Lazaroid Attenuates Edema by Stabilizing ATPase in the Traumatized Rat Brain

Abstract

Brain edema associated with the traumatic brain injury (TBI) is a clinical phenomenon that exacerbates delayed cell death and may threaten life for some patients. Edema formation following a primary cerebral insult is seen as a sequela of secondary THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES 143 Lazaroid Attenuates Edema by Stabilizing ATPase in the Traumatized Rat BrainRamazan Durmaz, Güngör Kanbak, Fahrettin Akyüz, Serap Isiksoy, Ferruh Yücel, Mine Inal, Esref Tel From -adenosinetriphosphatase (ATPase) activities, tissue malondialdehyde levels and the neuronal viability in the rat brain subjected to cerebral trauma. Methods: Traumatic brain injury (TBI) was introduced by applying a 75 gm. cm force to the right parietal cortex using the weight-drop method. The first set of animals was used for determining time course changes of the synaptosomal Na + /K + and Mg 2+/Ca 2+ -ATPase and the malondialdehyde levels and were sacrificed 2, 6 and 24h after lesion production. A group of the animals was treated with U-83836E proir to TBI and sacrificed 24h after cerebral injury. A second set of animals was used for evaluating the alterations in BBB disruption and tissue water content and were sacrificed 2, 6 and 24h after lesion production. Two groups of animals were treated with U-83836E and sacrificed after 2 and 24h following TBI. U-83836E was given intraperitoneally thirty minutes before trauma at a dose of 10 mg/kg. Neuronal necrosis was also evaluated in the groups of U-83836E and physiological saline-treated animals. Results: Extravasation of Evans blue into the traumatized hemisphere was maximum at 2h (p<0.001) and returned close to the control levels at 24h after TBI (p>0.05). Edema had developed progressively over time and reached the maximum degree of 2.1 % (p<0.001) at 24 h. U-83836E showed no effect on the BBB breakdown and the tissue water content at 2h and still had no effect on the BBB breakdown after 24h following the trauma (p>0.05), although it reduced edema after 24h (p<0.01). The losses of Na + /K + and Mg 2+ /Ca 2+ -ATPase activities were found as 39.5 % (p<0.001) and 29.4 % (p<0.01) of the control value, respectively, and remained at the decreased levels throughout the experiment. Malondialdehyde level continued to increase over time reaching up to 209 % (p<0.001) of the control value 24h after TBI. Both ATPase activities were improved to near control values (p>0.05) by the effect of U-83836E. U-83836E inhibited the increase of lipid peroxidation (p<0.001) and also salvaged neuronal necrosis (p<0.05). Conclusion: U-83836E given prophylactically after cerebral trauma appears to reduce edema, possibly by inhibiting increases in lipid peroxidation and by stabilizing ATPase. Further studies are recommended to verify the similar effects of the brain penetrating lazaroids when they are given after trauma.RÉSUMÉ: Le lazaroïd (U-83836E) atténue l'oedème en stabilisant l'activité Na + /K + et Mg 2+ /Ca 2+ -ATPase dans le cerveau de rat traumatisé. Objectif: Le but de cette étude était de déterminer la v...

MALDI Mass Spectrometric Imaging of Lipids in Rat Brain Injury Models

“…Since the rest of the brain served as control tissue for this experiment, this alteration in images for these two ions from the same phosphatidylcholine was a sensitive indicator of events taking place at the molecular level in the tissue environment. We suggest that the increase in Na + which could occur during edema (32) and after loss of the Na + /K + -ATPase activity (33) and cell death would lead to the observed change in the MALDI IMS alkali attachment ion abundances. Our dry sublimation method preserved the alkali metal ions transferred to the tissues during the biochemical event, since the matrix added much later was deposited from the gaseous state (19).…”

Mitochondrial protection after traumatic brain injury by scavenging lipid peroxyl radicals

“…Similarly, studies done in cell cultures have shown that LOO • radical scavengers inhibit oxidant-stimulated Ca ++ influxes (Kimura et al 1992;Munns and Leach 1995). Secondly, U-83836E has been shown to stabilize ATPase activity in the traumatized brain (Durmaz et al 2003) which can potentially help the cell preserve Ca ++ homeostasis. Thirdly, U-83836E has also been effective in abrogating Ca ++ leak from endoplasmic reticulum following oxidant treatment (Racay et al 1997).…”

“…1992; Munns and Leach 1995). Secondly, U‐83836E has been shown to stabilize ATPase activity in the traumatized brain (Durmaz et al. 2003) which can potentially help the cell preserve Ca ++ homeostasis.…”

Neuroprotective Role of Lazaroids Against Aluminium Chloride Poisoning

“…Thus this compound not only provides protection against LPO thereby reducing cell damage but also restores its propagation within the membranes and cellular organelles such as mitochondria where it may on rise [28]. Lazaroids have shown to interact with the cross model membrane in an in vitro membranous system, which may show its protection to not only cell membranes but also intracellular components against peroxidative attack [29]. It is believed that lazaroids can also protect membranes via a direct interaction with the lipid bilayer and by shielding membrane proteins from proteolytic attack by their antioxidant action.…”