Potential neuroprotective and therapeutic agents and their mechanisms for irradiation-induced brain injury

Abstract

Cranial-irradiation is associated with tissue damage resulting in neurocognitive impediments that adversely influence patient quality of life. Administration of radiation directly to the tumor may extend to the neighboring healthy tissues, which may induce acute to persistent oxidative stress, lessening neurogenesis, neuroinflammation, as well as vascular alterations, leading to neurocognitive sequelae as a result of decline in neuronal structural complexity as well as synaptic connections. Almost all the medications indicated in the treatment of irradiation-triggered brain injury work via signaling pathways that are associated with lessening chronic oxidative stress, which is considered a consequence of the inflammatory response, reduction of edema, as well as microglia activation. Some agents have both preventative as well as therapeutic potential via the amalgamation of both neuroprotective and therapeutic mechanisms above. Thus, in this review, agents such as baicalein, troxerutin, epigallocatechin gallate, quercetin, melatonin, valproic acid, lithium, neurosteroid progesterone as well as minocycline have been implicated as neuroprotective agents for irradiation-induced neurological deficits. Also, agents such as glucocorticoids, methylphenidate, vitamin E, bisdemethoxycurcumin, phosphodiesterases, edaravone, pioglitazone and fenofibrate, glutamate antagonists, human urinary kallidinogenase, bevacizumab, as well as hyperbaric oxygen have been implicated as therapeutic agents for irradiation-induced neurological deficits. Furthermore, agents such as angiotensin-converting enzyme, 3-N-butyl-phthalide, stem cell therapy, sphingosine-1-phosphate, gangliosides, and neurotrophins have been implicated as combined potential neuroprotective and therapeutic agents for irradiation-induced neurological deficits. The aim of this review is to elucidate the potential neuroprotective and therapeutic agents above and their mechanisms for irradiation-induced neurological deficits after brain irradiation.

Keywords

cranial / irradiation / neurogenesis / neuroinflammation / neuroprotective / therapy

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