Traumatic Brain Injury Causes an FK506-Sensitive Loss and an Overgrowth of Dendritic Spines in Rat Forebrain
Traumatic Brain Injury Causes an FK506-Sensitive Loss and an Overgrowth of Dendritic Spines in Rat Forebrain
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DOI：
10.1089/neu.2011.1761
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发表时间：
2012-01-20
影响因子：
4.2
通讯作者：
Churn, Severn B.
中科院分区：
文献类型：
--
作者：
Campbell, John N.;Register, David;Churn, Severn B.
创伤性脑损伤（TBI）可引起急性组织损失和通过反应性过程（如兴奋性毒性和炎症）引起进行性损伤。这些过程可能通过改变局部受损组织以外的神经回路而加重神经功能障碍。电路改变的一种方式可能涉及树突棘，这是一种微米大小的树突膜突起，支持大脑中大多数兴奋性突触。本研究采用改良的高尔基-考克斯技术追踪大鼠前脑区主细胞近端树突棘密度的变化。脊柱密度评估在1小时，24小时和1周后的横向液体冲击TBI中度严重程度。在TBI后1小时，在检查的任何脑区均未观察到脊柱密度的变化。然而，在创伤后24h，同侧新皮层第III层和背齿状回（dDG）的脊柱密度下降。这种明显的脊柱丢失可以通过损伤后单次给药钙调磷酸酶抑制剂FK506来预防。这些结果;与一项同伴研究一起，表明TBI模型中树突棘丢失的fk506敏感机制。此外，在TBI后1周，脊柱密度显著高于对照水平，CA1和CA3的双侧和dDG的同侧。CA1中明显的脊髓过度生长特别有趣，因为它可以解释先前报道的该脑区异常和潜在的癫痫性活动。
Traumatic brain injury (TBI) causes both an acute loss of tissue and a progressive injury through reactive processes such as excitotoxicity and inflammation. These processes may worsen neural dysfunction by altering neuronal circuitry beyond the focally-damaged tissue. One means of circuit alteration may involve dendritic spines, micron-sized protuberances of dendritic membrane that support most of the excitatory synapses in the brain. This study used a modified Golgi-Cox technique to track changes in spine density on the proximal dendrites of principal cells in rat forebrain regions. Spine density was assessed at 1 h, 24h, and 1 week after a lateral fluid percussion TBI of moderate severity. At 1 h after TBI, no changes in spine density were observed in any of the brain regions examined. By 24h after TBI, however, spine density had decreased in ipsilateral neocortex in layer and III and dorsal dentate gyrus (dDG). This apparent loss of spines was prevented by a single, post-injury administration of the calcineurin inhibitor FK506. These results; together with those of a companion study, indicate an FK506-sensitive mechanism of dendritic spine loss in the TBI model. Furthermore, by 1 week after TBI, spine density had increased substantially above control levels, bilaterally in CA1 and CA3 and ipsilaterally in dDG. The apparent overgrowth of spines in CA1 is of particular interest, as it may explain previous reports of abnormal and potentially epileptogenic activity in this brain region.