Summary
The understanding of delayed hippocampal death as a therapeutic window for post-ischemic treatment of the brain has led to numerous investigations focusing upon underlying cellular mechanisms and pharmacological potentials in gerbils and rats. Nevertheless, studies on the occurrence of delayed neuronal death in the human brain have been singular and dealt with only small files of patients. To complement these limited data, in the present study 26 adult patients with a history of a single cardiac arrest were included. Following successful resuscitation, individual survival ranged from less than 1 h to 186 days (\(\overline x \)= 11 days). The severity of the resultant ischemic injury in hippocampus CA1, among Purkinje cells, or in frontal neocortex, respectively, was quantified by direct counting of necrotic neurons. Additionally, hippocampal specimens were immunostained for neuron-specific enolase. The data obtained demonstrate the occurrence of delayed neuronal death in human hippocampus and, in a minor form, in cerebellar Purkinje cells. This is in contrasts to the immediate manifestation of ischemic neuronal necrosis in the neocortex. Unlike previous findings in experimental animals and in humans, the delay of CA1 cell death could be defined as lasting about 7 days following cardiac arrest. Moreover, the immunohistochemical results indicate delayed neuronal recovery in CA1, which in the time course reciprocally corresponds to delayed manifestation of hippocampal neuronal death. Interpretation of the results must consider the lack of information about the exact individual duration of cardiac arrest and resuscitation, as well as missing data concerning pre-ischemic physiological variables.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Benveniste H, Jorgensen MB, Diemer NH, Hansen AJ (1988) Calcium accumulation by glutamate receptor activation is involved in hippocampal cell damage after ischemia. Acta Neurol Scand 78:529–536
Duchen LW (1992) General pathology of neurons and neuroglia. In: Adams JH, Duchen LW (eds) Greenfield's neuropathology, 5th edn. Edward Arnold, London, pp 11–14
Hekmatpanah J (1973) Cerebral blood flow dynamamics in hypotension and cardiac arrest. Neurology 23:174–181
Hossmann K-A (1985) Post-ischemic resuscitation of the brain: selective vulnerability versus global resistance. Prog Brain Res 63:3–17
Hossmann V, Hossmann K-A (1973) Return of neuronal functions after prolonged cardiac arrest. Brain Res 60:423–438
Ito U, Spatz M, Walker JT, Klatzo I (1975) Experimental cerebral ischemia in Mongolian gerbils. Acta Neuropathol (Berl) 32:209–223
Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69
Kirino T, Tamura A, Sano K (1984) Delayed neuronal death in the rat hippocampus following transient forebrain ischemia. Acta Neuropathol (Berl) 64:139–147
Kirino T, Tamura A, Sano K (1985) Selective vulnerability of the hippocampus to ischemia — reversible and irreversible types of ischemic cell damage. Prog Brain Res 63:39–58
Kirino T, Tamura A, Sano K (1986) A reversible type of neuronal injury following ischemia in the gerbil hippocampus. Stroke 17:455–459
Kogure K, Tanaka J, Araki T (1988) The mechanism of ischemia-induced brain cell injury. Neurochem Pathol 9:145–170
Kuroiwa T, Bonnekoh P, Hossmann K-A (1990) Therapeutic window of CA1 neuronal damage defined by an ultrashortacting barbiturate after brain ischemia in gerbils. Stroke 21:1489–1493
Marangos PJ (1990) Neuron-specific enolase as a clinical tool in neurologic and endocrine disease. In: Gratzl M, Langley K (eds) Markers for neural and endocrine cells. VCH, Weinheim, pp 181–183
Matsumoto M, Yamamoto K, Homburger HA, Yanagihara T (1987) Early detection of cerebral ischemic damage and repair process in the gerbil by use of an immunohistochemical technique. Mayo Clin Proc 62:460–472
Monoghan DT, Cotman CW (1985) Distribution of N-methyl-d-aspartate-sensitive l[3H] glutamate binding sites in rat brain. J Neurosci 5:2909–2919
Olson JMM; Greenamyre JT, Penney JB, Young AB (1987) Autoradiographic localization of cerebellar excitatory amino acid binding sites in the mouse. Neuroscience 22:913–923
Petito CK, Feldman E, Pulsinelli WA, Plum F (1987) Delayed hippocampal damage in humans following cardiorespiratory arrest. Neurology 37:1281–1286
Pulsinelli WA (1985) Selective vulnerability: morphological and molecular characteristics. Prog Brain Res 63:29–37
Ross CA, Bredt D, Snyder SH (1990) Messenger molecules in the cerebellum. Trends Neurosci 13:216–222
Rothman SM, Olney JW (1987) Excitotoxicity and the NMDA receptor. Trends Neurosci 10:299–302
Sato M, Hashimoto H, Kosaka F (1990) Histological changes of neuronal damage in vegetative dogs induced by 18 minutes of complete global brain ischemia: two-phase damage of Purkinje cells and hippocampal CA1 pyramidal cells. Acta Neuropathol 80:527–534
Siesjö BK (1988) Mechanisms of ischemic brain damage. Crit Care Med 16:954–963
Spielmeyer W (1925) Zur Pathogenese der örtlich elektiven Gehirnveränderungen. Z Neurol Psychiatr 99:756–777
Symon L (1985) Flow thresholds in brain ischemia and the effects of drugs. Br J Anaesth 57:34–41
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Horn, M., Schlote, W. Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia. Acta Neuropathol 85, 79–87 (1992). https://doi.org/10.1007/BF00304636
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00304636