The acute transcriptome response of the midbrain/diencephalon to injury in the adult mummichog (Fundulus heteroclitus).

Adult fish produce new cells throughout their central nervous system during the course of their lives and maintain a tremendous capacity to repair damaged neural tissue. Much of the focus on understanding brain repair and regeneration in adult fish has been directed at regions of the brainstem and forebrain; however, the mesencephalon (midbrain) and diencephalon have received little attention. We sought to examine differential gene expression in the midbrain/diencephalon in response to injury in the adult fish using RNA-seq. Using the mummichog (Fundulus heteroclitus), we administered a mechanical lesion to the midbrain/diencephalon and examined differentially expressed genes (DEGs) at an acute recovery time of 1 h post-injury. Comparisons of whole transcriptomes derived from isolated RNA of intact and injured midbrain/diencephalic tissue identified 404 DEGs with the vast majority being upregulated. Using qPCR, we validated the upregulation of DEGs pim-2-like, syndecan-4-like, and cd83. Based on genes both familiar and novel regarding the adult brain response to injury, these data provide an extensive molecular profile giving insight into a range of cellular processes involved in the injury response of a brain regenerative-capable vertebrate.

[Diencephalic syndrome].

Diencephalic structures are thalamus, hypothalamus, epithalamus, subthalamus and hypophysis. Diencephalic structures injury lead to several syndromes: diencephalic dysthermia, hypothalamic obesity, pediatric diencephalic syndrome, Cushing's disease, etc. Diencephalic syndrome manifests in 15-33% of patients with TBI. The goal of our study was to describe diencepalic syndrome in patients in neurointensive care unit. 76 patients took part in the study, 43 women and 33 men among them. The age of patients ranged from 19 to 77 years. All patients had consciousness disorders (CD) and dysnatremia. The patients were divided into 6 groups according to the number of somatic organ dysfunctions (SOD). 12 patients had only dysnatremia and CD without SOD (91.7% of them with benign outcome; 7.3% of them with poor outcome (GOS-3)). 11 patients in the second group had CD, dysnatremia and 1 SOD (45.5% of them had benign outcome; 54.5%--poor outcome). In the third group patients had 2 SOD (42% of them had poor outcome (GOS-3) and 33%--lethal outcome (GOS-1)). The worst outcome was in the 6th group, where patients had 5 SOD. All the patients in that group died. So, in patients with neurosurgical pathology in chiasmal area dienchephalic syndrome manifests by combination of CD, dysnatremia and at least 1 SOD. The number of SOD determines the outcome and severity of diencephalic syndrome.

A unique pattern of intracranial pressure in a patient with traumatic paroxysmal sympathetic storm.

Paroxysmal sympathetic storm (PSS), or diencephalic seizure, usually appears in patients with severe traumatic brain injury and is characterized by various sympathetic symptoms. The physiological effects of this syndrome are not well studied. The authors monitored intracranial pressure (ICP) in a patient with PSS and reviewed its impact on the physiology and management of the syndrome. A 12-year-old male patient was involved in a traffic accident. Upon arrival at the emergency room, his Glasgow Coma Scale score was 5 and he showed decerebration. A brain CT showed an intracerebral hematoma in the right basal ganglia, at which point craniotomy and removal of the hematoma were performed. Continuous intracranial monitoring was performed using the fiber-optic intraparenchymal method. Beginning the day after the trauma, the patient began exhibiting sympathetic symptoms including intermittent episodes of fever, tachycardia, increased blood pressure, tachypnea, diaphoresis and decerebrate rigidity. These episodes were accompanied by ICP elevation of greater than 20 mm Hg. ICP was decreased during hyperventilation, and the episodic symptoms subsided as ICP normalized. PaCO(2) was periodically altered in association with hyperventilation. Electroencephalogram did not show epileptiform discharges, and the sympathetic spells were aborted by continuous intravenous midazolam infusion. The authors report on a pattern of ICP monitoring in association with PSS. Traumatic PSS should be recognized in the appropriate setting to prevent secondary brain damage.

Abnormal cortical network activation in human amnesia: A high-resolution evoked potential study.

Little is known about how human amnesia affects the activation of cortical networks during memory processing. In this study, we recorded high-density evoked potentials in 12 healthy control subjects and 11 amnesic patients with various types of brain damage affecting the medial temporal lobes, diencephalic structures, or both. Subjects performed a continuous recognition task composed of meaningful designs. Using whole-scalp spatiotemporal mapping techniques, we found that, during the first 200 ms following picture presentation, map configuration of amnesics and controls were indistinguishable. Beyond this period, processing significantly differed. Between 200 and 350 ms, amnesic patients expressed different topographical maps than controls in response to new and repeated pictures. From 350 to 550 ms, healthy subjects showed modulation of the same maps in response to new and repeated items. In amnesics, by contrast, presentation of repeated items induced different maps, indicating distinct cortical processing of new and old information. The study indicates that cortical mechanisms underlying memory formation and re-activation in amnesia fundamentally differ from normal memory processing.

The extended hippocampal-diencephalic memory system: enriched housing promotes recovery of the flexible use of spatial representations after anterior thalamic lesions.

The anterior thalamic (AT) nuclei constitute an important component of an extended hippocampal-diencephalic system, and severe persisting memory deficits are normally found after AT damage. This study examined whether postoperative enrichment promotes the recovery of the flexible use of spatial representations in rats with AT lesions. After training to swim from a single constant start position to a submerged platform in a Morris water maze, rats with AT lesions that were housed in standard cages (AT-Std) performed poorly when required to swim to the platform from novel start positions during probe trials. By contrast, rats with AT lesions but housed in enriched environments (AT-Enr), like sham-lesion rats, showed relatively little disruption when tested with novel start positions. AT-Std rats also initially showed impaired acquisition of the task, whereas AT-Enr rats learned at a similar rate to that of the Sham-Std group. Beneficial effects of enrichment were replicated in the subsequent standard water maze procedure that used varying start positions throughout training to acquire a new platform location. Although it is clear that AT damage can severely disrupt episodic-like memory processes, and appear to be a core part of the interlinked neural systems subserving episodic memory, the current findings strongly encourage study on the adaptive response of the brain to thalamic lesions and prospects for the development of rehabilitation programs in cases of anterograde amnesia associated with diencephalic injury.

Functional MRI study of diencephalic amnesia in Wernicke-Korsakoff syndrome.

Anterograde amnesia in Wernicke-Korsakoff syndrome is associated with diencephalic lesions, mainly in the anterior thalamic nuclei. Whether diencephalic and temporal lobe amnesias are distinct entities is still not clear. We investigated episodic memory for faces using functional MRI (fMRI) in eight controls and in a 34-year-old man with Wernicke-Korsakoff syndrome and diencephalic lesions but without medial temporal lobe (MTL) involvement at MRI. fMRI was performed with a 1.5 tesla unit. Three dual-choice tasks were employed: (i) face encoding (18 faces were randomly presented three times and subjects were asked to memorize the faces); (ii) face perception (subjects indicated which of two faces matched a third face); and (iii) face recognition (subjects indicated which of two faces belonged to the group they had been asked to memorize during encoding). All activation was greater in the right hemisphere. In controls both the encoding and recognition tasks activated two hippocampal regions (anterior and posterior). The anterior hippocampal region was more activated during recognition. Activation in the prefrontal cortex was greater during recognition. In the subject with Wernicke-Korsakoff syndrome, fMRI did not show hippocampal activation during either encoding or recognition. During recognition, although behavioural data showed defective retrieval, the prefrontal regions were activated as in controls, except for the ventrolateral prefrontal cortex. fMRI activation of the visual cortices and the behavioural score on the perception task indicated that the subject with Wernicke-Korsakoff syndrome perceived the faces, paid attention to the task and demonstrated accurate judgement. In the subject with Wernicke-Korsakoff syndrome, although the anatomical damage does not involve the MTL, the hippocampal memory encoding has been lost, possibly as a consequence of the hippocampal-anterior thalamic axis involvement. Anterograde amnesia could therefore be the expression of damage to an extended hippocampal system, and the distinction between temporal lobe and diencephalic amnesia has limited value. In the subject with Wernicke-Korsakoff syndrome, the preserved dorsolateral prefrontal cortex activation during incorrect recognition suggests that this region is more involved in either the orientation or attention at retrieval than in retrieval. The lack of activation of the prefrontal ventrolateral cortex confirms the role of this area in episodic memory formation.

Semantic acquisition in childhood amnesic syndrome: a prospective study.

Amnesic patients can acquire new semantic knowledge despite a profound deficit of episodic memory. Although retrospective studies have been carried out on adults and children, prospective studies have been restricted to adults. The aim of the present work was to assess the acquisition of new semantic knowledge in amnesic children. The semantic protocol, composed of short, illustrated texts, was based on an original methodology which included an assessment of episodic memory on two occasions. Two amnesic children acquired new concepts despite major episodic disturbance, illustrated notably by a lack of recollection in episodic tasks. Our findings lend weight to the assumption that forming new semantic knowledge does not necessarily involve episodic memory, and provide methodological pointers for children's neuropsychological rehabilitation.

Functional subdivisions of the ascending visual pathways in the pigeon.

This study represents an attempt to examine an alternative view of the functional architecture of the ascending visual pathways in pigeons. According to this conception the pars dorsalis (GLd) of the thalamofugal system represents the lateral monocular field of view and is frontally blind to a large extent. The tectofugal system, on the other hand, processes frontal visual input within the framework of asymmetrical tectorotundal connections. As a result, the left, but not the right, rotundus should be able to integrate to an important degree the input from both eyes via the tecta of both hemispheres. Two lesion studies were conducted to test these assumptions. In the first psychophysical experiment, the visual acuity was determined in head-fixed pigeons. After thresholds were determined, stereotaxic lesions were placed in the GLd and/or the rotundus. Multiple regressions between structure specific lesion extents and postoperative threshold alterations demonstrated that only GLd lesions contributed to acuity reductions. In the second experiment the acuity threshold of pigeons under binocular and monocular conditions was determined in a conventional skinner box before GLd and/or rotundus lesions. Multiple regression analyses showed that rotundus--but not GLd lesions--contributed to performance losses. The left rotundus lesions were significantly related to threshold elevations under both monocular conditions, while the right rotundus only contributed together with the left rotundus to binocular performance. The double dissociation revealed in these experiments indicates that the ascending pathways in pigeons are functionally segregated and differentially process frontal and lateral as well as left- and right-sided inputs.

Recall and recognition memory in patients with focal frontal, temporal lobe and diencephalic lesions.

Patients with frontal, temporal lobe, or diencephalic lesions were compared with healthy controls on measures of recall and recognition memory for word lists. Exposure times were titrated to match recognition memory scores 30 s after the end of word-list presentation as closely as possible. Using this technique, we failed to find a disproportionate impairment in recall memory in either the frontal lobe lesion patients or in the amnesic (temporal lobe and diencephalic) patients, compared with healthy controls. Consistent with this finding, performance on these tasks showed highly significant correlations with anterograde memory quotients (despite the titration procedure), but not with executive/frontal function tasks. On the other hand, the frontal lobe lesion group showed disproportionate benefit in the recall of semantically categorised words, compared with unrelated words. This may indicate an impairment in retrieval or access, compared with the amnesic (temporal lobe and diencephalic) patients, and/or an inability to organise their learning of unrelated words spontaneously, compared with healthy controls.

Thalamic locus mediates hypoxic inhibition of breathing in fetal sheep.

The effects of lesions rostral to the brain stem on breathing responses to hypoxia were determined in chronically catheterized fetal sheep (>0.8 term). These studies were designed to test the hypothesis that the diencephalon is involved in hypoxic inhibition of fetal breathing. As in normal fetuses, hypoxia inhibited breathing with transection rostral to the thalamus or transection resulting in virtual destruction of the thalamus but sparing most of the parafascicular nuclear complex. Neuronal lesions were produced in the fetal diencephalon by injecting ibotenic acid through cannulas implanted in the brain. Hypoxic inhibition of breathing was abolished when the lesions encompassed the parafascicular nuclear complex but was retained when the lesions spared the parafascicular nuclear region or when the vehicle alone was injected. A new locus has been identified immediately rostral to the midbrain, which is crucial to hypoxic inhibition of fetal breathing. This thalamic sector involves the parafascicular nuclear complex and may link central O2-sensing cells to motoneurons that inhibit breathing.

The relationships between temporal lobe and diencephalic structures implicated in anterograde amnesia.

The relationship between the anterograde amnesic syndromes associated with diencephalic and temporal lobe pathology is examined in the light of recent findings. It is proposed that a common feature of anterograde amnesia is damage to part of an "extended hippocampal system" comprising the hippocampus, the fornix, the mammillary bodies, and the anterior thalamic nuclei. Damage to this system results in deficits in the recall of episodic information, the core symptom of anterograde amnesia. In contrast, lesions in this system need not disrupt tests of recognition memory when they primarily tax familiarity judgements. It is assumed that familiarity judgements depend on other regions (e.g. the rhinal cortex in the case of temporal lobe amnesia) and that the extended hippocampal system is principally involved in those aspects of recognition that are retrieval-based rather than familiarity-based. These proposals arise from new evidence on the performance of delayed nonmatching-to-sample by animals, from a meta-analysis of the performance of amnesic subjects on a test of recognition memory, and from new research into the pattern of connections between the medial temporal lobe and the medial diencephalon in primates.

Increases in sulphated glycoprotein-2 mRNA levels in the rat brain after transient forebrain ischemia or partial mesodiencephalic hemitransection.

Sulphated glycoprotein-2, thought to be involved in programmed cell death in peripheral organs, has been detected at increased levels in brain degenerative states. In this paper we have investigated the regional and cellular expression of this protein during development of brain lesion. With this aim sulphated glycoprotein-2 mRNA levels were studied in models of ischemic (transient forebrain ischemia) or mechanical (partial mesodiencephalic hemitransection) brain injuries using in situ hybridization histochemistry. Marked increases in sulphated glycoprotein-2 mRNA were observed in lesioned brains in both models. In addition, we report a shift in the regional distribution of positive cells in both lesion models 1-7 days post-lesion. After transient forebrain ischemia, sulphated glycoprotein-2 mRNA increases were always localized in selectively vulnerable regions (caudate-putamen, hippocampal formation), showing a temporal change in the pattern of intraregional distribution from less to more lesioned parts. In the case of mechanical lesion at 1 day, increased labelling had a widespread distribution on the lesioned side and was also observed on the intact side near the midline. In contrast, at 7 days increased labelling was restricted to regions directly lesioned (either areas whose input and/or output connections were severed by the transection or areas which were directly affected by the mechanical lesion). Analysis at the cellular level revealed that at both time intervals and in both lesion models most cell bodies overlain by dense clusters of specific grains were non-neuronal cells. The distribution patterns and their change over time suggest that at least some of these cells are inflammatory and phagocytic cells. The majority of degenerating neuronal cells after ischemia did not show increased levels of sulphated glycoprotein-2 mRNA. However, seven days after hemitransection and at all time intervals after transient ischemia, some cells clearly identifiable as neurons exhibited increased sulphated glycoprotein-2 mRNA levels.

Equivalent impairment of spatial and nonspatial memory following damage to the human hippocampus.

The hippocampus has sometimes been proposed to function as a cognitive map, a memory system that stores information about allocentric space. Work with experimental animals and memory-impaired patients has raised difficulties with this view by showing that the hippocampus is not performing an exclusively spatial function. However, the possibility has remained that the hippocampus plays a special role in spatial memory or a disproportionately large role in spatial memory compared to other kinds of memory. This study compared spatial and nonspatial memory in amnesic patients with lesions of the hippocampal formation or diencephalon. Subjects studied an array of 16 toy objects and were subsequently tested for object recall, object recognition, and memory for the location of the objects. Control subjects were tested after long retention intervals in order to equate their object memory performance with that of the patients. The main finding was that, when the performance of amnesic patients on the object memory tests was matched to the object memory performance of control subjects, spatial memory performance of the amnesic patients also matched the spatial memory performance of the control subjects. The results were the same for the two groups of patients. These findings suggest that the hippocampus is not especially involved in spatial memory. Spatial memory is simply one instance of a broader category of memory that requires the hippocampus. While cognitive mapping in its most abstract sense may describe hippocampal function, our results support alternative formulation, suggesting that the hippocampus is necessary for the rapid acquisition of relational, configural, or declarative (as opposed to purely spatial) information.

Psychiatry of diencephalon damages. A case report.

The diencephalon syndrome due to head injury in a 60-year-old woman is reported. The dicenphalon syndrome of the patient offered a variety of productive psychic and somatopsychic symptoms without reduction of intelligence; these included optic and acoustic hallucinations, delusions, cenesthesic hallucinations, disturbances of body schema and distinct functional disorders of the vegetative system. Autopsy findings of the brain were obtained in the 1.5 years up to her death. The problems of diencephalon syndrome related with suspected organic bases of schizophrenia and rhythmicity of diencephalogenic impulse reduction are discussed.

[Clinico-immunologic evaluation of the sequelae of closed craniocerebral injuries]. / Kliniko-immunologicheskaia otsenka posledstvii zakrytoi cherepno-mozgovoi travmy.

Sixty-four patients were examined clinically and immunologically at a long-term period following craniocerebral trauma. In patients with a history of head trauma impaired adaptation mechanisms were shown to underlie the neurologic disorders, which was reflected in changes in the natural immunity system. The severity and duration of natural resistance impairments were correlated with the gravity of clinical manifestations. The study of the time-course of natural resistance parameters allows the objective evaluation of the degree of central nervous system recovery following closed craniocerebral trauma.

[Various immunologic aspects of craniocerebral injuries]. / Nekotorye immunologicheskie aspekty cherepno-mozgovoi travmy.

The authors analysed cellular and humoral immunity in 104 patients with different types of craniocerebral injury. It was found that the T system immunity reflects the state of the main mechanisms of the organism's nonspecific resistance while its changes are determined by the level of the brain injury. A marked decrease in the T system values in the acute period of the injury with subsequent rapid restoration reflects an adequate total adaptational reaction of the organism and is characteristic of mild and moderate brain contusion. A normal or high level of cellular immunity values in the acute period of the injury with subsequent profound and prolonged immunodepression is evidence of the absence of this reaction and, consequently, of the deficiency of the nonspecific resistance mechanisms resulting from damage to the brain structures regulating these processes. Such reaction of the immune system was disclosed in severe brain contusion. The periodical character of changes in the organism's immune system after injury may serve as the basis for the therapeutic tactics.

Breathing alterations in head injured patients.

Breathing abnormalities in patients affected by acute cerebral damage are herein studied as neurological signs of localizing value for the neurological diagnosis of the level of the lesion. Incidence and types of abnormal breathing pattern correlate with neurological syndromes, and in a given neurological syndrome the presence of these alterations entails a more severe outcome. Tachypnea shows the most significant correlations from a diagnostic and prognostic point of view.

Blink reflexes in severe traumatic coma.

Blink reflexes were studied in 21 patients in coma after severe head injury. Our observations suggest that blink reflexes are a simple, objective, neurophysiological test to evaluate brainstem function. Correlations between these reflexes and the anatomoclinical stanges of coma and the Glasgow coma scale have been established. Presence of the early R1 component shows the integrity of at least a part of the pontine structures. The appearance of the late R2 component is correlated with a better chance of recovery from coma.