Effect of tetramethylpyrazine on the spatial learning and memory function of rats after focal cerebral ischemia

Background: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arterial resistance, increases cerebral blood flow, and improves microcirculation. Objective: To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats Design: A randomized controlled trial. Setting: Department of Human Anatomy and Histological Embryology, School of Medicine, Xi'an Jiaotong University. Materials: Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi'an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co.Ltd (Lot Number: 2004051106, Specification: 2 mL/piece). Methods: The experiments were carried out in School of Medicine of Xi'an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method: sham-operated group, cerebral ischemia control group, low-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections. Main outcome measures: The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed. Results: Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. 1 The rats in the cerebral ischemia control group manifested obvious spatial cognitive deficits in the place navigation trial and spatial probe trial. The mean values of escape latency in the sham-operated group, low, middle and high-dose TMP groups were obviously shorter than that in the cerebral ischemia control group [(23.92±2.21), (41.84±3.74), (39.5±3.80), (31.38±3.72), (61.60±3.61) s, P < 0.05-0.01]. In the spatial probe trial, significant differences in the percentage of time spending in the former platform quadrant and frequency of crossing the former platform site in the sham-operated group, lose, middle and high-dose TMP groups were obviously higher or more than those in the cerebral ischemia control group [(36.27±3.42) %, (35.84±2.54)%, (38.43±3.08)%, (36.51±1.96)%, (22.24±3.46)%; (11±1), (10±1), (8±1), (8±1), (4±1) times, P < 0.01]. 2 In the morphological observation, the numbers of neurons in ipsilateral (left) parietal cortex in the sham-operated group, low, middle and high-dose TMP groups were obviously more than that in the cerebral ischemia control group [(98±8), (65±5), (53±6), (57±6), (37±6)/0.625 mm², P < 0.01), but the number of neurons in left hippocampus had no obvious differences among the groups (P > 0.05). Conclusion: TMP can improve obviously the spatial learning and memory function after permanent focal cerebral ischemia in rats, and the neuroprotective role of the drug in cortex may be involved in its mechanism.