Rudge J S, Mather P E, Pasnikowski E M, Cai N, Corcoran T, Acheson A, Anderson K, Lindsay R M, Wiegand S J
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
Exp Neurol. 1998 Feb;149(2):398-410. doi: 10.1006/exnr.1997.6737.
Systemic administration of the excitotoxin kainic acid to adult rats results in a well defined pattern of loss of the CA1 and CA3 pyramidal neurons of the hippocampus. Prior to this neuronal loss, brain-derived neurotrophic factor (BDNF) mRNA is substantially increased. We show here that BDNF protein is increased after excitotoxic insult in specific areas of the hippocampus, reaching maximal levels 24 h after the insult. BDNF protein levels in the hippocampus increase in direct relation to the severity of seizure. Up to 7 days after injection of kainic acid, levels of full-length TrkB protein were unchanged, whereas levels of truncated TrkB protein were significantly increased by 12 h. To determine whether elevations in BDNF protein levels are potentially beneficial to hippocampal neurons exposed to an excitotoxic stress, we infused exogenous BDNF prior to and during the period of neuronal death caused by kainic acid. We find that administration of high levels of exogenous BDNF does not affect severity of seizure, but does in fact, exacerbate the injury caused by kainic acid, specifically to CA3 pyramidal neurons. Although there was a trend toward sparing of CA1 pyramidal neurons on the side infused with BDNF, this was not significant. In the same paradigm, infusion of exogenous NT-3 had no effect.
向成年大鼠全身注射兴奋性毒素海人酸会导致海马体CA1和CA3锥体神经元出现明确的损失模式。在这种神经元损失之前，脑源性神经营养因子（BDNF）mRNA会大幅增加。我们在此表明，兴奋性毒性损伤后海马体特定区域的BDNF蛋白增加，损伤后24小时达到最高水平。海马体中BDNF蛋白水平的增加与癫痫发作的严重程度直接相关。注射海人酸后长达7天，全长TrkB蛋白水平未变，而截短的TrkB蛋白水平在12小时时显著增加。为了确定BDNF蛋白水平升高是否对遭受兴奋性毒性应激的海马体神经元有潜在益处，我们在海人酸引起的神经元死亡之前和期间注入外源性BDNF。我们发现，给予高水平的外源性BDNF不会影响癫痫发作的严重程度，但实际上会加剧海人酸造成的损伤，特别是对CA3锥体神经元的损伤。尽管在注入BDNF的一侧有保护CA1锥体神经元的趋势，但并不显著。在相同的实验模式中，注入外源性NT-3没有效果。
