Ilgaz Akdogan

Grape seed extract has superior beneficial effects than vitamin E on oxidative stress and apoptosis in the hippocampus of streptozotocin induced diabetic rats.

We aimed to investigate the effects of grape seed extract (GSE) and vitamin E (Vit E) on oxidative stress and apoptosis in the hippocampus of streptozotocin-induced diabetic rats. In Control, Diabetic, and Diabetic treated with GSE (Diabetic+GSE) and vitamin E (Diabetic+Vit E) groups, oxidative stress index (OSI), TUNEL staining and Bcl-2, Bcl-XL, Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB gene expressions were evaluated. OSI was significantly increased in the plasma and hippocampus of the Diabetic compared to Control group and decreased in Diabetic+GSE and Diabetic+Vit E groups compared to Diabetic. TUNEL positive neurons significantly increased in the hippocampus of the Diabetic group compared to Control and decreased in Diabetic+GSE (more prominently) and Diabetic+Vit E groups compared to Diabetic. In the hippocampus of the Diabetic group, Bcl-2 and Bcl-XL gene expressions were significantly decreased; Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB gene expressions were significantly increased compared to Control. In Diabetic+GSE and Diabetic+Vit E groups, Bcl-2 gene expressions were significantly increased; Bcl-XL gene expressions did not differ compared to the Diabetic group. The expression of Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB genes in the Diabetic+GSE group and the expression of caspase-3 and -9, TNF-α, and NF-κB genes in the Diabetic+Vit E group were significantly decreased compared to Diabetic. In conclusion, GSE (more prominently) and vitamin E decreased oxidative stress and neuronal apoptosis occurring in the hippocampus of diabetic rats.

Hippocampal neuron number loss in rats exposed to ingested sulfite

Sulfite, which is continuously formed in the body during metabolism of sulfur-containing amino acids, is commonly used in preservatives. It has been shown that there are toxic effects of sulfite on many cellular components. The aim of this study was to investigate the possible toxic effects of sulfite on pyramidal neurons by counting cell numbers in CA1 and CA2-CA3 subdivisions of the rat hippocampus. For this purpose, male albino rats were divided into a control group and a sulfite group (25 mg/kg). Sulfite was administered to the animals via drinking water for 8 weeks. At the end of the experimental period, brains were removed and neurons were estimated in total and in a known fraction of CA1 and CA2-CA3 subdivisions of the left hippocampus by using the optical fractionator method—a stereological method. Results showed that sulfite treatment caused a significant decrease in the total number of pyramidal neurons in three subdivisions of the hippocampus (CA1 and CA2-CA3) in the sulfite group compared with the control group (p < 0.05, Mann Whitney U test). It was concluded that exogenous administration of sulfite causes loss of pyramidal neurons in CA1 and CA2-CA3 subdivisions of the rat hippocampus.

Penicillin-induced epilepsy model in rats: Dose-dependant effect on hippocampal volume and neuron number

This study was designed to evaluate the penicillin-induced epilepsy model in terms of dose-response relationship of penicillin used to induce epilepsy seizure on hippocampal neuron number and hippocampal volume in Sprague-Dawley rats. Seizures were induced with 300, 500, 1500 and 2000IU of penicillin-G injected intracortically in rats divided in four experimental groups, respectively. Control group was injected intracortically with saline. Animals were decapitated on day 7 of treatment and brains were removed. The total neuron number of pyramidal cell layer from rat hippocampus was estimated using the optical fractionator method. The volume of same hippocampal areas was estimated using the Cavalieri method. Dose-dependent decrease in hippocampal neuron number was observed in three experimental groups (300, 500 and 1500IU of penicillin-G), and the effects were statistically significant when compared to the control group (P<0.009). Dose-dependent decrease in hippocampal volume, on the other hand, was observed in all three of these groups; however, the difference compared to the control group was only statistically significant in 1500IU of penicillin-G injected group (P<0.009). At the dose of 2000IU penicillin-G, all animals died due to status seizures. These results suggest that the appropriate dose of penicillin has to be selected for a given experimental epilepsy study in order to demonstrate the relevant epileptic seizure and its effects. Intracortical 1500IU penicillin-induced epilepsy model may be a good choice to practice studies that investigate neuroprotective mechanisms of the anti-epileptic drugs.

Increased Tunel Positive Cells in CA1, CA2, and CA3 Subfields of Rat Hippocampus Due to Copper and Ethanol Co-Exposure

Copper (Cu) is an essential element for life. However, it is toxic at excessive doses, whereas exposure to ethanol (EtOH) has known to cause morphological changes, degeneration, and neuronal loss in central nervous system. A previous investigation by the authors’ group showed that Cu and EtOH co-treatment cause severe hippocampal neuronal loss in CA1, CA2, and CA3 subfields of rat hippocampus. This study was designed to analyze the possible mechanism(s) of action of this effect. In addition, the possible neurogenesis in response to a potent neurodegenerative treatment in rat hippocampus was analyzed. Results demonstrated that Cu and EtOH induced neuronal loss in rat hippocampus was in correlation with the increased cell death analyzed on the basis of TdT-mediated dUTP nick end labeling (TUNEL) assay. On the other hand, neuronal regenerative activity was detectable in analyzed CA1, CA2, and CA3 subfields of the rat hippocampus analyzed on the basis of 5-bromo-2′-deoxy-uridine (BrdU) labeling assay; however, this activity in treated group was not significantly different from that of control group.

Experimental Epilepsy Models and Morphologic Alterations of Experimental Epilepsy Models in Brain and Hippocampus

Epilepsy is a neurological disease arising from abnormal and uncontrollable electrical firings of a group of neurons appearing in the central nervous system. Experimental epilepsy models have been developed to assess the pathophysiology of epileptic seizures and to search for new effective anti-epileptic drugs. This chapter is designed to describe characteristics of experimental epilepsy models and morphological and anatomical changes of brain, particularly hippocampus (Figure 1), in these models. Because of the hippocampal neuronal hyperexcitability during epileptic seizures, hippocampus has been one of the best choices in terms of target area that reveals most efficiently the effects of seizures in experimental epilepsy models. The purpose of the study determines which model should be chosen for epilepsies. This type of studies may have three purposes: 1. Developing new drugs, 2. Exploring the mechanisms, 3. Determining the relationships between basic events and the development of events for epilepsy. An ideal model of epilepsy should have the following characteristics: 1. Seizures should be as the spontaneous recurrent seizures, 2. Seizures should be similar to seizures in humans, 3. The EEG pattern should be similar to related type of epilepsy, and 4. The frequency of seizures should be sufficient to test acute and chronic effects of drugs. However, there is no single model that meets all these criteria. Some researchers classify seizures according to generation of the epilepsy model, not according to seizures in humans. Experimental models are divided into three groups according to this classification: 1. experimental seizures induced by chemical convulsants or by electrical stimulation, 2. reflex epilepsies, and 3. idiopathic epilepsies. Epileptic seizures are classified in three groups: 1. Partial seizures, which can be further subdivided into simple partial seizures and complex partial seizures. 2. Generalized seizures which can be further subdivided into tonic, clonic, tonic-clonic (grand mal), absence (petit-mal) seizures, and status epilepticus. 3. Unclassified seizures. In experimental epilepsy studies, animal models have been developed according to this classification (Table-1).

Bilateral symmetric junctional infarctions of the cerebellum: a case report

The advances in neuroimaging have improved clinicoanatomic correlations in patients with stroke. Junctional infarct is a distinct term, used to describe border zone infarcts of the posterior fossa. We presented computed tomography (CT) and magnetic resonance imaging (MRI) findings in a rare case of bilateral symmetrical junctional infarcts between the superior cerebellar artery (SCA) and posterior inferior cerebellar artery (PICA) territories. In addition to precise knowledge of arterial territories required to achieve accurate localization of ischemic lesions on CT and MRI, the radiologist must also be aware of radiologic features and geographic territories of cerebellar arteries and their junctional infarctions.

Effect of nifedipine on hippocampal neuron number in penicillin-induced epileptic rats.

AIM Epileptic seizures lead to neuronal loss in the hippocampus. Experimental epilepsy can be induced by direct application of various chemicals to cerebral cortex. Nifedipine is an L-type voltage-dependent calcium channel blocker. In spite of several studies that show the seizure-suppressing effects of nifedipine, it has been shown that nifedipine does not suppress but conversely increases epileptic seizures. Similarly, contradictory effects of nifedipine have been reported, such as neuroprotection, failed neuroprotection and neurotoxicity. We therefore aimed to investigate the effect of nifedipine on hippocampal neuronal loss in penicillin induced epileptic rats in this study. MATERIAL AND METHODS The effect of nifedipine on total hippocampal neuron number was estimated by using the optical fractionator method (an unbiased stereological method) in penicillin-G induced epileptic rats. RESULTS The total number of hippocampal neurons in the control group was 183687 ± 3184. In the penicillin-induced group, the total neuron number significantly decreased to 146318 ± 3042 compared to the control group. In the nifedipine group, the neuron number significantly decreased to 128873 ± 1157 compared to both control and penicillin-induced groups. CONCLUSION Nifedipine increased neuronal loss and did not suppress epileptic seizures in penicillin-induced epileptic rats. Nifedipine could not protect against hippocampal neuronal loss in penicillin-induced epileptic rats.