Related factors of neural cell apoptosis in rats following brain laceration

Yunchi BAI; Zhisheng KAN; Jie BAI

ABSTRACT

BACKGROUND:

As the selective susceptible region following cerebral injury, hippocampus was found to be more sensitive to the extrinsic stimulation which would stimulate hippocampus region, then result in post-traumatic excessive expression of some immediate early genes, over release of excitatory amino acid and delayed death of nerve cells.

OBJECTIVE:

To study the relationship between the expression of nitrogen monoxide (NO) and endothelin and the apoptosis of nerve cell in cerebral hippocampus region following brain laceration.

DESIGN:

A comparative study based on paired t test and multiple linear correlative analysis.

SETTING:

Neurosurgery Department of Kailuan Hospital Affiliated to Northern China Coal Medical College.MATERIALSThis study was carried out at Molecular Biological Laboratory of Northern China Coal Medical College, from February to June 2003. Totally 126 healthy male Wistar rats, grade two, with body mass of 250-350 g,were randomly divided into three groups experimental group and control group of 60 rats, normal group of 6 rats, moreover the experimental group and control group were subdivided into 0.5 hour, 1 hour, 3 hours, 6 hours,12 hours, 24 hours, 72 hours, 120 hours, 168 hours, 240 hours time point subgroups with 6 rats in each subgroup.

METHODS:

Left parietal lobe laceration model was established on experimental rats by modified Feeney's free-drop traumatic method; rats in control group were only subjected to parietal skull opening without injury; rats in normal group were received no treatment. The level of Serum NO and endothelin, as well as the number of apoptosis nerve cell at hippocampus region were detected at each time point by using nitric acid deoxidase method, ELISA and in situ terminal labeled technique(TUNEL).MAIN OUTCOME

MEASURES:

Level of serum NO and endothelin,apoptosis of nerve cells in hippocampus region following brain laceration.

RESULTS:

Data of 126 rats were statistically analyzed without loss. ① The expression of serum NO, endothelin and apoptosis of nerve cells in hippocampus region of experimental rats All amounted to the peak level at post-Iaceration 6 hours [(81.45±2.41) mmol/L, (20.29 ±1.63) ng/L], which began to decline from onset of 12 hours [(66.11±1.97) mmol/L, (20.14±1.63)ng/L]. The level of NO at each time point from post-laceration 0.5 hour to 120 hours, and the level of endothelin of from 0.5 hour to 168 hour were significantly higher in experimental group in contrast with normal group and control group (t=3.33-27.91, P ＜ 0.01). ② The apoptosis of nerve cells in hippocampus region of experimental rats The apoptosis reached to the top at post-laceration 168 hours (27.33±l.86)x102/mm2, which began to decline at 240 hours (21.67±2.07) ×l02/mm2. No apoptosis cells could be observed in normal hippocampus, and less in control group. ③ The correlation of the level of NO and endothelin with the number of apoptosis of nerve cells in hippocampus region There was obviously positive correlation (r=0.838, P ＜ 0.01; r=0.281, P ＜ 0.05).

CONCLUSION:

There are definite correlation between the level of NO and endothelin and the number of nerve cells of apoptosis at hippocampus following cerebral laceration. NO and endothelin interacted each other,which involved in the pathophysiological process of cerebral laceration, and consequently resulted in the apoptosis of nerve cells in hippocampus region.