Ischemia/reperfusion-induced brain edema and changes of superoxide dismutase activity in rat brain tissue

Xiaoyang QIU; Maoqing GONG; Tinghua WANG

ABSTRACT

BACKGROUND:

The free radicals induced by cerebral ischemia/reperfusion consist mainly of xanthine oxidase, which induces cell swelling in the infarcted area.

OBJECTIVE:

To observe the changes of cerebral ischemia/reperfusioninduced changes in the activity of cerebral superoxide dismutase (SOD), an enzyme responsible for free radical clearance, and investigate the effect of apurin, a inhibitor of purine oxidase, on cellular water content in the brain tissue with ischemia/reperfusion injury.

DESIGN:

Completely randomized controlled study.

SETTING:

Department of Neurology of the Central Hospital Affiliated to Shenyang Medical College, Department of Neurosurgery of the First Hospital Affiliated to China Medical University, and Liaoning Provincial Orthopedic Hospital for Limb Disabilities.MATERIALS The experiment was conducted in the Laboratory of the Central Hospital Affiliated to Shenyang Medical College from May 2003 to April 2004. Forty Wistar rats were subjected to a 6-hour cerebral ischemia and randomized into 4 equal groups to receive intragastric administration of 100 mg/kg apurin (ischemia + apurin group), oxolinic acid suspension of the same dose (ischemia+ oxolinic acid group), 100 mg/kg apurin after a 2-hour reperfusion (Ischemia/reperfusion + apurin group), or oxolinic acid of the same dosage after the 2-hour reperfusion (ischemia/reperfusion + oxolinic acid goup), respectively. The rats in apurin group had intragastric administration of 100 mg/kg apurin 48, 24 and 1 hour before occlusion of the cervical internal carotid artery (CICA) to induce the ischemia, respectively. Oxolinic acid was given in the two oxolinic acid groups in the same manner.

METHODS:

Water content of brain tissue of rats was measured after 6 hours of CICA occlusion in the two ischemia groups and after the 2-hour perfusion in the two ischemia/reperfusion groups. Distribution of SOD in the brain tissue was observed with SOD immunostaining.MAIN OUTCOME

MEASURES:

Distribution of SOD and water content in the brain tissue of rats.

RESULTS:

In the two oxolinic acid groups, Cu-Zn SOD staining identified obviously increased staining intensity in the ischemic foci. Mn SOD staining in ischemia+oxolinic acid group resulted in increased circular staining surrounding the vessels in the ischemic foci, with also obvious staining of the vascular wall and neural cells. The ischemic foci of the ischemia/reperfusion + oxolinic acid group showed diffuse but lightly weaker staining. Cu-Zn SOD staining in the two apurin groups revealed no significant difference. In the two oxolinic acid groups, endothelial cell nuclear swelling of the arteriole, protrusion of the mid-layer myocytes, and expansion of the vascular membrane were observed, with the tissues surrounding the vessels appearing spongy. These changes were less severe in the two apurin groups. The water content in the brain tissue was (78.56±0.30) % in ischemia + apurin group and (78.85±0.49) % in ischemia/reperfusion + apurin group, significantly lower than that of (79.08±0.33) % in ischemia + oxolinic acid group and (79.86±0.49) % in ischemia/reperfusion + oxolinic acid group (P ＜ 0.05).

CONCLUSION:

Apurin can relieve tissue injury after cerebral ischemia/reperfusion by inhibition of SOD.