Bertorelli R, Adami M, Di Santo E, Ghezzi P
Schering-Plough Research Institute, Milan, Italy.
Neurosci Lett. 1998 Apr 17;246(1):41-4. doi: 10.1016/s0304-3940(98)00221-3.
Focal cerebral ischemia in rats produces elevated levels of tumor necrosis factor (TNF)alpha in the ischemic brain region. To better understand the modulation of TNF during brain ischemia processes we carried out studies in a model of permanent middle cerebral artery occlusion (MCAo) in the rat. In non-treated ischemic animals, the maximum expression of TNF was observed at 12 h (246.1+/-33 U/g) in the ischemic cortex and declined reaching near zero levels 24 h after MCAo. Given 10 min after MCAo, MK 801 (3 mg/kg, i.p.), a non-competitive NMDA receptor antagonist, exerted significant neuroprotection as measured by 47% reduction of total volume of infarction (P < 0.01 vs. ischemic-control). At the high dose of 3 mg/kg i.p., dexamethasone (DEX), which is known to reduce brain edema, decreased infarct size by 50% (P < 0.01 vs. ischemic-control). Both MK 801 and DEX reduced TNF production in the ipsilateral cortex of ischemic animals by 61 and 73%, respectively (P < 0.01 vs. ischemic-control). The data indicate that TNF levels increase after brain infarction, whereas they are reduced by neuroprotective agents, such as MK 801 and DEX, which act on different cellular levels.
大鼠局灶性脑缺血会使缺血脑区的肿瘤坏死因子（TNF）α水平升高。为了更好地理解脑缺血过程中TNF的调节机制，我们在大鼠永久性大脑中动脉闭塞（MCAo）模型中开展了研究。在未经治疗的缺血动物中，缺血皮层中TNF的最大表达量在12小时时观察到（246.1±33 U/g），并在MCAo后24小时下降至接近零水平。在MCAo后10分钟给予非竞争性NMDA受体拮抗剂MK 801（3 mg/kg，腹腔注射），通过测量梗死总体积减少47%显示出显著的神经保护作用（与缺血对照组相比，P < 0.01）。已知可减轻脑水肿的地塞米松（DEX），腹腔注射高剂量3 mg/kg时，梗死面积减少50%（与缺血对照组相比，P < 0.01）。MK 801和DEX均可使缺血动物同侧皮层中的TNF产生分别减少61%和73%（与缺血对照组相比，P < 0.01）。数据表明，脑梗死后脑内TNF水平升高，而作用于不同细胞水平的神经保护剂如MK 801和DEX可使其降低。
