Adenovirus-Mediated Glial Cell Line-Derived Neurotrophic Factor (GDNF) Expression Protects against Subsequent Cortical Cold Injury in Rats

Neurobiology of Disease

Dirk M. Hermann¹  Ertugrul Kilic¹  Sebastian Kügler¹  Stefan Isenmann¹  Mathias Bähr¹ 

[1] Department of Neurology, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076, Tübingen, Germany;

关键词: adenoviral gene therapy;    brain trauma;    cortex trauma;    neurotrophin;    nitric oxide synthetase;    vasogenic edema;   

DOI  :  

来源: DOAJ

【 摘 要 】

We examined whether brain damage after focal cortex trauma may be attenuated by adenoviral delivery of the glial cell line-derived neurotrophic factor (GDNF) gene. For this reason, injections of vehicle, of an adenoviral vector deleted in the E1 region (Ad-dE1) or a vector expressing the GDNF gene from a CMV promoter (Ad-GDNF) were stereotactically placed in the rat sensorimotor cortex, and one day later cold lesions of the cerebral cortex were induced. Lesions were associated with pronounced brain swelling one day after injury. The degree of brain swelling was significantly attenuated by Ad-GDNF delivery (Ad-GDNF: 7.4 ± 2.2%, Ad-dE1: 21.1 ± 4.9%, vehicle: 20.9 ± 5.0% of contralateral; mean ± SEM, P < 0.05). Furthermore, Ad-GDNF treatment resulted in a significant reduction of the lesion volume seven days after lesioning (Ad-GDNF: 21.8 ± 2.8 mm3, Ad-dE1: 44.1 ± 1.6 mm3, vehicle 40.9 ± 8.6 mm3, P < 0.05). The decrease in the lesion size was associated with a reduction in the number of inducible nitric oxide (iNOS)(+), activated caspase-3(+) and DNA fragmented cells in the perilesion rim, as revealed by immunocytochemistry and terminal transferase biotinylated-dUTP nick end labeling (TUNEL). In Ad-GDNF-treated animals, the number of caspase-3(+) and TUNEL(+) cells was also reduced in the lesion-remote thalamus. The present study shows that adenoviral GDNF delivery is protective in focal cortex trauma.

【 授权许可】

Unknown