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Recent studies suggest that capillaries, neurons, and astrocytes form a functional unit that serves to maintain cerebral homeostasis. Physiological interactions between all these components of the neurovascular unit control cerebral microcirculation, while abnormal regulatory mechanisms lead to cerebral dysfunction and disease states, such as Alzheimer’s disease (AD). Using electron microscopy, we studied a fragment of the frontotemporal cortex obtained intraoperatively from a patient with established AD. The objective of our study was to assess the ultrastructure of the components of the neurovascular unit. Such ultrastructural studies allow analyzing the structural process of new blood vessels formation and also the appearance of neurons and astrocytes contributing to the neurovascular unit. We suggest that dysfunction of particular components of the neurovascular unit underlies AD and ultimately leads to neurodegeneration.
Poly(ADP-ribose) polymerase (PARP EC 2.4.2.30) is a key enzyme in the DNA repair machinery, but its excessive stimulation during reperfusion after ischemia could play a critical role in cell death. Our previous study indicated that the PARP inhibitor 3-aminobenzamide (3-AB) significantly protected neuronal cells against death after a short ischemic insult. In this study we investigated the effect of 3-AB on the ischemia-evoked alterations in intracellular organelles. Gerbils were submitted to 3 min of transient forebrain ischemia followed by reinstitution of recirculation for 1-7 days. Electron microscopy showed only the signs of necrotic cell death after ischemia-reperfusion. The examination of specimens revealed a pronounced protective effect of 3-AB on the swelling of astrocytes and neurons 1 day after the ischemic insult. 3-AB also decreased the swelling of pericytes, but it had no effect on the accumulation of osmiophilic inclusions and fibril formation in astrocytes. 3-AB decreased the ischemia-induced swelling of mitochondria. The protective effects of 3-AB on cellular ultrastructure were also observed 7 days after reperfusion. These findings indicate that the inhibition of PARP may have a protective effect on cell swelling and on the state of intracellular organelles after a short-term ischemic episode.
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Glial scar instability after brain injury

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Glial scar is formed following surgical damage to the cerebral cortex. In the present study we examined the ultrastructural status of the cerebral cortex 14 to 180 days following surgical damage to cerebral parenchyma. The results showed a contribution of astrocytes, but also mesodermal cells, to the process of scar formation. Furthermore, our study showed that the process initiated by trauma did not terminate with the formation of a glial scar. Late phases of repair following tissue damage were associated with lytic processes and a disassembly of the cerebral parenchyma. These findings indicate a changing and unstable nature of the glial scar and its components.
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The aging corotid body

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The respiratory system is subject to the aging process, which could limit its responsiveness to hyperventilatory stimuli. Attenuation of the ventilatory response to hypoxia in old age is, as yet, an unresolved issue. Such attenuation may be germane for the pathogenesis of respiratory disorders developing more often in elderly subjects. The aim of this study was to determine the potential adverse effects of age on the morphology and function of carotid bodies. Morphology was studied at the level of electron microscopy on carotid bodies dissected from adult young (3 months) and old (>2 years) rats and function by comparing the hypoxic ventilatory response in populations of young (mean age 24 years) and old (mean age 71 years) female subjects. The human protocol consisted of a progressive hypoxia test, based on a rebreathing technique in a closed system. The hypoxic ventilatory response was evaluated from the slopes of minute ventilation on arterial oxygen saturation. The results of the morphological study showed degenerative changes developing with age in the ultrastructure of carotid bodies. On the other side, respiratory responses to hypoxia in old women were well preserved and were no less than those in young women. Therefore, a discrepancy appeared between the morphological and functional aspects. These findings suggest development of compensatory mechanisms in brain respiratory areas which maintain primary defensive reflexes, such as the hyperventilation of hypoxia.
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