Biomedical subjects

Tolga F Koroglu

Publications and source records attributed to Tolga F Koroglu.

5 recordsLinked to original sources

PubMed2005

Erythropoietin downregulates bax and DP5 proapoptotic gene expression in neonatal hypoxic-ischemic brain injury.

BACKGROUND: Perinatal asphyxia is an important cause of neonatal mortality and subsequent serious sequelae such as motor and cognitive deficits and seizures. The ameliorative effect of erythropoietin (Epo) on experimental hypoxic-ischemic brain injury in neonatal rats has been recently reported. Recent studies also confirm the antiapoptotic effect of Epo in a variety of in vitro and in vivo neuronal injury models including hypoxic-ischemic brain injury. However, molecular mechanisms of Epo protection and antiapoptotic effect in this model are unclear. Epo may exert its antiapoptotic effect via the differential regulation of the expression of genes involved in the apoptotic process. OBJECTIVES: Thus, in the present study, we studied the effects of systemically administered Epo on antiapoptotic (bcl-2, bcl-XL), proapoptotic (bax and DP5) gene expression following hypoxic-ischemic brain injury in neonatal rats. METHODS: Seven- day-old Wistar rat pups were divided into three groups: control group (n=15), saline-treated group (n=17), and Epo-treated group (n=18). Rat pups were subjected to left carotid artery occlusion followed by 2.5 h of hypoxic exposure. Epo-treated group received an intraperitoneal injection of recombinant human Epo at a dose of 1,000 units/kg, saline-treated group received an intraperitoneal injection of saline at the same volume of Epo. Forty-eight hours after hypoxia, 3 animals in each group were killed for histopathological evaluation. To detect DNA fragmentation in cell nuclei, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling reaction was applied. Bcl-2 and bax protein expression were also analyzed with immunohistochemistry. For reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, rats were sacrificed 4, 12, and 24 h after hypoxia. Bcl-2, bcl-XL, bax, and DP5 mRNA expression were analyzed by RT-PCR. RESULTS: Epo significantly prevented hypoxia-ischemia-induced bax and DP5 mRNA upregulation in brain tissue. Epo did not show any effect on bcl-XL transcription altered by injury. However, Epo reversed injury-induced downregulation in bcl-2 transcription. Modulating effects of Epo on bcl-2 and bax protein expression were also revealed by immunohistochemistry. CONCLUSIONS: These results suggest that Epo exerts a neuroprotective effect against hypoxic-ischemic brain injury, at least partially, via the differential regulation of the expression of genes involved in apoptotic process.

Animals↗

PubMed2004

RNA interference in neuroscience.

One of the most exciting findings in recent years has been the discovery of RNA interference (RNAi). RNAi is an important system that allows sequence-specific gene silencing through targeted degradation of mRNA by cognate double-stranded RNA (dsRNA). RNAi plays a role in endogenous cellular processes, such as developmental control and heterochromatin formation, and serves as an antiviral defense mechanism. Recent findings suggest that RNAi and related pathways are involved in protecting the genome against instabilities caused by transposons and repetitive sequences. Several rapidly developing RNAi methodologies provide a new approach for elucidation of gene functions. RNAi technology is also currently being evaluated as a potentially useful method to develop highly specific dsRNA-based gene-silencing therapeutics. In this paper, we review the use of RNAi in neuroscience research and as a possible therapeutic tool for treatment of neurological diseases.

Animals↗

PubMed2004

Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxia-ischemia in rats.

It is well known that neonatal hypoxic-ischemic brain injury leads to mental retardation and deficits in cognitive abilities such as learning and memory in human beings. The ameliorative effect of erythropoietin (Epo) on experimental hypoxic-ischemic brain injury in neonatal rats has been recently reported. However, the effect of Epo on cognitive abilities in the hypoxic-ischemic brain injury model is unknown. The aim of this study is to investigate the effects of Epo on learning-memory, behavior and neurodegeneration induced by hypoxia-ischemia. Seven days old Wistar Albino rat pups have been used in the study (n = 28). Experimental groups in the study were: (1) saline-treated hypoxia-ischemia group, (2) Epo-treated (i.p., 1000 U/kg) hypoxia-ischemia group, (3) sham-operated group, (4) control group. In hypoxia-ischemia groups, left common carotid artery was ligated permanently on the seventh postnatal day. Two hours after the procedure, hypoxia (92% nitrogen and 8% oxygen) was induced for 2.5 h. Epo was administered as a single dose immediately after the hypoxia period. When pups were 22 days old, learning experiments were performed using Morris water maze. On the 20th week, when brain development is accepted to be complete, learning experiments were repeated. Rats were then perfused and brains removed for macroscopic and microscopic evaluation. Epo treatment immediately after hypoxic-ischemic insult significantly improved long-term neurobehavioral achievements when tested during the subsequent phase of brain maturation and even into adulthood. Histopathological evaluation demonstrated that Epo also significantly diminished brain injury and spared hippocampal CA1 neurons. In conclusion, Epo administrated as a single dose immediately after neonatal hypoxic-ischemic insult provides benefit over a prolonged period in the still developing rat brain. Since the wide use of Epo in premature newborns, this agent may be potentially beneficial in treating asphyxial brain damage in the perinatal period.

Analysis of Variance↗

PubMed2004

Erythropoietin and the nervous system.

Erythropoietin (Epo) is a hematopoietic growth factor and cytokine which stimulates erythropoiesis. In recent years, Epo has been shown to have important nonhematopoietic functions in the nervous system. Nonerythropoietic actions of Epo include a critical role in the development, maintenance, protection and repair of the nervous system. A wide variety of experimental studies have shown that Epo and its receptor are expressed in the nervous system and Epo exerts remarkable neuroprotection in cell culture and animal models of nervous system disorders. In this review, we summarize the current knowledge on the neurotrophic and neuroprotective properties of Epo, the mechanisms by which Epo produces neuroprotection and the signal transduction systems regulated by Epo in the nervous system.

Animals↗

PubMed2004

Erythropoietin as a novel neuroprotectant.

PURPOSE: To provide an overview of the current knowledge on neuroprotective properties of Erythropoietin (Epo), mechanisms by which Epo produces neuroprotection, and signaling pathways regulated by Epo in the nervous system. METHODS: The Medline database was searched for articles on the neuroprotective properties of Epo. Experimental and clinical studies were systematically reviewed. RESULTS: In addition to promoting the survival, proliferation, and differentiation of immature erythroid cells, Epo and the Epo receptor (EpoR) have recently been shown to exist and function in the nervous system. The Epo/EpoR system plays a critical role in neurodevelopment and neuroprotection. Epo ameliorates or prevents neuronal injury by neuroprotective, anti-apoptotic, anti-inflammatory, anti-oxidant, angiogenic, neurogenic and neurotrophic effects in cell culture and animal models of neurological diseases. The clinical effectiveness of recombinant human Epo in ischemic stroke in human patients has also been reported recently. CONCLUSION: Recent studies suggest that Epo is a potential novel neurotherapeutic agent and further clinical studies are warranted.

Animals↗