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The American Journal of Pathology Jan 1995The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis,... (Review)
Review
The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage.
Topics: Animals; Apoptosis; Cell Death; Humans; Necrosis
PubMed: 7856735
DOI: No ID Found -
The Veterinary Clinics of North... Apr 2018Equine dysautonomia (ED; also known as equine grass sickness) is a neurological disease of unknown cause, which primarily affects grazing adult horses. The clinical... (Review)
Review
Equine dysautonomia (ED; also known as equine grass sickness) is a neurological disease of unknown cause, which primarily affects grazing adult horses. The clinical signs reflect degeneration of specific neuronal populations, predominantly within the autonomic and enteric nervous systems, with disease severity and prognosis determined by the extent of neuronal loss. This review is primarily focused on the major clinical decision-making processes in relation to ED, namely, (1) clinical diagnosis, (2) selection of appropriate ancillary diagnostic tests, (3) obtaining diagnostic confirmation, (4) selection of treatment candidates, and (5) identifying appropriate criteria for euthanasia.
Topics: Animals; Horse Diseases; Horses; Primary Dysautonomias
PubMed: 29398183
DOI: 10.1016/j.cveq.2017.11.010 -
Developmental Neurobiology Oct 2018After axonal injury, chromatolysis (fragmentation of Nissl substance) can occur in the soma. Electron microscopy shows that chromatolysis involves fission of the rough... (Review)
Review
After axonal injury, chromatolysis (fragmentation of Nissl substance) can occur in the soma. Electron microscopy shows that chromatolysis involves fission of the rough endoplasmic reticulum. In CNS neurons (which do not regenerate axons back to their original targets) or in motor neurons or dorsal root ganglion neurons denied axon regeneration (e.g., by transection and ligation), chromatolysis is often accompanied by degranulation (loss of ribosomes from rough endoplasmic reticulum), disaggregation of polyribosomes and degradation of monoribosomes into dust-like particles. Ribosomes and rough endoplasmic reticulum may also be degraded in autophagic vacuoles by ribophagy and reticulophagy, respectively. In other words, chromatolysis is disruption of parts of the protein synthesis infrastructure. Whereas some neurons may show transient or no chromatolysis, severely injured neurons can remain chromatolytic and never again synthesize normal levels of protein; some may atrophy or die. Ribonuclease(s) might cause the following features of chromatolysis: fragmentation and degranulation of rough endoplasmic reticulum, disaggregation of polyribosomes and degradation of monoribosomes. For example, ribonucleases in the EndoU/PP11 family can modify rough endoplasmic reticulum; many ribonucleases can degrade mRNA causing polyribosomes to unchain and disperse, and they can disassemble monoribosomes; Ribonuclease 5 can control rRNA synthesis and degrade tRNA; Ribonuclease T2 can degrade ribosomes, endoplasmic reticulum and RNA within autophagic vacuoles; and Ribonuclease IRE1α acts as a stress sensor within the endoplasmic reticulum. Regeneration might be improved after axonal injury by protecting the protein synthesis machinery from catabolism; targeting ribonucleases using inhibitors can enhance neurite outgrowth and could be a profitable strategy in vivo. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018.
Topics: Animals; Axons; Endoplasmic Reticulum, Rough; Humans; Nerve Regeneration; RNA; Retrograde Degeneration; Ribonucleases; Ribosomes; Trauma, Nervous System
PubMed: 30027624
DOI: 10.1002/dneu.22625 -
Acta Neuropathologica Communications Mar 2023Traumatic brain injury (TBI) is now recognized as an insult triggering a dynamic process of degeneration and regeneration potentially evolving for years with chronic...
Traumatic brain injury (TBI) is now recognized as an insult triggering a dynamic process of degeneration and regeneration potentially evolving for years with chronic traumatic encephalopathy (CTE) as one major complication. Neurons are at the center of the clinical manifestations, both in the acute and chronic phases. Yet, in the acute phase, conventional neuropathology detects abnormalities predominantly in the axons, if one excludes contusions and hypoxic ischemic changes. We report the finding of ballooned neurons, predominantly in the anterior cingulum, in three patients who sustained severe TBI and remained comatose until death, 2 ½ weeks to 2 ½ months after the traumatic impact. All three cases showed severe changes of traumatic diffuse axonal injury in line with acceleration/deceleration forces. The immunohistochemical profile of the ballooned neurons was like that described in neurodegenerative disorders like tauopathies which were used as controls. The presence of αB-crystallin positive ballooned neurons in the brain of patients who sustained severe craniocerebral trauma and remained comatose thereafter has never been reported. We postulate that the co-occurrence of diffuse axonal injury in the cerebral white matter and ballooned neurons in the cortex is mechanistically reminiscent of the phenomenon of chromatolysis. Experimental trauma models with neuronal chromatolytic features emphasized the presence of proximal axonal defects. In our three cases, proximal swellings were documented in the cortex and subcortical white matter. This limited retrospective report should trigger further studies in order to better establish, in recent/semi-recent TBI, the frequency of this neuronal finding and its relationship with the proximal axonal defects.
Topics: Humans; Coma; Diffuse Axonal Injury; Retrospective Studies; Brain Injuries, Traumatic; Brain; Neurons; Axons
PubMed: 36899399
DOI: 10.1186/s40478-023-01516-x -
Veterinary Pathology Jan 2023This report describes 2 events of degenerative myelopathy in 4- to 27-day-old piglets, with mortality rates reaching 40%. Sows were fed rations containing low levels of...
This report describes 2 events of degenerative myelopathy in 4- to 27-day-old piglets, with mortality rates reaching 40%. Sows were fed rations containing low levels of pantothenic acid. Piglets presented with severe depression, weakness, ataxia, and paresis, which were more pronounced in the pelvic limbs. No significant gross lesions were observed. Histologically, there were degeneration and necrosis of neurons in the spinal cord, primarily in the thoracic nucleus in the thoracic and lumbar segments, and motor neurons in nucleus IX of the ventral horn in the cervical and lumbar intumescence. Minimal-to-moderate axonal and myelin degeneration was observed in the dorsal funiculus of the spinal cord and in the dorsal and ventral nerve roots. Immunohistochemistry demonstrated depletion of acetylcholine neurotransmitters in motor neurons and accumulation of neurofilaments in the perikaryon of neurons in the thoracic nucleus and motor neurons. Ultrastructurally, the thoracic nucleus neurons and motor neurons showed dissolution of Nissl granulation. The topographical distribution of the lesions indicates damage to the second-order neurons of the spinocerebellar tract, first-order axon cuneocerebellar tract, and dorsal column-medial lemniscus pathway as the cause of the conscious and unconscious proprioceptive deficit, and damage to the alpha motor neuron as the cause of the motor deficit. Clinical signs reversed and no new cases occurred after pantothenic acid levels were corrected in the ration, and piglets received parenteral administration of pantothenic acid. This study highlights the important and practical use of detailed neuropathological analysis to refine differential diagnosis.
Topics: Animals; Swine; Female; Pantothenic Acid; Spinal Cord; Neurons; Medulla Oblongata; Spinal Cord Diseases; Swine Diseases
PubMed: 36250539
DOI: 10.1177/03009858221128920 -
Frontiers in Veterinary Science 2022Dogs frequently suffer from traumatic spinal cord injury (SCI). Most cases of SCI have a favorable prognosis but 40-50% of dogs with paraplegia and absence of...
Dogs frequently suffer from traumatic spinal cord injury (SCI). Most cases of SCI have a favorable prognosis but 40-50% of dogs with paraplegia and absence of nociception do not regain ambulatory abilities, eventually leading to euthanasia. Microglia and infiltrating macrophages play a crucial role in inflammatory process after SCI. However, little is known about microglia/macrophage phenotypes representing a potential target for future therapeutic strategies. In the present study, the microglia/macrophage phenotype was characterized by immunohistochemistry in the morphologically unaltered canine spinal cord (10 control dogs) and during acute and subacute SCI (1-4 and 5-10 days post injury, 9 and 8 dogs, respectively) using antibodies directed against IBA1, MAC387, MHC-II, lysozyme, EGR2, myeloperoxidase, CD18, CD204 and lectin from (BS-1). The expression of these markers was also analyzed in the spleen as reference for the phenotype of histiocytic cells. Histological lesions were absent in controls. In acute SCI, 4 dogs showed mild to moderate hemorrhages, 2 dogs bilateral gray matter necrosis and 6 dogs mild multifocal axonal swellings and myelin sheath dilation. One dog with acute SCI did not show histological alterations except for few dilated myelin sheaths. In subacute SCI, variable numbers of gitter cells, axonal changes and dilated myelin sheaths were present in all dogs and large areas of tissue necrosis in 2 dogs. Neuronal chromatolysis was found in 3 dogs with acute and subacute SCI, respectively. In control dogs, microglia/macrophage constitutively expressed IBA1 and rarely other markers. In acute SCI, a similar marker expression was found except for an increase in MAC387-positive cells in the spinal cord white matter due to an infiltration of few blood-borne macrophages. In subacute SCI, increased numbers of microglia/macrophages expressed CD18, CD204 and MHC-II in the gray matter SCI indicating enhanced antigen recognition, processing and presentation as well as cell migration and phagocytosis during this stage. Interestingly, only CD204-positive cells were upregulated in the white matter, which might be related to gray-white matter heterogeneity of microglia as previously described in humans. The present findings contribute to the understanding of the immunological processes during SCI in a large animal model for human SCI.
PubMed: 36262531
DOI: 10.3389/fvets.2022.942967 -
Journal of Neurochemistry Oct 2006Injury to axons elicits changes in macromolecule synthesis in the corresponding cell bodies that are critical for an effective regenerative response. For decades the... (Review)
Review
Injury to axons elicits changes in macromolecule synthesis in the corresponding cell bodies that are critical for an effective regenerative response. For decades the most easily studied aspect of this phenomenon was the onset of chromatolysis, a suite of structural changes in the cell body characterized by swelling, shifting of the nucleus and dispersal of Nissl bodies. The question: 'what is the signal for chromatolysis?' received no less than 10 possible answers in a comprehensive review article published more than three decades ago. Here we come back to this 36 years old question, and review progress on understanding the mechanism of retrograde injury signaling in lesioned peripheral nerves. Recent work suggests that this is based on local axonal synthesis of critical carrier proteins, including importins and vimentin that link diverse signaling molecules to the dynein retrograde motor. A multiplicity of binding sites and of potential signaling molecules, including transcription factors and MAP kinases (Erk, Jnk), may allow diverse options for information-rich encoding of the injury status of the axon for transmission to the cell body.
Topics: Animals; Axonal Transport; Axons; Humans; Models, Neurological; Nerve Regeneration; Signal Transduction; Trauma, Nervous System
PubMed: 16899067
DOI: 10.1111/j.1471-4159.2006.04089.x -
Veterinary Sciences Dec 2022This paper aims to report clinical, laboratory, radiographic, and pathological features in a case of cervical vertebral stenotic myelopathy (CVSM) affecting a...
This paper aims to report clinical, laboratory, radiographic, and pathological features in a case of cervical vertebral stenotic myelopathy (CVSM) affecting a 4-month-old Nelore calf for the first time. During physical examination, the calf could stand if assisted when lifting by the tail but fallen to the ground when trying to walk. Attempts to flex and extend the neck to the right side failed. Radiographs findings consisted of reduced intervertebral spaces, and misalignments between the endplates, more evident between the C3 and C4 vertebrae, resulting in narrowing of the spinal canal and compression of the spinal cord. Grossly, C4 showed cranial articular surface malformation, abnormal metaphyseal growth plate development, reduced vertebral body size and deformity. Histologically, C4 showed an abnormal vertebral bone development characterized by moderate replacement of trabecular bone by fibrous tissues, multifocal areas of dystrophic hyaline cartilage development, and cartilaginous growth failure along the metaphyseal growth plate. Cervical spinal cord within the stenotic vertebral canal showed swollen neurons with central chromatolysis, areas of Wallerian degeneration, and necrotic debris. In contrast with the well-known Wobbler syndrome in horses, the etiology of CVSM in cattle remains undetermined, and further genetic and pathological studies must be conducted to elucidate it.
PubMed: 36548860
DOI: 10.3390/vetsci9120699 -
Basic and Clinical Neuroscience 2022The neurotoxic effects of aluminum exposure during the critical period of neurodevelopment have been well documented. This study investigated the known protective...
INTRODUCTION
The neurotoxic effects of aluminum exposure during the critical period of neurodevelopment have been well documented. This study investigated the known protective effects of calcium supplementation on the cerebellum of juvenile Wistar rats following aluminum-induced neurotoxicity during lactation.
METHODS
Four groups of juvenile rats were exposed via lactation to distilled water (control group), aluminum (40 mg/kg/d), calcium supplement (50 mg/kg/d), and a combination of both aluminum and calcium from postnatal day 4 to day 28. The cerebella of the animals were excised to access the levels of antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPx]), lipid peroxidation (malondialdehyde), histomorphological alterations (hematoxylin and eosin staining), Nissl profile (cresyl fast violet staining), and glial activation (glial fibrillary acidic protein immunohistochemistry).
RESULTS
Lactational aluminum significantly decreased the activities of superoxide dismutase and glutathione peroxidase while exacerbating lipid peroxidation and reactive astrocyte in cerebellar lysates. Lactational calcium supplementation normalized the activities of SOD and GPx, thereby preventing excessive lipid peroxidation and glial activation. Despite no apparent changes in the general histology of the cerebellum, aluminum-induced chromatolysis changes in the Purkinje cell layer, which was counteracted by the antioxidant propensities of calcium supplementation.
CONCLUSION
These findings support that calcium supplementation significantly protects the cerebellum against aluminum-induced oxidative stress, chromatolysis, and neuroinflammation.
PubMed: 37323952
DOI: 10.32598/bcn.2022.1347.2 -
The Journal of Neuroscience : the... May 1987States of phosphorylation of neurofilament proteins were examined in the perikarya of rat sensory and motor neurons between 3 and 28 d following either a distal...
States of phosphorylation of neurofilament proteins were examined in the perikarya of rat sensory and motor neurons between 3 and 28 d following either a distal transection [6-7 cm from the L4-L5 dorsal root ganglia (DRG)] or a proximal transection (1-2 cm from the L4-L5 DRG) of the sciatic nerve. Paraffin sections of the right (experimental) and left (control) L4 and L5 DRG from animals with unilateral transection of the right distal sciatic nerve were stained immunocytochemically with monoclonal antibodies to phosphorylation-dependent (NF-P), dephosphorylation-dependent (NF-dP), or phosphorylation-independent (NF-ind) epitopes on the largest (NF200), mid-sized (NF150), or smallest (NF68) neurofilament protein subunits. Increased immunoreactivity to NF-P on NF200 and NF150 was detected in experimental DRC at 10 d, peaking by 20 d, and declining to near control levels by 28 d. Conversely, immunoreactivity to NF-dP declined in experimental DRG beginning at 6 d, reaching a maximum decline at 10-16 d, and returning to near control levels by 28 d. Immunocytochemical changes were confirmed with biochemical studies on tissue homogenates that demonstrated an increase of immunoreactivity to NF-P and a decrease of reactivity to NF-dP in the experimental DRG. Changes in immunoreactivities to NF-P and NF-dP were observed only in the perikarya of large neurons and were closely associated with chromatolytic changes in these neurons. Marked enhancement of chromatolysis, as well as the immunoreactivities to NF-P and NF-dP, occurred following a proximal (left side) versus distal (right side) transection in the same animal.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Denervation; Ganglia, Spinal; Histocytochemistry; Immunoenzyme Techniques; Intermediate Filament Proteins; Motor Neurons; Neurofilament Proteins; Neurons, Afferent; Nissl Bodies; Peripheral Nerves; Phosphorylation; Rats; Rats, Inbred Strains; Sciatic Nerve; Spinal Cord
PubMed: 3106591
DOI: 10.1523/JNEUROSCI.07-05-01586.1987