Circulating insulin‐like growth factor I and functional recovery from spinal cord injury under enriched housing conditions

Abstract

Voluntary locomotor training as induced by enriched housing of rats stimulates recovery of locomotion after spinal cord injury (SCI). Generally it is thought that spinal neural networks of motor- and interneurons located in the ventral and intermediate laminae within the lumbar intumescence of the spinal cord, also referred to as central pattern generators (CPGs), are the 'producers of locomotion' and play a pivotal role in the amelioration of locomotor deficits after SCI. It has been suggested that locomotor training provides locomotor-specific sensory feedback into the CPGs, which stimulates remodeling of central nervous system pathways, including motor systems. Several molecules have been proposed to potentiate this process but the underlying mechanisms are not yet known. To understand these mechanisms, we studied the role of insulin-like growth factor (IGF) I in functional recovery from SCI under normal and enriched environment (EE) housing conditions. In a first experiment, we discovered that subcutaneous administration of IGF-I resulted in better locomotor recovery following SCI. In a second experiment, detailed analysis of the observed functional recovery induced by EE revealed full recovery of hindlimb coordination and stability of gait. This EE-dependent functional recovery was attenuated by alterations in the pre-synaptic bouton density within the ventral gray matter of the lumbar intumescence or CPG area. Neutralization of circulating IGF-I significantly blocked the effectiveness of EE housing on functional recovery and diminished the EE-induced alterations in pre-synaptic bouton density within the CPG area. These results support the use of IGF-I as a possible therapeutic aid in early rehabilitation after SCI.

Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

“…33 We acquired and studied five uninterrupted runs with the CatWalk system on the day of open field testing, considering ''consistent coordination'' when Regularity Index (RI) ( Table 1) scored 100% in 5/5 runs; ''frequent coordination'' when RI scored 100% in 3/5 or 4/5 runs; ''occasional coordination'' when RI scored 100% in 1/5 or 2/5, and ''no coordination'' when RI scored 100% in 0/5 runs. We also used the BBB subscoring scale to improved the sensitivity of the BBB by scoring the higher motor functions (i.e., toe clearance, predominant paw position, trunk stability, and tail position) regardless of the other BBB parameters, adding them together to yield a single score (maximum score = 13).…”

“…Changes in PD variability represent a measure of interlimb coordination: during uninterrupted locomotion, coordinated limb pairs show very small phase dispersion variability, whereas limbs that move largely autonomously display a high variability. 33,49 We averaged the values of complementary pairs to perform statistical analysis: PD diagonal pairs is the average between left forward-right hindlimb (LF-RH) and right forward-left hindlimb (RF-LH) and PD ipsilateral pairs is the average between right forward-right hindlimb (RF-RH) and left forward-left hindlimb (LF-LH). We also estimated the PD variability of pectoral (LF-RF) and pelvic (LH-RH) girdles.…”

“…CatWalk measures a large number of both static and dynamic gait parameters and enables quantitative assessment of locomotion. 33,[35][36][37][38][39] Briefly, the CatWalk system consists of a glass runway that contains light from a fluorescent tube. Internal reflection causes the light to be restricted to the glass surface plate under normal circumstances.…”

Massage Accelerates Brain Development and the Maturation of Visual Function

“…It is known that EE and physical exercise increase IGF-1 in the brain (Carro et al, 2000(Carro et al, , 2001Koopmans et al, 2006;Sale et al, 2007).…”

Environmental Influences on Visual Cortex Development and Plasticity

“…One group of molecules particularly sensitive to experience are neurotrophins, a family of secreted factors critically involved in structural and functional plasticity during development and in adulthood [46]. An important line of research deals with the potential therapeutic effects of EE: indeed, it has been shown that enriching the housing environment delays the progression of, and facilitates recovery from, various nervous system dysfunctions, including neurodevelopmental disorders, neurodegenerative diseases, different types of brain injury and psychiatric disorders [47][48][49][50][51][52][53][54]. These studies have profound consequences for humans.…”