Factors Involved in the Functional Motor Recovery of Rats with Cortical Ablation after GH and Rehabilitation Treatment: Cortical Cell Proliferation and Nestin and Actin Expression in the Striatum and Thalamus.

Margarita Heredia,Adelaida Sánchez Riolobos,Natalia Rodríguez,Virginia Sánchez Robledo,Antonio De La Fuente,Pablo Devesa,José María Criado,Jesús Devesa

doi:10.3390/ijms20225770

Margarita Heredia, Adelaida Sánchez Riolobos + Show 6 more

Open Access

https://doi.org/10.3390/ijms20225770

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Abstract

Previously we demonstrated, in rats, that treatment with growth hormone (GH) and rehabilitation, carried out immediately after a motor cortical ablation, significantly improved the motor affectation produced by the lesion and induced the re-expression of nestin in the contralateral motor cortex. Here we analyze cortical proliferation after ablation of the frontal motor cortex and investigate the re-expression of nestin in the contralateral motor cortex and the role of the striatum and thalamus in motor recovery. The rats were subjected to ablation of the frontal motor cortex in the dominant hemisphere or sham-operated and immediately treated with GH or the vehicle (V), for five days. At 1 dpi (days post-injury), all rats received daily injections (for four days) of bromodeoxyuridine and five rats were sacrificed at 5 dpi. The other 15 rats (n = 5/group) underwent rehabilitation and were sacrificed at 25 dpi. GH induced the greatest number of proliferating cells in the perilesional cortex. GH and rehabilitation produced the functional recovery of the motor lesion and increased the expression of nestin in the striatum. In the thalamic ventral nucleus ipsilateral to the lesion, cells positive for nestin and actin were detected, but this was independent on GH. Our data suggest that GH-induced striatal nestin is involved in motor recovery.

Highlights

Traumatic brain injury (TBI) represents one of the biggest health problems in developed countries, both because of the number of deaths it causes as well as the high percentage of those affected who suffer from some type of motor and/or cognitive disability as a result of the injury
Our results indicate that the ablation of the frontal motor cortex induced cell proliferation in the perilesional injured cortical area in the rats sacrificed at 5 dpi, an effect significantly enhanced by growth hormone (GH); this is in concordance with the findings that we observed in the hippocampus of rats in which we induced damage with kainic acid, and GH administration increased the number of newly formed neural precursors [24]
In this study we demonstrated that the treatment with GH, administered immediately after the frontal motor cortex ablation, and rehabilitation, induced a functional recovery of the deficit in manual ability caused by the lesion in adult rats; we observed that this ablation stimulated cell proliferation in the perilesional cortex and this effect was significantly enhanced by GH treatment in animals sacrificed at 5 dpi, it decreased markedly at 25 dpi

Summary

Introduction

Traumatic brain injury (TBI) represents one of the biggest health problems in developed countries, both because of the number of deaths it causes as well as the high percentage of those affected who suffer from some type of motor and/or cognitive disability as a result of the injury. Some patients with TBI or stroke show spontaneous and gradual improvement during the first 6–12 months after the injury [2] This improvement is attributed to structural and functional compensatory changes that occur in the damaged brain, carried out by what is described as neuroplastic mechanisms. While it is clear that rehabilitation plays an important role in recovery from neurological injury, its effects are strongly increased when it is accompanied by medical treatments, as previously suggested [3] One of these treatments consists of the administration of growth hormone (GH), a hormone that, together with its mediator insulin-like growth factor (IGF-I), plays a key role in fetal neurodevelopment [16,17], and significantly contributes to enhancing the effects of rehabilitation after a brain injury in animal models [18,19,20,21,22,23,24,25,26] and human patients [27,28,29,30,31,32,33,34]

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