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/

The sodium-potassium activated and magnesium dependent adenosine-5'-tr iphosphatase (Na+-K+/Mg+2 ATPase EC.3.6.1.3.) activity and lipid perox idation and early ultrastructural findings were determined in rat brai n at the acute stage of ischaemia produced by permanent unilateral occ lusion of the middle cerebral artery (MCA). The effects of the pretrea tment with intravenous high-dose methylprednisolone (MP) on these bioc hemical indices and ultrastructural findings were also evaluated in th e same model. The rats were divided into four groups. In group I, 10 r ats were used to determine Na+-K+/Mg+2 ATPase activity and the extent of lipid peroxidation by measuring the malondialdehyde (MDA) content a nd normal ultrastructural findings. In group II on 20 rats, only subte mporal craniectomy was done in order to determine the effects of the s urgical procedure on these indices and findings. This group was treate d intravenously with saline solution before occlusion. In group III wi th MCA occlusion, saline solution was administered intravenously to 20 rats in the same amount of methylprednisolone used in group IV, ten m inutes before the occlusion. In Group IV, a single high-dose (30 mg/kg ) of methylprednisolone was administered intravenously, ten minutes be fore occlusion in 20 rats. After occlusion of the middle cerebral arte ry, Na+-K+/Mg+2 ATPase activity was decreased promptly in the first te n minutes in the ischaemic hemisphere and remained at a lower level th an the contralateral hemispheres in the same group and the normal leve ls in group I, during 120 minutes of ischaemia. A single dose methylpr ednisolone pretreatment prohibited the inactivation of Na+-K+/Mg+2 ATP ase. On the other hand, there was significant difference in malondiald ehyde content between group I and group III. Malondialdehyde levels we re significantly increased following ischaemia and a non-significant i ncrease was observed in the contralateral hemisphere. Methylprednisolo ne treatment significantly decreased malondialdehyde content on the si de of the ischaemic hemisphere. We conclude that there is a positive r elationship between membrane-bound enzyme Na+-K+/Mg+2 ATPase activity, malondialdehyde content and early ultrastructural changes in the trea ted group with MP. These data suggest that the pretreatment injection of high doses (30 mg/kg) methylprednisolone contribute to the protecti on 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.