目的 通过大鼠局灶性脑缺血实验，探讨神经生长因子(NGF)在大脑局部脑缺血情况下通过血脑屏障（BBB）的最佳时间及机制，为NGF在临床上的应用提供新的用药途径。 方法  对65只健康雄性SD大鼠采用改良的线栓法制备局灶性脑缺血模型，按缺血后不同时间点，给予每只大鼠注入125 Ⅰ-NGF，利用γ射线计数仪检测γ计数量，观察缺血不同时间BBB通透性的改变。脑缺血后BBB通透性最大的时间点（缺血3 d）大鼠为实验组（15只），不制造脑缺血动物为对照组（15只）。对大鼠行脑冠状切片，通过放射自显影观察成影部位、面积及亮度。利用透射电子显微镜观察脑缺血不同时间BBB的变化。  结果  随脑缺血时间延长，BBB通透性逐渐增加，其中脑缺血后第3天BBB通透性最大，而后又逐渐减弱。在BBB相同通透性情况下，γ计数显示，伴随用药时间的延长对照组和实验组γ计数均有所增加，实验组各时间点γ计数高于对照组，两组比较差异均有显著性（P＜0.05），以用药 4 h γ计数最高。放射自显影结果显示，对照组给药1 h整个大脑不显影，4 h及7h脑室及室周脑组织显影，面积约占脑冠状切面的4.1%，亮度明显；实验组给药1 h右侧大脑表面显影，面积约占脑冠状切面的6%，亮度较强，4 h及7h除了脑室及室周脑组织显影外，在右侧脑额叶（FL）、顶叶（AL）和颞叶皮质和髓质中有大面积显影，面积占脑冠状切面的36.2%～47.3%，亮度很强。 结论 随着大鼠脑缺血时间延长BBB通透性增加，其中缺血3 d通透性最强；大鼠局灶脑缺血3 d用药4 h 125Ⅰ-NGF进入BBB量最大，在额叶、顶叶及颞叶显影最明显。NGF能通过局灶性脑缺血的血脑屏障，可能为临床给药途径提出新思路。

Objective  To investigate the optimal time and mechanism of nerve growth factor（NGF）crossing the bloodbrain barrier (BBB) under cerebral ischemia in rats through focal cerebral ischemia experiments in rats, and to provide a new way for the clinical application of NGF.   Methods  A total of 65 healthy Sprague-Dawlay (SD) male rats were prepared by using a modified suture method  to prepare focal cerebral ischemia models. Rats were injected with 125Ⅰ-NGF, and the γ count was measured with a γ-ray counter to observe the changes in BBB permeability at different times of ischemia. At the time point at which BBB permeability was greatest after cerebral ischemia (3 days ischemia), the rats were used as the experimental group (n=15). Coronal sections of the rats were subjected to autoradiography, and the imaging site, area and brightness were observed. The changes of blood-brain barrier at different times of cerebral ischemia with transmission electron microscope were observed.   Results  With the prolongation of cerebral ischemia time, the permeability of BBB increased gradually, and the permeability of BBB was the largest after 3 days of cerebral ischemia, and then weakened gradually. With the same permeability of BBB, the γ count showed that the γ counts of the control group and the experimental group increased with the prolonged medication time. The γ counts of the experimental group at each time point were higher than the control group. Significant difference (P<0.05) was found, and the highest γ count at 4 hours. The result  of autoradiography showed that the entire brain was not developed in the control group for 1 hour, and the ventricles and periventricular brain tissues were developed in 4 hours and 7 hours. The area occupied about 4.1% of the cerebral coronal section, and the brightness was obvious. The area was about 6% of the coronal section of the brain, and the brightness was strong. In addition to the development of the ventricles and periventricular brain tissues at 4 hours and 7 hours, in the right frontal lobe (FL), parietal lobe (AL) and temporal lobe, there was a large area in the medulla and the medulla, which covered 36.2% to 47.3% of the coronal section of the brain. The brightness was very strong.   Conclusion  BBB permeability increases with prolonged cerebral ischemia in rats, of which the permeability is the strongest at 3 days of ischemia; rats with focal cerebral ischemia at 3 days for 4 hours, 125Ⅰ-NGF enters the BBB in the largest amount, in the frontal and parietal. The temporal lobe is most obvious. NGF can pass the blood-brain barrier of focal cerebral ischemia and may become a new breakthrough in clinical drug delivery.