Mustafa Ayberk Kurt

Possible Neuroprotective Effects of Magnesium Sulfate and Melatonin as Both Pre- and Post-Treatment in a Neonatal Hypoxic-Ischemic Rat Model

Background: Perinatal hypoxia-ischemia is a major cause of mortality and long-term neurological deficits. Objectives: The objective of this study was to compare the effects of two neuroprotective agents; magnesium sulfate and melatonin, administered alone or in combination, on brain infarct volume and TUNEL positivity in a neonatal hypoxic-ischemic (HI) rat model. Methods: After being anesthetized, 7-day-old pups (n = 80) underwent ischemia followed by exposure to hypoxia for 2 h. The pups were then divided equally and randomly into 4 groups in order to receive the vehicle (saline, control group), magnesium sulfate, melatonin or a combination of magnesium sulfate and melatonin. Treatments were administered intraperitoneally three times; the first being just before ischemia, the second after hypoxia and the third 24 h after the second dose. The pups were sacrificed on postnatal day 10, their brains harvested and evaluated for infarct volume and neuronal apoptosis. Results: Percent infarcted brain volume was significantly reduced in pups receiving the drugs (either magnesium sulfate, melatonin or their combination) compared with those receiving the vehicle. In addition, TUNEL staining showed markedly reduced numbers of TUNEL-positive cells per unit area in the CA1, CA3 and dentate gyrus regions of the hippocampus and in the cortex. However, no statistically significant differences were found regarding percent infarcted brain volume and number of TUNEL-positive cells among the drug-treated groups. Conclusions: Magnesium sulfate and melatonin, two agents acting at different stages of HI brain damage, administered either alone or in combination, significantly reduced the percent infarcted brain volume and TUNEL positivity, suggesting that these agents may confer a possible benefit in the treatment of infants with HI encephalopathy.

Neuroprotective effects of melatonin administered alone or in combination with topiramate in neonatal hypoxic-ischemic rat model.

PURPOSE The objective of this study was to compare the effects of two neuroprotective agents; melatonin, a free radical scavenger and topiramate, AMPA/kainate receptor antagonist, administered alone or in combination in neonatal hypoxic-ischemic model. METHODS After being anesthetized, 7-day-old pups underwent ischemia followed by exposure to hypoxia. The pups were divided into 4 groups in order to receive the vehicle, melatonin, topiramate and combination of topiramate and melatonin. These were administered intraperitoneally for three times; the first before ischemia, the second after hypoxia and the third 24 hours after the second dose. After sacrification, infarct volume and apoptosis were evaluated. RESULTS Percent infarcted brain volume was significantly reduced in rats which received drugs compared with those which received the vehicle. The number of TUNEL positive cells per unit area in hippocampus and cortex were markedly reduced in drug treated groups compared with control group. No significant differences were found regarding percent infarcted brain volume and number of TUNEL positive cells among drug-treated groups. CONCLUSIONS Melatonin and topiramate, administered either alone or in combination significantly reduced the percent infarcted brain volume and number of TUNEL positive cells suggesting that these agents may confer benefit in treatment of infants with hypoxic-ischemic encephalopathy.

The peri-microvascular edema in hippocampal CA1 area in a rat model of sepsis

Encephalopathy is a common complication of sepsis. However, little is known about the morphological changes that occur in the brain during sepsis. In this study, fecal peritonitis was induced in Wistar rats, which had been monitored for 4 h before their brains were removed and samples from the CA1 area taken. In addition to higher blood pressure with a decreasing pattern and a significant drop in rectal temperature, an increased heart rate and marked respiratory failure were observed. The tissue was investigated and compared with corresponding hippocampal samples taken from sham‐operated and not operated control groups. Significantly more peri‐microvascular edema was found in the hippocampal CA1 area in the septic group. The percentages of the peri‐microvascular edema were 158.57 ± 3.6%, 122.84 ± 1.5% and 120.24 ± 1.9% in the fecal peritonitis group, sham‐operated and not operated control groups, respectively. The results may suggest that the edema observed around the microvessels may participate in the pathogenesis of the septic encephalopathy probably by causing in the microvascular permeability characteristics.

A case with coincidence of aberrant right subclavian artery and common origin of the carotid arteries.

An aortic arch variant was found in a 63 year-old male cadaver during routine dissection. An aberrant right subclavian artery (ARSA) arose from the distal aortic arch after the left subclavian artery and coursed to the right and upward behind the trachea and esophagus. A common origin for the carotid arteries (COCA) accompanied this variant of the right subclavian artery.

Effects of Propofol on Epileptiform Activity and Hippocampal Morphology inFebrile Convulsions and Pilocarpine Induced Seizures

Abstract Epidemiological and recent prospective analyses of long Febrile Seizures (FS) support the idea that such seizures can provoke Temporal Lobe Epilepsy (TLE) in some children. Because of the high prevalence of these seizures, if epilepsy was to arise as their direct consequence, this would constitute a significant clinical problem. Animal studies have revealed that exposure of hippocampal neurons to FS early in life, particularly prolonged or frequently repetitive FS, or together with brain malformation, may lead to sustained dysfunction of these cells including long-term memory impairment or epileptogenesis, in spite of the absence of neuronal damage. We established a hyperthermia model of febrile convulsions in young adult rats, and studied the effects of propofol treatment general anesthetic acting via GABA-A receptor on epileptiform activity and the morphological features of medial temporal lobe. We found statistically significant neuronal losses in the CA1, CA3 and dentate gyrus regions of hyperthermiaapplied rats as compared to the control rats. We also observed that propofol administration suppressed epileptic discharges in EEG and prevented clinical seizures behaviors. It took a median of 11 (range, 6-40) minutes for propofol to stop seizures. We conclude that prevention of epilepsy-related damage can be achieved via epileptogenesis-based clinical approaches, and that propofol is an effective agent in the hyperthermia-induced status epilepticus model.

Contents Vol. 99, 2011

S. Andersson, Helsinki E. Bancalari, Miami, Fla. J. Bhatia, Augusta, Ga. G. Buonocore, Siena W. Carlo, Birmingham, Ala. I. Choonara, Derby T. Curstedt, Stockholm C. Dani, Florence B. Darlow, Christchurch M. Fujimura, Osaka M. Hallman, Oulu W.W. Hay, Jr., Aurora, Colo. S.E. Juul, Seattle, Wash. M. Kaplan, Jerusalem B. Kramer, Maastricht R.J. Martin, Cleveland, Ohio C.J. Morley, Cambridge J. Neu, Gainesville, Fla. P.C. Ng, Hong Kong M.W. Obladen, Berlin A.G.S. Philip, Sebastopol, Calif. M. Post, Toronto E. Saliba, Tours O.D. Saugstad, Oslo M.S. Schimmel, Jerusalem B. Schmidt, Philadelphia, Pa. M.P. Sherman, Columbia, Mo. E.S. Shinwell, Rehovot K. Simmer, Perth, W.A. J. Smith, Tygerberg B. Sun, Shanghai N. Vain, Buenos Aires F. van Bel, Utrecht J.N. van den Anker, Washington, D.C. M. Vento Torres, Valencia M. Weindling, Liverpool J.A. Widness, Iowa City, Iowa Fetal and Neonatal Research