Changes of prostaglandin in early brain injury and therapeutic effect of indomethacin

Yuanfu TAN; Yaohua LI

ABSTRACT

BACKGROUND:

Traumatic brain injury generates a cascade of arachidonic acid metabolic events that mainly presented by the increment of prostaglandin and oxygen free radicals. Indomethacin can potently inhibit the activity of cyclooxygenase, decrease the synthesis of prostaglandins, and may decrease the production of oxygen free radical, and thus may attenuate the pathological changes of brain injury.

OBJECTIVE:

To observe the changes of prostaglandin in early brain injury and after indomethacin intervention, so as to explore the pharmacological mechanism of indomethacin.

DESIGN:

A randomized and controlled trial based on experimental animals.

SETTING:

Department of neurosurgery and department of cerebral surgery in a university hospital.MATERIALS This study was carried out at the Laboratory of Neurosurgery Department, Medical College of Southeast University between March and September 2000. Thirty-six hybrid cats were randomly divided into normal control group, brain injury group and indometbacin intervention group, with 12 cats in each group.

INTERVENTIONS:

Brain injury was simulated according to previously reported grading mechanical traumatic animal model establishment; cats with medium brain injury were enrolled in this study. The ultimate concentrations of prostacyclin (PGI2) and thromboxane A (TXA2) to 6-keto-prostaglandin F 1 alpha(6-keto-PGF1α) and thromboxane B2(TXB2) in brain vein blood, as well as total brain superoxide dismutase(SOD) and cerebral water content were measured 6 hours after trauma.MAIN OUTCOME

MEASURES:

6-keto-PGF1α, TXB2, SOD, and cerebral water content.

RESULTS:

Both 6-keto-PGF1α and TXB2 in brain vein blood remarkably increased in early brain injury[from(0.057±0.010) g/L to (0.264±0. 126) g/L, from(0. 060 ±0. 012) g/L to(0. 134 ±0. 048) g/L respectively], with the increment of the former higher than the latter, the ratio of TXB2/6-keto-PGF1α decreased from 1. 052 ±0. 145 to 0. 545 ±0. 184, and cerebral water content increased from(77.39 ± 0. 36)% to (78.06±0.41)% ; meanwhile, total brain SOD significantly decreased from (94. 869 ± 5. 418) μkat/g to(54. 368 ± 3. 417) μ kat/g( P ＜ 0.01) . In contrast to brain injury group, the concentrations of 6-keto-PGF1α and TXB2 in indomethacin intervention group significantly decreased, which were similar to those of control group, but the total SOD significantly increased from (54. 368 ±3. 417) pkat/g to (81. 433 ±7. 268) μkat/g (P ＜0. 01), and water content lightly decreased without statistical significance( P ＞ 0. 1 ).

CONCLUSION:

PGI2 and TXA2 increase in early brain injury in experimental cat model, accompanied by free radical synthesis, resulting in the exacerbation of brain injury. Indomethacin may be helpful to relieve posttraumatic secondary brain injury by regulating the imbalance of PGT2 / TXA2 and decreasing the production of free radical.