Cell Proliferation in the Piriform Cortex of Rats with Motor Cortex Ablation Treated with Growth Hormone and Rehabilitation.

Margarita Heredia,Jesús Devesa,Adelaida Sánchez Riolobos,José María Criado,Virginia Sánchez-Robledo,Pablo Devesa,Antonio De La Fuente,Inés Gómez

doi:10.3390/ijms22115440

Margarita Heredia, Jesús Devesa + Show 6 more

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https://doi.org/10.3390/ijms22115440

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Abstract

Traumatic brain injury represents one of the main health problems in developed countries. Growth hormone (GH) and rehabilitation have been claimed to significantly contribute to the recovery of lost motor function after acquired brain injury, but the mechanisms by which this occurs are not well understood. In this work, we have investigated cell proliferation in the piriform cortex (PC) of adult rats with ablation of the frontal motor cortex treated with GH and rehabilitation, in order to evaluate if this region of the brain, related to the sense of smell, could be involved in benefits of GH treatment. Male rats were either ablated the frontal motor cortex in the dominant hemisphere or sham-operated and treated with GH or vehicle at 35 days post-injury (dpi) for five days. At 36 dpi, all rats received daily injections of bromodeoxyuridine (BrdU) for four days. We assessed motor function through the paw-reaching-for-food task. GH treatment and rehabilitation at 35 dpi significantly improved the motor deficit caused by the injury and promoted an increase of cell proliferation in the PC ipsilateral to the injury, which could be involved in the improvement observed. Cortical ablation promoted a greater number of BrdU+ cells in the piriform cortex that was maintained long-term, which could be involved in the compensatory mechanisms of the brain after injury.

Highlights

In 2020, traumatic brain injury (TBI) has been declared the third leading cause of death globally [1]
In the present study piriform cortex (PC) proliferation data have been obtained from only 6 animals, each one representative of the different experimental groups and controls investigated, this does not make them less valid; given that in these animals, the findings found would have participated in their behavioral results; since in our experiments, as in patients with TBI, each individual is unique and the mechanisms implemented after injury and those involved in the benefits of Growth hormone (GH) treatment may be unique or shared with other individuals
The data obtained in this study indicate that long-term GH treatment after ablation of the motor cortex induced a significant improvement in the deficit in manual skill caused by the injury, and an increase in cell proliferation of the piriform cortex ipsilateral to the injury

Summary

Introduction

In 2020, traumatic brain injury (TBI) has been declared the third leading cause of death globally [1]. This leads to the release of the excitatory neurotransmitter glutamate, which will bind to ionotropic receptors on target neurons [9]. In response to excitotoxicity due to increased intracellular Ca+2, there is an activation of microglia and resident astrocytes, and of leukocytes and macrophages released by the breakdown of the blood-brain barrier and vascular endothelium. In this way, a glial scar will appear around the damaged area to regulate extracellular glutamate levels and protect against initial trauma [5,10]

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