Unambiguous representation of overlapping serial events in the rat hippocampal formation.

The hippocampal formation is suggested to be crucial in unambiguous representation of overlapping temporal sequences in episodic memory. We hypothesized that, if this was true, the hippocampal formation neurons would differentially respond to the same elements even in different temporal sequences. The present study was designed to investigate hippocampal formation CA1 neuronal activity of rats during performance of a conditional delayed stimulus-response association task in which three stimuli were conditionally and serially presented with a delay. In the task, the pairs of the second and third stimuli were overlapped across the trials, but separated by the preceding first stimuli. Conditioned tones coming from one of three possible directions were followed, after a short delay, by one of three pairs of reinforcement series. The pairs consisted of air puff (aversive sensory stimuli) and tube protrusion (which allowed licking sucrose behavior) in the following combinations: air puff-tube protrusion, tube protrusion-tube protrusion and tube protrusion-air puff. The pairs were interposed by a 2 s delay. The three conditioned tone directions were associated with these three pairs in a one-to-one correspondence, and its association was conditional to three possible conditioned tone frequencies (300, 530, and 1,200 Hz). The responses of 107 neurons to the air puff and tube protrusion were analyzed by two-way ANOVA (task condition x reinforcement situation). Of 42 air puff-responsive and 64 tube protrusion-responsive neurons, 36 and 53 displayed significant main effects and/or significant interaction, respectively. Furthermore, neural responses during the delay periods were dependent on the task conditions. The results indicated that the majority of the hippocampal formation neurons showed task condition- and/or reinforcement situation-dependent responses, suggesting a crucial role of the hippocampal formation in representation of overlapping serial events in episodic memory.

Differential activation in the medial temporal lobe during a sound-sequence discrimination task across age in human subjects.

To elucidate the brain mechanisms to encode sequential events, event-related potentials (ERPs) were recorded during a sound-sequence discrimination task using young and middle-aged adult subjects. In the task, a series of six or 12 kinds of natural sounds were sequentially presented; 70-80% of the stimuli were presented in a fixed order (Non-target), but the remaining stimuli, in a random order (Target). The subjects were instructed to detect the Targets and press a button at the end of each Target. In a control task, the same sounds were randomly presented (Control), and they were instructed to press the button at the end of each sound. Behavioral results indicated that the young subjects learned the task faster than did the middle-aged subjects. Positive ERP waves were evoked by Targets and Non-targets in the parieto-occipital area around 300-700 ms after stimulus onset. The mean amplitudes during this period in the young subjects were larger in Target than Control conditions, and those in Target condition were larger in the young than middle-aged subjects. Furthermore, the mean amplitudes in the Target condition were significantly correlated with behavioral performance. Equivalent dipoles for the ERPs evoked by Targets were estimated in the medial temporal lobe including the hippocampal formation and parahippocampal gyrus. The results suggest that the ERPs around 300-700 ms latency are involved in sound-sequence information processing. Furthermore, decrease in amplitudes of this positivity in the middle-aged subjects suggests that age-related memory decline is associated with deficits in encoding and retrieval of unfamiliar sequence.

Reward value invariant place responses and reward site associated activity in hippocampal neurons of behaving rats.

To investigate the involvement of the hippocampal-accumbens system in goal-oriented displacement behaviors, hippocampal neuronal activity was recorded in rats learning and recalling new distributions of different volumes of liquid reward among the arms of a plus maze. Each arm had a reward box containing a water trough and identical visual cues that could be illuminated independently. As the water-restricted rat successively visited the respective boxes, it received 7, 5, and 3 drops of water, and then 1 drop, provided at 1-s intervals. (Reward distributions were reassigned daily and mid-session.) In the training phase, reward boxes were lit individually. In the recall phase, the lamps on all arms were lit and then turned off as the rat visited the boxes in order of descending value. Neuronal firing rates were analyzed for changes related to reward value or to shifts between learning and recall phases. The principal finding is that place responses remained unchanged after these manipulations and that these neurons showed no evidence of explicit coding of reward value. In addition, two other types of responses appeared while the rat was stationary at the reward boxes awaiting multiple rewards. These were observed primarily in neurons within the dentate gyrus, but also in CA1. Position-selective reward site responses were regular at 20-60 impulses per second, while position-independent discharges bursted irregularly at about 5 impulses per second. Such responses could explain controversial reports of reward dependence in hippocampal neurons. The higher incidence of the latter responses in the temporal ("ventral") hippocampus is consistent with the distinctive anatomical and functional properties of this subregion.

Active locomotion increases peak firing rates of anterodorsal thalamic head direction cells.

Head direction (HD) cells discharge selectively in macaques, rats, and mice when they orient their head in a specific ("preferred") direction. Preferred directions are influenced by visual cues as well as idiothetic self-motion cues derived from vestibular, proprioceptive, motor efferent copy, and command signals. To distinguish the relative importance of active locomotor signals, we compared HD cell response properties in 49 anterodorsal thalamic HD cells of six male Long-Evans rats during active displacements in a foraging task as well as during passive rotations. Since thalamic HD cells typically stop firing if the animals are tightly restrained, the rats were trained to remain immobile while drinking water distributed at intervals from a small reservoir at the center of a rotatable platform. The platform was rotated in a clockwise/counterclockwise oscillation to record directional responses in the stationary animals while the surrounding environmental cues remained stable. The peak rate of directional firing decreased by 27% on average during passive rotations (r(2) = 0.73, P < 0.001). Individual cells recorded in sequential sessions (n = 8) reliably showed comparable reductions in peak firing, but simultaneously recorded cells did not necessarily produce identical responses. All of the HD cells maintained the same preferred directions during passive rotations. These results are consistent with the hypothesis that the level of locomotor activity provides a state-dependent modulation of the response magnitude of AD HD cells. This could result from diffusely projecting neuromodulatory systems associated with motor state.

Optimum treatment strategy for superficial esophageal cancer: endoscopic mucosal resection versus radical esophagectomy.

This study was designed to determine the optimum treatment for a superficial esophageal cancer involving the mucosal or submucosal layer of the esophagus. The subjects were 150 patients with a superficial esophageal cancer who underwent endoscopic mucosal resection (EMR) or esophagectomy in Kurume University Hospital from 1981 to 1997. The mortality and morbidity rates, survival rate, and recurrence rate were retrospectively compared for (1) 35 patients who underwent EMR and 37 patients who underwent esophagectomy for a mucosal esophageal cancer and (2) 45 patients who underwent extended radical esophagectomy and 33 patients who underwent less radical esophagectomy for a submucosal esophageal cancer. Among the 72 patients with a mucosal cancer, lymph node metastasis/recurrence was observed in only one (1%); whereas of 78 patients with a submucosal cancer it was observed in 30 (38%). Among patients with a mucosal cancer the mortality and morbidity rates after EMR were lower than for those after esophagectomy. The survival rate after EMR was the same as that after esophagectomy. No recurrence was observed after either treatment modality. Among the patients with a submucosal cancer, the survival rate was higher and the recurrence rate lower after extended radical esophagectomy; than after less radical esophagectomy; the mortality and morbidity rates after extended radical esophagectomy were the same as those after less radical esophagectomy. Multivariate analysis demonstrated that the treatment modality (EMR versus esophagectomy) did not influence the survival of patients with a mucosal esophageal cancer, whereas it strongly influenced the survival of patients with a submucosal esophageal cancer. We concluded that EMR was the mainstay of treatment for a mucosal esophageal cancer, and extended radical esophagectomy was the mainstay of treatment for a submucosal esophageal cancer.

Lesions of the medial shell of the nucleus accumbens impair rats in finding larger rewards, but spare reward-seeking behavior.

The goal of this study was to help better understand the importance of the nucleus accumbens (Nacc) in the processing of position and reward value information for goal-directed orientation behaviors. Sixteen male Long-Evans rats, under partial water deprivation, were trained in a plus-maze to find water rewards in the respective arms which were lit in pseudo-random sequence (training trials). Each day one reward arm was selected to deliver six drops of water (at 1 s intervals) the others provided only one drop per visit. After 32 visits, probe trials were intermittently presented among training trials. Here, all four arms were lit and offered the previously assigned reward. The rats rapidly learned to go to the highly rewarded arm. Six trained rats were given bilateral electrolytic lesions in the Nacc shell, two others had unilateral lesions and eight had sham operations (with approved protocols). Field potentials evoked by fornix stimulation were recorded in lesion electrodes to guide placements. Only the lesioned rats showed significant impairments (P<0.05) in selecting the greater reward on probe trials. However on training trials, lesioned (and sham-operated) rats made only rare errors. While the motivation to drink and the capacity for cue-guided goal-directed orientation behavior was spared, lesioned rats were impaired in learning the location of the larger reward. The accumbens lesions apparently impaired integration of position and reward value information, consistent with anatomical and electrophysiological data showing the convergence of hippocampal, amygdalar, ventral tegmental area (VTA) and prefrontal cortical inputs there.

Influence of conflicting visual, inertial and substratal cues on head direction cell activity.

In order to navigate efficiently, animals can benefit from internal representations of their moment-to-moment orientation. Head-direction (HD) cells are neurons that discharge maximally when the head of a rat is oriented in a specific ("preferred") direction in the horizontal plane, independently from position or ongoing behavior. This directional selectivity depends on environmental and inertial cues. However, the mechanisms by which these cues are integrated remain unknown. This study examines the relative influence of visual, inertial and substratal cues on the preferred directions of HD cells when cue conflicts are produced in the presence of the rats. Twenty-nine anterior dorsal thalamic (ATN) and 19 postsubicular (PoS) HD cells were recorded from 7 rats performing a foraging task in a cylinder (76 cm in diameter, 60 cm high) with a white card attached to its inner wall. Changes in preferred directions were measured after the wall or the floor of the cylinder was rotated separately or together in the same direction by 45 degrees, 90 degrees or 180 degrees, either clockwise or counterclockwise. Linear regression analyses showed that the preferred directions of the HD cells in both structures shifted by approximately =90% of the angle of rotation of the wall, whether rotated alone or together with the floor (r2>0.87, P<0.001). Rotations of the floor alone did not trigger significant shifts in preferred directions. These results indicate that visual cues exerted a strong but incomplete control over the preferred directions of the neurons, while inertial cues had a small but significant influence, and substratal cues were of no consequence.

Magnetic resonance imaging and histologic evidence of postoperative back muscle injury in rats.

STUDY DESIGN: Postoperative back muscle injury was evaluated in rats by magnetic resonance imaging and histologic analyses. OBJECTIVE: To compare the magnetic resonance imaging manifestation of back muscle injury with the histologic findings in rats and to subsequently clarify the histopathologic appearance of the high intensity regions on T2-weighted images in human postoperative back muscles. SUMMARY OF BACKGROUND DATA: In a previous study, it was found that the signal intensity on T2-weighted images of the postoperative back muscles was increased in patients who had postsurgical lumbar muscle impairment, especially in those with a prolonged surgery duration. However, the specific histopathologic changes that cause the high signal intensity on T2-weighted images remain unclear. METHODS: Rats were divided into three groups: sham operation group, 1-hour retraction group, and 2-hour retraction group. Magnetic resonance imaging and histology of the multifidus muscles were examined before surgery and at 2, 7, and 21 days after surgery. RESULTS: T2-weighted imaging was more useful than T1-weighted imaging to estimate back muscle injury. The high signal intensity of the multifidus muscles on T2-weighted images remained 21 days after surgery only in the 2-hour retraction group. Histologically, the regeneration of the multifidus muscles was complete at 21 days after surgery in the 1-hour retraction group, but the regenerated muscle fibers in the 2-hour retraction group had a small diameter, and the extracellular fluid space remained large. CONCLUSION: The high signal intensity on T2-weighted images of the postoperative multifidus muscles in the regenerative phase may be due to an increased extracellular space and incomplete muscle fiber regeneration.

Position and behavioral modulation of synchronization of hippocampal and accumbens neuronal discharges in freely moving rats.

To understand how hippocampal signals are processed by downstream neurons, we analyzed the relative timing between neuronal discharges in simultaneous recordings in the hippocampus and nucleus accumbens of rats performing in a plus maze. In all, 154 pairs of cells (composed of 65 hippocampal and 56 accumbens neurons) were examined during the 1 s period prior to reward delivery. Cross-correlation analyses over a +/- 300-ms window with 10-ms bins revealed that 108 pairs had at least one significant histogram bin (P < 0.01). The most frequently occurring peaks of hippocampal firing prior to accumbens discharges appeared at latencies from -30-0 ms, corresponding to published values of the latency of the hippocampal pathway to the nucleus accumbens. Other peaks appeared most often at latencies multiples of about 110 ms prior to and after this, corresponding to theta rhythmicity. Since firing synchronization can result from several types of connectivity patterns (such as common inputs), a group of 18 hippocampus-accumbens pairs was selected as those most likely to have monosynaptic connections. The criterion was the presence of at least one highly significant peak (P < 0.001) at latencies corresponding to field potentials evoked in the accumbens by hippocampal stimulation. A significant peak occurred on all four maze arms for only one of these cell pairs, indicating positional modulation for the others. In addition, behavior dependence of the synchrony between these nucleus accumbens and hippocampus neurons was examined by studying data in relation to three different synchronization points: reward box arrival, box departure, and arrival at the center of the maze. This indicates that the functional connectivity between hippocampal and accumbens neurons was stronger when the rat was near reward areas. Ten of the hippocampal neurons in these 18 cell pairs showed 9-Hz (theta) rhythmic activity in autocorrelation analyses. Of these 10 cells, cross-correlograms from eight hippocampal-accumbens pairs also showed theta rhythmicity. Overall, these results indicate that the synchrony between hippocampus and nucleus accumbens neurons is modulated by spatial position and behavior, and theta rhythm may play an important role for this synchronization.

Effects of D2 dopamine receptor agonist and antagonist on brain activity in the rat assessed by functional magnetic resonance imaging.

The effects of D2 dopamine receptor agonist, bromocriptine (BROMO), and antagonist, haloperidol (HPD), on brain activity were investigated in rats by functional magnetic resonance imaging. T2*-weighted signal intensity was increased in the hypothalamus at 120 min after acute administration of BROMO, and in the ventral posterior and dorsomedial nuclei of the thalamus from 30 to 120 min. In contrast, the signal intensity was decreased in the caudate-putamen at 30 min after acute administration of HPD, in the hypothalamus from 30 to 60 min, and in the perirhinal cortex at 30 min. After chronic (2 weeks) HPD treatment, acute administration of HPD decreased signal intensity in the caudate-putamen at 60 min, in the hypothalamus at 30 min, the perirhinal cortex from 2 to 120 min, the dorsomedial and ventral posterior nuclei of the thalamus from 2 to 120 min, and the medial nucleus of the amygdala from 60 to 120 min. These results suggest that (1) the D2 receptor agonist increased the activity of the thalamic nuclei and the hypothalamus, while the D2 receptor antagonist suppressed brain activity in the regions where D2 receptors were present, (2) the suppression of brain activity in the thalamic nuclei and the perirhinal cortex by acute HPD administration was enhanced by chronic HPD treatment, and (3) the effects of antipsychotic drugs on the thalamus, amygdala, and perirhinal cortex may be related to their therapeutic efficacy, since clinical improvement in schizophrenic patients appears several days after the start of HPD treatment.

[HR-CT evaluation of lung parenchymal alterations in patients following breast conservation therapy].

Twenty patients with early-stage breast cancer treated with breast conservation surgery and definite radiation, underwent computed tomography (added HR-CT) of the lungs before, immediately after, and at one, six, and twelve months after radiotherapy. During the follow-up period, 17 (85%) of the patients developed parenchymal alterations in the irradiated lung volume. We classified the parenchymal alterations into seven patterns: pattern 1 = septal line, 2 = nodular opacity, 3 = ground-glass opacity, 4 = consolidation, 5 = curvilinear opacity, 6 = aircyst accumulation, and 7 = irregularity of pleural surface. From one to six months after radiotherapy, 14 patients developed nodular opacities and ground glass opacities in the irradiated lung field. At 12 months after radiotherapy, fourteen patients were found to have aircyst accumulation and irregularity of the pleural surface. In this study, none of the patients presented any abnormal findings immediately after irradiation. There was no relationship between central lung distance or boost irradiation and the parenchymal alterations in the lung. On the other hand, there was a close relationship between oral anti-cancer agents and lung lesions. In conclusion, HR-CT was useful to evaluate morphologic changes in the irradiated lung.

Comparison of technetium-99m-MIBI, technetium-99m-tetrofosmin, ultrasound and MRI for localization of abnormal parathyroid glands.

UNLABELLED: Abnormal parathyroid tissue can be identified by radionuclide imaging with either 99mTc-MIBI or 99mTc-tetrofosmin. This study compared the relative sensitivity of these two agents to localize parathyroid hyperplasia and adenoma. METHODS: Twenty patients with primary (n = 9) or secondary (n = 11) hyperparathyroidism were studied with 99mTc-MIBI and 99mTc-tetrofosmin parathyroid imaging, ultrasonography and MRI. Radionuclide images of the neck were acquired 10 min and 2-3 hr after radiopharmaceutical injection. The images were visually evaluated for abnormal focal areas of increased tracer localization in the neck and mediastinum. A parathyroid gland/normal thyroid tissue activity ratio (referred to as the P/T uptake ratio) was calculated for each positive scan. RESULTS: Of the 46 parathyroid glands surgically explored, the overall sensitivity and specificity of MIBI imaging were 83% and 83% (38/46); tetrofosmin imaging 87% and 83% (40/46); ultrasonography 78% and 40% (36/46); and MRI 80% and 60% (37/46), respectively. Both radiopharmaceuticals performed well in the nine patients found to have adenoma. The sensitivity and specificity of MIBI imaging were 100% and 100% (9/9); tetrofosmin imaging 100% and 100% (9/9); ultrasonography 78% and 67% (7/9); and MRI 100% and 100% (9/9), respectively. In the 37 glands with hyperplasia, MIBI imaging had a sensitivity of 78% and specificity of 75%; tetrofosmin imaging 84% and 75%; ultrasonography 78% and 43%; and MRI 73% and 60%, respectively. CONCLUSION: All imaging techniques localized abnormal parathyroid glands. The radiotracers have equal sensitivity for the localization of abnormal parathyroid glands. The sensitivity of these tracers was high as compared to ultrasonography or MRI.

Contribution of chorda tympani and glossopharyngeal nerves to taste preferences of rat for amino acids and NaCl.

To learn how the gustatory nerves convey information about the nutritionally dependent taste preference, intake of amino acid solutions and saline in rats with bilateral chorda tympani (CTX) and/or glossopharyngeal neurotomy (GPX) was determined during the feeding of a control diet (C) and a L-lysine (Lys) deficient diet (LD). Intact rats preferred L-arginine (Arg) more in C and Lys more in LD. The CTX group did not select nor ingest Lys in LD, and its intake of Arg was also low in C. The GPX group did not substantially alter its preference under both diets, while it did show an increase in total liquid intake. The preference changes in the CTX + GPX group appeared as combined effects of the CTX and the GPX groups. In an additional study, the preference for Lys shifted to higher concentrations and the total consumption of Lys increased in LD. The present data suggest that the chorda tympani nerves possibly function as discriminators of the nutritional information by altering the taste preference, and that the glossopharyngeal nerves may convey other functional taste information, such as aversive tastes, and sensory aspects of osmotic regulation. In addition, it is revealed that the animals have ability to search for a nutrient deficient in their body, and to ingest it to a level that at least nullifies the deficiency.

Recognition of deficient nutrient intake in the brain of rat withL-lysine deficiency monitored by functional magnetic resonance imaging, electrophysiologically and behaviorally.

EachL-amino acid (AA) in plasma and brain remains unchanged all day long while normal diet is available. But once restriction ofL-lysine (Lys) was introduced, strong anorexia happened. When Lys deficient diet was offered to rats, their growth were decreased depending upon dietary Lys intake, and they ingested Lys solution in choice quantitatively and both appetite and growth normalized. The recognition site for the deficit in rat's brain was identified by brain oxygenation using a functional MRI that higher signals in the ventromedial hypothalamus and lateral hypothalamic area (LHA) appeared, at 30-50 minutes after Lys injection i.p. and then recovered. Degree of Lys hunger, assayed by bar-pressing (50mg pellet of normal diet/30 presses), was suppressed by Lys micro-injection into the LHA, similar to free Lys ingestion but any other AA never did, suggesting the LHA as recognition site for Lys deficit in rats with Lys deficiency due to AA homeostasis.

Recognition and neural plasticity responding to deficient nutrient intake scanned by a functional MRI in the brain of rats with L-lysine deficiency.

Each L-amino acid (AA) in plasma and brain remains unchanged while normal diet is available. Once L-lysine (Lys) deficient diet was offered to rats, Lys in plasma and brain declined, and anorexia occurred. When solutions of AAs were offered, they selected the Lys solution, and their food intake and growth normalized. The single neuron activity in the lateral hypothalamic area of these rats suggested that neural plasticity occurred, specifically responding to Lys, both by iontophoretic application and during ingestion of AA. The recognition site for deficient nutrient intake in the brain of rats with Lys deficiency was identified by non-invasive magnetic resonance imaging (MRI 4.7 tesla, 40 cm bore in diameter) developed to monitor changes in cerebral blood flow and oxygenation in rat brain. Wistar strain young male rats fed with Lys deficient diet for 4 days, were adapted to be settled in the center of the bore. When they received a Lys injection intraperitoneally (0.2 M, 10 mL/kg), a signal intensity decrease in the medial and lateral hypothalamus appeared 30 minutes later in T2 weighted images, reflecting increased oxygenation which lasted for 30 minutes, and then gradually recovered. These changes never occurred in any other areas of the brain of rats with Lys deficiency, i.e., the thalamus, the cortex, the hippocampus, etc. There were no changes in the signal intensity with control injection of saline. In addition, oxygen consumption in the brain of rats without Lys deficiency was not altered by intraperitoneal Lys injection. The present results suggest that in essential AA deficiency, the medial and lateral hypothalamus may play important roles in recognition responses to particular deficient nutrients in order to maintain homeostasis.

Generators of somatosensory evoked potentials investigated by dipole tracing in the monkey.

Generators of somatosensory evoked potentials, elicited by electrical stimulation of the median nerve in anaesthetized monkeys (Macaca fuscata), were investigated by submitting a three-dimensional reconstructed brain model to dipole tracing, which can equate surface potential distributions to an approximate corresponding equivalent dipole. The following components of the somatosensory evoked potentials were simultaneously recorded from 21-27 epidural electrodes: P7 (the letter indicates positive or negative polarity; the number indicates the approximate latency of the peak in ms) was recorded widely from various locations on both the left and right hemispheres, P10 was recorded near the anterior side of the central sulcus contralateral to the stimulation side, N10 was recorded near the posterior side of the contralateral central sulcus, P12 was recorded on both sides of the contralateral central sulcus, and P18 was recorded posterior to the contralateral central sulcus. Current source generators (dipoles) of each component of somatosensory evoked potentials were localized by dipole tracing: a dipole for P7 was located in the thalamus contralateral to the stimulation side; a dipole for P10 and N10 in the posterior wall of the contralateral central sulcus (area 3b); a dipole for P12 in the contralateral post central gyrus (areas 1 and 2); and a dipole for P18 in the anterior wall of the contralateral intraparietal sulcus (area 5). The locations and latencies of dipoles that generated cortical components of somatosensory evoked potentials, estimated by dipole tracing, were confirmed by direct cortical surface recording from a 16-25 electrode array placed directly on the cortical surface; and multiple unit recording from the anterior and posterior parietal cortices. After excision of area 5, P18 and N18 were abolished, whereas P10, N10, and P12 were not affected. The results suggest that dipoles for somatosensory evoked potentials progressed from the thalamus to area 5 via the primary somatosensory area. This progress is consistent with the hierarchical sequence of somatosensory information processing.

Ischemic neuronal damage specific to monkey hippocampus: histological investigation.

We previously reported lesions confined specifically to the hippocampus when produced by occluding eight vessels (the bilateral vertebral, common, internal, and external carotid arteries), which supply blood to the brain. However, histopathological changes in the primate brain, caused by ischemic injury, have not previously been thoroughly investigated. In the present study, macaque monkeys were subjected to 5-18-min ischemia by occluding the eight vessels. After the brains were perfused and fixed 5 days after the occlusion, all regions were histologically investigated for ischemic cell changes. Ischemia for 5 min produced no ischemic cell change. Ischemia for 10-15 min produced cell death limited to the deeper portion of the pyramidal cell layer of the CA1 subfield in the hippocampus. In most monkeys, no cell death was observed in any brain region outside of the hippocampus after ischemia for up to 15 min. Ischemia for 18 min produced more widespread cell death in the CA1 subfield of the hippocampus, and cell death was no longer confined to the hippocampus, but was observed in layers III, V, and VI of the neocortices, the striatum, and some other regions. Brains that were perfused and fixed 1 year after 15-min ischemic insult revealed no ischemic cell morphological change in any region, but the number of pyramidal cells in the CA1 subfield was decreased to about half. The results indicate that the CA1 subfield of the monkey hippocampus is the precise region of the brain most susceptible to ischemic insult in the primate forebrain, and after a critical time (15-min ischemia in this procedure) ischemic cell changes occur suddenly and extensively. Ischemia due to occlusion of eight arteries for 10-15 min could produce a model of human amnesia caused by transient ischemic insult.

Physiological results of monkey brain ischemia, and protection by a calcium blocker.

Physiological and histological investigation was undertaken to examine dynamic and metabolic changes due to transient ischemic insult of the monkey brain with and without postischemic treatment by the calcium entry blocker, NC-1100 (1 mg/kg, IV). Monkeys were subjected to temporary occlusion of the eight major arteries: bilateral common carotid, internal and external carotid, and vertebral arteries. Blood flow was restored after 5-, 10-, 13-, and 15-min ischemia in different monkeys. The amplitudes of extradural, cortical, and hippocampal electroencephalograms decreased severely within 1-6 min after beginning occlusion. Complete recovery of these electroencephalograms required more than 1 h. During ischemia, significant change was obvious in arterial glucose, and systolic, diastolic, and mean blood pressure, all of which increased. There were no significant physiological differences between the untreated and NC-1100-treated groups, except decreased diastolic blood pressure and slightly lower postischemic heart rate in the treated group. These small differences might be accounted for by the effect of the calcium blocker. Ten to 15 minutes ischemia caused cell changes, including cell death, which were confined almost exclusively to the CA1 subfield of untreated hippocampi examined the fifth day after occlusion. However, no ischemia-induced cell change was observed in the CA1 subfield of hippocampi subjected to 10 to 15 min ischemia in the NC-1100-treated group. It was concluded that a calcium entry blocker can protect neurons from mild ischemia-induced injury and might ameliorate morphological damage and functional impairment of the brain due to ischemia in patients who suffer transient anoxic or hypoxic injury. The present physiological data should contribute to their clinical treatment.

A case of a primary hepatic tumor causing segmental changes on imaging and its relation to Zahn's infarct.

A 69-year-old female was admitted to our hospital for further examination of an intrahepatic mass which had been found while undergoing a complete physical examination. The mass measured 4 cm in size and was located in the medial segment (S4) of the liver. On computed tomography (CT), S4 was observed to be 'atrophied' and was well enhanced segmentally. A celiac angiogram showed segmental staining, and a transarterial portogram demonstrated portal stoppage of S4 from the left branch. However, no segmental intensity difference was seen on magnetic resonance imaging (MRI). An aspiration biopsy showed adenocarcinoma and thus an operation was performed under a tentative diagnosis of intrahepatic cholangiocarcinoma. The postoperative diagnosis of the tumor was combined hepatocellular and cholangiocellular carcinoma. However, no histological abnormality was seen in S4, contrary to the expectation of Zahn's infarct. In this study, we discuss the mechanism and imaging findings of Zahn's infarct, the possible reasons as to why no pathological change was seen in S4, as well as stress the rarity of reports on Zahn's infarct in cases of portal thrombus due to hepatocellular carcinoma.