Neurogenesis, Exercise, and Cognitive Late Effects of Pediatric Radiotherapy

Abstract

Brain cancer is a common type of childhood malignancy, and radiotherapy (RT) is a mainstay of treatment. RT is effective for tumor eradication, and survival rates are high. However, RT damages the brain and disrupts ongoing developmental processes, resulting in debilitating cognitive “late” effects that may take years to fully manifest. These late effects likely derive from a long-term decrement in cell proliferation, combined with a neural environment that is hostile to plasticity, both of which are induced by RT. Long-term suppression of cell proliferation deprives the brain of the raw materials needed for optimum cognitive performance (such as new neurons in the hippocampus and new glia in frontal cortex), while chronic inflammation and dearth of trophic substances (such as growth hormone) limit neuroplastic potential in existing circuitry. Potential treatments for cognitive late effects should address both of these conditions. Exercise represents one such potential treatment, since it has the capacity to enhance cell proliferation, as well as to promote a neural milieu permissive for plasticity. Here, we review the evidence that cognitive late effects can be traced to RT-induced suppression of cell proliferation and hostile environmental conditions, as well as emerging evidence that exercise may be effective as an independent or adjuvant therapy.

Desempenho Intelectual Pós Tratamento de Câncer: Um Estudo com Crianças

“…A combinação entre neurocirurgia, quimioterapia intratecal e radioterapia de crânio e neuroeixo -adotada nos protocolos de tratamento de crianças com meduloblastoma, parecem potencializar os danos cognitivos, notadamente através da redução da velocidade de processamento de informações (Reddick et al, 2014;Rodgers et al, 2013).…”

“…Estudos demonstram que a exposição à radiação resulta em perda generalizada de substância branca e cinzenta ao longo de todo o tecido cerebral. Entretanto, estudos recentes vêm apontando que tais efeitos incidem de forma expressiva em regiões hipocampais, cujo impacto se torna ainda mais deletério por atingir regiões de intensa atividade de neurogênese (Rodgers, Trevino, Zawaski, Gaber, & Leasure, 2013). Nesse sentido, a redução do volume de substância branca, decorrente do impacto na mielinização, vascularização e da supressão da proliferação de células, parece estar no cerne das alterações cognitivas encontradas em pacientes submetidos à radioterapia de crânio (Brinkman et al, 2012;Palmer et al, 2012;Rieken et al, 2011;Watanabe et al, 2011).…”

“…Tais impactos culminam no comprometimento da aquisição de novas habilidades e informações, resultando em decréscimos signifi cativos e progressivos nos escores de QI (Rodgers et al, 2013).…”

Treatment Related Cognitive Impairment in Pediatric Oncology Patients: A Brazilian Experience

“…Five years after radiation, significant structural damage to the brain appeared and continued to progress. Hippocampal volume, equally affected, has continuing bilateral white matter decrease until 3 years after the radiation end [19].…”

“…Studies show that radiation exposure results in generalized white and gray matter loss in the brain. However, its deleterious effects focus particularly in the hippocampus region because this is a primary site of neurogenesis [19]. Accordingly, reduction of white matter volume due to the impact on myelination, vascularity and suppression of proliferation of cells, appears to be at the core of cognitive changes [20][21][22][23][24].…”