Changes of aquaporin-4 expressions after experimental intracerebral hemorrhage

Yanhua LI; Shanquan SUN; Lüli LI; Tiejian WANG

ABSTRACT

BACKGROUND:

Aquaporin-4 may be one of the candidates for inducing the brain edema in ischemic stroke, however, it still has not been reported whether aquaporin-4 is involved in the formation of brain edema after intracerebral hemorrhage (ICH).

OBJECTIVE:

To observe the expression of aquaporin-4 of cerebral tissue in the pathologic course of hemorrhagic cerebral edema in rats, and investigate itsrelationship with the formation of brain edema following ICH.

DESIGN:

A randomized controlled experimental study.

SETTING:

Department of Neurology, People's Hospital of Guangxi Zhuang Autonomous Region; Research Room of Neurobiology, Chongqing University of Medical Sciences.MATERIALS This experiment was carried out in the Research Room of Neurobiology, Chongqing University of Medical Sciences between April and October 2003. Totally 120 adult healthy male Wistar rats, weighing 250-300 g, were provided by the Experimental Animal Center of Chongqing University of Medical Sciences.

METHODS:

The experiment had four parts, each part (n=30) was divided into the control group (n=5) and operation group (n=25), and then the latter was subdivided into 6-hour, 1, 3, 5 and 7-day following ICH groups with 5rats in each group. In the operation group, ICH models were established by infusing collagenase into left caudate nucleus of rats unilaterally. The operative process in the control group was the same as that in the operation group except for infusing collagenase. Standards for successful model establishment the paralytic forelimb flexed under abdomen after withdrawal,and the normal forelimb extended to the ground. ① The expression of aquaporin-4 was detected with immunohistochemistry. ② The expression of aquaporin-4 mRNA was assessed with in situ hybridizution. ③ The expression of aquaporin-4 mRNA was assessed with reverse transcription polymerase chain reaction (RT-PCR). ④ The pathological changes of hemorrhagic edema were observed under transmission electron microscope.MAIN OUTCOME

MEASURES:

① expression of aquaporin-4 mRNAand protein; ② pathological changes of hemorrhagic edema.

RESULTS:

The model establishments were all successful in the operation group, and all the rats were involved in the analysis of results without deletion. ① Comparison of the expression of aquaporin-4 mRNA and protein among the groups. There was no significant change in the control group. As compared with the control group, there was a significant increase of the expressions of aquaporin-4 mRNA and protein in the edematous tissue at 6 hours following ICH, and then reached the peaks at 3 days, and the expression of aquaporin-4 was still significantly higher than that in the control group at one week following ICH (t=12.65, P ＜ 0.01). ② The corresponding sequential pathological changes in the edematous tissue of rats in the operation group There was a gradual increase of intracellular edema within 1-3 days following ICH, and then the brain edema became aggravated at 3 days, an emergence of vasogenic edema and local edema tissue degeneration and necrosis were observed.

CONCLUSION:

The increased expression of aquaporin-4 was obviously enhanced following ICH, suggesting that aquaporin-4 may play an important role in the pathological course of hemorrhagic brain edema, and inhibition of aquaporin-4 expression may be an effective pathway to prevent and treat brain edema.