Preclinical and clinical evidence of IGF-1 as a prognostic marker and acute intervention with ischemic stroke

Abstract

Ischemic strokes are highly prevalent in the elderly population and are a leading cause of mortality and morbidity worldwide. The risk of ischemic stroke increases in advanced age, corresponding with a noted decrease in circulating insulin growth factor-1 (IGF-1). IGF-1 is a known neuroprotectant involved in embryonic development, neurogenesis, neurotransmission, cognition, and lifespan. Clinically, several studies have shown that reduced levels of IGF-1 correlate with increased mortality rate, poorer functional outcomes, and increased morbidities following an ischemic stroke. In animal models of ischemia, administering exogenous IGF-1 using various routes of administration (intranasal, intravenous, subcutaneous, or topical) at various time points prior to and following insult attenuates neurological damage and accompanying behavioral changes caused by ischemia. However, there are some contrasting findings in select clinical and preclinical studies. This review discusses the role of IGF-1 as a determinant factor of ischemic stroke outcomes, both within the clinical settings and preclinical animal models. Furthermore, the review provides insight on the role of IGF-1 in mechanisms and cellular processes that contribute to stroke damage.

Keywords: Somatomedin C; glia; ischemia; neurodegeneration; stroke.

Figure 1.

Regulation of IGF-1 mediated effects throughout the body. Left) IGF-1 signaling is tightly regulated by growth hormone control of hepatocytic IGF-1 production and release, IGFBP binding and dissociation in circulation, and its selective receptor, IGF-1R. Right) Known effects of IGF-1 in tissues throughout the body.

Figure 2.

Overlapping pathophysiologies and behavioral deficits associated with ischemic stroke and low levels of circulating IGF-1.

Figure 3.

Key cellular functions within the brain known to be regulated by IGF-1.