Survival effects of BDNF and NT-3 on axotomized rubrospinal neurons depend on the temporal pattern of neurotrophin administration

被引:101
作者
Novikova, LN [1 ]
Novikov, LN [1 ]
Kellerth, JO [1 ]
机构
[1] Umea Univ, Sect Anat, Dept Integrat Med Biol, S-90187 Umea, Sweden
关键词
fluorescent tracers; rat; spinal cord injury; TrkB; TrkC;
D O I
10.1046/j.1460-9568.2000.00978.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
This study shows that both BDNF and NT-3 can prevent cell death in axotomized adult rat rubrospinal neurons (RSNs), but that the efficacy of neuroprotection depends on the temporal pattern of treatment. At 8 weeks after cervical spinal cord injury, 51% of the RSNs had died. Subarachnoidal BDNF infusion into the cisterna magna for 4 weeks resulted in neuronal hypertrophy and 71% survival. Continuous infusion for 8 weeks into the lumbar subarachnoidal space with either BDNF or NT-3 gave similar survival rates, while a combination of BDNF and NT-3 resulted in 96% survival, although the cells were atrophic. When administration of either BDNF or NT-3 was delayed and performed during postoperative weeks 5-8, the number of surviving neurons was increased compared to early treatment. Delayed treatment with a combination of BDNF and NT-3 resulted in complete survival and a reduction in neuronal atrophy. A decreased expression of TrkB receptors and microtubule-associated protein-2 in the RSNs after axotomy was counteracted by BDNF and NT-3. Microglial activity remained increased even when complete cell survival was achieved. Thus, the combination of neurotrophins as well as the temporal pattern of treatment need to be adequately defined to optimize survival of injured spinal tract neurons.
引用
收藏
页码:776 / 780
页数:5
相关论文
共 26 条
[11]   CHARACTERIZATION OF GLIAL TRKB RECEPTORS - DIFFERENTIAL RESPONSE TO INJURY IN THE CENTRAL AND PERIPHERAL NERVOUS SYSTEMS [J].
FRISEN, J ;
VERGE, VMK ;
FRIED, K ;
RISLING, M ;
PERSSON, H ;
TROTTER, J ;
HOKFELT, T ;
LINDHOLM, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (11) :4971-4975
[12]   TRKC EXPRESSION IN THE INJURED RAT SPINAL-CORD [J].
FRISEN, J ;
ARVIDSSON, U ;
LINDHOLM, T ;
FRIED, K ;
VERGE, VMK ;
CULLHEIM, S ;
HOKFELT, T ;
RISLING, M .
NEUROREPORT, 1993, 5 (03) :349-352
[13]   GDNF is a trophic factor for adult rat corticospinal neurons and promotes their long-term survival after axotomy in vivo [J].
Giehl, KM ;
Schacht, CM ;
Yan, Q ;
Mestres, P .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1997, 9 (11) :2479-2488
[14]   COLLATERALS OF RUBROSPINAL NEURONS TO THE CEREBELLUM IN RAT - A RETROGRADE FLUORESCENT DOUBLE LABELING STUDY [J].
HUISMAN, AM ;
KUYPERS, HGJM ;
CONDE, F ;
KEIZER, K .
BRAIN RESEARCH, 1983, 264 (02) :181-196
[15]   OVERLAPPING AND ADDITIVE EFFECTS OF NEUROTROPHINS AND CNTF ON CULTURED HUMAN SPINAL-CORD NEURONS [J].
KATO, AC ;
LINDSAY, RM .
EXPERIMENTAL NEUROLOGY, 1994, 130 (02) :196-201
[16]   Intraparenchymal NGF injections in adult and aged rats induce long-lasting Trk tyrosine phosphorylation [J].
Knusel, B ;
Kaplan, DR ;
Hefti, F .
EXPERIMENTAL NEUROLOGY, 1996, 139 (01) :121-130
[17]   Ligand-induced down-regulation of Trk messenger RNA, protein and tyrosine phosphorylation in rat cortical neurons [J].
Knusel, B ;
Gao, H ;
Okazaki, T ;
Yoshida, T ;
Mori, N ;
Hefti, F ;
Kaplan, DR .
NEUROSCIENCE, 1997, 78 (03) :851-862
[18]   Effects of systemic administration of 2-(4-phenyl-piperidino)-cyclohexanol (vesamicol) and an organophosphate DDVP on the cholinergic system in brain regions of rats [J].
Kobayashi, H ;
Watanabe, T ;
Yasufuku, T ;
Suzuki, T ;
Saitoh, S ;
Takeno, K .
BRAIN RESEARCH BULLETIN, 1997, 43 (01) :17-23
[19]   PRELABELED RED NUCLEUS AND SENSORIMOTOR CORTEX NEURONS OF THE RAT SURVIVE 10 AND 20 WEEKS AFTER SPINAL-CORD TRANSECTION [J].
MCBRIDE, RL ;
FERINGA, ER ;
GARVER, MK ;
WILLIAMS, JK .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1989, 48 (05) :568-576
[20]   Fetal spinal cord transplants rescue some axotomized rubrospinal neurons from retrograde cell death in adult rats [J].
Mori, F ;
Himes, BT ;
Kowada, M ;
Murray, M ;
Tessler, A .
EXPERIMENTAL NEUROLOGY, 1997, 143 (01) :45-60