Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Dec 2007
Early exposure to general anesthesia causes significant neuronal deletion in the developing rat brain.
Frequent exposure of children to general anesthesia is common practice in modern medicine. Although previously unrecognized, recent in vitro and in vivo animal studies suggest that exposure to clinically relevant general anesthetics at the peak of brain development could be detrimental to immature mammalian neurons, as demonstrated by massive and widespread apoptotic neurodegeneration. ⋯ To examine the effects of general anesthesia, the pharmacological agents known to cause extensive neuronal inhibition, on synaptic proteins, and neuronal survival at the peak of synaptogenesis, we exposed 7-day-old rat pups to general anesthesia (midazolam, 9 mg/kg of body weight, subcutaneously, followed by 6 h of nitrous oxide 75 vol% and isoflurane 0.75 vol%). We found that this general anesthesia causes permanent neuronal deletion in the most vulnerable brain regions-the cerebral cortex and the thalamus-while transiently modulating protein levels of synaptophysin, synaptobrevin, amphiphysin, SNAP-25, and CaM kinase II.
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Ann. N. Y. Acad. Sci. · Dec 2007
Drug delivery to the spinal cord tagged with nanowire enhances neuroprotective efficacy and functional recovery following trauma to the rat spinal cord.
The possibility that drugs attached to innocuous nanowires enhance their delivery within the central nervous system (CNS) and thereby increase their therapeutic efficacy was examined in a rat model of spinal cord injury (SCI). Three compounds--AP173 (SCI-1), AP713 (SCI-2), and AP364 (SCI-5) (Acure Pharma, Uppsala, Sweden)--were tagged with TiO(2)-based nanowires using standard procedure. Normal compounds were used for comparison. ⋯ Interestingly, when these compounds were administered in identical conditions after tagging with nanowires, their beneficial effects on functional recovery and spinal cord pathology were further enhanced. However, topical administration of nanowires alone did not influence trauma-induced spinal cord pathology or motor functions. Taken together, our results, probably for the first time, indicate that drug delivery and therapeutic efficacy are enhanced when the compounds are administered with nanowires.
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Ann. N. Y. Acad. Sci. · Dec 2007
A select combination of neurotrophins enhances neuroprotection and functional recovery following spinal cord injury.
Previously, we have shown that topical application of brain-derived neurotrophic factor (BDNF) or insulin-like growth factor 1 (IGF-1) given within 5 to 30 min after a focal trauma to the rat spinal cord attenuates spinal cord injury (SCI)-induced breakdown of the blood-spinal cord barrier (BSCB), edema formation, motor dysfunction, and cell injury. This investigation was undertaken to find out whether a combination of select neurotrophins (BDNF, glial cell line-derived neurotrophic factor [GDNF], neurotrophin 3 [NT-3], or nerve growth factor [NGF]) will further enhance the neuroprotective efficacy of growth factors in SCI. The neurotrophins (0.1-1 microg/10 microL in phosphate-buffered saline) were applied 30, 60, or 90 min after injury topically over the traumatized spinal cord either alone or in combination. ⋯ These beneficial effects of neurotropins were absent when administered separately either 60 or 90 min after SCI. However, a combination of BDNF and GDNF (but not with NT-3 or NGF) given either 60 or 90 min after SCI significantly reduced the motor dysfunction and spinal cord pathology at 5 h. These novel observations suggest that a select group of neurotrophins in combination have potential therapeutic value for the treatment of SCI in clinical situations.
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Ann. N. Y. Acad. Sci. · Dec 2007
ReviewChromosomes and expression in human testicular germ-cell tumors: insight into their cell of origin and pathogenesis.
Human germ-cell tumors (GCTs) are a heterogeneous group of neoplasms. Based on epidemiology, anatomical site of presentation, histology, chromosomal constitution, and pattern of genomic imprinting, GCTs are classified into five entities. Within the testis, three types of GCTs can be diagnosed: type I (teratomas and yolk-sac tumors of neonates and infants); type II (seminomas and nonseminomas); type III (spermatocytic seminomas). ⋯ Many characteristics of human TGCTs reflect the nonmalignant counterparts from which they originate. Demonstration of these characteristics, in combination with the knowledge of the abnormal niche of these cells, normally occupied by spermatogonia, allows an informative method for (early) diagnosis. The conclusion is that TGCTs are embryonic cancers found in adults.
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Ann. N. Y. Acad. Sci. · Dec 2007
Review Historical ArticleNeuro- and cardioprotective effects of blockade of nitric oxide action by administration of methylene blue.
Methylene blue (MB), generic name methylthioninium (C(16)H(18)ClN(3) S . 3H(2)O), is a blue dye synthesized in 1876 by Heinrich Caro for use as a textile dye and used in the laboratory and clinically since the 1890s, with well-known toxicity and pharmacokinetics. It has experimentally proven neuroprotective and cardioprotective effects in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. ⋯ The physiological effects during reperfusion include stabilization of the systemic circulation without significantly increased total peripheral resistance, moderately increased cerebral cortical blood flow, a decrease of lipid peroxidation and inflammation, and less anoxic tissue injury in the brain and the heart. The last two effects are recorded as less increase in plasma concentrations of astroglial protein S-100beta, as well as troponin I and creatine kinase isoenzyme MB, respectively.