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H Aldskogius

Publications and source records attributed to H Aldskogius.

At least 55 records · Page 3Linked to original sources
PubMed1994

Motoneuron survival is not affected by the proximo-distal level of axotomy but by the possibility of regenerating axons to gain access to the distal nerve stump.

The aim of this study was to examine whether axotomy-induced motoneuron death in adult mammals differ: (1) with the distance between the site of injury and the nerve cell body, and (2) if contact between the transected nerve stumps is established after the injury, compared with cases where contact is prevented. The hypoglossal nerve of adult rats was transected either proximally in the neck (proximal injury) or close to the tongue (distal injury). The nerve stumps were then either deflected from each other in order to prevent axon regeneration into the distal nerve stump, or sutured. Three months later, the extent of nerve cell loss was examined bilaterally in cresyl violet-stained sections of the hypoglossal nucleus. In addition, we examined hypoglossal neuron survival twelve months after a proximal nerve transection with prevented regeneration. Our results show that there was no significant difference in neuronal survival after a proximal nerve transection compared with a distal one, neither if contact between the nerve stumps was established nor if it was prevented. However, contact between the transected nerve stumps increased the likelihood of neuronal survival significantly after both proximally and distally located injury compared to nerve injury with prevented regeneration. There was no significant decrease in nerve cell survival after twelve months with prevented reinnervation compared with survival after three months. These observations indicate that the extent of axotomy-induced motoneuron death in adult mammals does correlate with the proximo-distal level of peripheral injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Decreased GABA immunoreactivity in spinal cord dorsal horn neurons after transient spinal cord ischemia in the rat.

The number of GABA-like immunoreactive (LI) cells in lamina I-III of the rat spinal cord was significantly decreased bilaterally 48-72 h after photochemical induction of transient spinal cord ischemia compared to sham-operated controls. No significant changes in the number of GABA-LI cells were observed at cervical level. The number of GABA-LI cells was restored 2 weeks after ischemia. These data, together with recent behavioral and electrophysiological findings, suggest that decreased intraneuronal GABA levels after spinal cord ischemia may underlie the development of the temporary pain-like response to innocuous mechanical stimuli (allodynia) in rats after transient spinal cord ischemia.

Animals↗
PubMed1994

BDNF and NT-3 rescue sensory but not motoneurones following axotomy in the neonate.

Following axotomy of the sciatic nerve in the neonatal rat, there is loss of almost half of the sensory neurones of the lumbar dorsal root ganglia (DRG) and a similar number of spinal motoneurones. Consistent with effects in vitro, the neurotrophins BDNF and NT-3 have previously been shown to afford partial rescue of motoneurones at 1 week following axotomy. Using stereological quantitative methods we show here that at the longer time point of 3 weeks, local application of BDNF or NT-3 to the proximal stump of a lesioned sciatic nerve failed to rescue motoneurones (44% and 51% loss, respectively), but provided almost complete rescue of the loss of 41% of DRG neurones seen in L4 and L5 of vehicle-treated control animals.

Animals↗
PubMed1994

Co-induction of neuronal interferon-gamma and nitric oxide synthase in rat motor neurons after axotomy: a role in nerve repair or death?

Induction of an interferon-gamma-like molecule, previously isolated from neurons (N-IFN-gamma), and of the neuronal isoform I of the synthetic enzyme of the free radical nitric oxide, nitric oxide synthase I, as well as of NADPH-diaphorase, were examined in axotomized dorsal motor vagal and hypoglossal neurons. Unilateral transection of the vagal and hypoglossal nerves was performed in the same rat and an induction of N-IFN-gamma and nitric oxide synthase I immunostaining as well as NADPH-diaphorase histochemical positivity was observed in the ipsilateral motoneurons after 2-4 days. The immuno- and enzyme-histochemical positivities were much stronger in the dorsal motor vagal neurons than in hypoglossal neurons. Two and 4 weeks after axotomy N-IFN-gamma immunoreactivity and NADPH-diaphorase positivity persisted in the former, but started to decrease in the latter neurons. Previous data have shown that 23 weeks after nerve transection the majority of the dorsal motor vagal neurons are lost, while the majority of the hypoglossal neurons survive. The high and persistent expression of N-IFN-gamma and nitric oxide synthase I after axotomy in the dorsal motor vagal neurons, that are largely destined to die, indicates that the co-induction of these two molecules may be implicated in the pathogenesis of neuronal degeneration.

Amino Acid Oxidoreductases↗
PubMed1994

A bromodeoxyuridine labelling study of proliferating cells in the brainstem following hypoglossal nerve transection.

The proliferative activity in the hypoglossal nucleus following hypoglossal nerve injury has been studied with the 3H-thymidine analogue, bromodeoxyuridine (BrdUrd). BrdUrd was injected into cisterna magna of the rat brain 2 h prior to killing and subsequently visualised with immunofluorescence. The peak of BrdUrd labelling in the hypoglossal nucleus occurred at 2 d following nerve transection and a lower level at 4 and 7 d postoperatively. BrdUrd labelled cells were also found outside the anatomical boundaries of the hypoglossal nucleus, conceivably mainly corresponding to the dendritic extension of the axotomised neurons. It is therefore concluded that microglial cells are activated in relation to the entire intramedullary portion of the axotomised neurons and not only in the immediate vicinity of the perikarya. Double labelling experiments with specific markers for astrocytes, oligodendrocytes and microglial cells showed that only microglial cells were BrdUrd positive at all postoperative survival times examined. It is therefore concluded that microglial cells are the only glial cell type which proliferate in the hypoglossal nucleus following peripheral nerve injury.

Animals↗
PubMed1994

The innervation of the splenic capsule in the guinea pig: an immunohistochemical and ultrastructural study.

The innervation of the capsule of the guinea pig spleen was studied by light microscopy using an indirect fluorescent-labelled antibody technique, as well as by electron microscopy. A dense network of nerve fibres immunoreactive to the general neuronal marker, protein gene product 9.5 was observed in tangential sections through the capsule corresponding to the subcapsular compartment. The PGP 9.5-immunoreactivity in the fibres appeared to a large extent to be colocalised with tyrosine hydroxylase and neuropeptide Y (NPY) immunoreactivities as well as with synaptophysin immunoreactivity. Only very occasional fibres with substance P or calcitonin-gene-related peptide immunoreactivity were observed in tangential sections of the capsular region. By electron microscopy unmyelinated nerve fibres in the capsule were found to contain a large number of small dense-cored as well as clear vesicles and large dense-cored vesicles in varicose parts of the axons. The axolemma of the varicose regions was often naked, devoid of Schwann cells, and sometimes appeared denser than the nonspecialised parts of the membrane. These naked regions were observed in single sections to be apposed to splenic cells with variable intervals of extracellular space and interposed basal lamina material. Another type of contact was characterised by a very close association with splenic cells with no basal lamina interposed between the plasma membranes of the axon and the splenic cell. An intimate ultrastructural relationship was often also seen between varicose vesicle-containing axons and neighbouring axons in the nerve fibre bundles. The results show that the splenic capsule and its immediate neighbouring regions are innervated by catecholaminergic, NPY-containing fibres, which appear to establish different types of relations with the splenic cells as well as with one another.

Animals↗
PubMed1993

The innervation of the mystacial pad of the rat as revealed by PGP 9.5 immunofluorescence.

The innervation of the mystacial pad in the rat was investigated with the aid of antihuman protein gene product (PGP) 9.5 immunofluorescence. PGP 9.5 is ubiquitin carboxyl-terminal hydrolase, which is distributed throughout neuronal cytoplasm. This technique revealed all previously known innervation as well as a wide variety of small-caliber axons and some endings of large-caliber afferents that had not been observed before. Newly revealed innervation affiliated with vibrissal-follicle sinus complexes included 1) fine-caliber, radially oriented processes in the epidermal rete ridge collar; 2) a loose network of fine-caliber, circumferentially arrayed processes in the centrifugal part of the mesenchymal sheath at the level of the ring sinus; 3) a loose haphazard network of fine-caliber and medium-caliber processes in the mesenchymal sheath and among the trabeculae of the cavernous sinus; 4) a loose network of circumferentially arrayed processes within the mesenchymal sheath of the cavernous sinus and in close proximity to the basement membrane; 5) a dense network of reticular-like endings provided by large-caliber afferents to the mesenchymal sheath in the upper part of the cavernous sinus; and 6) fine-caliber innervation to the dermal papilla at the base of all vibrissal shafts. In the intervibrissal skin, a dense distribution of fine-caliber individual and clustered profiles was detected in the epidermis. In addition to previously known innervation, Merkel endings were consistently observed in the epidermis at the mouths of guard hairs, loose networks of fine-caliber axons were found around the necks of occasional guard hairs, and fine-caliber profiles were frequently affiliated with vellus hairs. Vascular profiles were heavily innervated throughout the dermis. Axons and motor end plates of the facial nerve innervation to papillary muscles also were labeled. Transection of the infraorbital nerve eliminated all but the facial nerve innervation. Unilateral removal of the superior cervical ganglion eliminated the innervation to the dermal papillae but caused no other noticeable reduction. PGP 9.5-like immunofluorescence was also moderately expressed in apparent Schwann cells, in Merkel cells only in the external root sheath of vibrissal follicles, and in apparent dendritic and/or Langerhans cells usually located in the epidermis and occasionally in the follicles. PGP 9.5-like immunofluorescence persisted in highly vacuolated profiles along the usual courses of medium to large-caliber axons 2 weeks after nerve transection. The possible functional role of the newly discovered innervation is considered along with that of previously identified afferents.

Animals↗
PubMed1993

Evidence for activation of astrocytes via reactive microglial cells following hypoglossal nerve transection.

Following peripheral nerve injury, resident microglial cells proliferate and astrocytes undergo hypertrophy, as evidenced, e.g., by an increase in the levels of glial fibrillary acidic protein (GFAP). In a previous study we have shown that infusion of cytosine arabinoside (ARA-C) into the rat brain blocks the axotomy-induced proliferation of microglial cells. This experimental approach has been used in the present study in order to explore the issue of whether the reactive microglial cells are mediators of the increased GFAP expression in the hypoglossal nucleus of the rat following axotomy. Quantitative analysis of sections processed for immunocytochemistry or in situ hybridization demonstrated a marked increase in GFAP-like immunoreactivity and GFAP-mRNA, respectively, in the ipsilateral hypoglossal nucleus 4 and 7 days after axotomy in control experiments. These increases failed to occur in axotomized animals treated with ARA-C. Therefore, our data are compatible with the hypothesis that activation of astrocytes following axotomy as measured by increased expression of GFAP and its mRNA is induced secondarily to the microglial response.

Animals↗
PubMed1993

Primary sensory afferents in the thymus of the guinea pig demonstrated with anterogradely transported horseradish peroxidase conjugates.

After injections of wheat germ agglutinin- or B-subunit of cholera toxin-horseradish peroxidase (HRP) conjugates into the C2-C4 dorsal root ganglia of the guinea pig and anterograde axonal transport of the conjugates, labeled nerve fibers were found in the thymus mainly on the ipsilateral side. The distribution of the HRP-labeled fibers was similar to that of nerves immunoreactive to substance P and calcitonin gene-related peptide, which were partly colocalized. The results show that the thymus is innervated by primary sensory afferents which have their cell bodies in dorsal root ganglia.

Afferent Pathways↗
PubMed1993

Regeneration of hypoglossal nerve axons following blockade of the axotomy-induced microglial cell reaction in the rat.

The aim of the present study was to examine whether inhibition of the microglial cell reaction around axotomized motoneurons affects the subsequent regeneration process of the injured axons. The microglial cell reaction in the hypoglossal nucleus of the rat was blocked by infusion of cytosine-arabinoside (ARA-C) into the ventricular system. Axon regeneration was evaluated by determining the number and size distribution of myelinated axons at a defined level distal to the crush site, the number of neurons which could be retrogradely labelled from the distal stump as well as the number of motor endplates in the tongue at various times following injury. No significant difference was observed for any of these parameters between ARA-C-treated and untreated animals. Therefore, it is concluded that the microglial cell reaction is not necessary for peripheral nerves to regenerate and restore target contact at a normal rate and to a normal extent.

Animals↗
PubMed1993

Infusion of cytosine-arabinoside into the cerebrospinal fluid of the rat brain inhibits the microglial cell proliferation after hypoglossal nerve injury.

The present study describes a method to inhibit selectively the microglial cell proliferation following peripheral nerve injury. Continuous infusion of cytosine-arabinoside (ARA-C) from an osmotic minipump to the fourth ventricle or cisterna magna completely blocks the proliferation of microglial cells that normally occurs following hypoglossal nerve transection. This treatment had no significant effect on other glial cells or on the expected morphological changes in the axotomized hypoglossal motorneurons. The method opens up new possibilities for analyzing the functional role of the axotomy-induced microglial cell reaction.

Animals↗
PubMed1993

Differentiation and axonal outgrowth pattern of fetal dorsal root ganglion cells orthotopically allografted into adult rats.

Fetal allogeneic dorsal root ganglia (DRG) between 13 and 15 days (E13-E15) were transplanted into the enucleated fourth and fifth lumbar (L4, L5) ganglionic capsules of adult rat hosts. Some of the grafts were prelabeled with the vital carbocyanine dye DiI. Three to 9 months later, neuroanatomic tracers were applied singly or in combination to the sciatic nerve at a transection site 2-3 cm distal to the ganglion and to the dorsal quadrant of the spinal cord. Tissues in selected cases were stained with antibodies to calcitonin gene-related peptide (CGRP) or to neurofilament protein (antibody RT-97) as evidence of neuronal differentiation and axonal growth. In two grafted animals serial sections were made across the root-cord junction which was examined by light and electron microscopy. This material was compared to similarly prepared sections from two nongrafted animals subjected to dorsal root crush. Some grafted ganglion neurons survived for the 3-9 months of the study. Many of these cells became labeled after tracers were applied to the peripheral nerve, to the lumbar spinal cord, or to both. Additional signs of differentiation included expression of CGRP and neurofilament protein immunoreactivity in neuronal cell bodies and processes. Electron microscopic examination showed many small diameter fibers, both myelinated and unmyelinated, in the grafted root on both sides of the PNS/CNS junction. The results with this orthotopic transplantation model show that fetal DRG neurons can differentiate in an adult host and grow axonal branches into peripheral nerves as well as centrally through the dorsal root toward the spinal cord. In addition, our findings suggest that some of the centrally growing fibers cross the PNS/CNS border into the mature spinal cord.

Animals↗
PubMed1993

Synaptic density of axotomized hypoglossal motorneurons following pharmacological blockade of the microglial cell proliferation.

The purpose of the present study was to examine the possible role of reactive microglia in the removal of presynaptic terminals following motor axon injury. Quantitative electron microscopy was used to examine synaptic numbers and total relative synaptic coverage on hypoglossal neuronal perikarya following hypoglossal nerve transection in the rat with or without pharmacological blockade of the axotomy-induced microglial cell proliferation. In a previous study we have shown that the axotomy-induced microglial cell proliferation is selectively inhibited by continuous infusion of cytosine-arabinoside (ARA-C) into the ventricular system of the adult rat brain. Adopting this procedure in the present study resulted in an almost complete elimination of reactive microglia. There was a statistically significant decrease in the number of synapses and the relative synaptic coverage in untreated as well as ARA-C-treated animals 4 and 7 days after nerve transection. Immunocytochemical labeling of terminals in the hypoglossal nucleus using antibodies to synaptophysin showed a reduction in immunoreactivity around hypoglossal nerve cell bodies ipsilateral to nerve transection in both groups of animals. These results indicate that reactive microglia are not responsible for detachment of presynaptic terminals following motor axon injury.

Animals↗
PubMed1993

Combination of non-specific cholinesterase histochemistry and immunofluorescence staining for the study of the sensory innervation of skin and muscle.

In the present study we describe the application of the non-specific cholinesterase (nChE) histochemical method for the detection of encapsulated sensory nerve endings prior to immunofluorescence staining of the sensory nerve fibres. The nChE staining of Schwann-derived structures surrounding sensory terminals allowed us to identify unequivocally the sensory corpuscles in the skin and the muscle proprioceptors (muscle spindles and Golgi tendon organs) in longitudinal sections of muscle tissue. The nChE staining of sensory nerve endings and immunofluorescence-labelled nerve fibres and their terminals could be viewed and photographed in the same section using appropriate filters. Since nChE activity persists in terminal Schwann cells for a long time after loss of the sensory axons, this combined enzyme- and immunohistochemical approach is also useful for experimental studies involving denervation and re-innervation of sensory nerve endings.

Animals↗
PubMed1993

A quantitative analysis of the microglial cell reaction in central primary sensory projection territories following peripheral nerve injury in the adult rat.

The time course of the microglial cell reaction in central nervous system primary sensory projection territories has been examined following peripheral nerve injury in the adult rat using qualitative and quantitative analysis of immunoreactivity with the monoclonal antibody OX-42, which recognises the complement receptor CR3. The regions examined included the gracile nucleus, the column of Clarke and the spinal cord dorsal horn (superficial and deep laminae separately) after unilateral sciatic nerve transection, and the spinal trigeminal nucleus following unilateral infraorbital nerve transection. In all territories examined a qualitative increase in OX-42 immunoreactivity was observed 24 h postlesion. Further, quantitative analysis revealed an exponential development of the OX-42 immunoreactivity, with a peak at one week postlesion, thereafter showing a slow exponential decline. Our results show that the signal (or signals) that induces the microglial cell response in primary sensory projection territories is rapid in comparison to previously described central degenerative changes following peripheral nerve lesions (transganglionic degeneration). These findings are compatible with the hypothesis that activated microglia play a pathogenetic role in the development of transganglionic degeneration.

Afferent Pathways↗
PubMed1993

Expression of mRNAs for neurotrophin receptors in the dorsal root ganglion and spinal cord during development and following peripheral or central axotomy.

Expression of mRNAs for the protein tyrosine kinases trk, trkB and trkC, encoding essential components of high-affinity neurotrophin receptors, was studied in the spinal cord and dorsal root ganglion during normal development and in the adult rat following peripheral and central axon injury. Northern blots revealed multiple trkB transcripts in the embryonic, early postnatal and adult spinal cord with different patterns of expression during development. The levels of 9.0 kb and 4.8 kb trkB transcripts, encoding a full-length trkB receptor, increased progressively during embryonic development with maximal levels around birth, followed by a decline at adulthood. In contrast, the level of 7.5/7.0 kb trkB transcripts, encoding a truncated trkB receptor, reached maximal levels shortly after birth and similar levels remained in the adult animal. In the spinal cord a 4.7kb trkC transcript was detected with maximal levels shortly after birth. In situ hybridization revealed a uniform labeling throughout the spinal cord for both trkB and trkC mRNAs with maximal intensities of labeling shortly after birth. The level of the 2.4 kb trkB transcript in the spinal cord increased 5-fold 8 days after a crush lesion of the sciatic nerve or the dorsal root, while no change was seen in the levels of the other trkB transcripts. No change in the 4.7 kb trkC mRNA was seen following these two injuries, although increased levels of several smaller size trkC transcripts were observed. For both trkB and trkC, similar size transcripts as seen in the spinal cord were also detected in adult rat dorsal root ganglia. Consistent with previous observations of decreased levels of cytoskeletal proteins after peripheral and central axotomy, the level of neurofilment light chain mRNA decreased markedly in the dorsal root ganglia following a crush lesion of the sciatic nerve or of the dorsal root. A small decrease was also seen in the level of preprotachykinin-A mRNA encoding the protein precursor of substance P. In the same animals, the levels of all five trkB transcripts increased 3-fold in the dorsal root ganglia in response to these two injuries. A small increase was also seen in the level of trkC mRNA. The level of brain-derived neurotrophic factor (BDNF) mRNA increased two-fold in the dorsal root ganglia following either of the two lesions, while no change was detected in trk mRNA following these two injuries.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗