HDT Preconditioning Inducing Brain Ischemic Tolerance In MCAO Rats

Background: In 1990, Kitagawa et al found that the neural cells in the gerbil cerebrum developed a resistance to ischemic neural damage after a brief reversible period. This phenomenon, which has been designated as "ischemic tolerance", has drawn attention in investigating its mechanism. However, the possibility of clinical application of the preconditioning methods is not yet to be elucidated, because of their toxicities or side effects. It is very important to search for a better preconditioning method. Therefore, we designed this study to investigate whether the head-down tilt bed rest(HDT) pretreatment induced ischemic tolerance in focal cerebral ischemia and to study the possible mechanism.Objective: To investigate the preprotective effects and the possible mechanism of HDT on the permanent middle cerebral artery occlusion (MCAO) in the animal model of the ischemia of rats brain.Methods: Twenty-eight male SD rats were devided into four groups randomly: H group(HDT); D group: interfered with Danshen droplet pills(3 pills,tid); C group(operation); N group(pseu-operation, the inserted thread length of N group is 15mm). The rat model of MCAO was established with the suture method after intervention with HDT or drug for 7 days. 24 hours post-operation, infarct size and infarction neurological deficits were measured. The histological damage was evaluated by HE staining. The serum level of VEGF before operation was measured by ELISA in H group and C group.Results: Compared with N group, there was significant difference in neurologic function in each operation group after 4 or 8 hours of the onset of occlusion, and there was no significant difference among groups H, D and C. The infarct volume of H and C groups were significantly smaller than those of C group ((294.94± 63.39 mm3 vs 169.39±37.00 mm3 and 185.66± 33.64 mm3, p<0.05, respectively) after 24 hours of permanent MCAO. In H or D groups, the histological damage of the penumbra area was reduced and neurological deficit was improved. However, there were no significant differences among groups H, D and C. The content of serum VEGF of H group was higher than that of C group before operation( p<0.05). At the same time, there was negative relation between the content of serum VEGF and the infarct volume(r = -0.594). Conclusion: The rat model of MCAO made by better Zea-Longa method is easier to gain success, simpler to operate, better to reproduct. The preconditioning by HDT will alleviate neuronal damage, reduce infarct volume and ameliorate neurological outcome. The brain tolerance may be associated with up-regulation of the content of serum VEGF.