Neuroprotective agents effective against radiation damage of central nervous system.

Ionizing radiation caused by medical treatments, nuclear events or even space flights can irreversibly damage structure and function of brain cells. That can result in serious brain damage, with memory and behavior disorders, or even fatal oncologic or neurodegenerative illnesses. Currently used treatments and drugs are mostly targeting biochemical processes of cell apoptosis, radiation toxicity, neuroinflammation, and conditions such as cognitive-behavioral disturbances or others that result from the radiation insult. With most drugs, the side effects and potential toxicity are also to be considered. Therefore, many agents have not been approved for clinical use yet. In this review, we focus on the latest and most effective agents that have been used in animal and also in the human research, and clinical treatments. They could have the potential therapeutical use in cases of radiation damage of central nervous system, and also in prevention considering their radioprotecting effect of nervous tissue.

Effects of low and high deprenyl dose on antioxidant enzyme activities in the adult rat brain.

We evaluated the effects of low dose deprenyl (LDD, 0.0025 mg/kg per day) and high dose deprenyl (HDD, 0.25 mg/kg per day) treatment of male Wistar rats for 30 days on the activities of SOD and CAT in the cortex, striatum, and hippocampus. Total SOD and MnSOD activities were increased with LDD (p <0.05) in the cortex (0.74 ± 0.03; 0.31 ± 0.02), striatum (0.75 ± 0.02; 0.27 ± 0.03) and CA1 region of the hippocampus (0.75 ± 0.02; 0.29 ± 0.03) compared to the control (0.53 ± 0.02; 0.15 ± 0.02), but reduced (p <0.05) with HDD compared to the LDD group. CAT activity was increased (p <0.05) with LDD in the cortex (27.34 ± 3.11), striatum (22.22 ± 1.85), and hippocampal CA1 region (16.62 ± 2.15) compared to control (10.33 ± 1.01), while a decrease was induced by HDD in the striatum (9.85 ± 1.09) compared to LDD. There was a significant (p <0.05) difference in number of Fluoro Jade B positive CA1 neurons induced by LDD (21.14 ± 2.85%) and HDD (12.61 ± 1.42%), as well as the number of NeuN positive CA1 neurons after LDD (183.35 ± 11.14 cells/mm) and HDD (238.45 ± 14.11 cells/mm (p < 0.05). Deprenyl showed a potential in improving the neurological outcome and reducing the oxidative damage.

Neuroprotection and antioxidants.

Ischemia as a serious neurodegenerative disorder causes together with reperfusion injury many changes in nervous tissue. Most of the neuronal damage is caused by complex of biochemical reactions and substantial processes, such as protein agregation, reactions of free radicals, insufficient blood supply, glutamate excitotoxicity, and oxidative stress. The result of these processes can be apoptotic or necrotic cell death and it can lead to an irreversible damage. Therefore, neuroprotection and prevention of the neurodegeneration are highly important topics to study. There are several approaches to prevent the ischemic damage. Use of many modern therapeutical methods and the incorporation of several substances into the diet of patients is possible to stimulate the endogenous protective mechanisms and improve the life quality.

Postconditioning Effectively Prevents Trimethyltin Induced Neuronal Damage in the Rat Brain.

Trimethyltin (TMT) is a toxic substance formerly used as a catalyst in the production of organic substances, as well as in industry and agriculture. TMT poisoning has caused death or severe injury in many dozens of people. The toxicity of TMT is mediated by dose dependent selective damage to the limbic system in humans and other animals, specifically the degeneration of CA1 neurons in the hippocampus. The typical symptoms include memory loss and decreased learning ability. Using knowledge gained in previous studies of global ischaemia, we used delayed postconditioning after TMT intoxication (8 mg/kg i.p.), consisting of applying a stressor (BR, bradykinin 150 µg/kg i.p.) 24 or 48 hours after the injection of TMT. We found that BR had preventive effects on neurodegenerative changes as well as learning and memory deficits induced by TMT intoxication.

Effect of Bradykinin Postconditioning on Ischemic and Toxic Brain Damage.

Brain damage caused by ischemia or toxic agents leads in selectively vulnerable regions to apoptosis-like delayed neuronal death and can result in irreversible damage. Selectively vulnerable neurons of the CA1 area of hippocampus are particularly sensitive to ischemic damage. We investigated the effects of bradykinin (BR) postconditioning on cerebral ischemic and toxic injury. Transient forebrain ischemia was induced by four-vessel occlusion for 10 min and toxic injury was induced by trimethyltin (TMT, 8 µg/kg i.p.). BR as a postconditioner at a dose of 150 µg/kg was applied intraperitoneally 48 h after ischemia or TMT intoxication. Experimental animals were divided into groups according to the length of survival (short-3 and 7 days, and long-28 days survival) and according to the applied ischemic or toxic injury. Glutamate concentration was lowered in both CA1 and dentate gyrus areas of hippocampus after the application of BR postconditioning in both ischemic and toxic brain damage. The number of degenerated neurons in the hippocampal CA1 region was significantly lower in BR-treated ischemic and toxic groups compared to vehicle group. The behavioral test used in our experiments confirms also the memory improvement in conditioned animals. The rats' ability to form spatial maps and learn was preserved, which is visible from our Barnes maze results. By using the methods of delayed postconditioning is possible to stimulate the endogenous protective mechanisms of the organism and induce the neuroprotective effect. In this study we demonstrated that BR postconditioning, if applied before the onset of irreversible neurodegenerative changes, induced neuroprotection against ischemic or toxic injury.