Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Diffuse Axonal Injury”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed2006

Ex vivo measurement of brain tissue viscoelasticity in postischemic brain edema.

Knowledge of the biomechanical properties of postischemic brain tissue is important for understanding the mechanisms of postischemic secondary brain tissue injury. We describe the method and results of biomechanical property measurement in ex vivo postischemic brain tissue by applying an indentation method. Mongolian gerbils were subjected to a transient unilateral hemispheric ischemia. At day 1 after ischemia, multi-parametric MRI was performed, the brain was removed under anesthesia, sliced, and kept in a container with silicone oil for the measurement. A compression probe attached to a pressure transducer was inserted to a pre-determined depth at the regions of interest and maintained at a constant speed. A pressure relaxation curve was recorded for the calculation of elasticity modulus (E) and viscosity modulus (eta) according to Maxwell-Voigt's 3-element model. One day after ischemia, E and eta decreased to 78.7% and 73.1% of the control level, respectively. This decrease corresponded to a mild decrease in apparent diffusion coefficient (ADC) and magnetization transfer ratio, and an increase in T2 value. Tissue water content increased to 105.1% of control. Microvacuolation with demyelination and axonal disruption was evident in the postischemic brain tissue.

Animals↗
PubMedDate not supplied

Therapy study on the experimental injury of spinal cord. IV. High doses of methyl-prednisolone.

The effect of large glucocorticosteroid hormones administered to two groups of adult rabbits with an experimental acute injury of the spinal cord was studied. In the former (10 rabbits), each animal received intravenous 30 mg/kg body weight of prednisolone-21-sodium-hemisuccinate after 30 minutes and further 15 mg/kg b.w. at intervals of 2, 24 and 48 hours since injury. In the latter (40 rabbits), each animal received 15 mg/kg b.w. methyl-prednisolone-21-hydrogen-sodium-hemisuccinate at 30 min, 2, 24 and 48 h postinjury. A group of 20 injured rabbits with the same experimental conditions was used as controls without glucocorticoid treatment. Clinically, both treated groups of rabbits showed a significant improvement of posterior limb movements and in the general state of health compared with the controls. The mean motor score (according to a 5-score scale) indicated a significant difference between the two treated groups (2.3 and 2.6, respectively and 1.7 for the controls). Histologically, the modifications correlated with the clinical posttraumatic symptomatology and severity in all the three groups: histopathological modifications consisted in oedema, ischaemic cells, diffuse microglial hyperplasia, microhaemorrhages, all of them located in the central gray matter. In all cases with a severe clinical evolution (score of 1-3), aggravated histopathological modifications both in the gray and white matter are evidenced: necrosis; vacuolization; cavitation; myelinic and axonal fragmentation, demyelination, mesenchymo-glial scar reaction. In all groups, regenerated nervous fibres were noticed in the dense scar of the injured cord.

Animals↗
PubMedDate not supplied

Development of a bioartificial nerve graft. II. Nerve regeneration in vitro.

A promising alternative for the repair of peripheral nerve injuries is the bioartificial nerve graft, or BNG, comprised of a tubular conduit preseeded with Schwann cells, which are an effective substrate for enhancing nerve regeneration. The physical properties of the conduit, porosity and wall thickness, as well as the Schwann cell seeding density, were tested for their effect on axon growth using rat dorsal root ganglia. These parameters can influence the amount of nutrients and growth factors made available to the neural tissue. Results show that a greater wall thickness and lower porosities have a detrimental effect on the growth of the axons. Over a four week period, axons extended 3.2 mm for the optimum case (DeltaR = 0.82 mm, epsilon = 0.75) compared to 1.8 and 1.6 mm for a lower porosity (0.55) and a greater wall thickness (1.4 mm), respectively. A maximum in the growth rate occurs at a porosity of 75% for Schwann cell seeded conduits but not for unseeded ones. When compared to mass transfer predictions, the results suggest that, at higher porosities, more growth factors diffuse out of the conduit, while at low porosities there is competition for nutrients. Increasing the Schwann cell seeding density enhances growth but also leads to an increase in the number of axons along the length of the conduit. This is indicative of branching of the axons, which requires additional resources to maintain and can lead to painful neuroma formation. Wall thickness and porosity were found not to have any significant effect on the axon number sprouting from the dorsal root ganglia and the mean diameter (p > 0.05). Considerations need to be made, not just on the polymer used, but also on its porosity, wall thickness, and Schwann cell seeding density. These parameters can be adjusted to create a bioartificial nerve graft that provides the optimal environment for nerve growth.

Analysis of Variance↗
PubMed2003

Preterm children have disturbances of white matter at 11 years of age as shown by diffusion tensor imaging.

Preterm birth frequently involves white matter injury and affects long-term neurologic and cognitive outcomes. Diffusion tensor imaging has been used to show that the white matter microstructure of newborn, preterm children is compromised in a regionally specific manner. However, until now it was not clear whether these lesions would persist and be detectible on long-term follow-up. Hence, we collected diffusion tensor imaging data on a 1.5-T scanner, and computed fractional anisotropy and coherence measures to compare the white matter integrity of children born preterm to that of control subjects. The subjects for the preterm group (10.9 +/- 0.29 y; n = 9; birth weight or= 2500; gestational age, >or= 37 wk). We found that the preterm group had lower fractional anisotropy values in the posterior corpus callosum and bilaterally in the internal capsules. In the posterior corpus callosum this difference in fractional anisotropy values may partially be related to a difference in white matter volume between the groups. An analysis of the coherence measure failed to indicate a group difference in the axonal organization. These results are in agreement with previous diffusion tensor imaging findings in newborn preterm children, and indicate that ex-preterm children with attention deficits have white matter disturbances that are not compensated for or repaired before 11 y of age.

Anisotropy↗
PubMed1993

Close apposition among neighbouring axonal endings in a neuroma.

Axons in intact peripheral nerve trunks constitute independent afferent and efferent communication channels. However, when nerves are severed, several different forms of axon-axon cross-excitation develop in association with the injury site. In this study we have examined experimental sciatic nerve-end neuromas in rats with special interest in the compartmentalization of individual axons, and the barriers that separate close neighbours. At postinjury times at which functional coupling is known to occur, neuromas were found to contain many examples of axons in which adjacent membrane faces come into close contact without an intervening Schwann cell process. These occur in bundles containing from two to as many as 30 individual nerve fibres wrapped in a common Schwann cell sheath. The surface area of close apposition between axon pairs ranges up to several tens of micron2. Closely apposed axon profiles may be outgrowing branches of a single parent axon, but anterograde tracer data indicate that many belong to independent neurons. Closely apposed axons are separated from one another, and from associated Schwann cell processes, by a cleft about 130 A wide. No synapses, gap junctions or tight junctions were observed. Extracellular tracer studies using La3+ and Ruthenium Red indicated that the cleft system is patent, permitting the free diffusion of small molecules between the space adjacent to the axolemma and the bulk extracellular compartment. Together, these data provide a structural basis for interfibre interactions based on local electrical current flow (ephaptic crosstalk), as well as coupling mediated by K+ ions and neurotransmitter molecules.

Animals↗
PubMed2003

Three-dimensional MRI of cerebral projections in rat brain in vivo after intracortical injection of MnCl2.

In this study we investigated the potential of in vivo MRI detection of axonal Mn2+ transport for tracing neuronal projections originating in the sensorimotor cortex in healthy and lesioned rat brains. Special attention was given to the potential of visualizing neuronal sprouting of central nervous system across the midline. After injecting unchelated MnCl2 into the forelimb area of sensorimotor cortex of 18 healthy and 10 lesioned rats corticofugal projections could be traced through the internal capsule to the cerebral peduncle and the pyramidal decussation. Although the neuronal tract was visible as early as 6 h after MnCl2 injection, best contrast was achieved after 24-48 h. Beside the cortico-spinal tract, the cortico-thalamic fibres were also visualized by anterograde Mn2+ transport. Cortico-striatal fibres were partially masked by the very high signal near the MnCl2 injection site but could be discerned as well. Slight, diffuse signal enhancement of cortical tissue contralateral to the MnCl2 injection site in healthy rat brains suggests interhemispheric connections or passive diffusion of Mn2+. However, enhanced fibre tract contrast connecting both hemispheres was visible 16 weeks after onset of focal photothrombotic cortical injury. In conclusion our study has shown that we were able to visualize reproducibly the main descending corticofugal projections and interhemispheric connections by non-invasive MRI after localized injection of MnCl2. The appearance of interhemispheric Mn2+-enhanced fibres after photothrombotic focal injury indicates that the method may bear potential to follow non-invasively gross plastic changes of connectivity in the brain after injury.

Animals↗
PubMed1985

[Intrahypothalamic connections of the lateral hypothalamus].

Using the axon degeneration method by R. Fink and L. Heimer, organization of intrathalamic connections between various areas of the lateral hypothalamus have been studied after unisided electrolitic lesion. At any location of the injury foci, similar patterns are observed in ipsilateral distribution of degenerating fibers along the whole lateral preoptico-hypothalamic area. The most massive degeneration is observed in the zone where the medial forebrain bundle (MFB) fibers run. The degenerating fibers spread forward--into the septal area, and backward--into the mesencephalic part of the brain. The rostral and caudal parts of the lateral hypothalamus, taking part in formation of the MFB collateralies towards the thalamus, are connected with various thalamic nuclei. Massive preterminal degeneration in the perifornical zone and single argerophile granules in the medial hypothalamus convincingly demonstrate an important role of the intermediate zone for connections of its medial and lateral parts with each other. The conclusion that the intrahypothalamic connections of the lateral hypothalamus are realized within the MFB system supports the modern notion on a close connection of the lateral hypothalamus with the system of longitudinal diffuse bundles of fibers of the medial anterocerebral pathway that run through it.

Animals↗
PubMed2004

The relationship between diffuse axonal damage and fatigue in multiple sclerosis.

BACKGROUND: Fatigue is a common and distressing symptom for patients with multiple sclerosis (MS). There is growing evidence that fatigue in MS has a central nervous system component. We hypothesized that diffuse cerebral axonal damage could be associated with fatigue and used proton magnetic resonance spectroscopy to noninvasively measure axonal damage or loss in the brains of patients with MS. OBJECTIVE: To assess the strength of the relationship between central brain N-acetylaspartate and fatigue. DESIGN: Data from 73 patients who had undergone proton magnetic resonance spectroscopy imaging and completed the Fatigue Severity Scale questionnaire were analyzed. RESULTS: The N-acetylaspartate-creatine ratio (NAA/Cr) was significantly lower in the high-fatigue group than the low-fatigue group (mean +/- SD, 2.69 +/- 0.29 and 2.99 +/- 0.33, respectively. P =.003). Independent of the Kurtzke Expanded Disability Status Scale, T2 lesion volume, age, and disease duration, NAA/Cr was significantly lower in the high-fatigue group as compared with the low-fatigue group. There was a statistically significant linear correlation between the Fatigue Severity Scale scores and NAA/Cr (Spearman rank rho = -0.361, P =.02). CONCLUSIONS: The results of this study, combined with those of others, suggest that widespread axonal dysfunction is associated with fatigue in MS. Increased recruitment of cortical areas and pathways in response to brain injury may be responsible for the patient's sense that the effort required to perform actions is disproportionately high.

Adult↗
PubMed1999

Neuropathological sequelae of traumatic injury in the brain. An overview.

The identification and interpretation of brain damage resulting from head injury is often not easy. The most obvious structural damage, which is identified post-mortem by neuropathologists, may not be the most reliable alteration with regard to clinico-pathological correlations. For example patients with a fracture of the skull, a severe cerebral contusion or a large intracerebral hematoma that is successfully treated can lead to a complete recovery if no other types of brain damage are present. Thus more subtle forms of pathology, which are often present and some of which can only be identified microscopically, may be more important. It is therefore necessary to get deeper insights into the consequences of brain injury. Though of course not exclusively, this aim can be reached by autopsy. Primary traumatic brain lesions result immediately from mechanical injury. Secondary alterations injuries develop through intracranial and extracranial trauma sequelae, which determine the course and outcome of brain damage. Traumatic brain damage can be classified as focal or diffuse. It may sometimes be difficult to distinguish traumatic from ischemic brain injury. One difference, however, is that the initial events of trauma involve mechanical distortion of the brain. Mechanoporation as traumatic defect in the cell membrane has recently been found to be one of the first steps which leads via ionic influxes to the activation of immediate early genes. Oxygen radicals and cell membrane lipid peroxidation occur also very early. Increased intracellular calcium, activation of phospholipases and calpains furthermore damage the membrane and cytoskeleton and block the axoplasmatic transport, by which delayed cell death can appear. For the description of the extent of traumatically induced brain damage and the possible clinico-pathological correlations it is necessary to take these alterations into consideration as specifically as possible. Neuropathology can contribute to this aim.

Animals↗
PubMed1990

Implantation of cultured sensory neurons and Schwann cells into lesioned neonatal rat spinal cord. II. Implant characteristics and examination of corticospinal tract growth.

The purpose of this study was to test the effectiveness of implants derived from peripheral neural tissue to serve as bridges following interruption of the developing corticospinal tract (CST). Implants prepared from purified populations of cultured dorsal root ganglion neurons (DRGNs) and Schwann cells (SCs) (Kuhlengel et al., J. Comp. Neurol. 293:63-73, 1990) were placed into thoracolumbar regions of neonatal rat spinal cord from which a 2-mm length of dorsal columns had been removed by suction. These cords were examined by a number of techniques 10 days to 6 months later. The implants, recognizable by their DRGN content, filled the vacated dorsal columns and survived the longest periods examined. The most effective method to maintain implant position was dorsal placement of collagen-coated Nitex filter. Implants were inserted either at the time of lesioning or 5 days later. The implant survival rate was better (72% vs. 50%) and meningeal scarring was less with immediate implantation, but delayed implantation resulted in better implant-cord fusion and the implant better filled the lesion cavity. DRGN/SC implants became well vascularized without leptomeningeal cells; this may explain why implant survival was not improved with leptomeningeal cell addition. Particularly well-differentiated implants (full extracellular matrix production and myelination) did not fuse as well with cord as did those less well differentiated. The addition of nerve growth factor to the Nitex filter collagen coating led to improved survival of DRGNs in implants. Electron microscopy showed that astrocytes populated the implant-cord junction region and migrated into implants. Typical SCs related to nonmyelinated and myelinated axons were present in implants. Close proximity of astrocytes and central myelin to SCs and peripheral myelin demonstrated good implant integration with cord. Clusters of SCs, astrocytes, and axons, all enclosed within a common basal lamina, were observed in implants. Immunostaining for GFAP and laminin confirmed our microscopy findings that SCs did not migrate from implant into host but that astrocytes left host tissue to enter implants. Neuroanatomical tracing of CST neurons with HRP-WGA showed that labeled fibers were not present in the implant but were fasciculated just beneath in gray matter. These fibers remained clustered in gray matter underneath the ventral dorsal columns caudal to the lesion. In lesioned but not implanted rats, labeled fibers were only diffusely distributed in gray matter. Delayed implantation led to more variation in fasciculation compared with immediate implantation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1976

Retrograde transport of horseradish peroxidase in transected axons. 3. Entry into injured axons and subsequent localization in perikaryon.

Horseradish peroxidase (HRP) applied to crushed mouse sciatic nerves diffused through the damaged perineurium into the endoneurium. In the injured area, HRP passed into damaged myelinated and unmyelinated axons forming columns of reaction product, which extended for several millimeters proximally to the lesion. Ultrastructurally, HRP adhered to the inner surface of the axoplasm and to the surfaces of neurotubules and neurofilaments in such columns. At more proximal levels axons contained HRP in vesicular and tubular organelles and, later, nerve cell bodies of the corresponding spinal ganglia showed HRP, accumulation in cytoplasmic vesicles, cup-shaped bodies, multivesicular bodies and tubules of agranular endoplasmic reticulum. Markedly less HRP reached neurons in the spinal ganglia when applied to the nerve 30 or 60 min after the crush. After such time intervals solid HRP containing axons were also less frequently observed. Conceivably, HRP enters crushed axons momentarily after a crush as an injured cell reaction. Subsequently it is incorporated into organelles higher up in the axons, from where retrograde transport to the perikaryon will fellow. This phenomenon of a sudden non-specific influx of exogenous macromolecules into axotomized neurons and their subsequent transport to the perikaryon might be relevant for development of certain biochemical and morphological responses, e.g. lysosomal alterations, of the neuron to an axonal injury.

Animals↗
PubMed1994

Synaptic pathology and glial responses to neuronal injury precede the formation of senile plaques and amyloid deposits in the aging cerebral cortex.

The cerebral cortices of macaques (ranging in age from 10 to 37 years; n = 17) were analyzed by immunocytochemistry and electron microscopy to determine the cellular and subcellular localizations of the amyloid precursor protein and beta-amyloid protein, the cellular participants in the formation of senile plaques and parenchymal deposits of the beta-amyloid protein, and the temporal/spatial development of these lesions. Amyloid precursor protein was enriched within the cytoplasm of pyramidal and nonpyramidal neuronal cell bodies in young and old monkeys. In the neuropil, amyloid precursor protein was most abundant within dendrites and dendritic spines; few axons, axonal terminals, and resting astrocytes and microglia contained the amyloid precursor protein. At synapses, amyloid precursor protein was found predominantly within postsynaptic elements and was enriched at postsynaptic densities of asymmetrical synapses. The earliest morphological change related to senile plaque formation was an age-related abnormality in the cortical neuropil characterized by the formation of dense bodies within presynaptic terminals and dendrites and an augmented localization of the amyloid precursor protein to astrocytes and microglia. In most monkeys > 26 years of age, the neocortical parenchyma exhibited neuritic pathology and plaques characterized by swollen cytoplasmic processes, interspersed somata of neurons, and reactive glia within or at the periphery of senile plaques. Neurites and reactive astrocytes and microglia within these plaques were enriched with the amyloid precursor protein. In diffuse plaques, nonfibrillar beta-amyloid protein immunoreactivity was visualized within cytoplasmic lysosomes of neuronal perikarya and dendrites and the cell bodies and processes of activated astrocytes and microglia. In mature plaques, beta-amyloid protein immunoreactivity was associated with extracellular fibrils within the parenchyma; some cytoplasmic membranes of degenerating dendrites and somata as well as processes of activated glia showed diffuse intracellular beta-amyloid protein immunoreactivity. We conclude that morphological abnormalities at synapses (including changes in both pre- and postsynaptic elements) precede the accumulation of the amyloid precursor protein within neurites and activated astrocytes and microglia as well as the deposition of extracellular fibrillar beta-amyloid protein; neuronal perikarya/dendrites and reactive glia containing the amyloid precursor protein are primary sources of the beta-amyloid protein within senile plaques; and nonfibrillar beta-amyloid protein exists intracellularly within neurons and nonneuronal cells prior to the appearance of extracellular deposits of the beta-amyloid protein and the formation of beta-pleated fibrils.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed2002

Functional redundancy of ventral spinal locomotor pathways.

Identification of long tracts responsible for the initiation of spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. Pathways derived from the mesencephalic locomotor region and pontomedullary medial reticular formation responsible for fictive locomotion in decerebrate preparations project to the thoracolumbar levels of the spinal cord via reticulospinal axons in the ventrolateral funiculus (VLF). However, white matter regions critical for spontaneous over-ground locomotion remain unclear because cats, monkeys, and humans display varying degrees of locomotor recovery after ventral SCIs. We studied the contributions of myelinated tracts in the VLF and ventral columns (VC) to spontaneous over-ground locomotion in the adult rat using demyelinating lesions. Animals received ethidium bromide plus photon irradiation producing discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, VC, VLF-VC, or complete ventral white matter (CV). Behavior [open-field Basso, Beattie, and Bresnahan (BBB) scores and grid walking] and transcranial magnetic motor-evoked potentials (tcMMEP) were studied at 1, 2, and 4 weeks after lesion. VLF lesions resulted in complete loss or severe attenuation of tcMMEPs, with mean BBB scores of 18.0, and no grid walking deficits. VC lesions produced behavior similar to VLF-lesioned animals but did not significantly affect tcMMEPs. VC-VLF and CV lesions resulted in complete loss of tcMMEP signals with mean BBB scores of 12.7 and 6.5, respectively. Our data support a diffuse arrangement of axons within the ventral white matter that may comprise a system of multiple descending pathways subserving spontaneous over-ground locomotion in the intact animal.

Animals↗
PubMed1994

Astrocytes inhibit Schwann cell proliferation and myelination of dorsal root ganglion neurons in vitro.

Schwann cells promote the regrowth of nerve fibers in both the PNS and CNS and might thus be of value in strategies to promote repair following injury or demyelination in the CNS. The effectiveness of Schwann cells in promoting repair could, however, be limited by interactions with reactive astrocytes that are prominent at lesioned and demyelinated sites. To investigate this possibility, experiments were performed to determine the influence of cortical astrocytes on Schwann cell proliferation and myelination of dorsal root ganglion (DRG) neurons in vitro. DRG neurons from embryonic rats and Schwann cells, astrocytes, and fibroblasts isolated from the sciatic nerve, cerebral cortex, and cranial periosteum, respectively, of neonatal rats were purified and then recombined to provide neuron-Schwann cell, neuron-Schwann cell-astrocyte, and neuron-Schwann cell-fibroblast cultures. Astrocytes inhibited both neuron-dependent Schwann cell proliferation and the myelination of axons by Schwann cells. The expression of galactocerebroside, but not of the O4 antigen, was inhibited by astrocytes, suggesting that astrocytes blocked Schwann cell differentiation prior to the onset of myelination. Ultrastructural analysis of the cultures also indicated that both axonal ensheathment and the segregation of large axons into 1:1 relationships were decreased in the presence of astrocytes. Astrocytes did not affect the expression of the basal lamina components type IV collagen and laminin, and basal lamina formation assessed by electron microscopy was only slightly decreased. Some of these inhibitory effects appear to be mediated by diffusible factors since astrocyte-conditioned medium also reduced Schwann cell myelination. Fibroblasts or fibroblast-conditioned medium did not induce such inhibitory effects, indicating that the effects were astrocyte specific. We conclude that cortical astrocytes release a soluble factor(s) that inhibits specific aspects of neuron-Schwann cell interactions leading to myelination.

Animals↗
PubMed1983

Deposition of scar tissue in the central nervous system.

Standard parasagittal lesions were placed stereotactically in the cerebral hemispheres of neonatal and adult rats in order to compare scarring in the immature and mature animal. Lesions were examined by light and electron-microscopy and immunofluorescence to study the astrocyte reaction, collagen deposition, and the formation of the basement membrane of the glia limitans. Normal mature scarring characterized by the deposition of collagen, astrocyte end-feet alignment over a glia limitans, and the permanent presence of mesodermal cells (fibroblasts and macrophages) in the core of the lesion, does not occur in wounds before 8-10 days post-partum (dpp). Instead there is no deposition of collagen, and only a transitory astrocyte response occurs with the formation of an interrupted glia limitans. These latter features disappear with time so that the wound is ultimately obliterated by the growth of axons and dendrites through the lesion. Mature scarring is attained over 8-12 dpp when increasing amounts of collagen are deposited and a continuous permanent glia limitans is formed. The acquisition of the mature response to injury from 8-12 dpp may be correlated with the presence of increasing titres of a fibroblast growth factor (FGF), derived from autolytic digestion of injured brain tissue. We have investigated FGF activity using a 3 T 3 fibroblast tissue culture assay to detect mitogenic activity in brain extracts from rats lesioned at different ages and from leukodystrophic mice which have no myelin. Our results show that high titres of FGF are present in the developing brain long before myelination commences, and that normal levels of FGF are found in the brains of leukodystrophic mice which have no myelin. Scarring in brain lesions in these mutants is quite normal.

Animals↗
PubMed2004

Increased expression of vasopressin v1a receptors after traumatic brain injury.

Experimental evidence obtained in various animal models of brain injury indicates that vasopressin promotes the formation of cerebral edema. However, the molecular and cellular mechanisms underlying this vasopressin action are not fully understood. In the present study, we analyzed the temporal changes in expression of vasopressin V1a receptors after traumatic brain injury (TBI) in rats. In the intact brain, the V1a receptor was expressed in neurons located in all layers of the frontoparietal cortex. The V1a receptor-immunoreactive product was predominantly localized to neuronal nuclei and had both a diffused and punctate staining pattern. The V1a receptors were also expressed in astrocytes, especially in layer 1 of the frontoparietal cortex. In these cells, two distinctive patterns of immunopositive staining for V1a receptors were observed: a diffused cytosolic staining of cell bodies and processes and a clearly punctate staining pattern that was predominantly localized to the astrocytic cell bodies. The real-time reverse-transcriptase polymerase chain reaction analysis of changes in mRNA for the V1a receptor demonstrated that after TBI, there is an early (4 h post-TBI) increase in the number of transcripts in the ipsilateral frontoparietal cortex, when compared to the contralateral hemisphere or the sham-injured rats. This increase in the message was followed by the up-regulation of expression of the V1a receptors at the protein level. This was most evident in cortical astrocytes in the areas surrounding the lesion. The number of the V1a receptor-immunopositive astrocytes in the traumatized parenchyma gradually increased, starting at 8 h and peaking at 4-6 days after TBI. Furthermore, a redistribution of V1a receptors from the astrocytic cell bodies to the astrocytic processes was observed. In addition to astrocytes, an increased expression of V1a receptors was found in the endothelium of both blood microvessels and the large-diameter blood vessels in the frontoparietal cortex ipsilateral to injury. This increase in the V1a receptor expression was apparent between 2 and 4 days after TBI. As early as 1-2 h following the impact, there was also a striking increase in the number of the V1a receptor-immunopositive beaded axonal processes, with greatly enlarged varicosities, that were localized to various areas of the injured parenchyma. It is suggested that the increased expression of V1a receptors plays an important role in the vasopressin-mediated formation of edema in the injured brain.

Animals↗
PubMed1990

[Experimental head injury of rabbits using pendulum impactor. An electron microscopic study].

Brain damage in the early stage of experimental head injury was studied under electron microscope, especially with respect to the permeability of the blood brain barrier and damage to nerve fibers. Lightly anesthetized rabbits were treated by intravenous injection of horseradish peroxidase (150-250 mg/kg) and were subjected to occipital impacts with a pendulum impactor. The animals were then perfused with a 2.5% glutaraldehyde mixture. Small blocks of the brain were sampled, incubated, postfixed, and embedded in Epon. These sections were observed under an electron microscope without staining. The authors' criteria of concussion have been previously published. There were three nonconcussion, 11 nonlethal concussion and seven lethal concussion animals. All cases of lethal concussion showed subarachnoid hemorrhage (SAH) in the brainstem and 57% of them showed microscopic parenchymal perivascular hemorrhages in the brainstem. Fifty-five percent of the nonlethal concussion cases showed SAH in the brainstem with a little parenchymal hemorrhage. The nonconcussion cases showed no hemorrhagic change except contusions and/or SAH of the cerebellum. Hemorrhagic changes were frequently seen in the cerebrum and cerebellum of nonlethal and lethal concussion cases without correlation to the severity of concussion. Under electron microscope, nonconcussion cases showed mild splitting of myelins. In nonlethal concussion cases, swelling of perivascular astrocytic feet was seen to a moderate degree in the cerebrum, pons, and medulla oblongata and damage to axons and myelins were mainly seen in the pons and medulla oblongata. Many cored dense bodies containing peroxidase were diffusely recognized in vascular endothelial cells. In lethal concussion cases, beside findings seen in nonlethal concussion, intravascular peroxidase was seen to leak from the intravascular space through an opened tight junction to the extracellular space, axons and neurophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Radiation response of the rat cervical spinal cord after irradiation at different ages: tolerance, latency and pathology.

PURPOSE: The investigation of the age dependent single-dose radiation tolerance, latency to radiation myelopathy, and the histopathological changes after irradiation of the rat cervical spinal cord. METHODS AND MATERIALS: Rats, ages 1-18 weeks, were irradiated with graded single doses of 4 MV photons to the cervical spinal cord. When the rats showed definite signs of paresis of the forelegs, they were killed and processed for histological examination. RESULTS: The radiation dose in paresis due to white matter damage in 50% of the animals (ED50) after single dose irradiation was about 21.5 Gy at all ages > or = 2 weeks (mean 21.4 (mean 21.4 Gy; 95% CI 21.0, 21.7 Gy). Only the ED50 at 1 week was significantly lower (19.5 Gy; 18.7, 20.3 Gy). The latency to the development of paresis clearly changed with the age at irradiation, from about 2 weeks after irradiation at 1 week to 6-8 months after irradiation at age > or = 8 weeks. The white matter damage was similar in all symptomatic animals studied. The most prominent were areas with diffuse demyelination and swollen axons, often with focal necrosis, accompanied by glial reaction. This was observed in all symptomatic animals, irrespective of the age at irradiation. Expression of vascular damage appeared to depend on the age at irradiation. No vascular damage was observed in the rats irradiated at 1 week, clearly altered blood vessels were seen in animals symptomatic 10 weeks after irradiation at > or = 3 weeks, and vascular necrosis occurred after > or = 6 months in some rats irradiated at > or = 8 weeks. CONCLUSION: Although the latency to myelopathy is clearly age dependent, single dose tolerance is not age dependent at age > or = 2 weeks in the rat cervical spinal cord. The white matter damage is similar in all symptomatic animals studied, but the vasculopathies appear to be influenced by the age at irradiation. It is concluded that white matter damage and vascular damage are separate phenomena contributing to the development of radiation myelopathy, expression of which may depend on the radiation dose applied and the age at irradiation.

Age Factors↗