Biomedical subjects

J K Persson

Publications and source records attributed to J K Persson.

14 recordsLinked to original sources

PubMed2000

Photochemically-induced ischemic injury of the rat sciatic nerve: a light- and electron microscopic study.

Lesion of presumably ischemic origin of the rat sciatic nerve was induced photochemically by laser irradiation combined with systemic administration of a photosensitizing organic dye, erythrosin B. We have studied the pathologic features of the nerve after the photochemical insult with light- and electronmicroscopy and related them to behavioral signs of neuropathic pain. At the irradiated nerve site, occlusion of blood vessels was seen and the vessels were packed with aggregated thrombocytes, fibrins and deformed erythrocytes, supporting the notion that photochemical reaction caused intraneural ischemia. The degree of the nerve injury at the center of irradiation was related to the duration of the laser exposure. Brief irradiation (30 seconds) only caused identifiable injury to myelinated fibers, whereas longer irradiation (2 minutes) caused greater injury to myelinated and unmyelinated fibers, characterized by extensive axonal degeneration and demyelination. The rats irradiated for 2 minutes, but not 30 seconds, exhibited neuropathic pain-like behaviors, expressed as mechanical and cold allodynia. The nerve injury was most severe 7 days after ischemia and regeneration of both myelinated and unmyelinated fibers was observed 3 months later. The nerve caudal to the irradiation exhibited Wallerian degeneration 7 days after the insult, whereas at 10 mm proximal to the irradiation the nerve was largely normal. It is thus concluded that photochemically induced intraneural ischemia caused injury to both myelinated and unmyelinated fibers, with myelinated fibers being more susceptible. However, the development of neuropathic pain-like behaviors may require injury to the unmyelinated fibers.

Animals↗

PubMed2000

Physiological changes in pigs exposed to a blast wave from a detonating high-explosive charge.

The aim of this project was to study respiration, circulation, and brain activity in pigs during and after a blast wave exposure. Ten anesthetized pigs were used. Seven were exposed to blast and three were controls. Physiological parameters of respiration and circulation as well as cortical activity were followed from 30 minutes before until 120 minutes after the real or simulated blast. There were no significant changes in heart rhythm, cardiac output, arterial oxygen or carbon dioxide tension, blood pH, or mixed venous saturation during the experiment. The blast exposure caused intestinal injuries but no lung damage. A transient flattening of the electroencephalogram was seen immediately after the blast in four experimental animals, in contrast to the unchanged baseline electroencephalogram of the control animals. This momentary depression of cortical activity accompanied by short-lasting apnea indicates a blast wave-induced effect on the brainstem or higher controlling center.

Animals↗

PubMed1999

Microvascular lung tissue oxygenation--a methodological study in the pig.

The objective of the present study was to investigate the possibility of measuring lung tissue oxygen pressure (PtO2) distributions at the microvascular level, and also if a change in the lung tissue oxygenation could be detected during hypoventilation (50% reduction in ventilatory settings). Experiments were carried out on eight mechanically ventilated ketamine-anaesthetised pigs. A thoracotomy was performed through the third right intercostal space. PtO2 measurements were made using a Clark-type multiwire microelectrode placed onto the pleural surface of the middle lobe. PtO2 was measured during normoventilation, hypoventilation (3 minutes) (reduction of respiratory volume/minute and frequency by 50%), and a second period of normoventilation. Baseline PtO2 was 5.8 (range 4.4 to 10.3) kPa and decreased to 2.9 (range 1.6 to 4.2) kPa during hypoventilation, associated with some PtO2 values close to zero. The PtO2 increased to 5.4 (range 3.6 to 8.4) kPa during the second normoventilatory period, some values still close to zero. This study demonstrates that lung tissue PO2 registrations can be made in a suitable animal (pig) model, and that hypoventilation induced an almost reversible decrease in lung tissue oxygen pressure distributions. In addition, no microscopically visible tissue damage was inflicted by the electrode on the underlying lung surface.

Animals↗

PubMed1998

Photochemically-induced ischemia of the rat sciatic nerve produces a dose-dependent and highly reproducible mechanical, heat and cold allodynia, and signs of spontaneous pain.

Sensory abnormalities and changes in spontaneous behavior were examined after a photochemically induced ischemic lesion of the rat sciatic nerve. Male adult rats were anesthetized and the sciatic nerve was exposed. After the intravenous injection of a photosensitizing dye, erythrosin B, the exposed nerve was irradiated just proximal to the nerve trifurcation with light from an argon laser. Three different irradiation times were used, 30 s, 1 and 2 min. In sham-operated rats, the exposed sciatic nerve was irradiated for 2 min without prior injection of the erythrosin B. Rats were tested for the presence of mechanical, cold and heat allodynia or hyperalgesia. All the animals in the 1- and 2-min irradiation groups developed mechanical, cold and heat allodynia after nerve irradiation. A significant dose-dependent effect of laser exposure time was observed for all modalities tested (2 min > 1 min > 30 s = sham). The maximum effects were observed at 3 and 7 days postirradiation and remained present for up to 10 weeks. No significant contralateral effects were observed in any of the groups. In three separate groups of rats (1, 2 and 4 min of laser exposure), the presence of possible signs of spontaneous pain (paw shaking, paw elevation and freezing behavior) was tested. A significant and exposure time-dependent increase in spontaneous paw elevation and paw shaking was observed which was maximal at week 1, but resolved at 4 weeks (4 min > 2 min > 1 min > sham). In addition, animals in all ischemic groups, but not in the sham group, showed a significant increase in freezing behavior up to 4 weeks after nerve irradiation. Light microscopic evaluation of nerves removed 7 days post-irradiation, i.e. when maximal allodynia was observed, showed clear evidence of demyelination of large myelinated fibers. These data indicate that photochemically-induced peripheral nerve ischemia is associated with abnormal pain-related behaviors, including mechanical, thermal and cold allodynia and signs of spontaneous pain. The incidence and severity of the behavioral changes are clearly dependent on the exposure time and are probably due to, at least in part, a demyelinaton. These results partly confirm previous data using a similar technique and suggest that this may represent a new animal model for peripheral neuropathy of ischemic origin. The advantages of the present model are its good reproducibility and the fact that the nerve injury can be easily quantified and graded.

Animals↗

PubMed1998

Glial cell responses, complement, and clusterin in the central nervous system following dorsal root transection.

We have examined the glial cell response, the possible expression of compounds associated with the complement cascade, including the putative complement inhibitor clusterin, and their cellular association during Wallerian degeneration in the central nervous system. Examination of the proliferation pattern revealed an overall greater mitotic activity after rhizotomy, an exclusive involvement of microglia in this proliferation after peripheral nerve injury, but, in addition, a small fraction of proliferating astrocytes after rhizotomy. Immunostaining with the phagocytic cell marker ED1 gradually became very prominent after rhizotomy, possibly reflecting a response to the extensive nerve fiber disintegration. Lumbar dorsal rhizotomy did not induce endogenous immunoglobulin G (IgG) deposition or complement expression in the spinal cord dorsal horn, dorsal funiculus, or gracile nucleus. This is in marked contrast to the situation after peripheral nerve injury, which appears to activate the entire complement cascade in the vicinity of the central sensory processes. Clusterin, a multifunctional protein with complement inhibitory effects, was markedly upregulated in the dorsal funiculus in astrocytes. In addition, there was an intense induction of clusterin expression in the degenerating white matter in oligodendrocytes, possibly reflecting a degeneration process in these cells. The findings suggest that 1) complement expression by microglial cells is intimately associated with IgG deposition; 2) axotomized neuronal perikarya, but not degenerating central fibers, undergo changes which induce such deposition; and 3) clusterin is not related to complement expression following neuronal injury but participates in regulating the state of oligodendrocytes during Wallerian degeneration.

Animals↗

PubMed1997

A quantitative analysis of the glial cell reaction in primary sensory termination areas following sciatic nerve injury and treatment with nerve growth factor in the adult rat.

The time course of the astroglial cell reaction in the nucleus gracilis and the spinal cord dorsal horn was examined following sciatic nerve transection in the adult rat with qualitative and quantitative analysis of glial fibrillary acidic protein immunoreactivity and in situ hybridization for its mRNA. In addition, the potential effect of exogenous nerve growth factor (NGF) was examined on the astroglial and microglial cells in the spinal cord dorsal horn at certain time points following sciatic nerve transection. An increase in glial fibrillary acidic protein immunoreactivity as well as mRNA labelling was observed from 1 day after lesioning, with a peak at about 1 week and 2 days after lesioning, respectively, followed by a decline. However, NGF application during 1, 2 and 4 weeks following nerve transection did not result in any significantly reduced astroglial or microglial activity. Our results show that the astroglial cell response in the nucleus gracilis and the spinal cord dorsal horn is rapid in comparison with previously described central degenerative changes following peripheral nerve lesions (transganglionic degeneration), that the astroglial cell reaction develops concomitantly with the microglial cell reaction previously described and that the "signal" from the axotomized neurons which induces these reactions can not be prevented by exogenous NGF applied to the peripheral nerve.

Animals↗

PubMed1997

Surgical treatment of skin lesions induced by sulfur mustard ("mustard gas")--an experimental study in the guinea pig.

Sulfur mustard has been known as a chemical warfare agent since 1915 and its biological effects, e.g. acting as an alkylating agent reacting with nucleophiles in proteins and nucleic acids, are well known. Still, there is today no specific antidote against or treatment of sulfur mustard induced cutaneous lesions. Recently, a technique of treating thermal burns with early surgical excision followed by skin grafting has been established. The present study was undertaken to evaluate, if a similar technique could be of value in the treatment of sulfur mustard lesions. Under anaesthesia, guinea pigs were exposed to sulfur mustard vapour, followed six hours later by excision of the exposed skin segment. In animals where the skin defect was primary sutured, healing time was significantly shorter and increase in body mass greater compared to conservatively treated controls. No such differences were found if excision was followed by full thickness skin grafting. Further studies in other species are suggested to clarify the possible role of surgical excision of sulfur mustard skin lesions, followed by skin transplantation, in humans.

Animals↗

PubMed1995

The expression of different cytochemical markers in normal and axotomised dorsal root ganglion cells projecting to the nucleus gracilis in the adult rat.

Rat lumbar dorsal root ganglion neurones projecting to the nucleus gracilis in the brainstem were retrogradely labelled with Fluoro-Gold and analysed immunocytochemically for their expression of substance P-, calcitonin gene-related peptide-, galanin-, galanin message-associated peptide-, neuropeptide Y-, nitric oxide synthase- and carbonic anhydrase-like immunoreactivity as well as affinity to Griffonia (bandeiraea) simplicifolia lectin I--isolectin B4, RT97 and to choleragenoid. The analysis was made both in uninjured rats and in rats which had been subjected to unilateral sciatic nerve transection and partial resection 3 weeks earlier. The data showed that 6% of the L4 and L5 lumbar dorsal root ganglion cells that projected to the nucleus gracilis showed substance P-like immunoreactivity. Following nerve injury, none of the nucleus gracilis-projecting dorsal root ganglion cells showed substance P-like immunoreactivity. Nineteen per cent of the investigated cell population showed calcitonin gene-related peptide-like immunoreactivity in uninjured rats, but no nucleus gracilis-projecting calcitonin gene-related peptide-positive cells were found after nerve injury. Galanin- and galanin message-associated peptide-like immunoreactivity were found in 2% and 3%, respectively, of the Fluoro-Gold-labelled cell population normally and in 22% and 14%, respectively, after injury. No neuropeptide Y-positive cells were found in the Fluoro-Gold-labelled cell population normally, but after nerve injury, 96% of this population became neuropeptide Y-positive. Nitric oxide synthase-like immunoreactivity was found in 2% of the Fluoro-Gold-labelled cells normally and in 10% after injury. Two per cent of the Fluoro-Gold-labelled cells in the normal cases were stained by Griffonia (bandeiraea) simplicifolia lectin I--isolectin B4. After injury, however, no such double labelling was found. Thirty-four per cent of the Fluoro-Gold-labelled cell population was carbonic anhydrase positive normally, and 42% after injury. Seventy-five per cent of the Fluoro-Gold-labelled cells showed RT97 immunoreactivity normally and 12% after injury. Choleragenoid-like immunoreactivity was found in 99% of the Fluoro-Gold-labelled dorsal root ganglion cells normally and 81% after injury. Immunohistochemical visualisation of choleragenoid transganglionically transported from the injured sciatic nerve combined with neuropeptide Y immunocytochemistry showed that primary afferent fibres and terminals in the nucleus gracilis contain neuropeptide Y following peripheral nerve transection. Taken together, the results indicate that peripherally axotomised nucleus gracilis-projecting neurones undergo marked alterations in their cytochemical characteristics, which may be significant for the structural and functional plasticity of this system after injury.

Afferent Pathways↗

PubMed1995

Complement and clusterin in the spinal cord dorsal horn and gracile nucleus following sciatic nerve injury in the adult rat.

We provide evidence for activation of the complement cascade in the dorsal horn of the spinal cord and in the gracile nucleus in the brainstem following sciatic nerve transection in the adult rat. Immunocytochemical analyses showed immunoreactivity for endogenous immunoglobulin G as shown by immunostaining with F(ab')2 antibodies, as well as complement factors C1, C1q, C3, C3d and C9 in the appropriate central termination areas of the injured sciatic nerve. Results from double labelling immunocytochemistry showed a strong association between immunoglobulin and complement factors on the one hand and reactive microglia on the other. However, some complement immunoreactivity was also found in the neuropil, possibly representing secreted complement. In situ hybridization with an oligonucleotide probe showed a marked increase in C3 messenger RNA, indicating local synthesis of C3 protein. In parallel with activation of complement, there was an increased immunoreactivity for the putative complement inhibitor clusterin, which co-localized with glial fibrillary acidic protein-positive astrocytes. In situ hybridization showed an increased labelling of clusterin messenger RNA. These findings indicate that complement activation and up-regulation of complement inhibitors are prominent central responses to peripheral sensory nerve injury. These responses may therefore be important elements underlying so-called transganglionic degenerative changes in primary sensory axons and terminals.

Animals↗

PubMed1994

Distribution of c-fos expressing dorsal horn neurons after electrical stimulation of low threshold sensory fibers in the chronically injured sciatic nerve.

The distribution of proto-oncogene c-Fos protein-immunoreactive cells in the spinal cord dorsal horn was studied after electrical stimulation at A alpha/A beta-fiber intensity of normal and previously injured sciatic nerves in urethane anesthetized rats. No or only occasional Fos protein-like immunoreactive cells were seen after stimulation of the normal uninjured nerve or after nerve transection without stimulation. Electrical nerve stimulation at 3, 12, and 21 days after sciatic nerve transection resulted in substantial increases in the numbers of Fos protein-like immunoreactive cell nuclei in each of Rexed's laminae I-V. Combined demonstration of Fos protein-like immunoreactivity and of glial fibrillary acidic protein-like immunoreactivity (astroglia) or OX-42 immunoreactivity (microglia), indicated that the observed Fos protein-like response was confined to neurons and not to astroglia or microglia. Combined demonstration in the spinal cord of Fos protein-like immunoreactive neurons and neurons labeled retrogradely with Fluoro-Gold from the gracile nucleus showed that some of the Fos protein-like immunoreactive neurons in Rexed's laminae III and IV contributed to the postsynaptic dorsal column pathway. The results indicate that stimulation at A alpha/A beta-fiber intensity of a previously injured nerve gives rise to an abnormally increased activation pattern of postsynaptic neurons in the dorsal horn, some of which contribute to the postsynaptic dorsal column pathway.

Action Potentials↗

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

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

c-fos expression in gracilothalamic tract neurons after electrical stimulation of the injured sciatic nerve in the adult rat.

The number of c-fos protein-like immunoreactive (Fos-LI) cells in the gracile nucleus was determined after electrical stimulation at A alpha/A beta-fiber strength of the normal and of the previously injured sciatic nerve in adult rats. No Fos-LI cells were seen after electrical stimulation of the noninjured sciatic nerve, or after sciatic nerve injury without electrical stimulation. However, stimulation 21 days after sciatic nerve transection resulted in numerous Fos-LI cells in the ipsilateral gracile nucleus. Combined Fos immunocytochemistry and retrograde labeling from the thalamus showed that the majority (76%; range = 70-80%) of the cells in the gracile nucleus that expressed Fos-LI after nerve injury projected to the thalamus. The results indicate that morphological, biochemical, and physiological alterations in primary sensory central endings and second-order neurons, which have earlier been demonstrated in the dorsal column nuclei after peripheral nerve injury, are accompanied by changes in the c-fos gene activation pattern after stimulation of the injured sciatic nerve. A substantial number of the c-fos-expressing neurons project to the thalamus.

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↗