanoin oil), or a LCT-KD (rich in soybean oil). They were compared to another three groups (21 days old) receiving the same diets for just 10 days. CSD propagation was evaluated just after ending the dietary treatments. Results showed that short-term KD treatment resulted in a significant reduction of the CSD velocity of propagation (control group: 4.02+/-1.04mm/min; MCT-KD: 0.81+/-1.46mm/min and LCT-KD: 2.26+/-0.41mm/min) compared to the control group. However, long-term treatment with both KDs had no effect on the CSD velocity (control group: 3.10+/-0.41mm/min, MCT-KD: 2.91+/-1.62mm/min, LCT-KD: 3.02+/-2.26mm/min) suggesting that both short-term KDs have a positive effect in decreasing brain cerebral excitability in young animals. These data show for the first time that triheptanoin has an effect on central nervous system.

Direct evidence of inter-hemispheric modulation by callosal fibers: a cortical spreading depression study in well-nourished and early-malnourished adult rats

Inter-hemispheric modulation has been extensively studied, as it is critical for human behavior and could be involved in the development of neuropsychiatric disorders, such as major depression, epilepsy and stroke. Malnutrition early in life can alter brain processes such as inter-hemispheric modulation and these alterations can persist into adulthood. Here, we used cortical spreading depression (CSD) as a neurophysiological parameter to investigate inter-hemispheric modulation in 19 well-nourished and 18 early-malnourished male adult rats. CSD was evoked on the right frontal region and monitored at two parietal points on the same hemisphere. After a 2 h baseline recording, fibers projecting from the left to the right hemisphere via the corpus callosum were cut with a longitudinal lesion in the contralateral cortex and recording continued for two more hours. The results show that (1) baseline CSD propagation velocities were higher in the malnourished rats, as compared to the respective well-nourished controls; (2) post-lesion velocities increased in both nutritional groups, as compared with the baseline values; (3) this CSD increase persisted 3-7 days after lesion, suggesting a lasting effect and (4) in the malnourished group the post-lesion CSD enhancement was of smaller amplitude. Furthermore, a midline lesion (callosotomy) in eight well-nourished rats similarly facilitated CSD, suggesting the involvement of callosal fibers on this effect. No differences were found in sham-operated rats (21 well-nourished and 21 malnourished), as well as in a superficial (1 mm deep) contralateral lesion group (8 well-nourished). Results support the hypothesis of a lasting inhibitory contralateral influence on CSD propagation, which is attenuated, but not abolished, by early malnutrition.

Familial Hemiplegic Migraine

Familial hemiplegic migraine (FHM) is a rare and genetically heterogeneous autosomal dominant subtype of migraine with aura. Mutations in the genes CACNA1A and SCNA1A, encoding the pore-forming alpha(1) subunits of the neuronal voltage-gated Ca2+ channels Ca(V)2.1 and Na+ channels Na(V)1.1, are responsible for FHM1 and FHM3, respectively, whereas mutations in ATP1A2, encoding the alpha2 subunit of the Na+, K+ adenosinetriphosphatase (ATPase), are responsible for FHM2. This review discusses the functional studies of two FHM1 knockin mice and of several FHM mutants in heterologous expression systems (12 FHM1, 8 FHM2, and 1 FHM3). These studies show the following: (1) FHM1 mutations produce gain-of-function of the Ca(V)2.1 channel and, as a consequence, increased Ca(V)2.1-dependent neurotransmitter release from cortical neurons and facilitation of in vivo induction and propagation of cortical spreading depression (CSD: the phenomenon underlying migraine aura); (2) FHM2 mutations produce loss-of-function of the alpha2 Na+,K+-ATPase; and (3) the FHM3 mutation accelerates recovery from fast inactivation of Na(V)1.5 (and presumably Na(V)1.1) channels. These findings are consistent with the hypothesis that FHM mutations share the ability of rendering the brain more susceptible to CSD by causing either excessive synaptic glutamate release (FHM1) or decreased removal of K+ and glutamate from the synaptic cleft (FHM2) or excessive extracellular K+ (FHM3). The FHM data support a key role of CSD in migraine pathogenesis and point to cortical hyperexcitability as the basis for vulnerability to CSD and to migraine attacks. Hence, they support novel therapeutic strategies that consider CSD and cortical hyperexcitability as key targets for preventive migraine treatment.

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.

After-effects of transcranial direct current stimulation (tDCS) on cortical spreading depression

Abnormal cortical excitability influences susceptibility to cortical spreading depression (CSD) in migraine. Because transcranial direct current stimulation (tDCS) is capable of inducing lasting changes of cortical excitability, we investigated the after-effects of tDCS on the propagation velocity of CSD in the rat. Twenty-five anesthetised rats received either anodal, cathodal or sham tDCS. The stimulation was applied for 20 min at a current strength of 200 μA after the recording of three baseline CSD measurements. Starting 5 min after tDCS, a further three CSDs were elicited and CSD velocity recorded at intervals of 20 min. tDCS and CSD recording was performed under anaesthesia with chloralose and urethane. As compared to the baseline velocity of 3.14 mm/min, anodal tDCS induced a significant increase of propagation velocity during the first post-tDCS recording (3.49 mm/min). In contrast to anodal tDCS, neither cathodal tDCS nor sham tDCS, which consisted of an initial ramped DC stimulation lasting only 20 s, showed a significant effect on CSD propagation velocity. As anodal tDCS is known to induce a lasting increase of cortical excitability in the clinical setting, our results support the notion that CSD propagation velocity reflects cortical excitability. Since cortical excitability and susceptibility to CSD is elevated in migraine patients, anodal tDCS – by increasing cortical excitability – might increase the probability of migraine attack in these patients, even beyond the end of its application.

Contribution of hemodynamics and light scattering to the changes in optical intrinsic signal during cortical spreading depression in rats

Optical intrinsic signals (OIS) imaging has been shown a powerful method for characterizing the spatial and temporal pattern of the propagation of cortical spreading depression (CSD) with high resolution. However, the possible physiological mechanisms underlying these OIS during CSD still remain incompletely understood. In this study, spectroscopic recording of the changes in OIS during pinprick induced CSD were performed at the exposed cortex of -chloralose/urethane anesthetized Sprague-Dawley rats (male, n=12) using a fiber optic reflectance spectrometer (PC-1000, Ocean Optics Inc.) to estimate the contribution of hemodynamics and light scattering to the changes in OIS. The fiber probe (source-detector fiber separation: 0.2 mm) was placed at cortical parenchyma site avoiding large blood vessels. For each animal, five CSDs were elicited with an interval of half an hour. On each CSD induction, the spectra data was collected over a 400 seconds period at the rate of 2 Hz. The changes in the concentration of HbO2 and Hb, and changes in light scattering was estimated by fitting the experimental reflectance spectra data to a modified Beer-Lambert equation using a linear least squares fitting procedure, for a spectral range of 460630 nm. The fit was good with a residual error less than 5% in most experiments. In this experiment, four-phasic changes in OIS were observed at 460 nm 570 nm, but triphasic changes were observed at longer wavelength. The fitting results showed that the CSD induced an initial increase in concentration of HbO2 (amplitude: 9.03.7%), which was 26.218.6 s earlier than the onset of increase of Hb concentration. The increase in concentration of Hb reached its maximum value 47.25.9 s earlier than that of HbO2. Whereas the concentration of HbO2 showed a four-phasic change, the light scattering showed a triphasic change and the concentration of Hb only showed a biphasic change. The timing relationship between OIS and concentration of HbO2 and Hb indicated that the initial phase of the decreased IOS at 550 nm was only caused by the concentration increase of oxygenated hemoglobin at cortical parenchyma sites. But during the second phase of the increased optical reflectance at 550 nm, more complicated physiological mechanisms may be involved, not only the changes in concentration of HbO2, Hb and Hbt, but also the changes in light scattering contributed significantly to the increase of optical reflectance. When the concentration of HbO2 shows a small decrease (7.84.5%), the concentration of Hb increased 24.510.8%, simultaneously with a significant increase of light scattering. Interestingly, in our previous studies, a slight constriction of the pial arteries was observed during this phase of OIS. The constriction of the pial artery and the increase of concentration of total hemoglobin at cortical parenchyma site suggest that the regulations of the pial artery and capillary during this phase may be controlled by different mechanisms. During the followed third phase of light decrease at 550 nm, an increase of blood volume (concentration of total hemoglobin), an increase of oxygenation and decrease of scattering all contributed to the change of intrinsic optical signal.

Visualization of cortical spreading depression using manganese‐enhanced magnetic resonance imaging

Cortical spreading depression (CSD) was visualized using manganese-enhanced MRI (MEMRI) following topical application of KCl to the exposed rat cortex. MEMRI signal increase in the ipsilateral cortex relative to the contralateral control region was 60 +/- 30% following two KCl applications. MEMRI signal increase for a single (40%) versus double (80%) KCl application suggests an integration effect over successive CSD episodes. CSD-induced MEMRI enhancement involved cortical layers containing dense regions of apical dendrites, supporting the contention that these neuronal structures are necessary for propagation of CSDs. Subcortical enhancement was present in hippocampal and thalamic regions, most likely a result of neuronal connections with cortical layers 4 and 5. These results are consistent with previous studies of CSD using diffusion-weighted MRI and T(2) (*)-weighted MRI and should be useful for investigating CSD itself and its role in other neurologic disorders.

Inhomogeneous propagation of cortical spreading depression—detection by electro- and magnetoencephalography in rats

Spreading depression (SD) propagates in cortical regions that are different in their morphological and functional characteristics. We tested whether the propagation pattern of spreading depression was different between parts of the cortex. In six adult rats, we recorded the ECoG by a 4×4 electrode array that covered parts of the frontal, parietal cortex and the cingulate cortex. Simultaneously a 16-channel magnetoencephalogram was recorded to characterize the development and direction of intracortical ion movements accompanying this phenomenon. Spreading depression was initiated by occipital application of 0.3 molar KCl solution. Depolarization was observed, at first, at lateral cortical regions and then at medial cortical regions. Thereafter, the propagation velocity increased in medial cortical regions and was faster than in lateral regions. Negative potential shifts were detected by all electrodes, but the depolarization reached a maximum over lateral and caudal cortical regions. The recorded magnetic fields indicated the same orientation of currents underlying these fields, which was perpendicular to the wave front and points away from the depolarization region. Overall, the data indicated that propagation patterns of spreading depression differed between parts of the cortex and, thus, propagation was inhomogeneous. This propagation was accompanied by strong currents parallel to the cortical surface.

Spreading and Synchronous Depressions of Cortical Activity in Acutely Injured Human Brain

Cortical spreading depression (CSD) has been much studied experimentally but never demonstrated unequivocally in human neocortex by direct electrophysiological recording. A similar phenomenon, peri-infarct depolarization, occurs in experimental models of stroke and causes the infarct to enlarge. Our current understanding of the mechanisms of deterioration in the days after major traumatic or ischemic brain injury in humans has not yielded any effective, novel drug treatment. This study sought clear evidence for the occurrence and propagation of CSD in the injured human brain. In 14 patients undergoing neurosurgery after head injury or intracranial hemorrhage, we placed electrocorticographic (ECoG) electrodes near foci of damaged cortical tissue. Transient episodes of depressed ECoG activity that propagated across the cortex at rates in the range of 0.6 to 5.0 mm/min were observed in 5 patients; this rate of propagation is characteristic of CSD. We also observed, in 8 of the 14 patients, transient depressions of ECoG amplitude that appeared essentially simultaneous in all recording channels, without clear evidence of spread. These results indicate that CSD or similar events occur in the injured human brain and are more frequent than previously suggested. On the basis of these observations, we suggest that the related phenomenon, peri-infarct depolarization, is indeed likely to occur in boundary zones in the ischemic human cerebral cortex.

Investigation of feline brain anatomy for the detection of cortical spreading depression with magnetic resonance imaging.

Cortical spreading depression (CSD) and peri-infarct depolarisation (PID) are related phenomena that have been associated with the human clinical syndromes of migraine (CSD), head injury and stroke (PID). Nevertheless the existence of CSD in man remains controversial, despite the detection of this phenomenon in the brains of most, if not all, other animal species investigated. This failure to unambiguously detect CSD clinically may be at least partly due to the anatomically complex, gyrencephalic structure of the human brain. This study was designed to establish conditions for the study of CSD in the brain of a gyrencephalic species using the noninvasive technique of magnetic resonance imaging (MRI). The 3-dimensional (3D) gyrencephalic anatomy of the cat brain was examined to determine the imaging conditions necessary to detect CSD events. Orthogonal transverse, sagittal and horizontal T1-weighted image slices showed that the marginal and suprasylvian gyri were the most appropriate cortical structures to study CSD. This was in view of (1) their simple geometry: (2) their lengthy extent of grey matter orientated rostrocaudally in the cortex: (3) their separation by a sulcus across which CSD spread could be studied and (4) the discontinuity in the grey matter in these regions between the right and left hemispheres dorsal to the corpus callosum. The structure suggested by the T1-weighted images was corroborated by systematic diffusion tensor imaging to map the fractional anisotropy and diffusion trace. Thus a single horizontal image plane could visualise the neighbouring suprasylvian and marginal gyri of both cerebral hemispheres, whereas its complex shape and position ruled out the ectosylvian gyrus for CSD studies. With the horizontal imaging plane, CSD events were reproducibly detected by animating successive diffusion-weighted MR images following local KCl stimulation of the cortical surface. In single image frames, CSD detection and characterisation required image subtraction or statistical mapping methods that, nevertheless, yielded concordant results. In repeat experiments, CSD events were qualitatively similar in appearance whether elicited by sustained or transient KCl applications. Our experimental approach thus successfully describes cat brain anatomy in vivo, and elucidates the necessary conditions for the application of MRI methods to detect CSD propagation.

Investigation of feline brain anatomy for the detection of cortical spreading depression with magnetic resonance imaging

Cortical spreading depression (CSD) and peri-infarct depolarisation (PID) are related phenomena that have been associated with the human clinical syndromes of migraine (CSD), head injury and stroke (PID). Nevertheless the existence of CSD in man remains controversial, despite the detection of this phenomenon in the brains of most, if not all, other animal species investigated. This failure to unambiguously detect CSD clinically may be at least partly due to the anatomically complex, gyrencephalic structure of the human brain. This study was designed to establish conditions for the study of CSD in the brain of a gyrencephalic species using the noninvasive technique of magnetic resonance imaging (MRI). The 3-dimensional (3D) gyrencephalic anatomy of the cat brain was examined to determine the imaging conditions necessary to detect CSD events. Orthogonal transverse, sagittal and horizontal T -weighted image slices showed that the marginal and suprasylvian gyri were the most appropriate cortical structures to study CSD. This was in view of (1) their simple geometry: (2) their lengthy extent of grey matter orientated rostrocaudally in the cortex: (3) their separation by a sulcus across which CSD spread could be studied and (4) the discontinuity in the grey matter in these regions between the right and left hemispheres dorsal to the corpus callosum. The structure suggested by the T -weighted images was corroborated by systematic diusion tensor imaging to map the fractional anisotropy and diusion trace. Thus a single horizontal image plane could visualise the neighbouring suprasylvian and marginal gyri of both cerebral hemispheres, whereas its complex shape and position ruled out the ectosylvian gyrus for CSD studies. With the horizontal imaging plane, CSD events were reproducibly detected by animating successive diusion-weighted MR images following local KCl stimulation of the cortical surface. In single image frames, CSD detection and characterisation required image subtraction or statistical mapping methods that, nevertheless, yielded concordant results. In repeat experiments, CSD events were qualitatively similar in appearance whether elicited by sustained or transient KCl applications. Our experimental approach thus successfully describes cat brain anatomy in vivo, and elucidates the necessary conditions for the application of MRI methods to detect CSD propagation.

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.

Vasodilator Agents and Supracollicular Transection Fail To Inhibit Cortical Spreading Depression in the Cat

It remains an open question as to whether cortical spreading depression (CSD) is the pathophysiological correlate of the neurological symptoms in migraine with aura. In the experimental animal, CSD is an electrophysiological phenomenon mainly mediated via NMDA receptors. However, according to case reports in humans, visual aura in migraine can be alleviated by vasodilator substances, such as amyl nitrite and isoprenaline. There is also circumstantial evidence that brainstem nuclei (dorsal raphe nucleus and locus coeruleus) may play a pivotal role in the initiation of aura. In this study, CSD was elicited in alpha-chloralose anesthetized cats by cortical needle stab injury and monitored by means of laser Doppler flowmetry. Topical application of isoprenaline (0.1-1%) and amyl nitrite (0.05%) onto the exposed cortex had no effect on the elicitation or propagation of CSD. Also, after supracollicular transection, subsequent CSDs showed no differences in the speed of propagation and associated flow changes. We conclude from these data that--given CSD probably exists in humans during migraine--spreading neurological deficits during migraine aura are independent of brainstem influence and have a primarily neuronal rather than vascular mechanism of generation.

Intracerebral microdialysis markedly inhibits the propagation of cortical spreading depression.

It is accepted that the ionic composition of the medium perfused through a microdialysis probe should match that of the extracellular fluid (ECF) under physiological conditions. In contrast, the possibility that control artificial cerebrospinal fluid may influence the experimental or pathological conditions under study, by buffering changes in the ECF composition, has been neglected. Spreading depression (SD) is a propagating transient suppression of electrical activity due to cellular depolarization which may contribute to neuronal damage in focal ischaemia, and underlie the migraine aura Here we report that microdialysis markedly inhibits SD propagation, by buffering the sudden increase in extracellular K+ associated with this event. This effect is independent of the microdialysis flow rate and does not result from tissue injury following probe implantation. This finding clearly illustrates that microdialysis can influence the pathological conditions under investigation.

Pathophysiology of migraine and tension-type headache.

Cortical spreading depression is probably the event underlying the aura of migraine, and biochemical and other studies suggest that a state of increased excitability of central neurons may lead to development and propagation of cortical spreading depression. Anatomical studies delineate some of the sites involved in the central processing of craniovascular nociception. 5-Hydroxytryptamine receptors, particularly 5-HT1, exist at both neural and vascular sites and are implicated in the pathogenesis of migraine. Studies in tension-type headache suggest that its pathogenesis is multifactorial, with contributions from both central and peripheral factors.

A comparison of (+) SK & F 10047 and MK-801 on cortical spreading depression

MK-801 and (+)SK & F 10047 produced a dose-related inhibition of the EEG suppression and cortical hyperemia associated with cortical spreading depression (CSD) and reduced the CSD propagation rate; ED 50 = 1mg/kg, i.v. and15mg/kg, i.v., respectively. MK-801 had a delayed onset of action (inversely related to dose) and a prolonged duration of action at all doses (> 2h). In contrast, (+)SK & F 10047 had a rapid onset of action (< 30min) and a predictable dose-related duration of action. These results suggests that an efficacious compound acting with moderate affinity as a non-competitive antagonist at the NMDA-receptor channel may possess a preferable time-course and toxicity profile when compared to agents acting similarly, but with high affinity.

Cerebral hemodynamics during cortical spreading depression in rabbits

Effects of a sibgle cortical spreading depression (CSD), elicited by KCl microinjection, on diameter of pial arterioles and venules in the parieto-occipital cortex were examined in urethane-anesthetized adult rabbits using a closed cranial window. The velocity of CSD propagation was2.7±0.1mm/min (mean±S.E.M.). All arterioles (n=39) except for those in the retrosplenial region (n=6) increased their diameter significantly during CSD. The arteriolar dilation lasted for1.5±0.1min. Location of dilating arteriole and propagating CSD showed that they were always closely associated temporally. As a percentage change, diameters of smaller arterioles significantly increased (from60 ± 1to103 ± μm, 71%, n = 12) more than those of larger ones (from82 ± 2to129 ± 3 μm, 57%, n = 27). While venules with initial diameter of85 ± 4 μm(n = 5) did not dilate, those with initial diameter of49 ± 3 μm increased to57 ± 3 μm(16%, n = 8) for1.4 ± 0.2 min during CSD. The majority of the dilated venules started to increase their diameter after nearby arterioles had dilated maximally. Pial arterioles, which dilated during ipsilateral CSD, decreased their diameter significantly from78 ± 2to72 ± 3 μm(8%, n = 11) during contralateral CSD for13.8 ± 3.6min with similar onset latencies as those observed for the dilation. Indomethacin pretreatment significantly enhanced arteriolar dilation during CSD (from73 ± 4to138 ± 6 μm, 89%, n =4). The results indicate that pial arteriolar dilation observed during CSD is an active response, and probably caused by an excitatory rather than inhibitory effect accompanying CSD, and that prostanoids may play an important modulatory role.

Systemic ketamine blocks cortical spreading depression but does not delay the onset of terminal anoxic depolarization in rats

Ketamine (KET)-induced blockade of cortical spreading depression (CSD) was examined in rats ( n=51) anesthetized with pentobarbital (50 mg/kg). CSD was elicited by intracortical injection of 1 μl of 0.15 mol/l potassium acetate 10–40 min after i.p. injection of 6–50 mg/kg KET. KET was almost ineffective at 6 mg/kg but prevented CSD propagation at 12 mg/kg and at higher dosages. The blockade was maximal 20 min after injection. Terminal anoxic depolarization elicited by N 2 breathing developed in control rats after a latency which was not significantly different from that in rats pretreated with 50 and 100 mg/kg KET. The failure of CSD blocking dosages of KET to delay the onset of terminal anoxic depolarization indicates that excitotoxic amino acids play different roles in the mechanism of the anoxia-elicited and CSD-related autoregenerative ionic shifts.

Techniques for termination of reverberating spreading depression in rats.

Reverberation of cortical spreading depression (CSD) around a circular obstacle (thermocoagulation lesion) in the frontal cortex of anesthetized rats was elicited by appropriately timed and spaced applications of KCl. The probability of continued reverberation was increased by a pyrrolopyrimidine drug BW 58-271 (10 mg/kg) from 0.93 to 0.98. Three methods of reverberation arrest were tested: a) CSD propagation was blocked by an interfering CSD wave which was initiated in the rear of the reverberating wave, passing through a narrow segment of the circular pathway, and collided with the reverberating wave on the opposite side of the obstacle; b) CSD propagation through a part of the circular pathway was blocked by a 10-min application of 10% MgCl2 on the exposed cortical surface; c) 1-min asphyxia stopped RCSD by increasing the overall refractoriness of cortical tissue. Least reliable was the interference method which stopped reverberation, even with optimum timing, only in 42% of the trials. The magnesium blockade was reliable but slow, the reverberation stopping only 30 min after MgCl2 application. Asphyxia evoked in any phase of the reverberation cycle stopped RCSD reliably and immediately. The results obtained with the interference method confirm the predictions of the mathematical model of impulse reverberation in sheets of excitable tissue. Anoxia seems best suited for practical control of CSD reverberation in functional decortication studies.

Spreading depression in squirrel monkey lissencephalic cortex.

Abstract Spreading depression was elicited in the squirrel monkey's cerebral cortex to determine some parameters of cortical spreading depression (CSD) in a highly encephalized but semi-lissencephalic brain. Rate of CSD propagation, as indicated by a slow potential (SP) change, was slower than in other mammals but comparable to that reported in other primates. Frontal and occipital regions of the cortex differed in terms of SP amplitude, CSD threshold, SP waveform, and seizure threshold. It was concluded that the squirrel monkey would be an excellent preparation for studying the effects of CSD upon memory functions, interhemispheric transfer, and other phenomena in a highly encephalized brain.