Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.
Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.
复制标题
DOI：
10.1016/j.nbd.2013.12.001
复制
发表时间：
2014-03
影响因子：
6.1
通讯作者：
Scott RC
中科院分区：
文献类型：
--
作者：
Duffy BA;Chun KP;Ma D;Lythgoe MF;Scott RC
抗炎疗法是目前最有可能用于抗癫痫发生和长期癫痫发作后神经保护的候选药物。鉴于血管源性水肿被广泛认为对癫痫持续状态后的预后不利，临床上有时使用抗炎药地塞米松来缓解脑水肿。在这项研究中，我们进行了纵向磁共振成像，以评估地塞米松对癫痫持续状态后脑水肿和随后的神经保护的作用。锂-毛果芸香碱用于诱导大鼠癫痫持续状态。癫痫持续状态后，大鼠用盐水或地塞米松磷酸钠（10 mg/kg 或 2 mg/kg）进行后处理。通过磁共振成像（T2 弛豫测量）评估脑水肿，并使用海马体积测定作为神经元损伤的标志。在癫痫持续状态之前、48 小时和 96 小时进行 T2 松弛测量。癫痫持续状态后 18 至 21 天进行体积测量。出乎意料的是，与对照组相比，用地塞米松治疗的大鼠脑水肿更严重。此外，在初次损伤后 3 周，与对照组相比，地塞米松治疗的大鼠的海马体积较低。第 2 天和第 4 天的海马 T2 测量值与第 3 周时的海马体积相关。最后，癫痫持续状态后第一周的死亡率从未经治疗的大鼠的 14% 分别增加到使用 2 mg/kg 和 10 mg/kg 地塞米松治疗的大鼠的 33% 和 46%。这些发现表明地塞米松会加剧与癫痫持续状态相关的急性脑水肿和脑损伤。癫痫发作后给予地塞米松会导致水肿和脑损伤恶化。这一发现也适用于低至 2 毫克/公斤剂量的地塞米松。我们展示了自动海马体积测量用于治疗监测的用途。
Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10 mg/kg or 2 mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2 mg/kg and 10 mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus. Dexamethasone given following seizures caused a worsening of edema and brain injury. This finding also applied to doses dexamethasone as low as 2 mg/kg. We show the use of automated hippocampal volume measurement for therapy monitoring.
登录
查看更多内容
影响因子：
2.2
作者：
Holtman, L.;van Vliet, E. A.;Gorter, J. A.
通讯作者：
Gorter, J. A.
影响因子：
2.2
作者：
Holtman, Linda;van Vliet, Erwin A.;Gorter, Jan A.
通讯作者：
Gorter, Jan A.
影响因子：
6.1
作者：
Jung, Keun-Hwa;Chu, Kon;Roh, Jae-Kyu
通讯作者：
Roh, Jae-Kyu
影响因子：
2.1
作者：
Al-Shorbagy, Muhammad Y.;El Sayeh, Bahia M.;Abdallah, Dalaal M.
通讯作者：
Abdallah, Dalaal M.
影响因子：
10.9
作者：
Cardoso, M. Jorge;Leung, Kelvin;Ourselin, Sebastien
通讯作者：
Ourselin, Sebastien