Neuroprotective Effects of Memantine in the Retina of Glaucomatous Rats: An Electron Microscopic Study.

PURPOSE: In this experimental study, the effects of systemic memantine administration on the retinal ultrastructure of experimentally induced glaucomatous rats were investigated. METHODS: Twenty-four Wistar albino rats were included in this study. Glaucoma was induced by injecting sodium hyaluronate into the anterior chamber of the rats for a period of three weeks. As a control, 8 rats were sham treated (Group C). Glaucoma induced animals were divided into two groups; Group M (n = 8) received a single daily dose of 10 mg/kg memantine, and Group G received the same volume of saline (n = 8), via intraperitoneal route for a period of six weeks, starting with the induction of glaucoma. Then, all rats were sacrificed and the retinas were prepared for electron microscopic examination. Electron microscopic damage findings were graded between 0 and 4 and mean damage scores for each cell or layer was calculated for each group. Statistical comparison was made between group G and group M. RESULTS: Including the photoreceptor cells, marked ultrastructural changes were observed in the retinas of the animals in group G. The ultrastructural changes in group M were modest and there was no significant cell death. Statistical findings indicated these results. CONCLUSION: Results of the present study suggest that memantine treatment, when started in the early phase of glaucomatous process, may help to preserve the retinal ultrastructure and thus prevent neuronal injury in experimentally induced glaucoma.

Dose-dependent ultrastructural and morphometric alterations after erythropoietin treatment in rat femoral artery vasospasm model.

PURPOSE: Cerebral vasospasm is the common cause of poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). Although many agents are experimentally and clinicaly used to protect or recover from vasospasm, an effective neurotherapeutic drug is still missing. Erythropoietin (EPO) is recently a promising candidate. The aim of this study is to investigate the dose-dependent effects of recombinant human EPO (rhEPO) on arterial wall in a rat femoral artery vasospasm model. METHODS: Thirty two animals were divided into four groups: vasospasm without any treatment (group A), vasospasm +250 IU/kg rhEPO group (group B), vasospasm +500 IU/kg rhEPO group (group C), and control group (group D). Rat femoral artery vasospasm model was used. For groups B and C, 7 days of 250 IU/kg and 500 IU/kg intraperitoneal rhEPO in 0.3 ml saline were administered respectively; and for groups A and D, 0.3 ml saline were administered intraperitoneally without any treatment. After 7 days, histological and morphometric analyses were carried out. RESULTS: Vasospasm alone group demonstrated the highest vessel wall thicknesses, comparing to other groups (p < 0.001). While for groups B and C, vessel wall thickness values were significantly higher than the control group (p < 0.001), between these two groups, there was no significant difference achieved (p > 0.05). CONCLUSION: In our study, there was no significant difference between the two rhEPO treatment groups, but rhEPO treatment was shown to be histologically and morphometrically effective in vasospasm. However, if dosage of EPO treatment is augmented, successful results may be achieved.

Suramin increased telomerase activity in the c6 glioma/wistar experimental brain tumor model.

Glioblastoma multiforme (GBM) is the most treatment-resistant glioma variant. Significant roles for telomerase in etiology, recurrence and drug resistance of GBM have been highlighted. Suramin (Bayer, Leverkusen, Germany) is an antineoplastic agent that affects many cellular mechanisms including growth factor, purinergic receptor, cytokine and key cellular enzymes signaling. The aim of this study was to investigate whether suramin, 40 mg/kg, i.p., inhibits telomerase activity in a subcutaneous C6 glioma/Wistar experimental brain tumor model using PCR based telomeric repeat amplification assay. In comparison to the control group, suramin increased tumor volume and telomerase activity. We also used transmission electron microscopy to evaluate the alterations of cell morphology. Apoptosis was seen markedly in electron micrographs of the control group and anti-apoptotic activity of telomerase was verified in the electron micrographs of suramin-applied group. The in vitro inhibitory effects of suramin on telomerase activity in several cell lines except for brain tumors have been reported. Contrary to in vitro reports, our results were the first to demonstrate that suramin increased telomerase activity in a C6 glioma/Wistar experimental brain tumor. Large numbers of drugs exhibited apparent hormetic effects on cultured cancer cells and in vivo cancer growth. Several drug examples for their hormetic effects in vivo were listed as resveratrol, suramin, and tamoxifen. The action of suramin in the present study could be evaluated as one of the hormetic examples of suramin in vivo.