Summary
Focal seizure was induced in rat and cat neocortex by the topical application of aminopyridines. The epileptic character of the focal events was followed by surface and intracellular recordings of seizure activity. The pathologic alterations in the neurons, the glial cells, and the protein permeability of the neocortical blood vessels were investigated by means of light microscopy, using standard histological stainings and immunohistochemical detection of endogenous serum albumin. Diffusion of [3H] 4-aminopyridine in the neocortex was studied by light-microscopic autoradiography. The spreading of the neuropathologic changes strictly followed the diffusion of the tritiated compound, suggesting the gradual involvement of neocortical layers in the seizure process.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ágoston D, Hargittai P, Nagy A (1983) Effects of a 4-aminopyridine in calcium movements and changes of membrane potential in pinched-off nerve terminals from rat cerebral cortex. J Neurochem 41:745–751
Baranyi A, Fehér O (1979) Convulsive effects of 3-aminopyridine on cortical neurones. Electroencephalogr Clin Neurophysiol 47:745–751
Bowman WC, Savage AO (1981) Pharmacological actions of aminopyridines and related compounds. Rev Pure Appl Pharmacol Sci 2:317–371
Bradbury M (1979) The concept of a blood-brain barrier. Wiley, New York, pp 351–382
Brierley JB, Brown AB (1981) Letter to the editor. Acta Neuropathol (Berl) 55:319–322
Cammermeyer J (1972) Nonspecific changes of the central nervous system in normal and experimental material. In: Bourne GH (ed) The structure and function of nervous tissue, vol 6. Academic Press, New York, pp 131–251
Corsellis JAN, Meldrum BS (1976) Epilepsy. In: Blackwood W, Corsellis JAN, McMenemey WH (eds) Greenfield's neuropathology. Arnold, London, pp 771–795
De Robertis E, De Lores Arnaiz GR, Alberici M (1969) Ultrastructural neurochemistry. In: Jasper H, Ward AA, Jr, Pope A (eds) Basic mechanisms of the epilepsies. Little, Brown & Co Boston, pp 137–158
Evans EA, Sheppard HC, Turner JC, Warell DC (1974) A new approach to specific labelling of organic compounds with tritium: catalysed exchange in solution with tritium gas. J Label Comp 10:569–587
Knyihár E, Csillik B (1970) Localization of inhibitors of the acetylcholine- and GABA-synthesizing systems in the rat brain. An autoradiographic assay on the distribution of [14C] hemicholinium and [14C] thiosemicarbazide. Exp Brain Res 11:1–16
Kuhnt U, Mihály A, Joó F (1983) Stimulation-dependent calcium binding sites in the guinea pig hippocampal slice: an electrophysiological and electron-microscopic study. Brain Res 279:19–30
Llinás R, Walton K, Sugimori M, Simon S (1982) 3- and 4-Aminopyridine in synaptic transmission at the squid giant synapse. In: Lechat P, Thesleff S, Bowman WC (eds) Aminopyridines and similarly acting drugs: Effects on nerves, muscles, and synapses. Pergamon Press, Oxford, pp 69–79
Matsumoto H, Ajmone-Marsan C (1964) Cortical cellular mechanism in experimental epileptic seizures. Exp Neurol 9:286–304
Mezö I, Seprödi J, Teplán I, Morgat JL, Fromageout P, Tóth G, Sirokmán F (1978) Synthesis of (Tyr-3H)4-angiotensin II and (Phe-3H)8-angiotensin II via halogen derivatives of angiotensin II. J Label Comp Radiopharmacol 14:557–567
Mihály A, Jójárt I (1982) Late increase of blood-brain barrier permeability in acute neocortical seizure focus: possible relations to human epilepsy. Neuroscience [Suppl] 7:S147
Mihály A, Ágoston D (1984) 4-Aminopyridine-induced ultrastructural alterations of pinched-off nerve terminals from rat cerebral cortex. Exp Brain Res 54:385–389
Mihály A, Joó F, Szente M (1983) Neuropathological alterations in the neocortex of rats subjected to focal aminopyridine seizures. Acta Neuropathol (Berl) 61:85–94
Noebels JL, Pedley TA (1977) Anatomic localization of topically applied [14C] penicillin during experimental focal epilepsy in cat neocortex. Brain Res 125:293–303
Okada K, Ayala GF, Sung JH (1971) Ultrastructure of penicillin-induced epileptogenic lesion of the cerebral cortex in cats. J Neuropathol Exp Neurol 30:337–353
Petito CK, Schaefer JA, Plum F (1977) Ultrastructural characteristics of the brain and blood-brain barrier in experimental seizures. Brain Res 127:251–267
Prince DA (1983) Ionic mechanisms in cortical and hippocampal epileptogenesis. In: Jasper HH, van Gelder NM (eds) Basic mechanisms of neuronal hyperexcitability. Liss, New York, pp 213–243
Prince DA, Wong RKS (1981) Human epileptic neurons studied in vitro. Brain Res 210:323–333
Rogawski MA, Barker JL (1983) Effects of 4-aminopyridine on calcium action potentials and calcium current under voltage clamp in spinal neurons. Brain Res 280:180–185
Rogers AW (1973) Techniques of autoradiography. Elsevier, Amsterdam, pp 123–147
Rutledge LT (1978) Effects of cortical denervation and stimulation on axons, dendrites, and synapses. In: Cotman CW (ed) Neuronal plasticity. Raven Press, New York, pp 273–289
Schwartzkroin PA (1983) Mechanisms of cell synchronization in epileptiform activity. Trends Neurosci 6:157–160
Siesjö BK (1981) Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1:155–185
Sloviter RS (1983) “Epileptic” brain damage in rats induced by sustained electrical stimulation of the perforant path. I. Acute electrophysiological and light-microscopic studies. Brain Res Bull 10:675–697
Sternberger LA (1974) Immunocytochemistry. Prentice-Hall, New Jersey, pp 129–171
Szente M, Pongrácz F (1981) Comparative study of aminopyridine-induced seizure activities in primary and mirror foci of cat's cortex. Electroencephalogr Clin Neurophysiol 52:353–367
Thesleff S (1980) Aminopyridines and synaptic transmission. Neuroscience 5:1413–1419
Yeh JZ, Oxford GS, Wu CH, Narahashi T (1976) Interactions of aminopyridines with potassium channels of squid axon membranes. Biophys J 16:77–81
Ward AA, Jr (1969) The epileptic neuron: chronic foci in animals and man. In: Jasper J, Ward AA, Jr, Pope A (eds) Basic mechanisms of the epilepsies. Little, Brown & Co, Boston, pp 263–288
Wilmes F, Hossmann K-A (1979) A specific immunofluorescence technique for the demonstration of vasogenic brain edema in paraffin-embedded material. Acta Neuropathol (Berl) 45:47–51
Author information
Authors and Affiliations
Additional information
Supported by the Hungarian Ministry of Health (grant no. 06/4-01/449)
Rights and permissions
About this article
Cite this article
Mihály, A., Tóth, G., Szente, M. et al. Neocortical cytopathology in focal aminopyridine seizures as related to the intracortical diffusion of [3H] 4-aminopyridine. Acta Neuropathol 66, 145–154 (1985). https://doi.org/10.1007/BF00688690
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00688690