Turning the tide in stroke recovery: IGF-2 as a driver of neuroprotection, angiogenesis and neurogenesis.

Abstract

Stroke remains one of the leading causes of death and long-term disability worldwide, and despite advances in acute care, therapeutic options remain severely limited. The currently approved treatments, including reperfusion therapies with intravenous thrombolysis or endovascular thrombectomy, are constrained by narrow therapeutic windows, strict eligibility criteria, and limited accessibility. As a result, the majority of patients remain untreated and are left with permanent neurological impairments. This reality underscores the urgent need for new therapeutic approaches that not only preserve brain tissue immediately after stroke but also actively support long-term repair and recovery. Within this context, insulin-like growth factor 2 (IGF-2), traditionally known for its role in fetal growth and development, has emerged as a promising candidate. Unlike IGF-1, IGF-2 remains abundant in the adult brain, suggesting it may play a role in central nervous system maintenance and repair. This dissertation has four main aims to advance stroke research: 1) to evaluate the neuroprotective effects of IGF-2 and Des(1-6)IGF-2 on infarct size, 2) to investigate their impact on post-stroke neuroinflammation, 3) to examine their role in promoting angiogenesis in vitro and in ovo, and 4) to assess their effects on neural stem cell proliferation and migration. The overall goal is to clarify how IGF-2 and its analogs contribute to brain protection and brain repair.