scholarly journals Intraventricular administration of neurotrophic factor midkine ameriolates hippocampal delayed neuronal death following transient global ischemia in gerbils.

Nosotchu ◽  
1998 ◽  
Vol 20 (6) ◽  
pp. 720-724
Author(s):  
Yoshihiro Yoshida ◽  
Shinya Ikematsu ◽  
Sha-en Wang ◽  
Masamichi Goto ◽  
Jun-ichiro Tsutsui ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Neuronal Death ◽  
Global Ischemia ◽  
Delayed Neuronal Death ◽  
Intraventricular Administration ◽  
Transient Global Ischemia

Neuroprotective Effects of Dexmedetomidine in the Gerbil Hippocampus after Transient Global Ischemia 

1997 ◽  
Vol 87 (2) ◽  
pp. 371-377 ◽  
Author(s):  
Johanna Kuhmonen ◽  
Jaroslav Pokorny ◽  
Riitta Miettinen ◽  
Antti Haapalinna ◽  
Jukka Jolkkonen ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Global Ischemia ◽  
Neuroprotective Effects ◽  
Bilateral Carotid Occlusion ◽  
Bilateral Carotid ◽  
Adrenoceptor Agonists ◽  
Transient Global Ischemia ◽  
Alpha2 Adrenoceptor ◽  
Alpha2 Receptor ◽  
Dentate Hilus

Background Cerebral ischemia induces a massive release of norepinephrine associated with neuronal death in the brain. It has been demonstrated that alpha2-adrenoceptor agonists decrease the release and turnover of noradrenaline, and this might prove advantageous in counteracting the neurodegeneration in ischemic brain. Therefore, in the present study, the authors tested whether dexmedetomidine, a selective alpha2-receptor agonist, has neuroprotective effects in a gerbil transient global ischemia model. Methods Ischemia was induced by bilateral carotid occlusion for 5 min in diethylether-anesthetized normothermic gerbils. Dexmedetomidine was administered subcutaneously in four different treatment paradigms (6-8 animals/group): 3 or 30 microg/kg 30 min before and thereafter at 3, 12, 24, and 48 h after the occlusion, or 3 or 30 microg/kg at 3, 12, 24, and 48 h after the occlusion. Control animals were subjected to forebrain ischemia but received only saline injections. One week after occlusion, animals were transcardially perfused for histochemistry. Neuronal death in the CA1 and CA3 regions of the hippocampus and in the hilus of the dentate gyrus was evaluated in silver-stained 60-microm coronal sections. Results Compared with saline-treated ischemic animals, dexmedetomidine at a dose of 3 microg/kg given before and continued after the induction of ischemia reduced the number of damaged neurons in the CA3 area (2 +/- 3 vs. 17 +/- 20 degenerated neurons/mm2; P < 0.05). Also in the dentate hilus, the number of damaged neurons was reduced by dexmedetomidine (3 microg/kg) given before and continued after ischemia (5 +/- 7 vs. 56 +/- 42 degenerated neurons/mm2; P < 0.01). Conclusions The present data demonstrate that dexmedetomidine effectively prevents delayed neuronal death in CA3 area and in the dentate hilus in gerbil hippocampus when the management is started before the onset of ischemia and continued for 48 h after reperfusion. Inhibition of ischemia-induced norepinephrine release may be associated with neuroprotection by dexmedetomidine.

scholarly journals DNA Fragmentation Follows Delayed Neuronal Death in CA1 Neurons Exposed to Transient Global Ischemia in the Rat

1997 ◽  
Vol 17 (9) ◽  
pp. 967-976 ◽  
Author(s):  
Carol K. Petito ◽  
Jorge Torres-Munoz ◽  
Brenda Roberts ◽  
John-Paul Olarte ◽  
Thaddeus S. Nowak ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Neuronal Death ◽  
Nuclear Dna ◽  
P53 Protein ◽  
Global Ischemia ◽  
Delayed Neuronal Death ◽  
Ca1 Neurons ◽  
Morphological Studies ◽  
Eosinophilic Cytoplasm

Apoptosis is an active, gene-directed process of cell death in which early fragmentation of nuclear DNA precedes morphological changes in the nucleus and, later, in the cytoplasm. In ischemia, biochemical studies have detected oligonucleosomes of apoptosis whereas sequential morphological studies show changes consistent with necrosis rather than apoptosis. To resolve this apparent discrepancy, we subjected rats to 10 minutes of transient forebrain ischemia followed by 1 to 14 days of reperfusion. Parameters evaluated in the CA1 region of the hippocampus included morphology, in situ end labeling (ISEL) of fragmented DNA, and expression of p53. Neurons were indistinguishable from controls at postischemic day 1 but displayed cytoplasmic basophilia or focal condensations at day 2; some neurons were slightly swollen and a few appeared normal. In situ end labeling was absent. At days 3 and 5, approximately 40 to 60% of CA1 neurons had shrunken eosinophilic cytoplasm and pyknotic nuclei, but only half of these were ISEL. By day 14, many of the necrotic neurons had been removed by phagocytes; those remaining retained mild ISEL. Neither p53 protein nor mRNA were identified in control or postischemic brain by in situ hybridization with riboprobes or by northern blot analysis. These results show that DNA fragmentation occurs after the development of delayed neuronal death in CA1 neurons subjected to 10 minutes of global ischemia. They suggest that mechanisms other than apoptosis may mediate the irreversible changes in the CA1 neurons in this model.

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