Info

Dr Garys MS Treatment System

Natural Way to Cure Multiple Sclerosis

Get Instant Access

Microscopic Findings

Any tissue processing produces artifacts that have to be interpreted: fixation procedures as well as staining techniques. The artifacts are dependent on the time periods between death and fixation, the duration of the fixation process, the temperatures, etc. For example the freezing process of (brain) tissue leads to crystalline vacuoles within the tissue sections (Fig. 4.26a, b).

Additionally, the forensic neuropathologist fundamentally needs to be able to reliably distinguish between vital and postmortem changes (cf. Oehmi-chen 1995). This requires among other things the testing and use of novel histochemical and immuno-histochemical staining techniques that can help to establish the length of the postmortem interval.

So-called dark neurons (Fig. 4.26c) can appear among otherwise normal neurons. Dark neurons are irregularly contoured, shrunken neurons that are created by excessive pressure on unfixed postmortem tissue (Scharrer 1938; Cammermeyer 1961, 1975). Apical dendrites also have a dark coloration, sometimes in combination with a corkscrew-like appearance. There is a danger of confusing dark neu rons with ischemic cell necrosis. In our own investigations (Oehmichen and Gencic 1980a) we could observe that most, but not all dark neurons have a potent albumin uptake, an indication that they represent lesions of neuronal metabolism (and/or membrane).

Animal experiments demonstrate that the following three types of altered neurons appear at different postmortem intervals in rats (Oehmichen and Gencic 1980b):

1. Shrunken, hyperchromatic neurons, whose number declines as the postmortem interval proceeds.

2. Swollen and autolytic neurons, with a pale peri-karyon and nucleoplasm, and an absence of Nissl bodies. The nucleus can no longer be differentiated from the vacuolized and autolysing cytoplasm. The cells themselves have lost their contours and appear swollen and spherical. The swelling in particular represents the most fundamental postmortem change (whose differential diagnosis is retrograde degeneration).

3. Pericellular spaces surrounding neurons may be caused by postmortem autolytic processes that mimic edema, especially in the gray matter.

Children two years old and younger almost invariably exhibit periventricular and perivenous accumulation of cytoplasm-poor, lymphocyte-like mononu-clear cells which suggest an encephalitis (so-called pseudoencephalitis). Those cell aggregations consist of neuroblasts as an indication of development, not of an inflammatory process. This age group also regularly shows a superficial granule layer of the cerebellar cortex composed of germinal cells (matrix cells). These usually disappear some time between the second and fourth years of life.

In cases of sudden death with brief agony or if tissues have been poorly fixed (Hirano 1981), extensive acute swelling of oligodendroglia is common. In addition, a generalized swelling and clasmatodendrosis of astrocytes is often seen. These changes are rather slight compared to the neuronal changes. They must also be regarded as non-specific and do not constitute markers of edema.

Lindenberg (1982) points out that the state of the brain before circulatory arrest also plays a role. If the agony was brief (healthy person who died within minutes), neurons and glial cells may show marked postmortem ischemic cell injury (vacuolation, ho-mogenization, acute shrinkage associated with nuclear changes). Agony of long duration results in a largely unchanged cytology.

Not only does the architecture of the cells change, but their functional state and/or stainability with various reagents changes as well. Postmortem function and staining are influenced by many factors in addition to fixation procedures (time, temperature,

Fig. 4.26a-c. Minsinterpretable findings. a, c Crystalline vacu- tissue; b dark neurons as a postmortem phenomenon (a-c H&E; oles as seen within tissue sections after freezing of native brain magnification a x50, b X300, c X500)

and type of procedure). It is further known that the enzyme activity of cells and tissue depends in large part on the length of the postmortem interval (for a survey of findings prior to 1980 see Oehmichen 1980).

Numerous variables are known to affect the immunoreactivity of cells and tissue in the antigen-antibody reaction for immunohistologi-cal demonstration of epitopes (Grizzle et al. 2001). Among these variables are the interval between cellular death and fixation as well as the duration of fixation, the method of tissue processing, the preparation of paraffin blocks, the method of attaching tissue sections to microscopic slides, the interval between cutting tissue sections and immunostain-ing. To summarize, once findings are obtained by performing the relevant investigations, their proper interpretation requires long experience in the routine practice of neuropathology.

Bibliography

Ironside JW, Pickard JO (2002) Raised intracranial pressure, oedema and hydrocephalus. In: Graham DI, Lantos PL (eds) Greenfield's neuropathology, 7th edn, vol 1. Arnold, London, pp 193-231

Keane RW, Hickey WF (eds) (1997) Immunology of the nervous system. Oxford University Press, New York Lee JC (1982) Anatomy of the blood-brain barrier under normal and pathological conditions In: Haymaker W, Adams RD (eds) Histology and histopathology of the nervous system, vol 1. CC Thomas, Springfield, Ill., pp 798-870 Lindenberg R (1982) Tissue reactions in the gray matter of the central nervous system. In: Haymaker W, Adams RD (eds) Histology and histopathology of the nervous system. CC Thomas, Springfield, Ill., vol 1, pp 973-1275

References

Abbott NJ, Revest PA, Romero IA (1992) Astrocyte-endothelial interaction: physiology and pathology. Neuropathol Appl Neurobiol 18:424-433 Abe K (1999) Neurons. Necrotic vs apoptotic changes. In: Walz W (ed) Cerebral ischemia: molecular and cellular pathophysiology. Humana, Totowa, N.J., pp 217-232 Adachi M, Feigin I (1966) Cerebral oedema and the water content of normal white matter. J Neurol Neurosurg Psychiatry 29:446-450

Adams JH, Graham DI (1976) The relationship between ventricular fluid pressure and the neuropathology of raised intracranial pressure. Neuropathol Appl Neurobiol 2:323-332 Adams JH, Graham DI, Muray LS, Scott G (1982) Diffuse axonal injury due to non-missile head injury in humans: an analysis of 45 cases. Ann Neurol 12:557-563 Adams RD, Fisher CM, Hakim S et al. (1965) Symptomatic occult hydrocephalus with "normal" cerebrospinal-fluid pressure: a treatable syndrome. N Engl J Med 273:117-126 Adler DE, Milhorat TH (2002) The tentorial notch: anatomical variation, morphometric analysis, and classification in 100 human autopsy cases. J Neurosurg 96:1103-1112 Anthony DC, Ferguson B, Matyzak MK et al. (1997) Different matrix and metalloproteinase expression in cases of multiple sclerosis and stroke. Neuropathol Appl Neurobiol 23:406-415 Armstead WM, Kurth CD (1994) Different cerebral hemodynamic responses following fluid percussion brain injury in the newborn and juvenile pig. J Neurotrauma 11:487-497 Artru F, Philippon B, Berger M, Deleuze R (1976) Cerebral blood flow, cerebral metabolism and cerebrospinal fluid biochemistry in brain-injured patients after exposure to hyperbaric oxygen. Eur Neurol 14:351-364 Astrup J, Siesjö BK, Symon L (1981) Thresholds in cerebral ischemia - the ischemic penumbra. Stroke 12:723-725 Auer RN (2000) Pure hypoxic and ischemic insults. In: Research in legal medicine, vol 24. Schmidt-Römhild, Lübeck, pp 27-39 Bakay L, Lee JC (1965) Cerebral edema. Thomas, Springfield, Ill. Bakay L, Lee JC (1968) Effects of hypoxia on the ultrastructure of the central nervous system. Brain 91:697-702 Baron JL, Madri JA, Ruddle NH et al. (1993) Surface expression of a4 integrin by CD4 T-cells is required for their entry into brain parenchyma. J Exp Med 177:57-68 Barone FC (1999) Tumor necrosis factor a in stroke and neurotrauma. In: Ruffolo RR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Harwood Academic, New York, pp 327-348 Bauer J, Rauschka H, Lassmann H (2001) Inflammation in the nervous system: the human perspective. Glia 36:235-243 Beal MF (1995) Aging, energy, and oxidative stress in neurode-

generative disease. Ann Neurol 38:357-366 Bell BA, Syman L, Branston NM (1985) CBF and time thresholds for the formation of ischemic cerebral edema, and effect of reperfusion in baboons. J Neurosurg 62:31-41 Benveniste EN (1999) Cytokine expression in the nervous system. In: Keane RW, Hickey WF (eds) Immunology of the nervous system. Oxford University Press, New York, pp 419-459

Bernardes-Silva M, Anthony DC, Issekutz AC, Perry VH (2001) Recruitment of neutrophils across the blood-brain barrier: the role of E- and P-selectins. J Cereb Blood Flow Metab 21:1115-1124

Bevilaqua MP (1993) Endothelial-leukocyte adhesion molecules.

Annu Rev Immunol 11:767-804 Biagas KV, Grundl PD, Kochanek PM et al. (1996) Posttraumatic hyperemia in immature, mature, and aged rats: autoradiographic determination of cerebral blood flow. J Neurotrauma 13:189-200

Blank WF, Kirshner HS (1977) The kinetics of extracellular potassium changes during hypoxia and anoxia in the cat cerebral cortex. Brain Res 123:113-124 Blinzinger K, Kreutzberg G (1968) Displacement of synaptic terminals from regenerating motor neurons by microglial cells. Z Zellforsch Mikrosk Anat 85:145-157 Blumbergs PC, Scott G, Manavis J et al. (1995) Topography of axo-nal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury. J Neurotrauma 12:565-571 Bonecchi R, Bianchi G, Bordignon PP et al (1998) Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 187:129-134

Brightman MW, Reese TS (1969) Junctions between intimately apposed membranes in the vertebrate brain. J Cell Biol 40:648-677

Brodal P (1982) The central nervous system. Oxford University Press, New York

Broman T (1949) The permeability of the cerebral vessels in normal and pathological conditions. Munksgaard, Copenhagen Broman T, Steinwall O (1967) Model of the blood-brain barrier system. In: Klatzo I, Seitel-Berger F (eds) Brain edema. Springer, Berlin Heidelberg New York, pp 360-384 Brück W, Porada P, Poser S et al. (1995) Monocyte/macrophage differentiation in early multiple sclerosis lesions. Ann Neurol 38:788-796

Cameron HA, McKay RD (1999) Restoring production of hippo-

campal neurons in old age. Nat Neurosci 2:894-897 Cammermeyer J (1961) The importance of avoiding "dark" neurons in experimental neuropathology. Acta Neuropathol 1:345-352

Cammermeyer J (1975) Histochemical phospholipid reaction in ischemic neurons as an indication of exposure to postmortem trauma. Exp Neurol 49:252-272 Campbell IL (1991) Cytokines in viral diseases. Curr Opin Immunol 3:486-491

Cervos-Navarro J, Ferszt R (1977) Beitrag zur Ätiopathogenese der Koagulationsnekrose im Gehirn. In: Schneider V (ed) Festschrift Walter Krauland zum 65. Geburtstag. Universitätsdruckerei, Berlin, pp 129-139 Chan KH, Miller JD, Dearden NM (1992) Intracranial blood flow velocity after head injury: relationship to severity of injury, time, neurological status and outcome. J Neurol Neurosurg Psychiatry 55:787-791 Chan PH (1999) The role of superoxide radicals in the pathogenesis of cerebral ischemic cell death. In: Ruffolo RR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Harwood Academic, New York, pp 157-168 Chandler WF, Kindt GW (1976) Monitoring and control of intracranial pressure in non-traumatic encephalopathies. Surg Neurol 5:311-314

Chao CC, Hu S, Peterson PK (1997) Glia-mediated neurotoxicity. In: Ramington JS, Peterson PK (eds) In defence of the brain: new concepts in pathogenesis, treatment and prevention of CNS infections. Blackwell Science, Malden, Mass., pp 74-89 Chen MS, Huber AB, van der Haar ME et al. (2000) Nogo-A is a my-elin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403:434-439 Chirumamilla S, Sun D, Bullock MR, Colello RJ (2002) Traumatic brain injury induced cell proliferation in the adult mammalian central nervous system. J Neurotrauma 19:693-703 Choi DW, Rothman SM (1990) Role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci 13:171-182

Chu K, Kang D-W, Lee S-H, Kim M (2001) Diffusion-weighted MR findings in brainstem hypertensive encephalopathy: a possibility of cytotoxic edema. Eur Neurol 46:220-222 Clarke PGH (1998) Apoptosis versus necrosis. In: Koliatsos E, Ratou RR (eds) From cell death and diseases of the nervous system. Humana Press, Totowa, N.J., pp 3-25 Connor RCR (1968) Heart damage associated with intracranial lesions. Br Med J 3:29-31 Craig CG, D'sa R, Morshead CM et al. (1999) Migrational analysis of the constitutively proliferating subependyma population in adult mouse forebrain. Neuroscience 93:1197-1206 Cross AH, Manning PT, Keeling RM et al. (1998) Peroxinitrite formation within the central nervous system in active multiple sclerosis. J Neuroimmunol 88:45-56 Cserr HF, Knopf PM (1997) Cervical lymphatics, the blood-brain barrier, and immunoreactivity of the brain. In: Keane RW, Hickey WF (eds) Immunology of the nervous system. Oxford University Press, New York, pp 134-152 Dalkara T, Ayata C, Moskowitz MA (1999) Constitutive nitric oxide synthase and ischemic/excitotoxic brain injury. In: Ruffolo RR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Harwood Academic, New York, pp 85-96 Del Bigio MR (2004) Cellular damage and prevention in childhood hydrocephalus. Brain Pathol 14:317-324 Dietrich WD (1999) Inflammatory factors regulating the blood-brain barrier. In: Ruffolo RR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Harwood Academic, New York, pp 137-156 D'Souza SD, Bonetti B, Balasingam V et al (1996) Multiple sclerosis. Fas signaling in oligodendrocyte death. J Exp Med 184:2361-2370

Escola J, Hager H (1963) Elektronenmikroskopische Befunde über die Kollagenfaserbildung im Rahmen mesenchymaler Organisationsvorgänge bei experimentellen Koagulationsnek-rosen des Säugetiergehirns. Beitr Pathol Anat 128:25-38 Esiri MM, Kennedy PG (1997) Viral diseases. In: Graham DI, Lantos PL (eds) Greenfield's neuropathology, 6th edn, vol 2. Arnold, London, pp 3-62

Euler M von, Janson AM, Larsen JO, Seiger Ä et al (2002) Spontaneous axonal regeneration in rodent spinal cord alter isch-emic injury. J Neuropathol Exp Neurol 61:64-75 Fabry Z, Raine CS, Hart MN (1994) Nervous tissue as an immune compartment: the dialect of the immune response in the CNS. Immunol Today 15:218-224 Ferrer I, Planas AM (2003) Signaling of cell death and cell survival following focal cerebral ischemia: life and death struggle in the penumbra. J Neuropathol Exp Neurol 62:329-339 Fierz W, Endler B, Reske K, Wekerle H, Fontana A (1985) Astrocytes as antigen presenting cells. I. Induction of Ia expression on astrocytes by T-cells via immune interferon and its effect on antigen presentation. J Immunol 134:3785-3793 Fishman RA (1980) Cerebrospinal fluid in diseases of the nervous system. WB Saunders, Philadelphia, Pa. Fiskum G, Murphy AN, Beal MF (1999) Mitochondria in neurodegeneration: acute ischemia and chronic neurodegenerative diseases. J Cereb Blood Flow Metab 19:351-369 Fontana A, Kristensen F, Dubs R et al (1982) Production of prostaglandin E and an interleukin-1 like factor by cultured astrocytes and F-6 glioma cells. J Immunol 129:2413-2419 Fontana A, Fierz W, Wekerle H (1984) Astrocytes present myelin basic protein to encephalitogenic T cell lines. Nature 307:273-276

Frank E, Pulver M, De-Tribolet N (1986) Expression of class II major histocompatibility antigens on reactive astrocytes and en-dothelial cells within the gliosis surrounding metastases and abscesses. J Neuroimmunol 12:29-36 Frei K, Siepl C, Groscurth P et al (1987) Antigen presentation and tumor cytotoxicity by interferon-gamma treated microglial cells. Eur J Immunol 17:1271-1278 Gage FH (1998) Stem cells of the central nervous system. Curr

Opin Neurobiol 8:671-676 Garcia JH, Liu K-F, Ho K-L (1995) Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke 26:636-643

Garton HJL, Piatt JH (2004) Hydrocephalus. Pediatr Clin North Am 51:305-325

Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119:493-501 Gay FW, Dryre TJ, Dick GW, Esiri MM (1997) The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of primary demyelinating lesion. Brain 120:1461-1483 Gentleman SM, Nash AJ, Sweeting CJ et al. (1993) ß-Amyloid precursor protein (ß-APP) as a marker of axonal injury after head injury. Neurosci Lett 160:139-144 Gotoh K, Kikuchi H, Kataoka H et al (1998) Nitric oxide synthase immunoreactivity related to cold-induced brain edema. Neurol Res 20:637-642 Graeber MB, Blakemore WF, Kreutzberg GW (2002) Cellular pathology of the central nervous system. In: Graham DI, Lantos PL (eds) Greenfield's neuropathology, 7th edn, vol 1. Arnold, London, pp 123-191

Graham DJ, Lawrence AE, Adams JH et al (1987) Brain damage in non-missile head injury secondary to high intracranial pressure. Neuropathol Appl Neurobiol 13:209-217 Graham DI, Smith C, Reichard R et al. (2004) Trials and tribulations using b-amyloid precursor protein immunohistochemistry to evalute traumatic brain injury in adults. Forensic Sci Int 146:89-96

GrandPre T, Nakamura F, Vartanian T, Strittmatter SM (2000) Identification of the Nogo inhibitor of axon regeneration as a Re-ticulon protein. Nature 403:439-444 Granger DN, Kubes P (1994) The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion. J Leukoc Biol 55:662-675 Granville DJ, Carthy CM, Hunt DW, McManus BM (1998) Biology of disease. Apoptosis: molecular aspects of cell death and disease. Lab Invest 78:893-913 Grassmann CB, Potts DG (1974) Arachnoid granulations, radiology and anatomy. Radiology 113:95-100 Gray F (1997) Lesions of the central nervous system in the early stages of human immunodeficiency virus infection. Rev Neurol Paris 153:629-640 Greenwood J (1991) Mechanisms of blood-brain barrier breakdown. Neuroradiology 33:95-100 Griffin WS, Stanley LC, Ling C et al. (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 86:7611-7615 Grizzle WE, Stockard CR, Billings PE (2001) The effects of tissue processing variables other than fixation on histochemical staining and immunohistochemical detection of antigens. J Histotechnol 24:213 Haas CA, Donath C, Kreutzberg GW (1993) Differential expression of immediate early genes after transection of the facial nerve. Neuroscience 53:91-99 Harding B, Copp AJ (1997) Malformations. In: Graham DI, Lantos PL (eds) Greenfield's neuropathology, 6th edn, vol 1. Arnold, London, pp 397-533 Harlan JM, Liu DY (1992) Adhesion: its role in inflammatory disease. WH Freeman, New York Hart DNJ, Fabre JW (1981) Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med 153:347-361

Hart MN, Fabry Z (1995) CNS antigen presentation. Trends Neu-

rosci 18:475-481 Hartung HP, Heininger K, Schäfer B et al (1988) Immune mechanisms in inflammatory polyneuropathy. Ann NY Acad Sci 540:122-161

Haymaker W, Margoles C, Pentschew A et al (1961) Pathology of kernicterus and posticteric encephalopathy: presentation of 87 cases, with a consideration of pathogenesis and etiology. In: Swinyard CA (ed) Kernicterus and its importance in cerebral palsy. CC Thomas, Springfield, Ill., pp 21-52 Heiss WD (2000) Ischemic penumbra: evidence from functional imaging in man. J Cereb Blood Flow Metab 20:1276-1293 Heiss WD, Rosner G (1983) Functional recovery of cortical neurons as related to degree and duration of ischemia. Ann Neurol 14:294-301

Hickey WF, Kimura H (1988) Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239:290-292 Hickey WF, Hsu BL, Kimura H (1991) T-lymphocyte entry into the central nervous system. J Neurosci Res 28:254-260 Hickey WF, Lassmann H, Cross AH (1997) Lymphocyte entry and the initiation of inflammation in the central nervous system. In: Keane RW, Hickey WF (eds) Immunology of the nervous system. Oxford University Press, New York, pp 200-225 Hirai O, Handa H, Ishikawa M (1986) Cerebral blood volume as another cause of intracranial hypertension following cold-induced edema. In: Miller JD, Teasdale GM, Rowan JO, Galbraith SL, Mendelow AD (eds) Intracranial pressure VI. Springer, Berlin Heidelberg New York, pp 146-150 Hirano A (1981) A guide to neuropathology. Igaku-Schoin, Tokyo Hsu CY, Hu ZY, Doster SK (1995) Cell-mediated injury. In: Narayan RK, Wilberger JE, Povlishock JT (eds) Neurotrauma. McGraw-Hill, New York, pp 1433-1444 Huang F-P, Guohua XI, Keep RF et al (2002) Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg 96:287-293 Hughes JT (1978) Pathology of the spinal cord. Lloyd Luke, London, pp 181-190 Huppertz B, Frank H-G, Kaufmann P (1999) The apoptosis cascade - morphological and immunohistochemical methods for its visualization. Anat Embryol 200:1-18 Hurley RA, Bradley WG Jr, Latifi HT, Taber KH (1999) Normal pressure hydrocephalus: significance of MRI in a potentially treatable dementia. J Neuropsychiatry Clin Neurosci 11:297-300 Hynes RO (1992) Integrins: versatility, modulation, and signaling of cell adhesion. Cell 69:11-25 Iadecola C (1999) Inducible nitric oxide synthase gene expression and ischemic brain damage. In: Ruffolo RR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Harwood Academic, New York, pp 113-136

Ikegaya H, Heino J, Laaksonen H et al. (2004) Accumulation of plasma proteins in Purkinje cells as an indicator of blood-brain barrier breakdown. Forensic Sci Int 146:121-124 Ikuta F, Hirano A, Zimmerman HM (1963) An experimental study of postmortem alterations in the granular layer of the cer-ebellar cortex. J Neuropath Exp Neurol 22:581-590 Inuzuka T, Tamura A, Sato S et al. (1990) Changes in the concentration of cerebral protein following occlusion of the middle cerebral artery in rats. Stroke 21:917-922 Jacob H (1947) Zur histopathologischen Diagnose des akuten und chronisch rezidivierenden Hirnödems. Arch Psychiatr Z Ges Neurol Psychiatr 179:158-165 Jacob H, Pyrkosch W (1951) Frühe Hirnschäden bei Strangtod und in der Agonie. Arch Psychiat Z Neurol 187:177-186 Janzer RC, Friede RL (1979) Perisulcal infarcts: lesions caused by hypotension during increased intracranial pressure. Ann Neurol 6:339-404 Jean WC, Spellman SR, Nussbaum ES, Low WC (1998) Reperfusion injury after focal cerebral ischemia: the role of inflammation and the therapeutic horizon. Neurosurgery 43:1382-1397 Jellinger KA, Stadelmann C (2002) Problems of programmed cell death in neurodegenerative disorders. In: Oehmichen M,

Ritz-Timme S, Meissner C (eds) Aging. Morphological, biochemical, molecular and social aspects. In: Research in legal medicine, vol 27. Schmidt-Römhild, Lübeck, pp 123-144 Johnston I, Paterson A (1974) Benign intracranial hypertension II.

CSF pressure and circulation. Brain 97:301-312 Jones PA, Andrews PJD, Midgley S et al (1994) Measuring the burden of secondary insults in head injured patients during intensive care. J Neurosurg Anesthesiol 6:4-14 Kalmar B, Burnstock G, Vrbova G et al (2002) Upregulation of heat shock proteins rescues motor neurons from axotomy-in-duced cell death in neonatal rats. Exp Neurol 176:87-97 Kanthan R, Shuaib A (1995) Clinical evaluation of extracellular amino acids in severe head trauma by intracerebral in vivo microdialysis. J Neurol Neurosurg Psychiatry 59:326-327 Kapoor R, Davies M, Blaker PA et al (2003) Blockers of sodium and calcium entry protect axons from nitric oxide-mediated degeneration. Ann Neurol 53:174-180 Kempermann G, Kuhn HG, Gage FH (1998) Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci 18:3206-3212

Kempermann G, Gast D, Gage FH (2002) Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogen-esis by long-term environmental enrichment. Ann Neurol 52:135-143

Kermer P, Klöcker N, Bähr M (1999) Neuronal death after brain injury. Models, mechanisms, and therapeutic strategies in vivo. Cell Tissue Res 298:383-395 Keyvani K, Schallert T (2002) Plasticity-associated molecular and structural events in the injured brain. J Neuropath Exp Neurol 61:831-840

Kimelberg HK (1995a) Brain edema. In: Kettenmann H, Ransom BR (eds) Neuroglia. Oxford University Press, New York, pp 919-935

Kimelberg HK (1995b) Current concepts of brain edema. J Neurosurg 83:1051-1059 Kimelberg HK, Rutledge E, Feustel PJ (1997) Cell swelling and effects of alcohol in experimental neural trauma. In: Oehmi-chen M, König HG (eds) Neurotraumatology - biomechanic aspects, cytologic and molecular mechanisms. Schmidt-Römhild, Lübeck, pp 295-315 Klatzo I (1967) Neuropathological aspects of brain edema. J Neu-

ropathol Exp Neurol 26:1-14 Knopf PM, Basu D, Sirulnick E et al. (1994) B cell traffic and intrathecal antibody synthesis in normal brain. FASEB J 8:A248 Koo EH, Abraham CR, Potter H et al. (1991) Developmental expression of a-anti-chymotrypsin in brain may be related to astro-gliosis. Neurobiol Aging 12:495-501 Kooyk Y van, Wiel-van Kemenade E van de, Weder P et al. (1993) Lymphocyte function-associated antigen 1 dominates very late antigen 4 in binding of activated T-cells to endothelium. J Exp Med 177:185-190 Lajtha A (1968) Transport as control mechanism of cerebral metabolite levels. In: Lajtha A, Ford DH (eds) Brain barrier system. Elsevier, Amsterdam, pp 201-232 Langfitt TW, Weinstein JD, Kassell NF (1965) Cerebral vasomotor paralysis produced by intracranial hypertension. Neurology 15:632-641

Lassmann H (1998) Pathology of multiple sclerosis. In: Compston A (ed) McAlpine's multiple sclerosis, 3rd edn. Churchill Livingstone, London, pp 323-356 Leech PJ, Miller JD (1974) Intracranial volume/pressure relationships during experimental brain compression in primates. II. Effect of induced changes in arterial pressure. J Neurol Neurosurg Psychiatry 37:1099-1104 Leist M, Single B, Naumann H, Fava E et al (1990) Inhibition of mitochondrial ATP generation by nitric oxide switches apoptosis to necrosis. Exp Cell Res 249:396-403 Li GL, Ahlgren S, Farooque M et al. (1997) Lesions of axons and dendrites in spinal cord trauma. In: Oehmichen M, König HG (eds) Neurotraumatology - biomechanic aspects, cytologic and molecular mechanisms. In: Research in legal medicine, vol 17. Schmidt-Römhild, Lübeck, pp 187-201 Li GL, Farooque M, Holtz A, Olsson Y (1995) Microtubule-associ-ated protein 2 as a sensitive marker for dendritic lesion after spinal cord trauma: an immunohistochemical study in the rat. Restor Neurol Neurosci 8:189-197 Li S, Strittmatter SM (2003) Delayed systemic nogo-66 receptor antagonist promotes recovery from spinal cord injury. J Neurosci 23:4219-4227 Lindenberg R (1955) Compression of brain arteries as a pathogenic factor for tissue necrosis and their areas of predilection. J Neuropathol Exp Neurol 14:233-243 Lindenberg R (1982) Tissue reactions in the gray matter of the central nervous system. In: Haymaker W, Adams RD (eds) Histology and histopathology of the nervous system, vol 1. CC Thomas, Springfield, Ill., pp 973-1275 Liou AK, Clark RS, Henshall DC et al. (2003) To die or not to die for neurons in ischemia, traumatic brain injury and epilepsy: a review on the stress-activated signaling pathways and apop-totic pathways. Prog Neurobiol 69:103-142 Lipton SA (1998) Neuronal injury associated with HIV-1: approaches and treatment. Annu Rev Pharmacol Toxicol 38:159-177 Majno G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146:3-15 Marmarou A, Anderson RL, Ward JD et al (1991) NINCDS Traumatic coma data bank. Intracranial pressure monitoring methodology. J Neurosurg 75:S21-S27 Marmarou A, Barzo P, Fatouros P et al (1997) Traumatic brain swelling in head injured patients: brain edema or vascular engorgement? Acta Neurochir (Wien) 70:68-70 Marmarou A, Fatouros PP, Barzo P et al (2000) Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients. J Neurosurg 93:183-193 Marshall WJS, Jackson JLF, Langfitt TW (1969) Brain swelling caused by trauma and arterial hypertension. Arch Neurol 21:545-553

Massa PT, Dörries R, Meulen V ter (1986) Viral particles induce Ia antigen expression on astrocytes. Nature 320:543-546 Massa PT, Schimpl A, Wecker E, Meulen V ter (1987) Tumor necrosis factor amplifies measles virus-mediated Ia induction on astrocytes. Proc Natl Acad Sci USA 84:7242-7245 Matyszak MK, Lawson LJ, Perry VH, Gordon S (1992) Stromal macrophages of the choroid plexus situated at an interface between the brain and peripheral immune system consti-

tutively express major histocompatibility class II antigens. J Neuroimmunol 40:173-181 Matz PG, Lewen A, Chan PH (2001) Neuronal, but not microglial, accumulation of extravasated serum proteins after intracerebral hemolysate exposure is accompanied by cytochrome C release and DNA fragmentation. J Cereb Blood Flow Metab 21:921-928

McConkey DJ (1998) Biochemical determinants of apoptosis and necrosis. Toxicol Lett 3:157-168 McEver RP (1994) Selectins. Curr Opin Immunol 6:75-84 McGee AW, Strittmatter SM (2003) The Nogo-66 receptor: focusing myelin inhibition of axon regeneration. Trends Neurosci 26:193-198

Mcintosh TK, Saatman KE, Raghupathi R et al. (1998) The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms. Neuropathol Appl Neuro-biol 24:251-268

McKhan GM (2002) New neurons for aging brains. Ann Neurol 52:133-134

Medawar PB (1948) Immunity of homologous grafted skin. III. The fate of skin monografts transplanted to the brain, to subcutaneous tissue and to the anterior chamber of the eye. Br J Exp Pathol 29:58-69 Meeusen EN, Premier RR, Brandon MR (1996) Tissue-specific migration of lymphocytes: a key role for Th1 and Th2 cells? Immunol Today 17:421-424 Mendelow AD, Baethmann A, Czernicki Z et al (2000) A summary of the XIth International Brain Edema Symposium held in Newcastle-upon-Tyne, England in June 1999. In: Mendelow AD, Baethmann A, Czernicki Z et al (eds) Brain edema XI. Proceedings of the 11th International Symposium, Newcastle-upon-Tyne, UK, 6-10 June 1999, pp 9-10 Meyer A (1920) Herniation of the brain. Arch Neurol Psychiatry 4:387-400

Miller JD, Ironside JW (1997) Raised intracranial pressure, oedema and hydrocephalus. In: Graham DI, Lantos PL (eds) Greenfield's neuropathology. Arnold, London, pp 157-195 Miller JD, Becker DP, Ward JD et al (1977) Significance of intracranial hypertension in severe head injury. J Neurosurg 47:503-516

Miller JD, Butterworth JF, Gudeman SK et al (1981) Further experience in the management of severe head injury. J Neurosurg 54:289-299

Miyamoto O, Auer RN (2000) Hypoxia, hyperoxia, ischemia and brain necrosis. Neurology 54:362-371 Morgan BP (1999) Complement in brain inflammation and injury. In: Ruffolo RR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Har-wood Academic, New York, pp 283-296 Müller G (1930) Zur Frage der Altersbestimmung histologischer Veränderungen im menschlichen Gehirn unter Berücksichtigung der örtlichen Verteilung. Z Neurol Psychiat 124:1-112 Nawashiro H, Shima K, Chigasaki H (1995) Immediate cerebrovascular responses to closed head injury in the rat. J Neurotrau-ma 11:189-197

Niess C, Grauel U, Toennes SW, Bratzke H (2002) Incidence of axonal injury in human brain tissue. Acta Neuropathol (Berl) 104:79-84

Norenberg MD (1997) Astrocytes: normal aspects and response to CNS injury. In: Keane RW, Hickey WF (eds) Immunology of the nervous system. Oxford University Press, New York, pp173-199

Oehmichen M (1976a) Cerebrospinal fluid cytology. An introduction and atlas. WB Saunders, Philadelphia, Pa. Oehmichen M (1976b) Characterization of mononuclear phagocytes of human CSF using membrane markers. Acta Cytol 20:548-552

Oehmichen M (1978) Mononuclear phagocytes in the central nervous system. Springer, Berlin Heidelberg New York Oehmichen M (1980) Enzyme alterations in brain tissue during the early postmortal interval with reference to the histomor-phology: review of the literature. Z Rechtsmed 85:81-95 Oehmichen M (1982) Functional properties of microglia. In: Smith WT, Cavanagh JB (eds) Recent advances in neuropathology, vol 2. Churchill Livingstone, Edinburgh, pp 83-107 Oehmichen M (1983) Inflammatory cells in the central nervous system. Current state of basic research in immunology, pathology and forensic medicine. In: Zimmermann HM (ed) Progress in neuropathology, vol 5. Raven, New York, pp 227-335 Oehmichen M (1995) Estimating wound age and distinguishing intravital from postmortem processes in forensic medicine -introductory remarks. In: Oehmichen M, Kirchner H (eds) Research in legal medicine, vol 13, The wound healing process: forensic pathological aspects. Schmidt-Römhild, Lübeck, pp15-21

Oehmichen M, Gencic M (1980a) Postmortal diffusion of plasma albumin in rat brain. Z Rechtsmed 84:113-123 Oehmichen M, Gencic M (1980b) Postmortal histomorphologic and histozymatic alterations in rats brain. Pathol Res Pract 169:72-83

Oehmichen M, Huber H (1976) Reactive microglia with membrane features of mononuclear phagocytes. J Neuropathol Exp Neurol 35:30-39 Oehmichen M, Grüninger H, Wiethölter H, Gencic M (1979) Lymphatic efflux of intracerebrally injected cells. Acta Neuropathol (Berl) 45:61-65 Oehmichen M, Meissner C, Schmidt V et al. (1999) Pontine axonal injury after brain trauma and nontraumatic hypoxic-ischemic brain damage. Int J Leg Med 112:261-267 Oehmichen M, Ochs U, Meissner C (2000) Histochemical characterization of cytotoxic brain edema. Exp Pathol Toxicol 52:348-352

Oldendorf WH (1977) The blood-brain barrier. Exp Eye Res [Suppl] 25:177

O'Sullivan MG, Statham PF, Jones PA et al (1994) Role of intracra-nial pressure monitoring in severely head injured patients without signs of intracranial hypertension on initial computerised tomography. J Neurosurg 80:46-50 Pachter JS, Cries HE de, Fabry Z (2003) The blood-brain barrier and its role in immune privilege in the central nervous system. J Neuropathol Exp Neurol 62:593-604 Parsons AA, Hunter AJ (1999) Perspectives in neuroinjury and disease. In: Ruffolo RR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Harwood Academic, New York, pp 1-19

Perry VH, Gordon S (1997) Microglia and macrophages. In: Keane RW, Hickey WF (eds) Immunology of the nervous system. Oxford University Press, New York, pp 155-172 Perry VH, Bell MD, Anthony DC (1999) Unique aspects of inflammation in the central nervous system. In: Ruffolo RR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Harwood Academic, New York, pp 21-38 Pierpaoli C, Alger JR, Righini A et al. (1996) High temporal resolution diffusion MRI of global cerebral ischemia and reperfusion. J Cereb Blood Flow Metab 16:892-905 Platt N, Silva RP da, Gordon S (1998) Recognizing death: the phagocytosis of apoptotic cells. Trends Cell Biol 8:365-372 Polazzi E, Gianni T, Contestabile A (2001) Microglial cells protect cerebellar granule neurons from apoptosis: evidence for reciprocal signaling. Glia 36:271-280 Povlishock JT (1992) Traumatically induced axonal injury: patho-genesis and pathobiological implications. Brain Pathol 2:1-12

Prat A, Biernacki K, Wosik K, Antel JP (2001) Glial cell influence on the human blood-brain barrier. Glia 36:145-155 Prinjha R, Moore SE, Vinson M et al (2000) Inhibitor of neurite outgrowth in humans. Nature 403:383-384 Purpura DP (1975) Morphogenesis of visual cortex in preterm infants. In: Brazier MAB (ed) Growth and development of the brain: nutrition, genetic and environmental factors. Raven, New York, pp 33-45 Purpura DP (1976) Structure dysfunction relations in the visual cortex of preterm infants. In: Brazier MAP, Coceani F (eds) Dysfunction in infantile febrile convulsions. Raven, New York, pp 223-236

Quadbeck G (1967) Physiologie und Pathologie der Blut-Hirnschranke. Hippokrates 38:45-53 Quadbeck G (1968) Clinical importance of alterations in barrier. In: Lajtha A, Ford DH (eds) Brain barrier systems. Elsevier, Amsterdam, pp 343-361 Raghupathi R, Graham DI, McIntosh TK (2000) Apoptosis after traumatic brain injury. J Neurotrauma 17:927-938 Ramer MS, Priestley JV, McMahon SB (2000) Functional regeneration of sensory axons into the adult spinal cord. Nature 403:312-316

Reese TS, Karnowsky MJ (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34:207-217

Reichard RR, White CL, Hladik CL, Dolinak D (2003) Beta-amyloid precursor protein staining. I. Nonhomicidal pediatric medi-colegal autopsies. J Neuropathol Exp Neurol 62:237-247 Reilly CE (2002) Astrocytes instruct stem cells to differentiate into neurons. J Neurol 249:950-952 Rosenblum WI (1997) Histopathologic clues to the pathways of neuronal death following ischemia/hypoxia. J Neurotrauma 14:313-326

Rothwell N, Toulmond S, Allan S et al. (1999) Cytokines in acute brain injury and stroke. In: Ruffolo RR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Harwood Academic, New York, pp 471-482

Rubin LL (1997) Neuronal cell death: when, why and how. Br Med Bull 53:617-631

Scharrer E (1938) On dark and light - cells in the brain and liver.

Anat Rec 72:53-65 Schmid-Schönbein GW, DeLano FA, Costa J, Harris AG (1999) Parenchymal cell death and leukocyte-endothelial cell interaction in acute experimental inflammation. In: Ruffolo RR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Harwood Academic, New York, pp 39-52 Schoettle RJ, Kochanek PM, Magargee MJ et al. (1990) Early poly-morphonuclear leukocyte accumulation correlates with the development of posttraumatic cerebral edema in rats. J Neu-rotrauma 7:207-272 Scholz W (1953) Selective neuronal necrosis and its topistic patterns in hypoxemia and oligemia. J Neuropath Exp Neurol 12:249

Schröder ML, Muizelaar JP, Fatouros PP et al. (1998) Regional cerebral blood volume after severe head injury in patients with regional cerebral ischemia. Neurosurgery 42:1276-1280 Schwab ME (1993) Experimental aspects of spinal cord regeneration. Curr Opin Neurol Neurosurg 6:549-553 Schwab ME (2000) Finding the lost target. Nature 403:257-260 Schwab ME, Caroni P (1988) Oligodendrocytes and CNS myelin are nonpermissive substrates for neurite growth and fibroblast spreading in vitro. J Neurosci 8:2381-2393 Sedgwick JD, Hickey WF (1997) Antigen presentation in the central nervous system. In: Keane RW, Hickey WF (eds) Immunology of the nervous system. Oxford University Press, New York, pp 364-418 Seida M, Vass K, Tomida S, Wagner HG, Klatzo I (1989) Observations on cerebral ischaemia in cats at injury threshold levels. Neurol Res 11:205-212 Selhorst JB, Gudeman SK, Butterworth JF et al (1985) Papilledema after acute head injury. Neurosurgery 16:357-363 Sheriff FE, Bridges LR, Sivaloganatham S (1994) Early detection of axonal injury after human head trauma using immunocyto-chemistry for ß-amyloid precursor protein. Acta Neuropathol (Berl) 87:55-62

Simpson JE, Newcombe J, Cuzner ML, Woodroofe MN (1998) Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions. J Neuroimmunol 84:238-249 Simson PE, Criswell HE, Johnson KB (1991) Ethanol inhibits NMDA-evoked electrophysiological activity in vivo. J Pharmacol Exp Ther 257:225-231 Sobel RA, Mitchell ME, Fondren G (1990) Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. Am J Pathol 136:1309-1316 Song H, Stevens CF, Gage FH (2002) Astroglia induce neurogenesis from adult neural stem cells. Nature 417:39-44 Spielmeyer W (1922) Histopathologie des Nervensystems. Springer, Berlin Heidelberg New York Springer TA (1990) Adhesion receptors of the immune system.

Nature 346:425-434 Squier MV (1993) Acquired diseases of the nervous system. In: Keeling JW (ed) Fetal and neonatal pathology. Springer, Berlin Heidelberg New York, pp 571-593

Sternberger NH, Sternberger LA, Kies MW, Shear CR (1989) Cell surface endothelial proteins altered in experimental allergic encephalomyelitis. J Neuroimmunol 21:241-248 Strich SJ (1956) Diffuse degeneration of the cerebral white matter in severe dementia following head injury. J Neurol Neurosurg Psychiatry 19:163-185 Summer BE, Watson WE (1971) Retraction and expansion of the dendritic tree of motor neurones of adult rats induced in vivo. Nature 233:273-275 Svendsen CN (2002) The amazing astrocyte. Nature 417:29-32 Teasdale E, Cardos E, Galbraith S, Teasdale G (1984) CT scan in severe diffuse head injury: physiological and clinical correlations. J Neurol Neurosurg Psychiatry 47:600-603 Thompson AM (1970) Hyperosmotic effects on brain uptake of non-electrolytes. In: Crone CC, Lassen N (eds) Capillary permeability. Alfred Benzon Symposium II. Munksgaard, Copenhagen, pp459-472 Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312-1316 Traugott U (1987) Multiple sclerosis: relevance of class I and class II MHC-expressing cells to lesion development. J Neuroimmunol 16:283-302 Vermes I, Haanen C, Reutelingsperger CPM (1998) Molecular biology of apoptosis and programmed cell death. In: Aruoma OI, Halliwell B (eds) Molecular biology of free radicals in human diseases. OICA International, London, pp 225-286 Waksman BH (1997) A brief history of neuroimmunology. In: Keane RW, Hickey WF (eds) Immunology of the nervous system. Oxford University Press, New York Waterhouse NJ (2003) The cellular energy crisis: mitochondria and cell death. Med Sci Sports Exerc 35:105-110 Waxman SG (2003) Nitric oxide and the axonal death cascade. Ann Neurol 53:150-153

Weiss JM, Downie SA, Lyman WD, Berman JW (1998) Astrocyte-derived monocyte-chemoattractant protein-1 directs the transmigration of leukocytes across a model of the human blood-brain barrier. J Immunol 161:6896-6903 Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320:365-376

Weller RO, Shulman K (1972) Infantile hydrocephalus: clinical, histological and ultrastructural study of brain damage. J Neuro-surg 36:255-265 Windhagen A, Newcombe J, Dangond F et al. (1995) Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and in-terleukin 12 cytokine in multiple sclerosis lesions. J Exp Med 182:1985-1986

Yakovlev AG, Faden AL (1997) Traumatic brain injury regulates expression of ced-related genes modulating neuronal apop-tosis. In: Oehmichen M, König HG (eds) Neurotraumatology -biomechanic aspects, cytologic and molecular mechanisms. Schmidt-Römhild, Lübeck, pp 107-120 Zach O, Bauer HC, Richter K et al. (1997) Expression of a chemotac-tic cytokine (MCP-1) in cerebral capillary endothelial cells in vitro. Endothelium 5:143-153 Zinkernagel RM, Doherty PC (1974) Immunological surveillance against altered self components by sensitized T-lym-phocytes in lymphocytic choriomeningitis. Nature (Lond) 251:547-548

Zoppo GJ del (1997) Selectins, ICAMs, and integrins in CNS injury. In: Ruffolo PR, Feuerstein GZ, Hunter AJ, Poste G, Metcalf BW (eds) Inflammatory cells and mediators in CNS diseases. Har-wood Academic, New York, pp 395-412 Zwienenberg M, Muizelaar JP (1999) Severe pediatric head injury: the role of hyperemia revisited. J Neurotrauma 11:937-943

Was this article helpful?

0 0
All About Alzheimers

All About Alzheimers

The comprehensive new ebook All About Alzheimers puts everything into perspective. Youll gain insight and awareness into the disease. Learn how to maintain the patients emotional health. Discover tactics you can use to deal with constant life changes. Find out how counselors can help, and when they should intervene. Learn safety precautions that can protect you, your family and your loved one. All About Alzheimers will truly empower you.

Get My Free Ebook


Post a comment