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

Abstract

We have developed a functional vegetative model by an 18-min clamping of the ascending aorta combined with a bypass formation between the aorta to right atrium and the aorta to femoral vein. Complete global brain ischemia (CGBI) induced for 18 min with this model provided the following distinct advantages: cardiopulmonary functions were well preserved during postischemic recirculation, and all dogs survived without serious extracerebral complications. Neuronal damage in vegetative dog induced by an 18-min CGBI was studied by light and electron microscopy. The Purkinje cells and the hippocampal CA1 pyramidal cells showing clumping of nuclear chromatin and slightly increased stainability were observed after CGBI without recirculation. All these neurons showed transient increased stainability with microvacuolation 15 min after recirculation. Over 50% of these neurons showed virtually normal features 1 h after recirculation. Damage to these neurons progressed again slowly up to 6 h after recirculation. However, all these neurons had disintegrated 2-3 days after recirculation. A decrease in synaptic vesicles was observed in many presynaptic terminals in the molecular layers of the cerebellum after CGBI without recirculation. These changes in the presynaptic terminals progressed 15 min after recirculation. These results indicated that the damage to the Purkinje cells and the CA1 pyramidal cells induced by CGBI consisted of two phases, and that the change in the early phase was reversible. We speculate that the damage to the Purkinje cells in the early stage is related to the decrease of the synaptic vesicles in the presynaptic terminals.

Hypoxic changes in Purkinje cells of the human cerebellum

“…Darkened cells are characterized by an intensive (dark) staining of the perikaryal cytoplasm (so-called dark neurons, PC type III). These features are considered typical for neuronal necrosis and were described in Purkinje cells after intermittent hypoxia in rats [21] and after complete global brain ischemia in vegetative dogs [24]. To investigate the significance of the above-mentioned cytological criteria of cell necrosis for the diagnosis and timing of hypoxicinduced brain lesions, the various cell-types (PC I-III) were counted in samples from the cerebellar cortex of individuals with a history of acute or prolonged cerebral hypoxia/ ischemia before death.…”

“…Sato et al [24] investigated histological changes of neuronal damage in vegetative dogs induced by 18 min of complete global brain ischemia. The authors reported a two-phase damage of Purkinje cells and hippocampal CA1 pyramidal cells during cerebral ischemia and in the following recirculation period, whereby 50% of the damaged neurons had virtually recovered morphologically 1 h after recirculation but disintegrated 2-3 days later.…”

Pyruvate enhances neurological recovery following cardiopulmonary arrest and resuscitation

“…Oxidative and inflammatory cascades initiated during cerebral ischemia-reperfusion culminate in cell injury and death 7,8 which can continue for several days following transient ischemic insult. [9][10][11] Neuronal death following transient global ischemia involves both necrosis and apoptosis 12 and correlates with clinical impairment of function. 10 Pyruvate, a well documented natural antioxidant and metabolic fuel, 13 bolsters energy reserves and antioxidant redox state in post-ischemic and oxidant-injured myocardium.…”

Neuroprotective Effect of Taurine against Oxidative Stress-Induced Damages in Neuronal Cells

“…Excitatory amino acids including NMDA, AMPA and kainic acid are present in various regions of the CNS. AMPA induces neuronal degeneration, displaying cytoplasmic and nuclear condensation, neuron shrinkage (Gartwaite and Gartwait, 1991;, as well as some morphological characteristics of neurotoxicity observed in stroke head trauma and seizures (Kalimo et al, 1980;Soderfeldt et al, 1981;Griffins et al, 1984;Simon et al, 1984;Van Reempts, 1984;Sato et al, 1990;Vartanian et al, 1996). AMPA causes delayed cytotoxicity which is associated with various forms of apoptosis including DNA laddering into internucleosomal sized fragments and morphological damage .…”