Hatakeyama Tetsuhiro, Okauchi Masanobu, Hua Ya, Keep Richard F, Xi Guohua
Department of Neurosurgery, University of Michigan, USA ; Department of Neurological Surgery, Kagawa University, Japan.
Transl Stroke Res. 2013 Oct;4(5):546-53. doi: 10.1007/s12975-013-0270-5.
Intracerebral hemorrhage (ICH) is primarily a disease of the elderly. Deferoxamine (DFX), an iron chelator, reduces long-term neurological deficits and brain atrophy after ICH in aged rats. In the present study, we investigated whether DFX can reduce acute ICH-induced neuronal death and whether it affects the endogenous response to ICH (ferritin upregulation and hematoma resolution) in aged rats. Male Fischer 344 rats (18 months old) had an intracaudate injection of 100 μL autologous whole blood into the right basal ganglia and were treated with DFX (100 mg/kg) or vehicle 2 hours post-ICH and then every 12 hours up to 7 days. Rats were euthanized 1, 3, or 7 days later for neuronal death, ferritin and hematoma size measurements. Plasma ferritin levels and behavioral outcome following ICH were also examined. DFX treatment significantly reduced ICH-induced neuronal death and neurological deficits. DFX also suppressed ferritin upregulation in the ipsilateral basal ganglia after ICH and hematoma lysis (hematoma volume at day 7: 13.2±4.9 vs. 3.8±1.2 mm3 in vehicle-treated group, p<0.01). However, effects of DFX on plasma ferritin levels after ICH did not reach significance. In conclusion, DFX reduces neuronal death and neurological deficits after ICH in aged rats. It also affects the endogenous response to ICH.
脑出血(ICH)主要是一种老年疾病。去铁胺(DFX),一种铁螯合剂,可减少老年大鼠脑出血后的长期神经功能缺损和脑萎缩。在本研究中,我们调查了DFX是否能减少急性脑出血诱导的神经元死亡,以及它是否影响老年大鼠对脑出血的内源性反应(铁蛋白上调和血肿消退)。雄性Fischer 344大鼠(18个月大)在右侧基底节尾状核内注射100 μL自体全血,并在脑出血后2小时用DFX(100 mg/kg)或赋形剂治疗,然后每12小时治疗一次,持续7天。在1、3或7天后对大鼠实施安乐死,以测量神经元死亡、铁蛋白和血肿大小。还检查了脑出血后的血浆铁蛋白水平和行为结果。DFX治疗显著减少了脑出血诱导的神经元死亡和神经功能缺损。DFX还抑制了脑出血后同侧基底节中铁蛋白的上调和血肿溶解(第7天血肿体积:赋形剂治疗组为13.2±4.9 vs. 3.8±1.2 mm3,p<0.01)。然而,DFX对脑出血后血浆铁蛋白水平的影响未达到显著水平。总之,DFX可减少老年大鼠脑出血后的神经元死亡和神经功能缺损。它还影响对脑出血的内源性反应。
Transl Stroke Res. 2013-10
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