Pathology of nerve cell membranes in complicated and severe human brain traumatic injuries. An electron microscopic study using cortical biopsies

• Orlando J. Castejón Universidad del Zulia

Abstract

Cortical biopsies of ten patients with severe and complicated brain traumatic injuries were examined with transmission electron microscope to study the ultrastructural damage of nerve cell membranes. The nonpyramidal neurons, astrocytes and oligodendrocytes showed plasma membrane fragmentation and areas of focal necrosis, enlargement and degranulation of rough and smooth endoplasmic reticulum cisterns, Golgi complex membrane fragmentation, and irregular dilation and disasembly of nuclear envelope. The degenerated myelinated axons showed invaginations and fragmentation of axolemmal membrane, and myelin sheath vacuolization. Synaptic disassembly and disruption and disassembly of interastrocytary gap junctions were also found. Disruption of neuronal Ca2+ homeostasis, activation of phospholipases and calpain, peroxidative stress, hemoglobin cytotoxicity, glutamate cytotoxicity, and ischemia of brain parenchyma are discussed in relation with the nerve cell membrane damage.

References

Aronica, E., Gorter, J.A., Jansen, G.H., Leenstra, S., Yankava, B., Troost D. (2001). Expression of connexin 43 and connexin 32 gap-junction proteins in epilepsy-associated brain tumors and in the perilesional epileptic cortex. Acta Neuropathol., 101,449-459.

Boldyrev, A., Song, R., Dyatlov, V.A., Lawrence, D.A., Carpenter, D.O. (2000). Neuronal cell death and reactive oxygen species. Cell Mol. Neurobiol., 20, 433-450.

Braughler, J.M., Duncan, L.A, Chase RL (1985). Interaction of lipid peroxidation and calcium in the patogénesis of neuronal injury. Cent Nerv Syst Trauma 2, 269-28.

Castejón, O.J. (1985). Electron microscopic study of central axonal degeneration in traumatic human brain edema. J. Submicrosc. Cytol., 17, 703-718.

Castejón, O.J. (1998.) Morphological astrocytic changes in complicated human brain trauma. A light and electron microscopy study. Brain Injury, 12, 409-427.

Castejón, O.J., Valero, C., Diaz, M. (1995). Synaptic degenerative changes in human traumatic brain edema. An electron microscopic study of cerebral cortical biopsies. J. Neurosurg. Sci., 39, 47-65.

Castejón, O.J., Castejón, O.J., Castejón H.V. (2000). Oligodendroglial cell behaviour in traumatic oedematous human cerebral cortex: a light and electron microscopic study. Brain Injury, 14, 303-317.

Castejón, O.J., Castejón, O.J., H.V., Diaz, M., Castellano, A. (2001). Consecutive light microscopy, scanning-transmission electron microscopy and transmission electron microscopy of traumatic human brain oedema and ischaemic brain damage. Histol. Histopathol., 16, 1117-1134.

Castejón, O.J., Castejón, H.V., Zavala, M., Sanchez, M.E., Diaz, M. (2002). A light and electron microscopic study of oedematous human cerebral cortex in two patients with post-traumatic seizures. Brain Injury, 16, 331-346.

Castejón OJ, Acurero G. (2004). Traumatic axolemmal and cytoskeletal derangement in myelinated axons of human oedematous cerebral cortex and loss of consciousness. An electron microscopic study using cortical biopsies. J. Submicros. Cytol. Pathol., 36, 285-293.

Castejón, O.J., Castejón HV. (2004). Structural patterns of injured mitochondria in human oedematous cerebral cortex. Brain Injury, 18, 1107-1126.

Castejón O.J. (2004). Lysosome abnmormalities and lipofuscin content of nerve cells of oedematous human cerebral cortex. J. Submicrosc.Cytol. Pathol. 36,263-271.

Castejón, O.J., Arismendi, G.J. (2004). Nerve cell nuclear and nucleolar abnormalities in the human oedematous cerebral cortex. An electron microscopic stud y using cortical biopsies. J. Submicrosc. Cytol. Pathol. 36, 273-283.

Castejón, O.J. (2008). Electron Microscopy of Human Brain Edema. Astrodata. Maracaibo.pp17-34.

Castejón, O.J. (2011). Light and Electron Microscopic Observations in Nerve Cell Nucleolar Damage in Human Traumatic and Complicated Brain Injuries, Revista de la Universidad del Zulia, Vol. 2, Núm. 3, 133-149, Mayo-Agosto 2011.

Choi, B.H. (1993). Oxygen, antioxidants and brain dysfunction. Yonsei Med. J., 34, 1-10.

Cohadon, F. (1984). Cell membrane alterations during situations of acute stress to the cerebral parenchyma. Mechanisms, consequences and therapeutic perspectives. Neurochirurgie, 30, 69-83.

Cohadon, F., Rigonlet, M., Averet, N., Alligoni, E. (1989). Membrane damage in acute brain trauma. Italian J. Neurol. Sci., 10, 147- 155.

Cullen DK, Vernekar VN, LaPlaca MC. (2011). Trauma-induced plasmalemma disruptions in three-dimensional neural cultures are dependent on strain modality and rate. J Neurotrauma,28,2219-2233.

Engels, D.C., Siemmer, J.E., Vlug A.S., Maas, A.I., Weber, J.T. (2005). Combined effects of mechanical and ischemic injury to cortical cells: secondary ischemia increases damage and decreases effects of neuroprotective agents. Neuropharmacology, 49, 985-995.

Doutheil, J., Althausen, S., Treiman, M., Paschen, W. (2000). Effect of nitric oxide on endoplasmic reticulum calcium homeostasis., protein synthesis and energy metabolism. Cell Calcium, 27, 107-115.

Evans, P.H. (1993). Free radicals in brain metabolism and pathology. British Med. Bull. 49 (Suppl 3), 577-587.

Erb, D.E., Povlishock, J.T. (1988). Axonal damage in severe traumatic brain injury: an experimental study in cat. Acta Neuropathol. (Berl)., 76, 347-358.

Farkas O., Lifschitz J., Povlishock J.T. (2006). Mechanoporation induced by diffuse traumatic brain injury: an irreversible or reversible response to injury? J. Neurosci. 26, 3130-3140.

Gennarelli, T.A., Thibault, L.E., Adams, H., Graham, D.I., Thompson, C.J., Marcincin, R.P. (1985). Diffuse axonal injury and traumatic coma in the primate. In Dacey, R.G., Winn, H.R., Rimel, R.W., & Jane, J.A. (Eds.), Trauma of the Central Nervous System (pp. 169-193). New York: Raven Press.

Gennarelli, T.A. (1993). Mechanisms of brain injury. (1993). Emergency Med., 1, 5-11.

Ginsberg, M.D., Watson, B.D., Busto, R. (1988). Peroxidative damage to cell membranes following cerebral ischemia. A cause of ischemia brain injury. Neurochem. Pathol., 9, 171-173.

Haik, S., Peyrin, J.M., Lins, L., Rosseneu, M.Y., Brasseurs, R., Langeveld, J.P., Tagliavinio, F., Deslys, J.P., Lasmezas, C., Dormont, D. (2000). Neurotoxicity of the putative transmembrane domain of the prion protein. Neurobiol. Dis., 7, 646-656.

Harris JL, Yeh HW, Choi IY, Lee P, Berman NE, Swerdlow RH, Craciunas SC, Brooks WM. (2012). Altered neurochemical profile after traumatic brain injury: (1)H-MRS biomarkers of pathological mechanisms. J Cereb Blood Flow Metab. 2012 Aug 15. doi: 10.1038/jcbfm.2012.114. [Epub ahead of print]

Hayashi, T., Abe, K. (2004). Ischemic neuronal cell death and orgenellae damage. Neurol. Res. 26, 827-834.

Homayoun, P., Rodriguez, De Turco, E.B., Parkins, N.E., Lane D.C., Soblosky, J., Crey, J., Bazan, N.G. (1997). Delayed phospholipid degradation in rat brain after traumatic brain injury. J. Neurochem., 69, 199-205.

Hossain, M.Z., Peeling, J., Sutherland, R., Hertzberg E.L., Nagy J.I. (1994). Ischemia-induced cellular redistribution of the asrocytic gap junctional protein connexin43 in rat brain. Brain Res., 652:311-322.

Hu, B.R., Martone, M.E., Jones, Y.Z., Liu, C.L. (2000). Protein aggregation after transient cerebral ischemia. J. Neurosci., 20, 3191-3199.

Keuhl, F.A., Egans, R.N. (1980). Prostaglandins, arachidonic acid., and inflammation. Science, 210, 978-984.

Kurnellas, M.P., Nicot, A., Shull, G.E., Elkabes, S. (2005). Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal cord: a potential mechanism for neurodegeneration in multiple sclerosis and spinal cord injury. Faseb J. 19, 298-300.

La Placa, M.C., Thivault, L.E. (1998) Dynamic mechanical deformation of neurons triggers an acute calcium response and cell injury involving the N-methyl-D- aspartate glutamate receptor. J. Neurosci. Res. 52, 220-229.

Li W.E., Ochalski P.A., Hertzberg E.L., Nagy J.I. (1998). Immunorecognition, ultrastructure and phosphylation status of astrocytic gap junctions and connexin43 in rat brain after cerebral focal ischaemia. Eur. J. Neurosci., 10:2444-2463.

Lodish, H.F., Kong, N. (1990). Perturbation of cellular calcium blocks exit of secretory proteins from rough endoplasmic reticulum. J. Biol. Chem., 265, 10893-10899.

Luo, J., Shi, R. (2004). Acrolein induces axolemmal disruption, oxidative stress, and mitochondrial impairment in spinal cord tissue. Neurochem. Int. 44, 475-486.

Maxwell W.L., Kansagra A.M., Graham D.I., Dams J.H., Gennarelli T.A.(1988). Freeze-fracture studies of reactive myelinated nerve fibres after diffuse axonal injury. Acta Neuropathol., 76, 395-406.

Mengesdorf, T, Proud, C.G., Mies, G., Paschen, W. (2002). Mechanisms underlying suppression of protein synthesis induced by transient focal cerebral ischemia in mouse brain. Exp. Neurol., 177, 538-546.

Morley, P., Tauskela, J.S., Hakim, A.M. (1999). Calcium Overload. In W. Walz (Ed.), Cerebral Ischemia, (pp. 69-104). New Jersey: Humana Press.

Ochalski P.A., Sawchuk M.A., Hertzberg E.L., Nagy J.I., 1995. Astrocytic gap junction removal, connexin-3 redistribution, and epitope masking at excitatory amino acid lesion sites in rat brain. Glia, 14:279-294.

Nakase T., Fushiki S., Naus C.C. (2003a). Astrocytic gap junctions composed of connexin 43 reduce apoptotic neuronal damage in cerebral ischemia. Stroke, 34, 1987-1993.

Nakase T., Fushiki s., Sohl G., Theis M., Willecke K., Naus C.C. (2003b). Neuroprotective role of astrocytic gap junctions in ischemic stroke. Cell Commun. Adhes. 10, 413-417.

Paschen, W. (1996). Glutamate excitotoxicity in transient global cerebral ischemia. Acta Neurobiol Exp (Wars), 56, 313-322.

Paschen, W., Doutheil J. (1999). Disturbance of endoplasmic reticulum functions: A key mechanism underlying cell damage? In Baethmann, A., Glesnila, N.,Ringel, F., Eriskat, J (Eds.) Current Progress in the Understanding of Secondary Brain Damage from trauma and Ischemia. (pp1-5). Acta Neurochirug. (Supplement.) 73; Wien: Springer.

Paschen, W. (2000). Role of calcium in neuronal cell injury: which subcellular compartment is involved? Brain Res. Bull., 53, 409- 413.

Paschen, W. Frandsen A. (2001). Endoplasmic reticulum dysfunction--a common denominator for cell injury in acute and degenerative diseases of the brain? J. Neurochem., 79, 719-725.

Paschen, W., Mengesdorf, T., Althausen, S., Hotop, S. (2001). Peroxidative stress selectively down-regulates the neuronal stress response activated under conditions of endoplasmic reticulum dysfunction. J. Neurochem., 76, 1916-1924.

Paschen, W. (2003). Endoplasmic reticulum: a primary target in various acute disorders and degenerative diseases of the brain. Cell Calcium 34, 365-383.

Patts, S., Brodhum, M. (1999). Neuropathological sequelae of traumatic brain injury in the brain. An overview. Exp. Toxicol. Pathol., 51: 119-123.

Perez Velazquez, J.L., Kokarovtseva, L., Sarbaziha, R., Jeyapalan Z., Leshchenko Y., (2006). Role of gap junctional coupling in astrocytic net works in the determination of global ischaemiainduced oxidative stress and hippocampal damage. Eur. J. Neurosci., 23:1-10. 29.

Povlishock, J.T. (1986). Traumatically induced axonal damage without concomitant change in focally related neuronal somata and dendrites. Acta Neuropathol., (Berl) 70, 53-59.

Povlishock, J.T. (1992a). Traumatically induced axonal injury: pathogenesis and pathobiological implications. Brain Pathol., 2, 1-12.

Povlishock, J.T. (1992b). Ultrastructural studies of diffuse axonal injury in humans. Journal of Neurotrauma, 11, 173-186.

Saatman, K.E., Bozyczko-Coyne, D., Marcy, V., Siman, R., McIntosh, T.K. (1996). Prolonged calpain-mediated spectrin breakdown occurs regionally following experimental brain injury in the rat. J. Neuropathol. Exp. Neuro.l, 55, 850-860.

Saatman, K.E., Abai, B., Grosvenor, A., Vorwerk, C.K., Smith, D.H., & Meaney, D.F. (2003). Traumatic axonal injury results in biphasic calpain activation and retrogade transport impairment in mice. J. Cerebral Blood Flow Metab. 23, 34-42.

Sharma, H.S., Miclescu, A., Wiklund, L. (2011). Cardiac arrest-induced regional blood-brain barrier breakdown, edema formation and brain pathology: a light and electron microscopic study on a new model for neurodegeneration and neuroprotection in porcine brain. J. Neural Transm.118, 87-114

Shi R (2004). The dynamics of axolemmal disruption in guinea pig spinal cord following compression. J Neurocytol 33, 203-211.

Singleton, R.H., Zhu, J., Stone, J.R., Povlishock J.T. (2002). Traumatically induced axotomy adjacent to the soma does not result in acute neuronal death. J.Neurosci., 22, 701-802.

Singleton, R.H.,Povlishock. J.T. (2004). Identification and characterization of heterogeneous neuronal injury and death in regions of diffuse brain injury: evidence for multiple independent injury phenotypes. J. Neurosci. 24, 3543-3553.

Siesjo, B.K., Gar, C.D., & Bengtson, F. (1989). Free radicals and brain damage. Cerebrovasc. Brain Metab. Rev., 1, 165-171.

Sokka, A. L., Putkonen , N., Mudo, G., Pryaznikov, E. Reijonen, S. Khiroug, L., Belluardo N., Lindjolm, D., Korhonen, L. (2007). Endoplasmic reticulum strees inhibition protects against excitotoxic neuronal injuri in the rat brain. J. Neurosci. 24, 901-908.

Soroceanu, L., Manning, T.J. Jr., Sontheimer H. (2001).Reduced expressionof conexin-43 and functional gap junction coupling in human gliomas. Glia, 33,107-117.

Spuler, A., Tan, W.K.M., Mayer, F.B. (1996). Molecular events in cerebral ischemia. In Raffel, C., Hars G.R. (Eds.), The Molecular Basis of Neurosurgical Disease (pp. 248-269). Baltimore: William and Wilkins.

Sponne, I., Fifre, A., Koziel, V., Oster, T., Olivier, J.L., Pillot, T. (2004). Membrane cholesterol interferes with neuronal apoptosis induced by soluble oligomers but not fibrils of amyloid-bet peptide. Faseb J. 18, 836-838.

Tang, Y., Wu, P, Su, J., Xiang, J., Cai, D., Dong, Q. (2010). Effects of Aquaporin-4 on edema formation following intracerebral hemorrhage. Exp. Neurol., 223, 485-495.

Theriault E-, Frankenstein U.N., Hertzberg E.L., Nagy J.I. (1997). Connexin43 and astrocytic gap junctions in the rat spinal cord after acute compression injury. J. Comp. Neurol., 382, 199- 214.

Thompson, R.J., Zhou, N., and MacVicar, B.A. (2006). Ischemia opens neuronal gap junction hemichannels. Science, 924-927.

Traystman, R.J., Kirsch, J.R., Koehler, R.C. (1991). Oxygen radical mechanisms of brain injury following ischemia and reperfusion. J. Appl. Physiol., 71, 1185-1195.

Verdier, Y., Zarandi, M., Penke, B. (2004). Amyloid beta-peptide interactions with neuronal interactions with neuronal and glial cell plasma membrane: binding sites and implications for Alzheimer’s disease. J. Pept. Sci.10, 229-248.

Wang Y, Song JH, Denisova JV, Park WM, Fontes JD, Belousov AB. (2012) Neuronal gap junction coupling is regulated by glutamate and plays critical role in cell death during neuronal injury. J Neurosci., 32,713-725.

Wilberger, J., (1996). Molecular basis of head injury. In C. Raffel & G.R. Hars (Eds.), The Molecular Basis of Neurosurgical Disease. (pp. 296-03). Baltimore: William and Wilkins.

Yamaguchi, H., Maat-Schieman, M.L., van Duinen, S.G., Prins F.A., Neeskens P., Natte R., Roos R.A., (2000). Amyloid beta protein (Abeta) starts to deposit as plasma membrane-bound form in difuse plaques of brains from hereditary cerebral hemorrhage with amyloidosis-Dutch type, Alzheimer disease and nondemented aged subjects. J. Neuropathol. Exp. Neurol., 60,105-106.

Yi, H.H., Hoover, R., McIntosh, T., Hazell, A.S. (2006). Early, transient increase in complexin I and complexin II in the cerebral cortex following traumatic brain injury is attenuated by N-acetylcysteine. J. Neurotrauma, 23, 86-96.