Lazaroid attenuates edema by stabilizing ATPase in the traumatized rat brain.
OBJECTIVE
The aim of the present study was to determine the potential therapeutic value of the lazaroid U-83836E on blood brain barrier (BBB) breakdown and edema with respect to the changes in the synaptosomal Na+/K+ and Mg(2+)/Ca(2+)-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 24h. 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>.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).


CONCLUSIONS
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.
Durmaz
Ramazan
R
Department of Neurosurgery, Medical Faculty of Osmangazi University, TR-26480, Eskisehir, Turkey.
Kanbak
Güngör
G
Akyüz
Fahrettin
F
Isiksoy
Serap
S
Yücel
Ferruh
F
Inal
Mine
M
Tel
Esref
E
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001834:Body Water / Q000187:drug effects / Q000502:physiology; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy*; D017301:Ca(2+) Mg(2+)-ATPase / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002839:Chromans / Q000494:pharmacology*; D004487:Edema / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005070:Evans Blue; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
D002839:Chromans; D018696:Neuroprotective Agents; D010879:Piperazines; C066382:U 78517F; D005070:Evans Blue; D008315:Malondialdehyde; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase