Alterations in IGF-I, BDNF and NT-3 levels following experimental brain trauma and the effect of IGF-I administration

The effects of a unilateral, penetrating brain trauma on IGF-I, BDNF and NT-3 were studied immunocytochemicaly in the rat. BDNF and NT-3 were decreased in the peritraumatic area, but increased in the adjacent region, 4 and 12 h post-injury. One week following the trauma, BDNF remained low in the peritraumatic area, but was restored to normal levels in the adjacent, while no effect of injury on NT-3 levels was detected in either area. Injury resulted in an increase in IGF-I levels in the peritraumatic area, which was most pronounced 1 week following the trauma, indicating that IGF-I could participate in endogenous repair processes. We thus administered IGF-I immediately following the trauma and investigated its effects on injury-induced changes in neurotrophin levels. Administration of IGF-I partially reversed the injury-induced decrease in BDNF and NT-3 in the peritraumatic area observed 4 and 12 h post-injury, while at the same time-points, it completely cancelled the effects of injury in the adjacent region. One week after the trauma, BDNF levels were dramatically increased in both the peritraumatic and adjacent area, reaching levels even higher than those of the sham-operated animals, following IGF-I administration. Our results showing that IGF-I not only counteracts injury-induced changes in neurotrophins, but can also further increase their levels, indicate that this growth factor could mediate repair and/or protective processes, following brain trauma. (C) 2004 Elsevier Inc. All rights reserved.