Mihály Petkó

Propriospinal afferent and efferent connections of the lateral and medial areas of the dorsal horn (laminae I-IV) in the rat lumbar spinal cord

The different subdivisions along the mediolateral extent of the superficial dorsal horn of the spinal cord are generally regarded as identical structures that execute the function of sensory information processing without any significant communication with other regions of the spinal gray matter. In contrast to this standing, here we endeavor to show that neural assemblies along the mediolateral extent of laminae I‐IV cannot be regarded as identical structures. After injecting Phaseolus vulgaris leucoagglutinin and biotinylated dextran amine into various areas of the superficial dorsal horn (laminae I‐IV) at the level of the lumbar spinal cord in rats, we have demonstrated that the medial and lateral areas of the superficial dorsal horn show the following distinct features in their propriospinal afferent and efferent connections: 1) A 300‐ to 400‐μm‐long section of the medial aspects of laminae I‐IV projects to and receives afferent fibers from a three segment long compartment of the spinal dorsal gray matter, whereas the same length of the lateral aspects of laminae I‐IV projects to and receives afferent fibers from the entire rostrocaudal extent of the lumbar spinal cord. 2) The medial aspects of laminae I‐IV project extensively to the lateral areas of the superficial dorsal horn. In contrast to this, the lateral areas of laminae I‐IV, with the exception of a few fibers at the segmental level, do not project back to the medial territories. 3) There is a substantial direct commissural connection between the lateral aspects of laminae I‐IV on the two sides of the lumbar spinal cord. The medial part of laminae I‐IV, however, does not establish any direct connection with the gray matter on the opposite side. 4) The lateral aspects of laminae I‐IV appear to be the primary source of fibers projecting to the ipsi‐ and contralateral ventral horns and supraspinal brain centers. Projecting fibers arise from the medial subdivision of laminae I‐IV in a substantially lower number. The findings indicate that the medial and lateral areas of the superficial spinal dorsal horn of rats may play different roles in sensory information processing. J. Comp. Neurol. 422:312–325, 2000.

Distribution of calcitonin gene-related peptide immunoreactivity in the central nervous system of the forg, Rana esculenta

SummaryThe distribution of calcitonin gene-related peptide (CGRP), immunoreactive structures in the central nervous system of the frog, Rana esculenta, was studied using the peroxidase immunohistochemical method. Immunoreactive perikarya were found in all major parts of the brain. In the forebrain, neurons of the septohipocampal formation, the amygdala, the ventromedial and posterocentral thalamic nuclei, and the cerebrospinal fluid contacting neurons in the diencephalic periventricular organ showed immunoreactivity. The pear-shaped neurons of the optic tectum, and perikarya of the oculomotor nucleus in the midbrain were also immunoreactive. In the hindbrain, neurons of the cranial nerve motor nuclei, neurons of the superior vestibular nucleus, giant cells of the reticular formation, and preganglionic parasympathetic neurons of the superior salivatory nucleus were stained. Motoneurons presented immunostaining also in the spinal cord. Immunoreactive fibers were shown to occur in the olfactory tract, the striatum, the tegmentum and the basis mesencephali, the descending tract of the trigeminal nerve, the solitary tract, Lissauers tract, and the dorsal horn of spinal cord. A comparison of the distribution of CGRP immunoreactivity in the mammalian and amphibian central nervous system revealed that, in relation to the size of the brain, CGRP is more extensively distributed in the amphibian than in the mammalian limbic system.

Commissural propriospinal connections between the lateral aspects of laminae III-IV in the lumbar spinal cord of rats

It has been established that there is a strong functional link between sensory neural circuits on the two sides of the spinal cord. In one of our recent studies we provided a morphological confirmation of this functional phenomenon, presenting evidence for the presence of a direct commissural connection between the lateral aspects of the dorsal horn on the two sides of the lumbar spinal cord. By using a combination of neural tracing and immunocytochemical detection of neural markers like vesicular glutamate transporters, glutamic acid decarboxylase, glycine transporter, and met‐enkephalin (which are characteristic of various subsets of excitatory and inhibitory neurons), we investigated here the distribution, synaptic relations, and neurochemical characteristics of the commissural axon terminals. We found that the cells of origin of commissural fibers in the lateral aspect of the dorsal horn were confined to laminae III–IV and projected to the corresponding area of the contralateral gray matter. Most of the commissural axon terminals established synaptic contacts with dendrites. Axospinous or axosomatic synaptic contacts were found in limited numbers. We demonstrated that interactions among commissural neurons also exist. More than three‐fourths of the labeled axon terminals were immunostained for glutamic acid decarboxylase and/or glycine transporter, but none of them showed positive immunoreaction for met‐enkephalin and vesicular glutamate transporters. The results indicate that there is a substantial reciprocal commissural synaptic interaction between the lateral aspects of laminae III–IV on the two sides of the lumbar spinal cord and that this pathway may transmit both inhibitory and excitatory signals to their postsynaptic targets. J. Comp. Neurol. 480:364–377, 2004.

Disease-Associated Novel CD46 Splicing Variants and Pathologic Bone Remodeling in Otosclerosis†

Objective/Hypothesis: Otosclerotic bone is supposed to show unique CD46 expression pattern because otosclerosis is an organ‐specific disease with viral etiology.

Antimeasles immunoglobulin g for serologic diagnosis of otosclerotic hearing loss.

Hypothesis: Persistent measles virus infection of the otic capsule is suggested to be an etiologic factor in otosclerosis. Otosclerosis is a disease of complex unknown etiology causing progressive conductive and/or sensorineural hearing loss (HL).

Two Subgroups of Stapes Fixation: Otosclerosis and Pseudo-Otosclerosis†

Hypothesis: Stapes ankylosis is a disease with variable histopathology and can be caused by otosclerosis or pseudo‐otosclerosis. Viral pathogenesis of otosclerosis could be established only by correlative analysis: histologic examination of the stapes footplate and reverse‐transcriptase polymerase chain reaction (RT‐PCR) amplification of the viral RNA.

Histopathology of nonotosclerotic stapes fixations

Hypothesis: Different diseases without exact histopathologic classification can cause stapes ankylosis. Background: Otosclerosis is a complex bone remodeling disorder of the otic capsule due to persisting measles virus infection and consecutive inflammatory reaction. In fact, clinical and demographic features of otosclerosis have reference to stapes ankylosis. In the clinical practice, otosclerosis and stapes ankylosis are incorrect synonyms. Methods: Nonotosclerotic stapes footplates (n = 284) removed during stapedectomy were analyzed histologically. Otosclerosis was excluded during the histologic preselection (n = 437). Total RNA was extracted, and measles virus-specific reverse-transcriptase-polymerase chain reaction was performed. Results: Nonotosclerotic stapes ankylosis was associated with total absence of measles virus RNA. Six main types of nonotosclerotic stapes fixations could be distinguished histologically: annular calcification (n = 152; 53.5%), globular fibrosis (n = 49; 17.25%), lymphocytic infiltration (n = 31; 10.9%), hemosiderosis (n = 22; 7.75%), granulomas (n = 17; 6%) and amyloidosis (n = 13; 4.6%). Fragmentation of nonotosclerotic stapes footplates was infrequent (7%) during stapes surgery. Only 1 floating footplate (0.35%) was reported. Conclusion: Two thirds of nonotosclerotic stapes footplates represented complete pathologic bone remodeling. Unlike otosclerosis, nonotosclerotic stapes fixations were characterized by basic histopathologic findings without organ specificity that can also be identified in case of different diseases. Prevalence of nonotosclerotic stapes ankylosis is approximately 30 to 40% among stapes fixation cases. The long-term prognosis and surgical considerations theoretically differ from those of otosclerosis.

Histologic otosclerosis is associated with the presence of measles virus in the stapes footplate

Hypothesis: Persistent measles virus infection of the otic capsule is presumed to be one of the etiologic factors in otosclerosis. The viral pathogenesis of otosclerosis could be established only by correlative analysis: histologic examination of the stapes footplates and reverse-transcriptase polymerase chain reaction amplification of the viral RNA. At present, histologic analysis of the removed stapes footplates is the only appropriate method of distinguishing otosclerotic and nonotosclerotic stapes fixations. Background: The presence of measles virus was shown in otosclerotic patients by reverse-transcriptase polymerase chain reaction amplification of the viral RNA and detecting the viral proteins by immunohistochemistry. Methods: Nucleic acids (mRNA, vRNA, and DNA) were extracted from ankylotic stapes footplates of stapes fixation patients (n = 44). Measles virus genomic nucleoprotein RNA was amplified by seminested reverse-transcriptase polymerase chain reaction. Amplification results were correlated to postoperative histologic findings. Results: Measles virus RNA was detectable only in histologically otosclerotic stapes footplates (n = 32). Histology for virus-negative footplates (n = 12) excluded otosclerosis. Virus-negative stapes footplates showed annular calcification (n = 8), bone resorption with increased numbers of hemosiderophages (n = 2), and mononuclear cell infiltration with osteolysis (n = 2). Conclusion: Stapes ankylosis is a heterogenous disease causing conductive hearing loss with different causes. Nonotosclerotic stapes fixations may belong to degenerative disorders with variable histopathology. Otosclerosis is an inflammatory disease resulting from persisting measles virus infection of the otic capsule.

Activated Osteoclasts with CD51/61 Expression in Otosclerosis

Hypothesis: Stapes ankylosis is supposed to be a disease with variable histopathology caused by otosclerosis or pseudo‐otosclerosis. Persistent measles virus infection of the otic capsule could induce reactivation of quiescent embryonic osteoclasts in otosclerosis.

Propriospinal pathways in the dorsal horn (laminae I–IV) of the rat lumbar spinal cord

The spinal dorsal horn is regarded as a unit that executes the function of sensory information processing without any significant communication with other regions of the spinal gray matter. Within the spinal dorsal horn, however, the different rostro-caudal and medio-lateral subdivisions intensively communicate with each other through propriospinal pathways. This review gives an overview about these propriospinal systems, and emphasizes that the medial and lateral parts of the spinal dorsal horn show the following distinct features in their propriospinal interconnectivities: (a) A 100-300μm long section of the medial aspects of laminae I-IV projects to and receives afferent fibers from a three segment long compartment of the spinal dorsal gray matter, whereas the same length of the lateral aspects of laminae I-IV projects to and receives afferent fibers from the entire rostro-caudal extent of the lumbar spinal cord. (b) The medial aspects of laminae I-IV project extensively to the lateral areas of the dorsal horn. In contrast to this, the lateral areas of laminae I-IV, with the exception of a few fibers at the segmental level, do not project back to the medial territories. (c) There is a substantial direct commissural connection between the lateral aspects of laminae I-IV on the two sides of the lumbar spinal cord. The medial part of laminae I-IV, however, establishes only a minor commissural propriospinal connection with the gray matter on the opposite side.