ABSTRACT
Objective To investigate the effect of a selective muscarinic receptor antagonist (penehyclidine hydrochloride) in three vessel occlusion model of acute global cerebral ischemia-reperfusion in rats.Method One hundred and forty-four male SD rats were randomly divided into four groups:sham operated group,vehicle treated group (saline 1 ml,i.p.),scopolamine treated group (0.01 mg/kg,i.p.) and penehyclidine hydrochloride treated group (0.01 mg/kg,i.p.) with drugs injected 40 minutes before ischemia respectively.The ischemic duration was 10 minutes.The animals were subjected to motor activity tests (open field activity test,beam-walking test and grip test) at 24 hours or on the 3rd and 7th day after reperfusion.HE staining,TUNEL staining and immunohistochemical reactions of bax and bel-2 were carried out at the time points of 2,12,24 hours,3 and 7 days after reperfusion.TTC staining was carried out in some rats for assessment of infarction volume on the 4th day after reperfusion.Results As compared with the vehicle treated group,both penehyclidine hydrochloride treatment and scopolamine treatment decreased the numbers of apeptotie neurons (P
ABSTRACT
Gerbil forebrain ischemia/reperfusion(I/R) injury model was used to study the effects of D(1) and D(2) receptor agonists and antagonists on neuronal apoptosis of hippocampal CA1 area. All animals were tested for habituation deficits in an open field test on the 1st, 3rd and 7th days after reperfusion. The animals were then killed, and brains underwent paraffin embedding for hematoxylin-eosin staining, in situ terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling (TUNEL) staining and immunohistochemistry (bax, bcl-2). The result of open field test showed that the I/R group was significantly impaired (higher activity scores) when compared with the control group. Pretreatment with pergolide significantly reduced this habituation impairment. Forebrain ischemia for 5 min resulted in extensive CA1 apoptosis on the 3rd and 7th days after I/R injury. About 95% neurons in hippocampal CA1 area entered apoptosis and only 2%-7% pyramidal neurons stayed alive due to an inhibition of bcl-2 expression and an increase in bax expression. Pretreatment of pergolide attenuated neuronal damage caused by transient ischemia. Infusion of pergolide could induce the expression of bcl-2 and reduce the expression of bax. Pretreatment with SKF38393, SCH23390 and spiperone had no effects on these changes in this transient I/R injury model. All these results indicate that pergolide plays an important role in the protection of hippocampal neurons from apotosis through upregulating the expression of bcl-2 protein and reducing the expression of bax protein.