Biomedical subjects

H Aldskogius

Publications and source records attributed to H Aldskogius.

At least 73 records · Page 4Linked to original sources

PubMed1993

Diversity among reactive astrocytes: proximal reactive astrocytes in lacerated spinal cord preferentially react with monoclonal antibody J1-31.

An Astrocyte-specific antigen recognized by monoclonal antibody J1-31 is a more intense marker for proximal reactive astrocytes in lacerated rat spinal cord than is glial fibrillary acidic protein (GFAP). Thus, MAb J1-31 recognizes reactive astrocytes in the immediate vicinity of the lesion, whereas reactive astrocytes that are located at a distance from the lesion are not detected by immunofluorescent staining. These findings are relevant to the biochemical heterogeneity manifested respectively by reactive astrocytes located proximal and distal to a laceration-type injury of the spinal cord, and those that develop following axotomy with retrograde degeneration. Reactive astrocytes in the axotomy model are not stained with MAb J1-31, but are positive for GFAP.

Animals↗

PubMed1993

Novel surgical strategies to correct neural deficits following experimental spinal nerve root lesions.

In attempts to correct neural deficits following avulsion trauma, novel experimental strategies were developed. In rats, spinal roots were replanted superficially in the dorsal horn following dorsal root avulsion and concomitant denervation by ganglionectomy. Outgrowth from cord neurons in the dorsal horn into the implanted dorsal root was demonstrated by means of retrograde HRP labeling. Double labeling experiments showed that some of these neurons had retained their central projections while extending new processes into the implanted root. After dorsal root avulsion, sensory pathways might be reconstructed by substituting the lost input from damaged primary sensory neurons with induced peripheral outgrowths from secondary neurons. In primates, intraspinal replantation of avulsed ventral nerve roots was investigated as a surgical treatment for motor deficits that develop after severe brachial plexus injury. Two to 3 months after surgery there were EMG signs of reinnervation in previously denervated muscles, which were shortly followed by evidence of clinical recovery. A gradual improvement in the function of the affected arm occurred and motor behavior became normalized, although the EMG activity in the reinnervated muscles at maximal contraction was still reduced. The outcome of these experimental studies indicates that reconstructive surgery applied to the brachial plexus might be of value to restore functional deficits induced by traumatic spinal nerve root avulsions also in man.

Animals↗

PubMed1993

The response of central glia to peripheral nerve injury.

Microglial and astroglial cells undergo prompt responses to peripheral motor and sensory axon injury. These responses include proliferation of microglial cells as well as hypertrophy and increased levels of glial fibrillary acidic protein around the axotomized motoneurons and in the central projection territories of peripherally axotomized sensory ganglion cells. Proliferating microglial cells migrate towards reacting motoneurons, however, without directly apposing their cell membrane. Astroglial cells, on the other hand, increase their structural interrelationship with reacting motoneurons, seemingly at the expense of some presynaptic terminals. In sensory projection areas, microglial cells phagocytose degenerating axons and terminals. Beyond these observations, the functional role of the central glial cell response to peripheral nerve injury is obscure.

Animals↗

PubMed1993

Cholera toxin B-HRP and wheat germ agglutinin-HRP tracing of tensor tympani muscle motoneurons and processes in rabbits.

The brain stem position, organization and number of motoneurons innervating the rabbit tensor tympani muscle (TTM) were determined by retrograde axonal transport of cholera toxin B/horseradish peroxidase conjugate (CTB-HRP) and wheat germ agglutinin HRP conjugate (WGA-HRP) tracers. The synaptic input to the TTM motoneurons was examined with WGA-HRP. The results show the motoneurons of the TTM to be localized in a cluster ventro-lateral to the outer margin of the ipsilateral trigeminal motor nucleus (VMN) and dorso-lateral to the superior olive. The number of labeled cells was greater in the combined CTB-HRP/WGA-HRP injected cases. The TTM motoneurons were triangular and elongated in shape and smaller than those of the VMN. An extensive network of dendritic branches was present ventro-laterally in the vicinity of the superior olive. Similar, but less extensive collections of dendritic processes were observed to course dorso-medially, rostrally and caudally. Axons were observed to project first dorsally or laterally, towards the trigeminal motor root, then after a sharp turn coursed ventrally within the trigeminal motor root (VMR). Transneuronal transport of the WGA-HRP was not accomplished in any preparation, suggesting among other things, system or species differences in the effectiveness of the WGA-HRP conjugate as a transynaptic tracer. It is concluded that the TTM acoustic reflex in rabbits and other mammals, its threshold, prolonged contraction capacity, and its influence on middle ear sound transmission may be related to its demonstrated extensive synaptic field in the reflex chain, particularly in the area of the superior olive, while its many other physiological functions may be made possible by the number, location, and multi-dimensional orientation of its motoneurons and dendrites.

Animals↗

PubMed1992

WGA-HRP and choleragenoid-HRP as anterogradely transported tracers in vagal visceral afferents and binding of WGA and choleragenoid to nodose ganglion neurons in rodents.

The axonal and terminal labelling pattern in the brain stem resulting from the injection of horseradish peroxidase (HRP) conjugate of wheat germ agglutinin (WGA) or choleragenoid into the nodose ganglion of guinea pigs was examined. In addition, the binding profiles of WGA and choleragenoid in the nodose ganglion of guinea pig and rat were examined. The results show that WGA-HRP and choleragenoid-HRP (B-HRP) produce almost identical distribution of axonal and terminal labelling, the difference being some contralateral fibre labelling present only with B-HRP. However, WGA-HRP shows the strongest labelling at short survival times, whereas B-HRP requires longer postoperative survival times to reach maximum labelling intensity. All nodose ganglion neurons appear to bind WGA as well as choleragenoid although to a varying degree. The results of this and previous studies support the view that visceral sensory ganglion cells and the large light subpopulation of somatic dorsal root ganglion cells both bind choleragenoid, whereas the small dark somatic cells show affinity for WGA but rarely for choleragenoid.

Animals↗

PubMed1992

The effect of axon injury on microtubule-associated protein MAP2 mRNA in the hypoglossal nucleus of the adult rat.

High molecular weight microtubule-associated protein 2 (HW MAP2) is heavily concentrated in mature dendrites and may be critical for dendritic stability. Motor axon injury results in retraction of the dendritic tree which is associated with a decrease in MAP 2-like immunoreactivity (-LIR). Here we have shown with in situ hybridization that motor axon injury results in reduced expression of HW MAP2 mRNA in affected neurons. We conclude that axotomy induces a down-regulation of HW MAP2 synthesis.

Animals↗

PubMed1992

Collateral reinnervation and expansive regenerative reinnervation by sensory axons into "foreign" denervated skin: an immunohistochemical study in the rat.

Immunohistochemistry has been used to study, the capacity of different types of sensory axons in the saphenous nerve to extend into denervated glabrous skin territory after a chronic sciatic nerve lesion. In this study, the extension of the intact or regenerating thin peptidergic and coarse saphenous nerve fibres in adult and neonatal rats was determined. Substance P (SP) and calcitonin gene-related peptide (CGRP) antibodies were used as markers for thin axons and neurofilament (NF) antibodies for coarse axons. In addition, S-100 protein (S-100) antibodies, which primarily stain Schwann cells associated with myelinated axons, as well as innervated lamellated cells of Meissner corpuscles, were used. After a chronic sciatic nerve lesion in adult rats, thin dermal and epidermal SP-immunoreactive (IR) and CGRP-IR saphenous nerve fibres were present in an area lateral to that normally innervated by the saphenous nerve in the foot sole. In neonatally lesioned animals, thin dermal and epidermal SP-IR and CGRP-IR, as well as coarse dermal NF-IR fibres and S-100-IR cells, all of which derived from the saphenous nerve, were found in the sciatic nerve territory. In addition, some dermal SP-IR and CGRP-IR fibres were transiently present in the lateral part of the foot sole. After chronic sciatic nerve lesion and a concomitant crush injury of the saphenous nerve in adults or neonatals, thin dermal and epidermal SP-IR and CGRP-IR fibres, as well as coarse dermal NF-IR fibres and S-100-IR cells, were found in the innervation area normally occupied by the sciatic nerve. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in adult rats, the SP-IR and CGRP-IR fibres, as well as the NF-IR fibres and S-100-IR cells were restricted to the medial part of this area. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in neonatal rats, a few thin dermal SP-IR and CGRP-IR fibres were found in the lateral part of the foot sole as well. The findings of the present study together with those of previous morphological studies indicate that intact thin axons from the saphenous nerve, including those exhibiting peptide immunoreactivity, but not coarse saphenous axons, are capable of extending into "foreign" denervated glabrous skin after chronic sciatic nerve injuries. In neonatally sciatic-nerve-injured animals, both groups of axons spread from the intact saphenous nerve into the sciatic nerve territory.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1992

Splenic primary sensory afferents in the guinea pig demonstrated with anterogradely transported wheat-germ agglutinin conjugated to horseradish peroxidase.

The distribution of primary visceral afferents to the spleen of the guinea pig was studied after injections of wheat-germ agglutinin conjugated to horseradish peroxidase (HRP) into the left dorsal root ganglia at levels T7-T12. After anterograde transport of the tracer, labeled fibers were found in the nerves around the splenic artery in the hilus region and in the splenic parenchyma. The majority of labeled fibers in the spleen were detected in the white pulp. HRP-positive fibers were also observed in the red pulp and in the trabeculae. The distribution of the HRP-labeled fibers was in part similar to those of substance P-immunoreactive and calcitonin gene-related peptide-immunoreactive nerve structures. The results show that the anterograde tracing technique can be used successfully to investigate splenic primary afferent innervation.

Afferent Pathways↗

PubMed1992

The effect of axon injury on microtubule-associated proteins MAP2, 3 and 5 in the hypoglossal nucleus of the adult rat.

Microtubule-associated proteins appear to be critical elements in the stabilization of microtubules during neurite development. Axon injury results in a new burst of axonal growth activity as well as in partial dendritic involution. With this background we have examined the immunocytochemical staining pattern for microtubule-associated proteins 2, 3 and 5 in the hypoglossal nucleus of adult rats following unilateral hypoglossal nerve resection. From four days to six weeks postlesion a significant reduction in microtubule-associated protein 2-like immunoreactivity was observed in the neuropil and neuronal perikarya of the hypoglossal nucleus ipsilateral to nerve transaction. Microtubule-associated protein 5-like immunoreactivity was reduced in neuronal perikarya and neuropil four days to two weeks after injury. After six weeks microtubule-associated protein 5-like immunoreactivity had returned to normal levels. Microtubule-associated protein 3-like immunoreactivity, which was observed in glial cell perikarya and axons, but not neuronal perikarya or dendrites, appeared to be essentially unaltered. The reduced levels of microtubule-associated proteins 2 and 5 may be factors contributing to previously documented axotomy-induced dendritic retraction. The decrease in microtubule-associated protein 5 staining and absence of microtubule-associated protein 3 expression in axotomized neurons contrast with the situation in developing neurons, and demonstrate that the neuronal reaction to axon injury in mature mammals involves a specific series of events distinct from the developmental process.

Animals↗

PubMed1992

Photochemically induced transient spinal ischemia induces behavioral hypersensitivity to mechanical and cold stimuli, but not to noxious-heat stimuli, in the rat.

Pain-like sensory disorders lasting several days were observed in rats after transient ischemia in the lumbar region of the spinal cord. The ischemia was induced with a recently developed photochemical technique. Rats exhibited strong allodynia, a pain-like reaction to innocuous stimuli, to mechanical stimulation of the caudal trunk, hind limbs, and hind paws, which were areas innervated by the ischemic spinal segments. The rats also expressed hypersensitivity to cold stimuli. However, no changes in sensitivity to noxious heat could be detected with the hot-plate test. Furthermore, no morphological damage could be observed in the spinal cord at the light microscopic level in the majority of rats after transient spinal cord ischemia. The present results indicate that allodynia-like symptoms to mechanical stimuli after spinal ischemia may be mediated by myelinated afferents and could be associated with dysfunction of inhibitory transmission in the spinal cord. We suggest that this pain-related syndrome after spinal ischemia could be considered as an animal model of painful states of spinal origin.

Animals↗

PubMed1992

Centrifugal growth in orthotopic grafts of allogeneic dorsal root ganglia in adult rats: evidence for possible central ingrowth?

Fetal allogeneic dorsal root ganglion (DRG) transplants from 13-15 day rat embryo's (E13-E15) survived and differentiated when grafted orthopically (within the capsules of the excised 4th and 5th lumbar (L4-L5) ganglia) in adult rats. Survival of grafted neurones was established by prelabeling the grafts with a fluorescent vital dye (DiI) and visualizing the retained fluorescent marker 3 to 9 months later. Simultaneous retrograde tracing using fluorescent tracers applied in the spinal cord and peripheral nerve, respectively, yielded double-labeled dorsal root ganglion neurons, some of which were prelabeled. These findings demonstrate that prelabeled E13-E15 ganglia survive orthopic grafting, organotypically differentiate into mature DRG neurones, and can be double-labeled with fluorescent dyes applied to their peripherally and centrally directed processes. The presence of DiI containing cells which were retrogradely labeled from the spinal cord suggests that fetal (E13-E15) ganglia may have the capability of growing into a mature spinal cord.

Aging↗

PubMed1992

Evidence for activation of the complement cascade in the hypoglossal nucleus following peripheral nerve injury.

Following hypoglossal nerve transection in adult rats, immunoreactivity for complement factor C3 and one of its degradation products C3d as well as C4d and immunoglobulin G (IgG) was observed in the ipsilateral hypoglossal nucleus. Double-labelling experiments indicated that these antigens were present in perineuronally located reactive microglial cells. In addition, increased levels of complement factor C3-mRNA was found in perineuronally located cells ipsilateral to nerve lesion. These results suggest that the complement cascade is locally activated in the vicinity of axotomized neuronal perikarya and that microglial cells have a key role in this process, alternatively that C3, C3d, C4d and IgG are involved in other so far unknown processes.

Animals↗

PubMed1992

Chronic pain-related syndrome in rats after ischemic spinal cord lesion: a possible animal model for pain in patients with spinal cord injury.

We examined a pain-related syndrome, which includes mechanical allodynia and autotomy, in rats after ischemic spinal cord injury photochemically induced by laser irradiation for 5-20 min. This procedure results in an acute allodynia-like phenomenon which lasts for several days and is possibly related to dysfunction of the GABAB system in the spinal cord. In some animals this is followed by a chronic allodynia-like symptom with an onset varying between 1 week and 1.5 months after injury, expressed as a clearly painful reaction to light pressure applied to a skin area at or near the dermatome of the injured spinal segments. In the majority of rats the allodynia persists over several months, in some cases accompanied by autotomy of the hind paws. Pharmacological studies indicated that the allodynia in the majority of rats could be relieved by systemic tocainide (75 mg/kg). Morphine was only effective at a sedative dose (5 mg/kg). The allodynia was not relieved by baclofen, muscimol, clonidine or carbamazepine. Low-dose systemic pentobarbital (5 mg/kg) had a slight beneficial effect. Guanethidine (20 mg/kg, s.c.) did not abolish the allodynia in most of the rats. Histological examination revealed massive damage in the spinal cord. The dorsal roots of the irradiated segments were also injured. No morphological abnormalities were seen in the dorsal root ganglia. The mechanism that may account for this chronic pain-related syndrome in spinally injured rats probably involves abnormalities in the central nervous system. The allodynia seen in chronic spinally injured rats was similar to some painful symptoms in patients after spinal cord injury or stroke. It is suggested that the chronic allodynia-like phenomenon may represent an animal model for studying the mechanisms of chronic central pain.

Animals↗

PubMed1991

Ultrastructural changes in the gracile nucleus of the rat after sciatic nerve transection.

Ultrastructural changes in the gracile nucleus of the rat have been examined after peripheral nerve injury. The sciatic nerve of adult rats was transected at mid-thigh level, and after survival times ranging from 1 day to 32 weeks sections from the gracile nucleus were prepared for electron microscopic examination. Unoperated animals served as controls. Atypical profiles were regularly observed in the experimental cases at post-operative survival times from 3 days up to 32 weeks. It was sometimes not possible to classify these as preterminal axons or terminals, because synaptic contacts could not be identified. The two most common changes throughout the entire post-operative period were greatly expanded myelinated axons, or unmyelinated profiles containing numerous mitochondria, osmiophilic dense bodies and vacuoles. Atypical profiles were occasionally observed in unoperated control animals. The results clearly show that various types of degenerative changes occur in the gracile nucleus after peripheral nerve injury. These changes differ markedly from previously described transganglionic changes in other systems. It cannot be excluded that some of the changes reflect growth-related reactions, although the typical features of axon regeneration could not be found.

Animals↗

PubMed1991

The role of substance P and calcitonin gene-related peptide containing nerve fibers in maintaining fungiform taste buds in the rat after a chronic chorda tympani nerve injury.

Taste buds in the anterior part of the tongue of adult rats were denervated by unilateral resection of the chorda tympani nerve in the middle ear. Three months later one group of animals was perfused and their tongues were processed for demonstration of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactivity. Fungiform taste buds found on the denervated side showed increased numbers of intragemmal SP- and CGRP-immunoreactive (IR) fibers compared to the normal side. Compared to the normal side, the number of taste buds appeared to be fewer on the denervated side. Moreover, taste buds on this side seemed to be only partially restored. Another group of animals was given the neurotoxin capsaicin which causes a depletion of SP and CGRP from sensory axons. The animals were perfused 2 or 3 weeks after the capsaicin treatment, and their tongues prepared for SP and CGRP immunohistochemistry or for histological examination of taste buds. Very few SP- and CGRP-IR fibers were present in capsaicin-treated animals. In these animals almost all fungiform taste buds and papillae on the chorda tympani-injured side disappeared. In contrast, normal numbers of taste buds were still present on the contralateral side where the chorda tympani innervation remained intact. It is conceivable that taste buds on the chorda tympani-innervated part of the tongue, deprived of the normal chorda tympani-innervation, can regenerate and become reinnervated by SP- and CGRP-containing fibers, and that these are essential for partially restoring and maintaining the structure of the denervated taste buds and the fungiform papillae.

Animals↗

PubMed1991

The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat.

Protection by the NMDA receptor antagonist MK-801 against transient spinal cord ischemia-induced hypersensitivity was studied in rats. The spinal ischemia was initiated by vascular occlusion resulting from the interaction between the photosensitizing dye Erythrosin B and an argon laser beam. The hypersensitivity, termed allodynia, where the animals reacted by vocalization to nonnoxious mechanical stimuli in the flank area, was consistently observed during several days after induction of the ischemia. Pretreatment with MK-801 (0.1-0.5 mg/kg, iv) 10 min before laser irradiation dose dependently prevented the occurrence of allodynia. The neuroprotective effect of MK-801 was not reduced by maintaining normal body temperature during and after irradiation. There was a significant negative correlation between the delay in the administration of MK-801 after irradiation and the protective effect of the drug. Histological examination revealed slight morphological damage in the spinal cord in 38% of control rats after 1 min of laser irradiation without pretreatment with MK-801. No morphological abnormalities were observed in rats after pretreatment with MK-801 (0.5 mg/kg). The present results provide further evidence for the involvement of excitatory amino acids, through activation of the NMDA receptor, in the development of dysfunction following ischemic trauma to the spinal cord.

Amino Acids↗

PubMed1991

Allodynia-like effects in rat after ischaemic spinal cord injury photochemically induced by laser irradiation.

We report behaviours suggesting the presence of allodynia elicited by non-noxious brushing and mechanical pressure following photochemically induced ischaemic spinal cord injury in the rat. Female rats were intravenously injected with Erythrosin B and the T10 vertebra was irradiated with a laser beam for 1, 5 or 10 min. These procedures initiated an intravascular photochemical reaction, resulting in ischaemic spinal cord injury. After irradiation a clear allodynia was observed in most rats. The animals vocalized intensely to light touch during gentle handling and were clearly agitated to light brushing of the flanks. The vocalization threshold in response to the mechanical pressure measured with von Frey hairs was markedly decreased during this period. In some animals the existence of spontaneous pain was suggested by spontaneous vocalization. The duration of the allodynia varied among animals from several hours to several days. The severity and duration of allodynia seemed not to be related to the duration of irradiation. In sham-operated rats a slight, transient allodynia was also noted around the wound within a few hours after surgery, which was effectively relieved by systemic morphine (2 mg/kg, i.p.). Morphine (2 mg/kg, i.p.) also partially relieved the allodynia in spinally injured rats 4 h after irradiation. However, morphine, even at a higher dose (5 mg/kg, i.p.), failed to alleviate the allodynia in spinally injured rats 24-48 h after the injury. Systemic injection of the GABAB agonist baclofen (0.01-0.1 mg/kg, i.p.), but not the GABAA agonist muscimol (1 mg/kg, i.p.), effectively relieved allodynia during this period. Pretreatment with guanethidine 24 h and just prior to the irradiation (20 mg/kg, s.c.) did not prevent the occurrence of allodynia in spinal cord injured rats. The present observation is the first to show that ischaemic spinal cord injury could result in cutaneous mechanical allodynia. This phenomenon is resistant to morphine and may not involve the sympathetic system. Histological examination of allodynic animals 3 days after spinal cord injury revealed considerable morphological damage in the dorsal spinal cord of a rat irradiated for 5 min. The related dorsal roots were also slightly affected in this animal, while the dorsal root ganglia were normal. However, in rats irradiated for 1 min, despite the existence of strong allodynia, no damage could be found at this time in the spinal cord, dorsal roots or dorsal root ganglia. It is suggested that functional deficits in the GABAB system in the spinal cord may be related to this allodynia-like phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Synaptic detachment from hypoglossal neurons after different types of nerve injury in the cat.

Quantitative electron microscopy was used to examine synaptic numbers and total relative synaptic coverage on hypoglossal neuronal perikarya following transection or crush of the hypoglossal nerve in the cat. In cats subjected to nerve transection there was a statistically significant decrease in total synaptic coverage as well as in number of synaptic contacts/soma profile. After nerve crush there was a statistically significant decrease in total synaptic coverage but not in the number of synaptic contacts. These results indicate that the degree of synaptic detachment on motor neurons in the cat is influenced by the type of nerve injury.

Animals↗