Peterson R Scott, Fernando Gowry, Day Lainy, Allen Timothy A, Chapleau Jeanette D, Menjivar Jenny, Schlinger Barney A, Lee Diane W
Department of Physiological Science, University of California, Los Angeles, CA 90095, USA.
Dev Neurobiol. 2007 Dec;67(14):1867-78. doi: 10.1002/dneu.20548.
Estrogens can be neuroprotective following traumatic brain injury. Immediately after trauma to the zebra finch hippocampus, the estrogen-synthetic enzyme aromatase is rapidly upregulated in astrocytes and radial glia around the lesion site. Brain injury also induces high levels of cell proliferation. Estrogens promote neuronal differentiation, migration, and survival naturally in the avian brain. We suspect that glia are a source of estrogens promoting cell proliferation after neural injury. To explore this hypothesis, we examined the spatial and temporal relationship between glial aromatase expression and cell proliferation after neural injury in adult female zebra finches. Birds were ovariectomized and given a blank implant or one filled with estradiol; some birds were also administered an aromatase inhibitor or vehicle. All birds received penetrating injuries to the right hippocampus. Twenty-four hours after lesioning, birds were injected once with BrdU to label mitotically active cells and euthanized 2 h, 24 h, or 7 days later. The brains were processed for double-label BrdU and aromatase immunocytochemistry. Injury-induced glial aromatase expression was unaffected by survival time and aromatase inhibition. BrdU labeling was significantly reduced at 24 h by ovariectomy and by aromatase inhibition; effects were partially reversed by E2 replacement. Irrespective of ovariectomy, the densities of aromatase immunoreactive astrocytes and BrdU-labeled cells at known distances from the lesion site were highly correlated. These data suggest that injury-induced glial aromatization may influence the reorganization of injured tissue by providing a rich estrogenic environment available to influence cellular incorporation.
雌激素在创伤性脑损伤后具有神经保护作用。在斑胸草雀海马体受到创伤后，雌激素合成酶芳香化酶在损伤部位周围的星形胶质细胞和放射状胶质细胞中迅速上调。脑损伤还会诱导高水平的细胞增殖。雌激素在鸟类大脑中自然促进神经元的分化、迁移和存活。我们怀疑神经胶质细胞是神经损伤后促进细胞增殖的雌激素来源。为了探究这一假设，我们研究了成年雌性斑胸草雀神经损伤后神经胶质细胞芳香化酶表达与细胞增殖之间的时空关系。对鸟类进行卵巢切除，并植入空白植入物或填充有雌二醇的植入物；一些鸟类还被给予芳香化酶抑制剂或赋形剂。所有鸟类的右海马体都受到穿透性损伤。损伤后24小时，给鸟类注射一次BrdU以标记有丝分裂活跃细胞，并在2小时、24小时或7天后实施安乐死。对大脑进行双重标记BrdU和芳香化酶免疫细胞化学处理。损伤诱导的神经胶质细胞芳香化酶表达不受存活时间和芳香化酶抑制的影响。卵巢切除和芳香化酶抑制在24小时时显著降低了BrdU标记；雌激素替代部分逆转了这些作用。无论是否进行卵巢切除，在距损伤部位已知距离处，芳香化酶免疫反应性星形胶质细胞和BrdU标记细胞的密度高度相关。这些数据表明，损伤诱导的神经胶质细胞芳香化可能通过提供丰富的雌激素环境来影响细胞整合，从而影响损伤组织的重组。
