A study of the protective effects of lidocaine and nerve growth factor pretreatment on cerebral ischemia/reperfusion injury in gerbils

Abstract

To study the protective effects of lidocaine and nerve growth factor (NGF) pretreatment on cerebral ischemia/reperfusion (I/R) injury. Fifty-four Mongolian gerbils were randomly divided into nine groups: normal group (Group A), lidocaine control group (Group L), NGF control group (Group N), lidocaine pretreatment groups at the point of 12, 24, 48 hours (named respectively Group L12, L24, L48), NGF pretreatment groups with NGF given 12, 24, 48 hours before injury (named respectively Group N12, N24, N48), with 6 animals in each group. Except Group A, the carotid artery on both sides were occluded for 20 minutes, then they were released to allow reperfusion. Alteration of apoptosis was observed with terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and the expression of Bcl-2 and Bax was assessed by immunohistochemistry method. No apoptosis, Bcl-2 and Bax were found in Group A. In lidocaine or NGF pretreatment group, the expression of Bcl-2 (Group L12: 36.60 + or - 3.31, Group L24: 34.73 + or - 1.82, Group L48: 65.17 + or - 1.53; Group N12: 35.70 + or - 1.18 , Group N24: 37.30 + or - 3.86, Group N48: 62.77 + or - 2.91) was obviously increased comparing with control group (Group L: 24.53 + or - 1.48, Group N: 25.43 + or - 1.85), but the number of the apoptosis (Group L12: 32.87 + or - 0.99, Group L24: 31.90 + or - 4.14, Group L48: 24.50 + or - 0.70; Group N12: 32.80 + or - 1.27, Group N24: 32.83 + or - 1.30, Group N48: 23.30 + or - 0.86) and Bax expression (Group L12: 33.47 + or - 1.21, Group L24: 33.70 + or - 1.20, Group L48: 24.67 + or - 2.09; Group N12: 32.17 + or - 2.21, Group N24: 31.97 + or - 1.79, Group N48: 23.27 + or - 1.20) were significantly decreased comparing with the control group (the number of the apoptosis: Group L 67.43 + or - 3.92, Group N 67.80 + or - 3.82; Bax: Group L 59.73 + or - 1.32, Group N 59.37 + or - 1.54, P<0.05 or P<0.01). In lidocaine and NGF pretreatment groups, the number of cell apoptosis and expression Bax were significantly lower at 48 hours than those at 12 hours or 24 hours, but the cell expression Bcl-2 was obviously higher (all P<0.05). However, there was no difference between lidocaine and NEG pretreatment groups at each time point in regard of the number of cell apoptosis, expression of Bcl-2 and Bax. Lidocaine and NGF pretreatment before cerebral I/R can alleviate I/R injury to the cerebral tissue. The protective effect was most obvious when the treatment was given 48 hours before ischemia. The mechanism may be related with an increase in expression of Bcl-2 as well as a decrease in Bax level.