Fardell Joanna E, Vardy Janette, Monds Lauren A, Johnston Ian N
School of Psychology, The University of Sydney, Australia.
Concord Cancer Centre, Concord General Repatriation Hospital, Sydney Medical School, The University of Sydney.
Behav Brain Res. 2015 Sep 15;291:80-88. doi: 10.1016/j.bbr.2015.04.038. Epub 2015 Apr 28.
Chemotherapy treatment is associated with cognitive dysfunction in cancer survivors after treatment completion. The duration of these impairments is unclear. Therefore this paper aims to evaluate the lasting impact of varying doses of the chemotherapy oxaliplatin (OX) on cognition and peripheral neuropathy. In Experiment 1 rats were treated once a week for 3 weeks with either physiological saline (control) or 6 mg/kg OX i.p. and were assessed for peripheral neuropathy, using von Frey filaments, and cognitive function, using novel object and location recognition, up to 2 weeks after treatment completion. For Experiment 2 rats received 3 weekly i.p. injections of either physiological saline (control), 0.6 mg/kg, 2mg/kg or 6 mg/kg OX and assessed for peripheral neuropathy and cognitive function up to 11 months after treatment completion. Systemic OX treatment induced lasting effects on cognitive function at 11 months after treatment, and peripheral neuropathy at 1 month after treatment and these were dose dependent; higher doses of OX resulted in worse cognitive outcomes and more severe peripheral neuropathy.
化疗治疗与治疗结束后的癌症幸存者认知功能障碍有关。这些损伤的持续时间尚不清楚。因此,本文旨在评估不同剂量的化疗药物奥沙利铂(OX)对认知和周围神经病变的长期影响。在实验1中,大鼠每周接受一次治疗,持续3周,分别注射生理盐水(对照组)或6mg/kg奥沙利铂腹腔注射,并在治疗结束后长达2周的时间内,使用von Frey细丝评估周围神经病变,使用新物体和位置识别评估认知功能。在实验2中,大鼠每周接受3次腹腔注射,分别为生理盐水(对照组)、0.6mg/kg、2mg/kg或6mg/kg奥沙利铂,并在治疗结束后长达11个月的时间内评估周围神经病变和认知功能。全身奥沙利铂治疗在治疗后11个月对认知功能产生持续影响,在治疗后1个月对周围神经病变产生持续影响,且这些影响具有剂量依赖性;更高剂量的奥沙利铂导致更差的认知结果和更严重的周围神经病变。