Biomedical subjects

Hans-Arne Hansson

Publications and source records attributed to Hans-Arne Hansson.

12 recordsLinked to original sources

PubMed2006

Calvarial bone healing under spring distension at continuous forces.

The aim of the present study was to evaluate in young animals the dynamics of calvarial bone healing when exposing a bone defect to continuous forces for up to 13 weeks. Six-week-old rabbits after a sagittal suture strip craniectomy were randomized for either of the following protocols: (1) no spring was applied (n = 7); (2) a titanium-molybdenum alloy (TMA) lower-force spring was inserted across the craniectomy gap (n = 9); (3) a stainless steel (SS) higher-force spring was applied (n = 8), or (4) sham operation (n = 8). Results showed that the surgically created calvarial bone gap was after 3 weeks kept widened both when a spring of lower force (TMA) and when a spring exerting a higher force (SS) was applied. At 6 weeks, none of the rabbits of the spring-exposed (2 and 3) groups had any bone bridging the gap, while bone bridging was visible in animals of the 2 groups (1 and 4) lacking springs. Strikingly enough, in both spring-treated groups, the surgically created defect was still after 13 weeks incompletely bridged by bone, interposed by connective tissue, most evidently in those exposed to higher forces (SS). In contrast, a normal sagittal suture enclosed by lamellar bone was seen in both the sham and the strip groups. We conclude that exposing a surgically created calvarial bone defect to continuous mechanical forces delayed the bridging of the bone defect by at least 13 weeks, even if the force exerted by either spring was very low. In any case, when a higher force (SS group) was applied, the bone reunion was efficiently prevented. No side effects were recognized.

Animals↗

PubMed2005

Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA(A) dysregulation and impaired spatial learning.

During pregnancy, infection or immune responses induce cytokine release, which might influence fetal neurodevelopment, leading to neurodegenerative disease in adulthood. Because the hippocampus is a key area for learning and memory, we evaluated 4- and 24-wk-old rats for the effects of early and late prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology, expression of mRNA for IL-6, the gamma-aminobutyric acid receptor (GABA(Aalpha5)), the NR1 subunit of the N-methyl-D-aspartate receptor, and glial fibrillary acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning abilities. Late exposure increased serum IL-6 and hippocampal expression of IL-6 mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the hilus and astrogliosis; males had losses mainly in the CA2 and CA3 regions, and females in CA1. Expression of GABA(Aalpha5), NR1, and GFAP mRNA increased in late-exposed males and females at 4 and 24 wk. mRNA and protein levels of the apoptosis marker caspase-3 were increased in all late-exposed rats except males at 4 wk. Evaluation of hippocampus-dependent working memory in the Morris water maze at 20 wk of age showed increases in escape latency and time spent near the pool wall in all IL-6 adult rats, especially females. These findings suggest that fetal IL-6 exposure, especially in late pregnancy, leads to increased IL-6 levels in the circulation and hippocampus, abnormalities of hippocampal structural and morphology, and decreased learning during adulthood.

Adrenocorticotropic Hormone↗

PubMed2005

Vertebral fractures and separations of endplates after traumatic loading of adolescent porcine spines with experimentally-induced disc degeneration.

BACKGROUND: Abnormalities of the intervertebral discs have been found in a high frequency among young elite athletes. Several studies have also reported that the adolescent spine, especially the vertebral growth zones, is vulnerable to trauma. However, there is incomplete knowledge regarding the injury mechanism of the growing spine. In this study, the injury patterns of the adolescent porcine spine with disc degeneration were examined. METHODS: Twenty-four male pigs were used. A degenerative disc was created by drilling a hole through the cranial endplate of a lumbar vertebra into the disc. Two months later the animals were sacrificed and the degenerative functional spinal units (segments) were harvested. The segments were divided into three groups and exposed to axial compression, flexion compression or extension compression to failure. The load and angle at failure were measured for each group. The segments were examined with magnetic resonance imaging and plain radiography before and after the loading and finally examined macroscopically and histologically. FINDINGS: The degenerated segments required considerably more compressive load to failure than non-degenerated segments. Creating a flexion injury required significantly more load than an extension injury. Fractures and/or separations of the endplates from the vertebral bodies were seen at the margins of the endplates and in the growth zone. Only severe separations and fractures could be seen on plain radiography and magnetic resonance imaging. INTERPRETATION: The weakest part of the adolescent porcine lumbar spine with experimentally-induced degeneration, when loaded in axial compression, flexion compression or extension compression, was the growth zone, and, to a lesser extent, the endplate. Degenerated discs seem to withstand higher mechanical loads than non-degenerated discs, probably due to altered stress distribution.

Aging↗

PubMed2005

Detection of beta-endorphin in the cerebrospinal fluid after intrastriatal microinjection into the rat brain.

We have investigated to what extent microinjected beta-endorphin could migrate from the rat brain parenchyma into the CSF compartment. Exogenous rat beta-endorphin (0.1 nmol) was microinjected into the left striatum 1 mm from the lateral ventricle in anesthetized male rats. CSF samples were collected at different time points up to 2 h post-injection from a catheter affixed to the atlanto-occipital membrane of the cisterna magna. Radioimmunoassay and mass spectrometry were performed on the CSF samples, and brain sections were immunostained for beta-endorphin and mu-opioid receptors. The beta-endorphin injected rats showed a marked increase in beta-endorphin immunoreactive (IR) material in the CSF, with a peak at 30-45 min post-injection, and this beta-endorphin-IR material existed mainly as the intact beta-endorphin peptide. The immunohistochemistry results revealed the appearance of distinct beta-endorphin-IR cell bodies in the globus pallidus and the bed nucleus of stria terminalis supracapsular part, regions distant from the injection site, at 2 h post-injection of exogenous beta-endorphin. The beta-endorphin-IR in several of the globus pallidus cell bodies colocalized with the mu-opioid receptor-IR at the cell surface. These findings show that upon delivery of synthetic beta-endorphin, there is a significant intracerebral spread of the injected peptide, reaching regions far from the site of injection via diffusion in the extracellular space and flow in the cerebrospinal fluid. This may be of relevance when interpreting studies based on intracerebral injections of peptides, and advances our knowledge regarding the migration of compounds within the brain.

Animals↗

PubMed2005

Characterization of cell proliferation in the adult dentate under normal conditions and after kainate induced seizures using ribonucleotide reductase and BrdU.

Ribonucleotide reductase (RNR), an enzyme for DNA synthesis, was recently used as a marker of proliferating cells in the dentate gyrus and subventricular zone in normal adult mammalian brains. However, the duration of RNR expression in normal adult brain and the expression pattern of RNR in the adult dentate gyrus following brain injury have not been explored. In this study, we examined the duration of the RNR expression in newborn cells in the normal adult rat brain by analysis of RNR and BrdU double-labeled specimens at different time intervals after BrdU application. Secondly, we induced, in adult rats, seizures by kainic acid and investigated the changes in expression of RNR following seizures, and characterized the phenotype of RNR-positive cells using a variety of other markers. Our results revealed that RNR was detectable in proliferating cells from 2 h to at least 1 day. At 7 and 28 days after seizures, there was a fivefold increase in number of clusters of RNR-positive cells in the dentate gyrus, and a doubling of the number of BrdU-labeled cells in each cluster. Proliferating astrocytes and neuronal precursors were recognized in each RNR-positive cell cluster, and both types increased in number after seizures. Colocalization of RNR and activated caspase-3 was observed at 7 days, indicating that proliferating cells were susceptible to status epilepticus induced damage. RNR immunohistochemistry provides a useful approach in experiments investigating a change in cell proliferation, revealing the location, number, morphology and fate of newly formed cells after, e.g., brain injury.

Animals↗

PubMed2005

Transient, powerful pressures are generated in the brain by a rotational acceleration impulse to the head.

A rotational acceleration impulse to a head, as occurs at traffic accidents, sport injuries, assaults and falls, induces a diffuse brain damage that eventually could result in persistent neuropsychiatric deficits and neurodegeneration. Emphasis has been concentrated on the relative motion of the brain inside the skull during head impact, whereas less attention has been paid to whether intracranial pressure changes are generated and, if so, the implications thereof. In the present experimental study we investigated in an animal model system, based on rabbits, if a sagittal, anterior-posterior rotational acceleration of a head generated intracranial pressure changes, recorded by fibre optic pressure sensors, inserted ipsilaterally in the parieto-temporal and the occipital lobes. Two levels of rotational acceleration were used in the experiments; one higher, corresponding to the threshold limit for moderate diffuse brain injury, and one lower, close to being noninjurious. Several pressure recordings were performed in each rabbit at the two acceleration levels. The pressure recordings invariably revealed the same general characteristics of rapid, positive and negative pressures within the brain, with variations in amplitude and duration, lasting for up to 10 ms. A major finding was the generation of powerful negative pressures, as low as 0.3 bars in absolute pressure. The most prominent difference in amplitudes of the negative peak pressures between the two applied acceleration levels was demonstrated at the parieto-temporal location. The presented pressure recordings are the first to disclose the generation of transient, powerful intracerebral pressures at rotational acceleration of the head, which must be considered in studies of brain injury generation and distribution as well as prevention.

Acceleration↗

PubMed2003

Visualization of proliferating cells in the adult mammalian brain with the aid of ribonucleotide reductase.

Proliferating cells are hardly detectable in the adult mammalian brain by microscopy of stained sections, but after pre-labeling with radioactive thymidine or 5'-bromo-2-deoxyuridine (BrdU), either marks the nucleus, as do mitosis-related proteins such as Ki67 and PCNA. Engineered virus may also be used to mark proliferating cells. One alternative approach is to use the enzyme ribonucleotide reductase (RNR), expressed by proliferating cells, but not by quiescent ones. A monoclonal antibody against the M1 subunit of RNR was used to visualize proliferating cells in the brains of adult normal rats, rabbits, pigs and sheep. Stem cells were distinctly outlined. In the subgranular layer in the hippocampal dentate gyrus, most RNR immunoreactive cells were bipolar to multipolar, and had a large cell body and long processes. Two different populations of RNR expressing cells were visualized in the subventricular zone in the forebrain, one dominated by small, bipolar cells extending into the rostral migratory stream, while the other was formed by large multipolar cells, adjacent to the ependyma, with processes extending to the lateral ventricle. Furthermore, rare RNR-expressing cells were recognized throughout the brain. The RNR immunoreactive cells were immature, as they did not express any marker characterizing differentiated neurons and glial cells, except for a fraction that co-expressed the gliofibrillary acidic protein. BrdU and RNR were co-localized in proliferating cells in animals pretreated with BrdU. We conclude that RNR immunohistochemistry can accurately visualize proliferating cells, including stem cells, in adult mammalian brains. The occurrence of processes at cell proliferation is elucidated. Further, the advocated approach does not require any pre-labeling, and can be carried out on fixed tissues.

Animals↗

PubMed2003

Redistribution of neurofilaments and accumulation of beta-amyloid protein after brain injury by rotational acceleration of the head.

Rotational acceleration of the head, as occurs in falls, car crashes, and sport injuries, may result in diffuse brain damage, with acute and chronic neurological and psychiatric symptoms. The present study addresses the effects of rotational trauma on the neuronal cytoskeleton, which stabilizes perikaryal, dendritic and axonal shape and function. The study focuses upon the distribution of (1) the phosphorylated form of the heavy neurofilament subunit, (2) the light neurofilament subunit, and (3) beta-amyloid, a marker for brain injury. While normally restricted to axons, the phosphorylated heavy neurofilament subunits were drastically decreased in the axons after rotational trauma. Instead, they accumulated in the neuronal perikarya, normally devoid of the phosphorylated subunit. This alteration was seen, not only in the cerebral cortex, but also in the hippocampus, the cervical spinal cord, the cerebellum, the cranial nerves and the pyramidal tract. The distribution of the light subunit of neurofilaments was also altered post trauma. Only a weak beta-amyloid immunoreactivity was detected in the brains of control animals. Promptly after the trauma, a large number of beta-amyloid positive neurons appeared. Intensely co-localized immunoreactivity for the light subunit of neurofilaments and of beta-amyloid was seen 3 days after the rotational trauma axons of in the subcortical white matter and in the granule cell layer of the dentate gyrus as well as in neurons of the hypoglossal nucleus. The reported alterations in the central nervous system neurons are similar to those in the human brain after closed head injury and in chronic degenerative diseases. Regions of importance for social behavior, memory and body movement were affected.

Acceleration↗

PubMed2003

Impulse noise transiently increased the permeability of nerve and glial cell membranes, an effect accentuated by a recent brain injury.

A single exposure to intense impulse noise may cause diffuse brain injury, revealed by increased expression of immediate early gene products, transiently altered distribution of neurofilaments, accumulation of beta-amyloid precursor protein, apoptosis, and gliosis. Neither hemorrage nor any gross structural damage are seen. The present study focused on whether impulse noise exposure increased the permeability of nerve and glial cell membranes to proteins. Also, we investigated whether a preceding, minor focal surgical brain lesion accentuated the leakage of cytosolic proteins. Anaesthetized rats were exposed to a single impulse noise at either 199 or 202 dB for 2 milliseconds. Transiently elevated levels of the cellular protein neuron specific enolase (NSE) and the glial cytoplasmic protein S-100 were recorded in the cerebrospinal fluid (CSF) during the first hours after the exposure to 202 dB. A surgical brain injury, induced the day before the exposure to the impulse noise, was associated with significantly increased concentrations of both markers in the CSF. It is concluded that intense impulse noise damages both nerve and glial cells, an effect aggravated by a preexisting surgical lesion. The impulse of the shock wave, i.e. the pressure integrated over time, is likely to be the injurious mechanism. The abnormal membrane permeability and the associated cytoskeletal changes may initiate events, which eventually result in a progressive diffuse brain injury.

Animals↗

PubMed2002

Exposure to short-lasting impulse noise causes neuronal c-Jun expression and induction of apoptosis in the adult rat brain.

Exposure to impulse noise, above a certain intensity, is harmful to auditory function. Effects of impulse noise on the central nervous system (CNS) are largely unexplored, and there is little information on critical threshold values and time factors. We have recently shown that neurofilament proteins are affected in the cerebral cortex and the hippocampus. Now we show that impulse noise induces expression of the immediate early gene c-Jun products, proposed to play a role in the initiation of neuronal death, and apoptosis as revealed by TUNEL staining. Rat brains were investigated immunohistochemically 2 h to 21 days after exposure to impulse noise of 198 dB or 202 dB. c-Jun was expressed in neuronal perikarya in layers II-VI of the temporal cortex, the cingulate and the piriform cortices at 2 h to 21 days after both exposure levels. Granule neurons of the dentate gyrus and the CA1-3 in the hippocampus pyramidal neurons were similarly affected. The elevated expression of c-Jun products remained high at all postexposure times. TUNEL staining was positive among the same nerve cell populations 6 h after exposure and persisted even at 7 days at both exposure levels.

Animals↗

PubMed2002

Expression of c-Fos and c-Myc and deposition of beta-APP in neurons in the adult rat brain as a result of exposure to short-lasting impulse noise.

There is increasing evidence that impulse noise causes brain damage, but little is known about the mechanisms and extent of the response. Here, rat brains were investigated immunohistochemically for the expression of c-Fos, c-Myc, and beta-APP during the first 3 weeks postexposure to impulse noise of 198 or 202 dB. The expression of c-Fos and c-Myc increased at 2 h after exposure in neurons of the cerebral cortex, thalamus, and hippocampus, and this c-Fos immunoreactivity remained elevated for the entire observation period. The c-Myc immunoreactivity peaked at 18 h in both neurons and astrocytes but returned to control levels at 7 days. Abnormal deposition of beta-APP was evident within 6 h in the same brain regions. The beta-APP immunoreactivity was most prominent at 18 h and remained increased over the 21-day period assessed. The observed effects were similar to those described in humans following traumatic brain injury and in Alzheimer's disease. We conclude that impulse noise influences the brain in a fashion similar to that in cases with progressive CNS degeneration.

Amyloid beta-Protein Precursor↗

PubMedDate not supplied

Immunohistochemical staining patterns using epitope-specific antibodies indicate conformation variants of antisecretory factor/S5a in the CNS.

Antisecretory factor (AF/S5a/Rpn10) was originally identified through its ability to counteract pathological secretion. AF is also a potent anti-inflammatory agent, a neuromodulator, and an important component of the proteasome. Human AF has a calculated molecular mass of 41 kDa and a pI of 4.7. No family of AF-like proteins has been identified. AF has multiple functions in the cell, and different functional forms could exist as a result of post-translational modifications. Epitope-specific antibodies covering the entire length of AF were used to investigate whether modified forms of AF could be detected in the porcine spinal cord by Western blots, 2D gels, and immunohistochemistry (IHC). Western blot and 2D gels showed that all antisera detected a single protein with very similar molecular mass and pI. However, IHC resulted in an epitope-specific subcellular staining pattern. Antisera recognizing epitopes in the N-terminal part of AF, containing the antisecretory activity, showed a more restricted localisation than antisera directed at the C-terminal part, containing the ubiquitin-binding sites. We suggest that AF can exist in several conformational variants, perhaps due to differences in redox state and/or pH in the various cellular compartments. Such conformational changes could be of functional importance.

Amino Acid Sequence↗