Effects of genetic deficiency of cyclooxygenase-1 or cyclooxygenase-2 on functional and histological outcomes following traumatic brain injury in mice.
Effects of genetic deficiency of cyclooxygenase-1 or cyclooxygenase-2 on functional and histological outcomes following traumatic brain injury in mice.
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DOI：
10.1186/1471-2202-10-108
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发表时间：
2009-08-31
期刊：
影响因子：
2.4
通讯作者：
Loftin CD
中科院分区：
文献类型：
--
作者：
Kelso ML;Scheff SW;Pauly JR;Loftin CD
神经炎症有助于急性CNS损伤（包括创伤性脑损伤（TBI））的病理生理学。虽然前列腺素脂质介质的炎症有助于各种炎症反应，其在神经炎症的重要性尚不清楚。关于抑制前列腺素形成所需的酶，环氧合酶（考克斯）-1和考克斯-2，以改善TBI后的结果的功效，存在相互矛盾的报道。本研究的目的是通过利用考克斯-1或考克斯-2缺陷的小鼠来确定考克斯同种型在促成由TBI引起的病理过程中的作用。在轻度受控皮质撞击损伤后，比较考克斯-1缺陷小鼠或考克斯-2缺陷小鼠及其匹配的野生型对照之间的皮质组织损失量、小胶质细胞活化水平和功能恢复能力。考克斯-2的缺陷导致轻微（6%），虽然统计学上显著，增加保留皮层组织后TBI。考克斯-1的缺陷导致TBI后皮质组织损失没有可检测的影响。通过3[H]-PK 11195放射自显影测定，TBI在考克斯-1野生型和考克斯-1缺陷型小鼠的多个脑区域中产生类似的小胶质细胞活化增加。在考克斯-2野生型和考克斯-2缺陷型小鼠中，TBI增加了分析的所有脑区域中的3[H]-PK 11195结合。损伤后，与考克斯-2野生型小鼠相比，考克斯-2缺陷型小鼠海马齿状回和CA 1区的3[H]-PK 11195结合更强。在从TBI恢复4天后，在野生型、考克斯-1缺陷型和考克斯-2缺陷型小鼠中进行认知评估。通过Morris水迷宫中的获得和空间记忆保持测试确定，考克斯-1或考克斯-2的缺乏没有导致显著的认知效果。这些发现表明，考克斯-1或考克斯-2的缺陷都不足以改变小鼠TBI后的认知结果。
Neuroinflammation contributes to the pathophysiology of acute CNS injury, including traumatic brain injury (TBI). Although prostaglandin lipid mediators of inflammation contribute to a variety of inflammatory responses, their importance in neuroinflammation is not clear. There are conflicting reports as to the efficacy of inhibiting the enzymes required for prostaglandin formation, cyclooxygenase (COX) -1 and COX-2, for improving outcomes following TBI. The purpose of the current study was to determine the role of the COX isoforms in contributing to pathological processes resulting from TBI by utilizing mice deficient in COX-1 or COX-2. Following a mild controlled cortical impact injury, the amount of cortical tissue loss, the level of microglial activation, and the capacity for functional recovery was compared between COX-1-deficient mice or COX-2-deficient mice, and their matching wild-type controls. The deficiency of COX-2 resulted in a minor (6%), although statistically significant, increase in the sparing of cortical tissue following TBI. The deficiency of COX-1 resulted in no detectable effect on cortical tissue loss following TBI. As determined by 3[H]-PK11195 autoradiography, TBI produced a similar increase in microglial activation in multiple brain regions of both COX-1 wild-type and COX-1-deficient mice. In COX-2 wild-type and COX-2-deficient mice, TBI increased 3[H]-PK11195 binding in all brain regions that were analyzed. Following injury, 3[H]-PK11195 binding in the dentate gyrus and CA1 region of the hippocampus was greater in COX-2-deficient mice, as compared to COX-2 wild-type mice. Cognitive assessment was performed in the wild-type, COX-1-deficient and COX-2-deficient mice following 4 days of recovery from TBI. There was no significant cognitive effect that resulted from the deficiency of either COX-1 or COX-2, as determined by acquisition and spatial memory retention testing in a Morris water maze. These findings suggest that the deficiency of neither COX-1 nor COX-2 is sufficient to alter cognitive outcomes following TBI in mice.
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影响因子：
4.2
作者：
Dash, PK;Mach, SA;Moore, AN
通讯作者：
Moore, AN
影响因子：
3.6
作者：
Hickey, Robert W.;Adelson, P. David;Graham, Steven H.
通讯作者：
Graham, Steven H.
影响因子：
4.2
作者：
Hall, Edward D.;Bryant, Ying Deng;Sullivan, Patrick G.
通讯作者：
Sullivan, Patrick G.
DOI：
10.1046/j.1440-1681.2001.03549.x
发表时间：
2001-11-01
影响因子：
2.9
作者：
Cernak, I;O'Connor, C;Vink, R
通讯作者：
Vink, R
影响因子：
3.7
作者：
Koyfman, L;Kaplanski, J;Shapira, Y
通讯作者：
Shapira, Y