The effects of the pretreatment of intravenous high dose methylprednisolone on Na+-K+/Mg+2 ATPase and lipid peroxidation and early ultrastructural findings following middle cerebral artery occlusion in the rat

Abstract

The sodium-potassium activated and magnesium dependent adenosine-5'-triphosphatase (Na(+)-K(+)/Mg(+2) ATPase EC.3.6.1.3.) activity and lipid peroxidation and early ultrastructural findings were determined in rat brain at the acute stage of ischaemia produced by permanent unilateral occlusion of the middle cerebral artery (MCA). The effects of the pretreatment with intravenous high-dose methylprednisolone (MP) on these biochemical indices and ultrastructural findings were also evaluated in the same model. The rats were divided into four groups. In group I, 10 rats were used to determine Na(+)-K(+)/Mg(+2) ATPase activity and the extent of lipid peroxidation by measuring the malondialdehyde (MDA) content and normal ultrastructural findings. In group II on 20 rats, only subtemporal craniectomy was done in order to determine the effects of the surgical procedure on these indices and findings. This group was treated intravenously with saline solution before occlusion. In group III with MCA occlusion, saline solution was administered intravenously to 20 rats in the same amount of methylprednisolone used in group IV, ten minutes before the occlusion. In Group IV, a single high-dose (30 mg/kg) of methylprednisolone was administered intravenously, ten minutes before occlusion in 20 rats. After occlusion of the middle cerebral artery, Na(+)-K(+)/Mg(+2) ATPase activity was decreased promptly in the first ten minutes in the ischaemic hemisphere and remained at a lower level than the contralateral hemispheres in the same group and the normal levels in group I, during 120 minutes of ischaemia. A single dose methylprednisolone pretreatment prohibited the inactivation of Na(+)-K(+)/Mg(+2) ATPase. On the other hand, there was significant difference in malondialdehyde content between group I and group III. Malondialdehyde levels were significantly increased following ischaemia and a non-significant increase was observed in the contralateral hemisphere. Methylprednisolone treatment significantly decreased malondialdehyde content on the side of the ischaemic hemisphere. We conclude that there is a positive relationship between membrane-bound enzyme Na(+)-K(+)/Mg(+2) ATPase activity, malondialdehyde content and early ultrastructural changes in the treated group with MP. These data suggest that the pretreatment injection of high doses (30 mg/kg) methylprednisolone contribute to the protection of the brain from ischaemia with stabilization of the cell membrane by effecting the lipid peroxidation and the activation of Na(+)-K(+)/Mg(+2) ATPase.

Lazaroid Attenuates Edema by Stabilizing ATPase in the Traumatized Rat Brain

“…In the present study, inhibition of Na + /K + -ATPase activity was observed in the early phases following the trauma and remained at a decreased level throughout the first 24 h. A similar result was obtained in the studies of Ildan et al 34 and Jamme et al, 35 in which Na + /K + -ATPase activity diminished within a short period following the focal cerebral ischemia model in rats and remained below the control level over 120 minutes. On the other hand, the inhibition in the Mg 2+ /Ca 2+ -ATPase activity occurred soon after the trauma and became particularly marked at 24 h. This result is in accordance with the study of Parson et al 36 in which the inhibition of microsomal Mg 2+ /Ca 2+ -ATPase activity in rat brain subjected to global ischemia had increased to the maximum level after 60 minutes.…”

“…37,38 Experimental evidence suggests that the plasma membrane enzymes are a target site for neuroactive steroid action; methylprednisolone has been demonstrated to enhance Na + /K + and Mg 2+ -activated ATPase in the focal cerebral ischemia and spinal cord trauma animal models. 24,34 The present study provides evidence that U-83836E given prophylactically, enhances Na + /K + and Mg 2+ /Ca 2+ -ATPase activities, possibly by scavenging iron-catalyzed free radical formation, and inhibiting lipid peroxidation, 9 the latter of which was shown in our previous study. 39 21-aminosteroids have been shown to reduce edema in ischemic and traumatic brain injury, 15,16,40 possibly protecting the BBB from peroxidative damage.…”

Novel regimen through combination of memantine and tea polyphenol for neuroprotection against brain excitotoxicity

“…It is well documented that mitochondrial dysfunction associated with the loss of Ca 2+ homeostasis and enhanced cellular oxidative stress has long been recognized to play a major role in cell damage associated with excitotoxicity. Na + , K + ‐ATPase is known to be highly susceptible to free‐radical damage and lipid peroxidation because of its plasmalemmal embedding and its phospholipid requirement for maintenance of activity (Furui et al, 1990; Ildan et al, 1996). Mg 2+ ‐ATPase is also vulnerable to damage by reactive oxygen species.…”

Honokiol, a Neuroprotectant against Mouse Cerebral Ischaemia, Mediated by Preserving Na+, K+‐ATPase Activity and Mitochondrial Functions

“…A marked influx of Ca 2+ into neurones during ischaemia has been shown to provoke catastrophic events, leading to irreversible neuronal injury [23,24]. Additionally, Na + , K + ‐ATPase is known to be highly susceptible to free radical damage and lipid peroxidation due to its plasmalemmal embedding and its phospholipid requirement for maintenance of activity [25,26]. It is therefore proposed that the attenuation by honokiol of decreased Na + , K + ‐ATPase activity in response to ischaemia as described in the present report is due, at least in part, to the antioxidative action of the drug.…”

“…The time sequence of reactive oxygen species production during the first day of brain ischaemia, suggests that the machinery of reactive oxygen species formation is still processing in the freshly prepared synaptosomes. Reactive oxygen species is capable of oxidizing proteins, lipids and DNA, and thus alters the conformation and function of proteins; among them, Na + , K + ‐ATPase was found to be the most sensitive to be attacked [25,26]. As discussed above, the mitochondrial damage caused by the reactive oxygen species generated during brain ischaemia contributes to the neuronal cell death observed under this condition.…”