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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 47 (1979), S. 1-11 
    ISSN: 1432-0533
    Keywords: Experimental Concussion ; Peroxidase, neuronal uptake ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neuronal inundation with i.v. infused horseradish peroxidase was studied following concussive brain injury by means of both light and electron microscopy. In animals sustaining mechanical brain injury of insufficient intensity as to elicit either microscopic intraparenchymal hemorrhage or other neuropathological change, yet of sufficient intensity as to provoke a physiological concussive response, vascular peroxidase exudation concomitant with neuronal peroxidase inundation occurred throughout the raphe and reticular core. Initially such inundated neurons were totally flooded with the tracer and as such appeared reminiscent of cells visualized in Golgi preparations. However, over the course of a 24-h period these peroxidase flooded neurons apparently organized the peroxidase into vesicles and vacuoles which assumed a perinuclear position from where the peroxidase ultimately reached both the nucleus und nucleolus. It was remarkable that these events occurred without any evidence of subcellular alteration. We interpret such initial inundation with this protein tracer, its ultimate reorganization, and its nuclear and nucleolar uptake as being consistent with some form of subtle and transient neuronal perturbation. We speculate that as such this neuronal perturbation may constitute a morphological correlate of the concussive episode.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 76 (1988), S. 347-358 
    ISSN: 1432-0533
    Keywords: Axonal damage ; Brain trauma ; Brain parenchymal change
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Based upon recent clinical findings, evidence exists that severe traumatic brain injury causes widespread axonal damage. In the clinical setting, it has been assumed that such axonal damage is the immediate consequence of traumatically induced tearing. However, in laboratory studies of minor head injury, evidence for primary traumatically induced axonal tearing has not been found. Rather the traumatic event has been linked to the onset of subtle axonal abnormalities, which become progressively severe over time (i.e., 12–24 h). In the light of these discrepant findings, we investigated, in the present study, whether progressive axonal change other than immediate tearing occurs with severe traumatic brain injury. Anesthetized cats were subjected to high intensity fluid-percussion brain injury. Prior to injury all animals received cortical implants of horseradish peroxidase (HRP) conjugated to what germ agglutinin to anterogradely label the major motor efferent pathways. Such an approach provided a sensitive probe for detecting traumatically induced axonal abnormality via both light microscopy (LM) and transmission electron microscopy (TEM). The animals were followed over a 1- to 6-h posttraumatic course, and processed for the LM and TEM visualization of HRP. Through such an approach no evidence of frank traumatically induced tearing was found. Rather, with LM, an initial intra-axonal peroxidase pooling was observed. With time, unilobular HRP-containing pools increased in size and progressed to bi- or multilobulated profiles. Ultimately, these lobulated configurations separated. Ultrastructurally, the initial unilobular pool was associated with organelle accumulation and focal axolemmal distention without frank disruption. Over time, such organelle accumulations increased in size and sequestered into multiple pools reminiscent of the bi- and multilobulated structures seen with LM. Ultimately, these organelle accumulations became detached, resulting in physically separated proximal and distal organelle-laden swellings surrounded by a distended axolemma and thinned myelin sheath. The findings reject the hypothesis that axons are immediately torn upon impact.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Postischemic recirculation ; Complete cerebral ischemia ; Ischemic neuronal injury ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The neuronal response to complete cerebral ischemia (CCI) of 5–15 min duration was evaluated at the light and electron microscopic level subsequent to postischemic recirculation periods of up to 60 min. Following postischemic reperfusion, the homogeneous neuronal changes characteristic of permanent CCI were modified into a heterogeneous pattern of selectively vulnerable neuronal responses. Four basic types of neuronal injury were represented within this heterogeneous neuronal population. The Type I neuronal response was most numerous and consisted of chromatin clumping, nucleolar condensation and a breakdown of polysomes. This response may represent a reversal of some of the neuronal changes observed after permanent CCI. In addition to the above changes, Type II neurons contained swollen mitochondria and Golgi saccules which appeared as microvacuoles under the light microscope. Type III neurons displayed varying degrees of neuronal shrinkage and numerous swollen mitochondria. Type IV neurons were markedly shrunken and electron-dense with few identifiable subcellular structures. The distribution of Type I neurons was random but the other neuronal responses occurred in “selectively vulnerable” brain regions. The number of Type II, III, and IV neurons increased with extended insult durations but were unaffected by the length of recirculation. Ten minutes of CCI represented the threshold for a significant increase in the number of severely altered neurons. These findings suggest that considerable neuronal injury may be present after 10–15 min of CCI, and the lack of a recirculation period following CCI appears to afford the brain parenchyma an extensive degree of structural protection.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Cerebrovascular ; Acute hypertension ; Peroxidase ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of acute systemic hypertension on the intraparenchymal cerebral vasculature of cats was assessed by morphological means. Intravenous horseradish peroxidase administration coupled with light microscopy was employed to identify brain sites manifesting hypertension-induced peroxidase extravasation and therein the luminal surface of the intraparenchymal vasculature was examined with scanning electron microscopy (SEM). Comparable SEM studies were also conducted within sites reflecting no altered peroxidase permeability. Via these techniques, hypertension was recognized to evoke significant vascular change throughout the neuraxis. The luminal endothelia of that vasculature contained within the peroxidase extravasation sites demonstrated numerous plasmalemmal pits and the occasional presence of balloon- and crater-like lesions which were localized along the marginal lines. In sites demonstrating no peroxidase exudation, these plasmalemmal pits were infrequent; yet, the balloon and crater-like lesions, again localized along the marginal lines, were now conspicuous and regular endothelial features. Within the peroxidase extravasation sites, plasmalemmal pits could be identified within minutes of the onset of the hypertensive event, while in all loci endothelial balloons were observed prior to the appearance of craters. These results demonstrate that numerous plasmalemmal pits, the SEM correlates of vesicles observed with transmission electron microscopy, appear to be temporally and spatially linked to the peroxidase extravasation and as such this may suggest that these phenomena are causally linked. The significance of endothelial balloons and craters, which are most prevalent in sites not manifesting peroxidase extravasation, is unclear; however, based on a parallel study conducted in the pial vasculature, the suggestion is advanced that their appearance may be linked to the loss of microvascular autoregulation.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 70 (1986), S. 53-59 
    ISSN: 1432-0533
    Keywords: Brain trauma ; Axonal change ; Brain parenchymal change
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Traumatic head injury has long been associated with the genesis of reactive axonal change, which many believe to be a major factor in influencing neurological outcome. Although much significance has been attached to such a traumatically induced axonal change, little information exists as to whether such a reactive change occurs as an isolated event or rather as an event associated with concomitant focal tissue damage, possibly involving related neuronal somal and dendritic elements. This issue was critically assessed in mechanically brain-injured cats in which the anterograde axonal transport of horseradish peroxidase was employed to detect reactive axonal change. Following such traumatically induced reactive axonal change over a 21-day post-traumatic period, altered axons were consistently observed within the red, vestibular and reticular nuclei and any evidence for concomitant change within the related neuronal somal and dendritic elements was assessed using light and electron microscopy. Typically, such axonal change occurred without any evidence of focally related somatic or dendritic alteration. Isolated examples of reactive axons approximating neurons undergoing chromatolysis were observed. However, such neuronal chromatolytic change appeared not to be a primary response to trauma, but rather a response secondary to severence of these neurons' axonal projections. The results of this study demonstrate that, in mild to moderate head injury, reactive axonal change does occur in isolation from other forms of focal parenchymal abnormality. This finding, therefore, emphasizes the concept that the number of axons damaged is most likely related to the magnitude of any ensuing neurological abnormality.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 81 (1990), S. 162-177 
    ISSN: 1432-0533
    Keywords: Infusion edema ; Immunocytochemistry ; Clearance ; Electron microscopy ; Brain edema
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pathways and mechanisms by which edematous fluid accumulation in the extracellular space (ECS) clears from brain are poorly understood. The objective of this study was to explore, using immunocytochemical technique, the fate of a proteinaceous fluid added to the brain ECS and to study the clearance pathways. The protein movement of this edema fluid was investigated using the direct infusion model on rats. Rat albumin (20 μl) was slowly infused into the caudate-putamen of anesthetized adult rats and the spread and clearance of the edema was followed in various brain regions using immunocytochemical and conventional light and electron microscopy at 0, 1, 2, 3, 4, 6, and 8 days post-infusion. Our studies showed that protein-rich edema fluid cleared slowly from the brain, with 8 days required for the infusion albumin to exit completely from the brain parenchyma. Immediately following infusion, the albumin was distributed in the ECS of the white matter and the overlying deep cortical layers related to the infusion site. During the next 24 h, more of the infused albumin traveled through the ECS to the cortical surface where the albumin passed through the glia limitans to reach the subarachnoid front. Additionally, at 48 h post-infusion, that albumin, which had migrated to the ventricular wall, cleared from the ECS of the subependymal white matter and the ependymal clefts to reach the ventricular cerebrospinal fluid (CSF). In edematous regions, the perivascular spaces of venules and veins were filled with reaction product. Continuity of this perivascular reaction product existed from the deep edematous area to the temporobasal subarachnoid space from where the reaction product gradually disappeared from the parenchyma. From these studies we infer that during the late state of the resolution process the edema front moves toward both the ventricle and the cortical surface to reach the CSF. Thus, among the potential routes for edema clearance, the pathways leading to CSF clearance of fluid predominated. During this clearance process, neither neurons, glia nor the vascular endothelium showed any endocytotic response to the infused albumin throughout the 8-day course. We conclude from these observations that the CSF pathway is the major route of protein-rich edema clearance, when such clearance is not complicated by any concomitant CNS perturbation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Traumatic brain injury ; Hypothermia ; Blood-brain barrier ; Hypertension ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of moderate hypothermia on blood-brain barrier (BBB) permeability and the acute hypertensive response after moderate traumatic brain injury (TBI) in rats were examined. TBI produced increased vascular permeability to endogenous serum albumin (IgG) in normothermic rats (37.5°C) throughout the dorsal cortical gray and white matter as well as in the underlying hippocampi as visualized by immunocytochemical techniques. Vascular permeability was greatly reduced in hypothermic rats cooled to 30°C (brain temperature) prior to injury. In hypothermic rats, albumin immunoreactivity was confined to the gray-white interface between cortex and hippocampi with no involvement of the overlying cortices and greatly reduced involvement of the underlying hippocampi. The acute hypertensive response in normothermic rats peaked at 10 s after TBI (187.3 mm Hg) and returned to baseline within 50 s. In contrast, the peak acute hypertensive response was significantly (P〈0.05) reduced in hypothermic rats (154.8 mm Hg, 10 s after TBI) and returned to baseline at 30 s after injury. These results demonstrate that moderate hypothermia greatly reduces endogenous vascular protein-tracer passage into and perhaps through the brain. This reduction may, in part, be related to hypothermia-induced modulation of the systemic blood pressure response to TBI.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 31 (1975), S. 1447-1449 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The present study clearly demonstrates that by the 15th week of gestation dense core vesicles appear within the human cerebral cortex. These vesicles can be identified within axon cylinders, axon growth cones, and axon synaptic terminals. The role of these vesicles is speculative, yet, their very presence at this early fetal stage seems to reflect an advanced state of synaptic vesicle development.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1106
    Keywords: Brain trauma ; Degeneration ; Neuroplasticity ; GABAergic synapses ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Terminal loss and recovery were assessed in the cat dorsal lateral vestibular nucleus (dLVN) following diffuse axonal damage caused by experimental traumatic brain injury. Using sterile technique, anesthetized adult cats received a moderate fluid-percussion traumatic brain injury. After predetermined survival periods of 7–368 days, the animals were perfused and the dLVN prepared for the immunocytochemical visualization of GABAergic puncta/terminals at the light (LM) and electron (EM) microscopic levels. In controls, the Deiters' neuronal somata within the dLVN were encompassed by numerous GABA-immunoreactive puncta/terminals. Within 7 days of injury, axonal damage was seen scattered throughout the dLVN, and associated with this, some neuronal somata demonstrated a dramatic loss of perisomatic GABA-immunoreactive puncta, while other somata appeared unchanged. Ultrastructural examination demonstrated that the loss of immunoreactive puncta observed with LM was directly correlated with the presence of degenerating GABAergic terminals. Overall, these neuronal somata showed a reduction of perisomatic puncta/terminals to values approximately 25% of controls. Over a thirty day posttraumatic course, this pattern of scattered perisomatic puncta/terminal loss persisted, with some puncta/terminal return by 60 days postinjury. During the next six months, a recovery of the immunoreactive puncta/terminals was observed in relation to the deafferented somata, with perisomatic terminal numbers now reaching 75% of control values. Over the 7 to 12 month postinjury period, recovery continued, with virtually complete recovery observed in the later phases of this period. Importantly, throughout this recovery period, there was a consistent correlation between the light and electron microscopic findings. The observed diffuse pattern of terminal loss, followed a prolonged adaptive recovery process, suggests that traumatic injury with its attendant diffuse axonal injury and related diffuse deafferentation creates a unique environment for rather complete and adaptive synaptic recovery. As diffuse axonal injury is a common feature of human traumatic brain injury, we believe that these studies, performed in cat, help explain some of the initial morbidity as well as some of the partial recovery seen in head-injured man.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0533
    Keywords: Key words Regeneration ; Diffuse axonal injury ; GAP43 ; Neurofilament ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Traumatic brain injury in animals and humans is well known to cause axonal damage diffusely scattered throughout the brain without evidence of other brain parenchymal change. This observation has prompted some to posit that such damaged axons are well positioned to mount a regenerative attempt. The present study uses an immunocytochemical marker specific for regenerating neurites to explore this issue. Further, in an attempt to expedite and enhance any potential regenerative effort, this study evaluates the efficacy of intrathecally applied nerve growth factor. Three sets of experiments were performed in adult cats. One group of animals was subjected to moderate fluid percussion brain injury and followed for 7 or 14 days post injury, with the continuous intraventricular infusion of nerve growth factor delivered by implanted osmotic pumps. These animals were compared to a second group of time-matched, sham-operated animals receiving artificial cerebrospinal fluid infusion. To assess axonal damage immunohistochemical staining for the low molecular weight neurofilament subunit (NF-L) was carried out using an NR4 monoclonal antibody. To localize axons exhibiting a regenerative response immunohistochemical staining for the growth associated protein GAP43 was employed. In sham controls, at the light microscopic level NF-L-immunoreactive axonal swellings were numerous at 7 days, but by 14 days post injury their frequency declined markedly. In contrast, GAP43-immunoreactive, disconnected reactive axonal swellings were rarely observed at 7 days but were numerous at 14 days. Ultrastructural analysis at 14 days post injury of carefully matched sections revealed reactive axons demonstrating sprouting consistent with a regenerative effort. Analysis of tissue from animals of 14 days of survival indicated that supplementation with nerve growth factor did not appear to enhance the capacity of damaged brain axons to mount a regenerative attempt. Rather, it appears that regenerative efforts seen reflect a spontaneous response. A third group of adult cats, subjected to the same injury but not subjected to osmotic pump implantation, was allowed to survive for 22–28 days. Animals in this group also demonstrated GAP43 immunoreactivity in reactive axonal swellings in the brain stem. This study demonstrates that diffusely injured axons can mount a sustained regenerative attempt that is associated with a reorganization of their cytoskeleton and accompanied by an up-regulation of growth-associated proteins.
    Type of Medium: Electronic Resource
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