Susceptibility of hippocampal neurons to mechanically induced injury
Susceptibility of hippocampal neurons to mechanically induced injury
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DOI：
10.1016/s0014-4886(03)00254-1
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发表时间：
2003-11-01
影响因子：
5.3
通讯作者：
Cargill, RS
中科院分区：
文献类型：
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作者：
Geddes, DM;LaPlaca, MC;Cargill, RS
啮齿类动物创伤性皮质脑损伤的实验模型显示，海马体的特定区域（例如，CA3和肺门亚区）严重受伤，尽管他们的距离从最初的侮辱。由于NMDA受体密度增加和能量容量降低，海马神经元可能本质上比皮质神经元更容易受到机械损伤，如对缺血性损伤的敏感性增加所证明的。海马神经元的选择性脆弱性进行了评价，在TBI的体外模型中，无论是原代大鼠皮质或海马神经元（E17）接种到硅胶基板进行分级水平的机械拉伸。虽然皮质神经元在牵张诱导的膜通透性中表现出显著的更长时间的增加，但海马神经元的损伤导致细胞内游离钙浓度[Ca2+]（i）和细胞死亡的更大增加。在皮层神经元中，由于牵拉导致的[ATP]（i）缺陷在损伤后60分钟明显，但在24小时恢复，而在海马神经元中直到损伤后24小时才观察到[ATP]（i）的显著缺陷。MK 801预处理降低牵张诱导的海马和皮质培养物中的[Ca 2 +]（i）瞬变，从而否定区域特异性。然而，MK 801预处理并没有改善海马的活力和矛盾，显着增加皮层神经元的细胞死亡。由于海马体是负责与TBI相关的记忆缺陷和癫痫发作的主要大脑区域，因此了解为什么该区域被选择性损伤可能会导致更准确的机械耐受性以及有效的药物制剂的开发。(C)2003 Elsevier Science（美国）。All rights reserved.
Experimental models of traumatic cortical brain injury in rodents reveal that specific regions of the hippocampus (e.g., CA3 and hilar subfields) are severely injured despite their distance from the initial insult. Hippocampal neurons may be intrinsically more vulnerable to mechanical insult than cortical neurons due to increased NMDA receptor densities and lower energy capacities, as evidenced by increased susceptibility to ischemic insults. The selective vulnerability of hippocampal neurons was evaluated using an in vitro model of TBI in which either primary rat cortical or hippocampal neurons (E17) seeded onto silicone substrates were subjected to graded levels of mechanical stretch. Although cortical neurons exhibited significantly longer increases in stretch-induced membrane permeability, injury of hippocampal neurons resulted in larger increases in intracellular free calcium concentration [Ca2+](i) and cell death. [ATP](i) deficits due to stretch were apparent by 60 min after injury in cortical neurons but recovered by 24 h, whereas significant deficits in [ATP](i) were not observed in hippocampal neurons until 24 It after injury. MK801 pretreatment decreased the stretch-induced [Ca2+](i) transients in both hippocampal and cortical cultures, thereby negating the regional specificity. However, MK801 pretreatment did not improve hippocampal viability and paradoxically, significantly increased cell death among cortical neurons. As the hippocampus is the primary brain region responsible for the memory deficits and epileptic seizures associated with TBI, understanding why this region is selectively damaged could lead to the development of more accurate mechanical tolerances as well as effective pharmaceutical agents. (C) 2003 Elsevier Science (USA). All rights reserved.