The Role of Oxidative Stress in Etiopathogenesis of Chemotherapy Induced Cognitive Impairment (CICI)-"Chemobrain"

Abstract

Chemobrain or chemotherapy induced cognitive impairment (CICI) represents a new clinical syndrome characterised by memory, learning and motor function impairment. As numerous patients with cancer are long-term survivors, CICI represent a significant factor which may interfere with their quality of life. However, this entity CICI must be distinguished from other cognitive syndromes and addressed accordingly. At the present time, experimental and clinical research suggests that CICI could be induced by numerous factors including oxidative stress. This type of CNS injury has been previously described in cancer patients treated with common anti-neoplastic drugs such as doxorubicine, carmustine, methotrexate and cyclophosphamide. It seems that all these pharmacological factors promote neuronal death through a final common pathway represented by TNF alpha (tumour necrosis factor). However, as cancer in general is diagnosed more commonly in the aging population, the elderly oncological patient must be treated with great care since aging per se is also impacted by oxidative stress and potentiually by TNF alpha deleterious action on brain parenchyma. In this context, some patients may develop cognitive dysfunction well before the appearance of CICI. In addition, chemotherapy may worsen their cognitive function. Therefore, at the present time, there is an acute need for development of effective therapeutic methods to prevent CICI as well as new methods of early CICI diagnosis.

Keywords: aging; cancer; chemobrain; chemotherapy induced cognitive impairment; oxidative stress.

Figure 1.. Mechanisms underlying CICI

Chemotherapy of cancer generates free superoxide radicals in plasma which may cause the oxidation of Apolipoprotein A1 (ApoA1). Oxidated ApoA1 in turn promotes synthesis of TNF alpha which penetrates the blood brain barrier to further inflict apoptosis and neural death in the brain.

Figure 2.. Pathological conditions developed in elderly

Oxidative stress in old age leads to several pathological entities characterized by cognitive dysfunction.