Anatomic distribution of apoptosis in medulla oblongata of infants and adults

The aim of the study was to evaluate the distribution of apoptosis in the medullary nuclei of infants and adults who died of hypoxic‐ischaemic injury. Apoptosis was studied by terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labelling (TUNEL) in brainstems from 22 adults (7 subjects who died of opiate intoxication, 15 who died of other hypoxic‐ischaemic injury) and 10 infants. The nuclei examined included the hypoglossal, dorsal motor nucleus of the vagus, nucleus tractus solitarii, nucleus of the spinal trigeminal tract, cuneate, vestibular and inferior olivary nuclei. A morphometric analysis with the optical disector method was performed to calculate the mean percentages (± standard deviation) of TUNEL‐positive neuronal and glial cells for the sample populations. Opiate deaths did not have higher apoptotic indices than other adult hypoxic‐ischaemic deaths. Statistically significant differences between adults and infants were found in the neuronal apoptotic indices of the cuneate (28.2 ± 16.3% vs. 6.9 ± 8.7%), vestibular (24.7 ± 15.0% vs. 11.3 ± 11.4%), nucleus tractus solitarii (11.2 ± 11.2% vs. 2.3 ± 2.4%), dorsal motor nucleus of the vagus (6.8 ± 8.5% vs. 0.1 ± 0.2%) and hypoglossal (6.6 ± 5.7% vs. 0.1 ± 0.2%), indicating higher resistance of the neuronal populations of these infant medullary nuclei to terminal hypoxic‐ischaemic injury or post‐mortem changes. Differences in neuronal apoptotic index were also statistically significant among nuclei, suggesting differential characteristics of survival. Nuclei with higher neuronal apoptotic indices were the cuneate, vestibular and nucleus of the spinal trigeminal tract, which are located in the lateral medullary tegmentum and share the same vascular supply from the posterior inferior cerebellar artery.

[1]  N. Rance,et al.  Cystic brain stem necrosis in a premature infant after prolonged bradycardia , 1992, Acta Neuropathologica.

[2]  S. Lee,et al.  HIV‐1 expression protects macrophages and microglia from apoptotic death , 2004, Neuropathology and applied neurobiology.

[3]  Y. Agid,et al.  Apoptosis in dopaminergic neurons of the human substantia nigra during normal aging. , 1997, Histology and histopathology.

[4]  L. Pu,et al.  Etorphine inhibits cell growth and induces apoptosis in SK-N-SH cells: involvement of pertussis toxin-sensitive G proteins , 1997, Neuroscience Research.

[5]  R. De Caro,et al.  The distribution of mast cells in the human area postrema , 2004, Journal of anatomy.

[6]  K. Waters,et al.  Increased neuronal cell death after intermittent hypercapnic hypoxia in the developing piglet brainstem , 2003, Brain Research.

[7]  L. Hegyi,et al.  Cell death in perinatal hypoxic–ischaemic brain injury , 1997, Neuropathology and applied neurobiology.

[8]  W. Chan,et al.  Apoptosis and Bcl‐2 oncoprotein expression in the human fetal central nervous system , 1998, The Anatomical record.

[9]  S. Kiryu-Seo,et al.  Noxa Is a Critical Mediator of p53-Dependent Motor Neuron Death after Nerve Injury in Adult Mouse , 2005, The Journal of Neuroscience.

[10]  Jun Chen,et al.  Apoptosis in cerebral ischemia: executional and regulatory signaling mechanisms , 2004, Neurological research.

[11]  C. Petito,et al.  Evidence of apoptotic cell death in HIV encephalitis. , 1995, The American journal of pathology.

[12]  Mark J. West,et al.  New stereological methods for counting neurons , 1993, Neurobiology of Aging.

[13]  D. Choi,et al.  Apoptosis and Necrosis in Cerebrovascular Disease , 1999, Annals of the New York Academy of Sciences.

[14]  Gilles Fh.  Hypotensive brain stem necrosis. Selective symmetrical necrosis of tegmental neuronal aggregates following cardiac arrest. , 1969 .

[15]  Y. Lévy,et al.  Neuronal apoptosis in HIV infection in adults , 1995, Neuropathology and applied neurobiology.

[16]  R. Hammer,et al.  Effects of opiates on neuronal development in the rat cerebral cortex , 1993, Brain Research Bulletin.

[17]  D. Guidolin,et al.  Symmetrical selective neuronal necrosis in solitary tract nuclei , 2003, International Journal of Legal Medicine.

[18]  I. Törk,et al.  The internal organization of the human solitary nucleus , 1993, Brain Research Bulletin.

[19]  D. Troost,et al.  Nitric oxide synthase expression and apoptotic cell death in brains of AIDS and AIDS dementia patients. , 1999, AIDS.

[20]  A. Wyllie,et al.  Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics , 1972, British Journal of Cancer.

[21]  T. Slotkin,et al.  Neurobehavioral damage to cholinergic systems caused by prenatal exposure to heroin or phenobarbital: cellular mechanisms and the reversal of deficits by neural grafts. , 2000, Brain research. Developmental brain research.

[22]  H. J. G. Gundersen,et al.  The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis , 1988, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[23]  C. Petito,et al.  Effect of Postmortem Interval on In Situ End-Labeling of DNA Oligonucleosomes , 1995, Journal of neuropathology and experimental neurology.

[24]  S. Ferrara,et al.  C-FOS expression in the subnucleus gelatinosus of the human nucleus tractus solitarii. , 2004, Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia.

[25]  Nurcan Doruk,et al.  OPIOID NEUROTOXICITY: COMPARISON OF MORPHINE AND TRAMADOL IN AN EXPERIMENTAL RAT MODEL , 2004, The International journal of neuroscience.

[26]  Bente Pakkenberg,et al.  The size distribution of neurons in the motor cortex in amyotrophic lateral sclerosis , 2005, Journal of anatomy.

[27]  E. Alvord,et al.  Anoxic-ischemic encephalopathy in the human neonatal period. The significance of brain stem involvement. , 1977, Archives of neurology.

[28]  S. Salamat,et al.  Atlas of the Human Brainstem , 1997 .

[29]  T. Scaravilli,et al.  Selective stroke of the solitary tract nuclei in two cases of central sleep apnoea. , 2005, Clinical neuropathology.

[30]  Richard E. Harlan,et al.  Prenatal morphine treatment and the development of the striatum , 1994, Regulatory Peptides.

[31]  Shuxian Hu,et al.  Morphine induces apoptosis of human microglia and neurons , 2002, Neuropharmacology.

[32]  K. Waters,et al.  Neuronal Apoptosis in Sudden Infant Death Syndrome , 1999, Pediatric Research.

[33]  H. Hartung,et al.  Differentiation between cellular apoptosis and necrosis by the combined use of in situ tailing and nick translation techniques. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[34]  D. Guidolin,et al.  Solitary tract nuclei in acute heart failure. , 2000, Stroke.

[35]  R. Myers,et al.  Topography of lesions in newborn and infant brains following cardiac arrest and resuscitation. Damage to brain and hemispheres. , 1976, Biology of the neonate.

[36]  Leonardo Morsut,et al.  Microvascular patterns in human medullary tegmentum at the level of the area postrema , 2005, Journal of anatomy.

[37]  H J Gundersen,et al.  The efficiency of systematic sampling in stereology and its prediction * , 1987, Journal of microscopy.

[38]  F. Gilles.  Hypotensive brain stem necrosis. Selective symmetrical necrosis of tegmental neuronal aggregates following cardiac arrest. , 1969, Archives of pathology.

[39]  H. Gundersen,et al.  The efficiency of systematic sampling in stereology — reconsidered , 1999, Journal of microscopy.

[40]  R. Friede,et al.  Hypotensive brain stem necrosis or cardiac arrest encephalopathy? , 2004, Acta Neuropathologica.

[41]  H J Gundersen,et al.  Total number of neurons and glial cells in human brain nuclei estimated by the disector and the fractionator , 1988, Journal of microscopy.

[42]  G. Dawson,et al.  Cyclic AMP Protects Against Staurosporine and Wortmannin‐Induced Apoptosis and Opioid‐Enhanced Apoptosis in Both Embryonic and Immortalized (F‐11κ7) Neurons , 1998 .

[43]  B. Kosofsky,et al.  Mechanisms of action of drugs of abuse on the developing fetal brain. , 1999, Clinics in perinatology.

[44]  C. Petito,et al.  EFFECT OF POST-MORTEM INTERVAL AND FIXATIVE ON IN SITU END LABELING (ISEL) OF OLIGONUCLEOSOMES IN RAT BRAIN: 158 , 1995 .

[45]  G. Lazorthes.  Vascularisation et Circulation Cérébrales , 1961 .

[46]  A. Wyllie.  Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation , 1980, Nature.

[47]  P. Clarke,et al.  Developmental cell death: morphological diversity and multiple mechanisms , 2004, Anatomy and Embryology.

[48]  L. Epstein,et al.  Apoptotic neurons in brains from paediatric patients with HIV‐I encephalitis and progressive encephalopathy , 1995, Neuropathology and applied neurobiology.

[49]  R. Basheer,et al.  Chronic prenatal morphine treatment decreases Gαs mRNA levels in neonatal frontal cortex , 1992 .