Upon entry into the central nervous system (CNS), serum insulin-like growth factor-1 (IGF-I) modulates neuronal growth, survival, and excitability. Yet mechanisms that trigger IGF-I entry across the blood-brain barrier remain unclear. We show that neuronal activity elicited by electrical, sensory, or behavioral stimulation increases IGF-I input in activated regions. Entrance of serum IGF-I is triggered by diffusible messengers (i.e., ATP, arachidonic acid derivatives) released during neurovascular coupling. These messengers stimulate matrix metalloproteinase-9, leading to cleavage of the IGF binding protein-3 (IGFBP-3). Cleavage of IGFBP-3 allows the passage of serum IGF-I into the CNS through an interaction with the endothelial transporter lipoprotein related receptor 1. Activity-dependent entrance of serum IGF-I into the CNS may help to explain disparate observations such as proneurogenic effects of epilepsy, rehabilitatory effects of neural stimulation, and modulatory effects of blood flow on brain activity.

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This study aimed to investigate the suitability of using ultrasonograph muscle thickness (MT) measurements to estimate the muscle volume (MV) of the quadriceps femoris as an alternative approach to magnetic resonance imaging (MRI). The subjects were 46 men aged from 20 to 70 years who were randomly allocated to either a validation or a cross-validation group. In the validation group, multiple and simple regression equations, which used a set of MT values determined at mid-thigh and thigh length (1) and the product of pi, (MT/2)2, and l [pi x (MT/2)2 x l], respectively, as independent variables, were derived to estimate the MV measured by MRI. Because the two equations were cross-validated, the data from the two groups were pooled to generate the final prediction equations: MV (cm3)=(MT x 311.732)+(l x 53.346) -2058.529 as the multiple regression equation and MV (cm3) = [pi x (MT/ 2)2 x l] x 1.1176+663.040 as the simple regression equation. In the multiple regression equation, MT explained 75% of the variation in the MV measured by MRI. The r2 and the standard error of the estimate (SEE) of the equations were 0.824 and 175.6 cm3 (10.6%), respectively, for the multiple regression equation and 0.829 and 173.7 cm3 (10.5%), respectively, for the simple regression equation. Thus, the present results indicate that ultrasonograph MT measurements at mid-thigh are useful for estimating the MV of knee extensors. However, the observed SEE values suggest that the prediction equation obtained in this study may be limited to population studies rather than individual assessments in longitudinal studies.